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FXR REGULATOR, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION THEREOF AND USE THEREOF

20240239775 ยท 2024-07-18

    Inventors

    Cpc classification

    International classification

    Abstract

    The present invention relates to a compound capable of being used as an FXR regulator, a pharmaceutically acceptable salt or ester, a stereoisomer, a tautomer, a geometric isomer, a prodrug, a hydrate, a solvate or a crystalline form thereof, a metabolite form of same, or any combination or mixture of same, and also relates to a preparation method therefor, a pharmaceutical composition thereof and the use thereof.

    Claims

    1. A benzofuran derivative of formula (I): ##STR00466## wherein, R.sup.1 is (CH.sub.2).sub.nR.sup.4, wherein n is an integer from 0 to 6, R.sup.4 is an unsubstituted aromatic hydrocarbyl, a substituted aromatic hydrocarbyl, an unsubstituted heteroaryl, or a substituted heteroaryl; the substituted aromatic hydrocarbyl or the substituted heteroaryl means that the aromatic hydrocarbyl or heteroaryl is substituted with one or more groups selected from Group A; in formula (I), R.sup.2 is a hydroxyl, an unsubstituted C1-C6 alkoxy, a substituted C1-C6 alkoxy, or NR.sup.5R.sup.6, wherein R.sup.5 and R.sup.6 here are each independently selected from a group consisting of hydrogen, unsubstituted C1-C6 alkyl, and substituted C1-C6 alkyl; the substituted C1-C6 alkoxy means that one or more hydrogens on the C1-C6 alkoxy are substituted by groups selected from a group consisting of phenyl, halogen, nitro, hydroxyl and C1-C6 alkyl; the substituted C1-C6 alkyl means that one or more hydrogens on the C1-C6 alkyl are substituted by groups selected from a group consisting of phenyl, halogen, hydroxyl and C1-C6 alkyl; R.sup.3 is an unsubstituted C1-C6 alkyl or a substituted C1-C6 alkyl; the group in Group A refers to one or more of the following groups: halogen, nitro, cyano, substituted or unsubstituted aromatic hydrocarbyl, substituted or unsubstituted aryloxy, unsubstituted C1-C6 alkyl, unsubstituted C2-C6 alkenyl, carboxyl-substituted C2-C6 alkenyl, unsubstituted C2-C6 alkynyl, carboxyl-substituted C2-C6 alkynyl, carbamoyl, halogenated C1-C6 alkyl, aromatic hydrocarbyl-substituted C1-C6 alkyl, carboxyl-substituted C1-C6 alkyl, C1-C6 alkoxycarbonyl, unsubstituted C1-C6 alkoxy, halogenated C1-C6 alkoxy, unsubstituted C1-C6 alkylthio group, halogenated C1-C6 alkylthio group, C1-C6 alkylamide group, and substituted or unsubstituted heterocycloalkyl, wherein the substituted aromatic hydrocarbyl, substituted aryloxy or substituted heterocycloalkyl means that an aromatic hydrocarbyl, aryloxy or heterocycloalkyl is substituted with one or more groups selected from Group B, or that a C1-C6 alkyl and N in a heterocycloalkyl form a quaternary ammonium; the group in Group B is selected from: cyano, aromatic hydrocarbyl-substituted C1-C6 alkanoyl, aromatic hydrocarbyl-substituted C1-C6 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C6 alkanoyl, unsubstituted C1-C6 alkane sulfonyl, aromatic hydrocarbyl-substituted C1-C6 alkane sulfonyl, single- or double-C1-C6 substituted carbamoyl, carbamoyl, and C1-C6 alkoxycarbonyl; it is also required that, when R.sup.1 is (CH.sub.2).sub.nR.sup.4, n is 1, R.sup.4 is phenyl and R.sup.3 is methyl, R.sup.2 is not hydroxyl; or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the benzofuran derivative, metabolite forms thereof, or any combination or mixture thereof.

    2. The benzofuran derivative according to claim 1, wherein, in formula (I), R.sup.3 is methyl, and/or R.sup.2 is hydroxyl.

    3. The benzofuran derivative according to claim 1, wherein, in formula (I), R.sup.2 is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, tert-butoxy or benzyl; preferably, R.sup.2 is ethoxy.

    4. The benzofuran derivative according to claim 1, wherein, in formula (I), R.sup.2 is NR.sup.5R.sup.6, wherein R.sup.5 and R.sup.6 are each independently selected from a group consisting of hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, neopentyl, benzyl, and phenethyl; preferably, R.sup.2 is phenylethylamino.

    5. The benzofuran derivative according to any one of claims 1 to 4, wherein, in formula (I), n is 0; R.sup.4 is phenyl, naphthyl, pyridyl, or quinoline, or, phenyl, naphthyl, pyridyl, or quinoline substituted with one or more of the following groups: benzyl, phenoxy, halogen, nitro, cyano, carboxyl, unsubstituted C1-C6 alkyl, halogenated C1-C6 alkyl, halogenated C1-C6 alkoxy, carbamoyl, halogenated C1-C6 alkylthio, C1-C6 alkanoyl, morpholinyl, piperazinyl, piperazinmethyl, and piperidinyl, wherein the piperazinyl, piperazinylmethyl and piperidinyl are optionally substituted with one or more of the following groups: unsubstituted C1-C6 alkyl, phenyl-substituted C1-C6 alkyl, unsubstituted C1-C6 alkoxycarbonyl, unsubstituted C1-C6 alkanoyl, phenyl-substituted C1-C6 alkanoyl, C1-C6 alkane sulfonyl, single- or double-C1-C6 substituted carbamoyl; or C1-C6 alkyl and N in morpholinyl, piperazinyl, piperazinmethyl, and piperidinyl form a quaternary ammonium.

    6. The benzofuran derivative according to any one of claims 1 to 4, wherein, in formula (I), n is 1 or 2; R.sup.4 is phenyl, naphthyl, pyridyl, or quinoline, or, phenyl, naphthyl, pyridyl or quinoline substituted with one or more of the following groups: benzyl, phenoxy, halogen, nitro, cyano, carboxyl, unsubstituted C1-C6, halogenated C1-C4 alkyl, halogenated C1-C4 alkoxy, C1-C6 alkanoyl, carboxyl-substituted C1-C6 alkyl, C1-C6 alkoxycarbonyl, carbamoyl, halogenated C1-C4 alkylthio, unsubstituted C2-C6 alkenyl, carboxyl-substituted C2-C6 alkenyl, carbamoyl, morpholinyl, piperazinyl, piperazinylmethyl and piperidinyl, wherein the piperazinyl, piperazinylmethyl and piperidinyl are optionally substituted with one or more of the following groups: C1-C6 alkyl, phenyl-substituted C1-C6 alkyl, C1-C6 alkoxycarbonyl, C1-C6 alkanoyl, phenyl-substituted C1-C6 alkanoyl, C1-C4 alkane sulfonyl, single- or double-C1-C4 substituted carbamoyl.

    7. The benzofuran derivative according to claim 1, is selected from the following compounds: ethyl 3-methyl-5-(N-benzyl-N-phenethylsulfamoyl)benzofuran-2-carboxylate (F27-S8); ethyl 3-methyl-5-(N-(2-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-14); ethyl 3-methyl-5-(N-(2-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-15); ethyl 3-methyl-5-(N-(2-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-16); ethyl 3-methyl-5-(N-(2-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-17); ethyl 3-methyl-5-(N-(2-trifluoromethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-18); ethyl 3-methyl-5-(N-(2-nitrobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-19); ethyl 3-methyl-5-(N-(3-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-20); ethyl 3-methyl-5-(N-(3-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-21); ethyl 3-methyl-5-(N-(3-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-22); ethyl 3-methyl-5-(N-(3-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-23); ethyl 3-methyl-5-(N-(3-trifluoromethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-24); ethyl 3-methyl-5-(N-(3-nitrobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-25); ethyl 3-methyl-5-(N-([1,1-biphenyl]-3-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-26); ethyl 3-methyl-5-(N-3-phenoxybenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-27); ethyl 3-methyl-5-(N-(4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-28); ethyl 3-methyl-5-(N-(4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-29); ethyl 3-methyl-5-(N-(4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-30); ethyl 3-methyl-5-(N-(4-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-31); ethyl 3-methyl-5-(N-(4-trifluoromethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-32); ethyl 3-methyl-5-(N-(4-cyanobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-33); ethyl 3-methyl-5-(N-(4-(trifluoromethoxy)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-34); ethyl 3-methyl-5-(N-(4-(trifluoromethylthio)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-35); ethyl 3-methyl-5-(N-(4-isopropylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-36); ethyl 3-methyl-5-(N-(4-(tert-butyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-37); ethyl 3-methyl-5-(N-(4-acetylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-38); ethyl 3-methyl-5-(N-(4-(methoxycarbonyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-39); ethyl 3-methyl-5-(N-(4-(tert-butoxycarbonyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-40); ethyl 3-methyl-5-(N-(4-(2-methoxy-2-oxoethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-41); (E)-ethyl 3-methyl-5-(N-(4-(3-methoxy-3-oxoprop-1-en-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-42); ethyl 3-methyl-5-(N-(naphthalen-1-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-43); ethyl 3-methyl-5-(N-(quinolin-8-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-44); ethyl 3-methyl-5-(N-(naphthalen-2-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-45); ethyl 3-methyl-5-(N-(2,6-difluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-46); ethyl 3-methyl-5-(N-(2-fluoro-6-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-47); ethyl 3-methyl-5-(N-(2-fluoro-6-(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-48); ethyl 3-methyl-5-(N-(2,6-dichlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-49); ethyl 3-methyl-5-(N-(2,6-dimethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-50); ethyl 3-methyl-5-(N-(2,4-difluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-51); ethyl 3-methyl-5-(N-(2-fluoro-4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-52); ethyl 3-methyl-5-(N-(2-fluoro-4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-53); ethyl 3-methyl-5-(N-(2-fluoro-4-cyanobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-54); ethyl 3-methyl-5-(N-(2-fluoro-4-(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-55); ethyl 3-methyl-5-(N-(2-chloro-4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-56); ethyl 3-methyl-5-(N-(2-(trifluoromethyl)-4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-57); ethyl 3-methyl-5-(N-(2,4-bis(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-58); ethyl 3-methyl-5-(N-(2-trifluoromethyl-4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-59); ethyl 3-methyl-5-(N-(2,4-dichlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-60); ethyl 3-methyl-5-(N-(2-methyl-5-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-61); ethyl 3-methyl-5-(N-(2,6-difluoro-4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-62); ethyl 3-methyl-5-(N-([1,1-biphenyl]-4-ylmethyl-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-82); ethyl 3-methyl-5-(N-((2-cyano-[1,1-biphenyl]-4-yl)methyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-83); ethyl 3-methyl-5-(N-((2-(tert-butoxycarbonyl)-[1,1-biphenyl]-4-yl)methyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-84); ethyl 3-methyl-5-(N-(4-benzoylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-85); 3-methyl-5-(N-(2-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S14); 3-methyl-5-(N-(2-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S15); 3-methyl-5-(N-(2-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S16); 3-methyl-5-(N-(2-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S17); 3-methyl-5-(N-(2-trifluoromethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S18); 3-methyl-5-(N-(2-nitrobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S19); 3-methyl-5-(N-(3-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S20); 3-methyl-5-(N-(3-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S21); 3-methyl-5-(N-(3-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S22); 3-methyl-5-(N-(3-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S23); 3-methyl-5-(N-(3-trifluoromethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S24); 3-methyl-5-(N-(3-nitrobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S25); 3-methyl-5-(N-([1,1-biphenyl]-3-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S26); 3-methyl-5-(N-(3-phenoxybenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S27); 3-methyl-5-(N-(4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S28); 3-methyl-5-(N-(4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S29); 3-methyl-5-(N-(4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S30); 3-methyl-5-(N-(4-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S31); 3-methyl-5-(N-(4-(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S32); 3-methyl-5-(N-(4-carbamoylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S 33); 3-methyl-5-(N-(4-(trifluoromethoxy)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S34); 3-methyl-5-(N-(4-(trifluoromethylthio)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S35); 3-methyl-5-(N-(4-isopropylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S36); 3-methyl-5-(N-(4-tert-butylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S37); 3-methyl-5-(N-(4-acetylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S38); 3-methyl-5-(N-(4-carboxybenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S39); 3-methyl-5-(N-(4-(tert-butoxycarbonyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S40); 3-methyl-5-(N-(4-(carboxymethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S41); (E)-3-methyl-5-(N-(4-(2-carboxyvinyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S42); 3-methyl-5-(N-(naphthalen-2-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S43); 3-methyl-5-(N-(quinolin-8-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S44); 3-methyl-5-(N-(naphthalen-2-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S45); 3-methyl-5-(N-(2,6-difluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S 46); 3-methyl-5-(N-(2-fluoro-6-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S47); 3-methyl-5-(N-(2-fluoro-6-(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S48); 3-methyl-5-(N-(2,6-dichlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S 49); 3-methyl-5-(N-(2,6-dimethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S 50); 3-methyl-5-(N-(2,4-difluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S 51); 3-methyl-5-(N-(2-fluoro-4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S52); 3-methyl-5-(N-(2-fluoro-4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S53); 3-methyl-5-(N-(2-fluoro-4-(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S55); 3-methyl-5-(N-(2-chloro-4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S56); 3-methyl-5-(N-(2-(trifluoromethyl)-4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S57); 3-methyl-5-(N-(2,4-bis(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S58); 3-methyl-5-(N-(2-(trifluoromethyl)-4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S59); 3-methyl-5-(N-(2,4-dichlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S 60); 3-methyl-5-(N-(2-methyl-5-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S61); 3-methyl-5-(N-(2,6-difluoro-4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S62); 3-methyl-5-(N-([1,1-biphenyl]-4-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S82); 3-methyl-5-(N-(2-cyano-[1,1-biphenyl]-4-yl)methyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S83); 3-methyl-5-(N-((2-(tert-butoxycarbonyl)-[1,1-biphenyl]-4-yl)methyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S84); 3-methyl-5-(N-(4-benzoylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S85); ethyl 3-methyl-5-(N-phenyl-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-10); ethyl 3-methyl-5-(N-(4-benzylphenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-11); ethyl 3-methyl-5-(N-(4-phenoxyphenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-12); ethyl 3-methyl-5-(N,N-diphenylethylsulfamoyl)benzofuran-2-carboxylate (M8-13); ethyl 3-methyl-5-(N-(4-morpholinophenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-63); ethyl 3-methyl-5-(N-(4-(4-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-64); ethyl 3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-65); ethyl 3-methyl-5-(N-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-66); ethyl 3-methyl-5-(N-(4-(4-(propoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzo furan-2-carboxylate (M8-67); ethyl 3-methyl-5-(N-(4-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-68); ethyl 3-methyl-5-(N-(4-(4-benzoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-69); ethyl 3-methyl-5-(N-(4-(4-benzylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-70); ethyl 3-methyl-5-(N-(4-(4-(dimethylcarbamoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-71); ethyl 3-methyl-5-(N-(4-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-72); ethyl 3-methyl-5-(N-(4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-73); ethyl 3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-74); ethyl 3-methyl-5-(N-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl) pyridin-3-yl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-75); ethyl 3-methyl-5-(N-(4-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-76); ethyl 3-methyl-5-(N-(2-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-77); ethyl 3-methyl-5-(N-(3-(4-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-78); ethyl 3-methyl-5-(N-(4-morpholinobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-79); ethyl 3-methyl-5-(N-(4-(4-methylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-80); ethyl 3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-81); ethyl 3-methyl-5-(N-phenethyl-N-(4-phenoxybenzyl)sulfamoyl)benzofuran-2-carboxylate (M8-86); ethyl 3-methyl-5-(N-(2-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-87); ethyl 3-methyl-5-(N-(3-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-88); 3-methyl-5-(N-phenethyl-N-phenylsulfamoyl)benzofuran-2-carboxylic acid (F27-S10); 3-methyl-5-(N-(4-benzylphenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S11); 3-methyl-5-(N-(4-phenoxyphenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S12); 3-methyl-5-(N,N-diphenylethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S13); 3-methyl-5-(N-(4-morpholinophenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S63); 3-methyl-5-(N-(4-(4-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S64); 3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S65); 3-methyl-5-(N-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S66); 3-methyl-5-(N-(4-(4-(propoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S67); 3-methyl-5-(N-(4-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S68); 3-methyl-5-(N-(4-(4-benzoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S69); 3-methyl-5-(N-(4-(4-benzylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S70); 3-methyl-5-(N-(4-(4-(dimethylcarbamoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S71); 3-methyl-5-(N-(4-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S72); 3-methyl-5-(N-(4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S73); 3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S74); 3-methyl-5-(N-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-3-yl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S75); 3-methyl-5-(N-(4-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)phenyl)-N-phenethylsulfonamide)benzofuran-2-carboxylic acid (F27-S76); 3-methyl-5-(N-(2-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S77); 3-methyl-5-(N-(3-(4-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S78); 3-methyl-5-(N-(4-(4-morpholinobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S79); 3-methyl-5-(N-(4-(4-methylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S80); 3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S81); 3-methyl-5-(N-(4-(4-phenoxybenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S86); 3-methyl-5-(N-(2-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S87); 3-methyl-5-(N-(3-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S88); ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M9-1); ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)benzyl)sulfamoyl)benzofuran-2-carboxylate (M9-2); 4-(2-((2-(ethoxycarbonyl)-3-methyl-N-phenethylbenzofuran)-5-sulfonylamino)phenyl)-1,1-dimethylpiperazin-1-ium (M10-90); ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-91); ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-92); ethyl 3-methyl-5-(N-(2-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-93); ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94); ethyl 3-methyl-5-(N-(2-(4-(4-(benzylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-95); ethyl 3-methyl-5-(N-(2-(4-(benzoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-96); ethyl 3-methyl-5-(N-(2-(4-methylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-98); 4-(2-((2-(ethoxycarbonyl)-3-methyl-N-benzylethylbenzofuran)-5-sulfonylamino)phenyl)-1,1-dimethylpiperazin-1-ium (M10-99); ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-100); ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-101); ethyl 3-methyl-5-(N-(2-(4-methanesulfonylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-102); ethyl 3-methyl-5-(N-(2-(4-(3,3-dimethylbutyryl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-103); ethyl 3-methyl-5-(N-(2-(4-benzylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-104); ethyl 3-methyl-5-(N-(2-(4-benzoylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-105); 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylic acid (F27-S89); 4-(2-((2-carboxy-3-methyl-N-phenethylbenzofuran)-5-sulfonylamino)phenyl)-1,1-dimethylpiperazin-1-ium (F27-S90); 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S91); 3-methyl-5-(N-(2-(4-(dimethylcarbamoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S92); 3-methyl-5-(N-(2-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S93); 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzo furan-2-carboxylic acid (F27-S94); 3-methyl-5-(N-(2-(4-(4-(benzylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S95); 3-methyl-5-(N-(2-(4-(benzoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S96); 3-methyl-5-(N-(2-(piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S97); 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S98); 4-(2-((2-carboxy-3-methyl-N-phenethylbenzofuran)-5-sulfonamido)methyl)phenyl)-1,1-dimethylpiperazin-1-ium (F27-S99); 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S100); 3-methyl-5-(N-(2-(4-(dimethylcarbamoyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S101); 3-methyl-5-(N-(2-(4-(methylsulfonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S102); 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzo furan-2-carboxylic acid (F27-S103); 3-methyl-5-(N-(2-(4-benzylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S104) and 3-methyl-5-(N-(2-(4-benzoylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S105); or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the benzofuran derivative, metabolite forms thereof, or any combination or mixture thereof.

    8. A pharmaceutical composition, comprising the benzofuran derivative according to any one of claims 1 to 7.

    9. Use of a benzofuran derivative of formula (II) as an FXR modulator: ##STR00467## wherein, R.sup.1 is (CH.sub.2).sub.nR.sup.4, wherein n is an integer from 0 to 6, R.sup.4 is an unsubstituted aromatic hydrocarbyl, a substituted aromatic hydrocarbyl, an unsubstituted heteroaryl, or a substituted heteroaryl; the substituted aromatic hydrocarbyl or the substituted heteroaryl means that the aromatic hydrocarbyl or heteroaryl is substituted with one or more groups selected from Group A; in formula (II), R.sup.2 is a hydroxyl, an unsubstituted C1-C6 alkoxy, a substituted C1-C6 alkoxy, or NR.sup.5R.sup.6, wherein R.sup.5 and R.sup.6 here are each independently selected from a group consisting of hydrogen, unsubstituted C1-C6 alkyl, and substituted C1-C6 alkyl; the substituted C1-C6 alkoxy means that one or more hydrogens on the C1-C6 alkoxy are substituted by groups selected from a group consisting of phenyl, halogen, nitro, hydroxyl and C1-C6 alkyl; the substituted C1-C6 alkyl means that one or more hydrogens on the C1-C6 alkyl are substituted by groups selected from a group consisting of phenyl, halogen, hydroxyl and C1-C6 alkyl; R.sup.3 is an unsubstituted C1-C6 alkyl or a substituted C1-C6 alkyl; the group in Group A refers to one or more of the following groups: halogen, nitro, cyano, substituted or unsubstituted aromatic hydrocarbyl, substituted or unsubstituted aryloxy, unsubstituted C1-C6 alkyl, unsubstituted C2-C6 alkenyl, carboxyl-substituted C2-C6 alkenyl, unsubstituted C2-C6 alkynyl, carboxyl-substituted C2-C6 alkynyl, carbamoyl, halogenated C1-C6 alkyl, aromatic hydrocarbyl-substituted C1-C6 alkyl, carboxyl-substituted C1-C6 alkyl, C1-C6 alkoxycarbonyl, unsubstituted C1-C6 alkoxy, halogenated C1-C6 alkoxy, unsubstituted C1-C6 alkylthio group, halogenated C1-C6 alkylthio group, C1-C6 alkylamide group, and substituted or unsubstituted heterocycloalkyl, wherein the substituted aromatic hydrocarbyl, substituted aryloxy or substituted heterocycloalkyl means that an aromatic hydrocarbyl, aryloxy or heterocycloalkyl is substituted with one or more groups selected from Group B, or that a C1-C6 alkyl and N in a heterocycloalkyl form a quaternary ammonium; the group in Group B is selected from: cyano, aromatic hydrocarbyl-substituted C1-C6 alkanoyl, aromatic hydrocarbyl-substituted C1-C6 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C6 alkanoyl, unsubstituted C1-C6 alkane sulfonyl, aromatic hydrocarbyl-substituted C1-C6 alkane sulfonyl, single- or double-C1-C6 substituted carbamoyl, carbamoyl, and C1-C6 alkoxycarbonyl; or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the benzofuran derivative, metabolite forms thereof, or any combination or mixture thereof.

    10. The use according to claim 9, wherein, the use of the benzofuran derivative as an FXR modulator, preferably, as an FXR antagonist or inhibitor, includes but is not limited to lipid-lowering activity, anti-hyperlipidemic activity, anti-dyslipidemic activity, anti-atherosclerotic activity, anti-obesity activity, and/or anti-diabetic activity.

    11. A compound of formula (I), or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the compound, metabolite forms thereof, or any combination or mixture thereof; ##STR00468## wherein, Q is selected from a group consisting of hydrogen, 6- to 10-membered aryl, 5- to 14-membered heteroaryl, 3- to 6-membered cycloalkyl, and 3- to 6-membered heterocyclyl; optionally, the 6- to 10-membered aryl, the 5- to 14-membered heteroaryl, the 3- to 6-membered cycloalkyl, and the 3- to 6-membered heterocyclyl are substituted with one or more M, M is selected from the following groups: halogen, nitro, hydroxyl, cyano, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 alkanoyl, and C1-C6 amido; L.sup.1 is absent or selected from (CH.sub.2).sub.n, n is an integer selected from 1 to 6; optionally, (CH.sub.2).sub.n is substituted with one or more groups selected from the following: phenyl, halogen, nitro, cyano, hydroxyl, C1-C6 alkyl, deuterium, and tritium; R.sup.1 is (CH.sub.2).sub.nR.sup.4, wherein n is an integer from 0 to 6, R.sup.4 and the group in Group A are as defined in any one of claims 1-6 or 9. the group in Group B is selected from: cyano, aromatic hydrocarbyl-substituted C1-C6 alkanoyl, aromatic hydrocarbyl-substituted C1-C6 alkyl, unsubstituted C1-C6 alkyl, unsubstituted C1-C7 alkanoyl, unsubstituted C1-C6 alkane sulfonyl, aromatic hydrocarbyl-substituted C1-C6 alkane sulfonyl, single- or double-C1-C6 substituted carbamoyl, carbamoyl, C1-C6 alkoxycarbonyl, unsubstituted 3- to 6-membered cycloalkylcarbonyl, substituted 3- to 6-membered cycloalkylcarbonyl, substituted 5- to 14-membered heteroarylcarbonyl, unsubstituted 5- to 14-membered heteroarylcarbonyl, unsubstituted C2-C6 alkenylcarbonyl, unsubstituted 5- to 10-membered heterocyclylcarbonyl, and substituted 5- to 10-membered heterocyclylcarbonyl; W is 5- to 6-membered heteroaryl; R.sup.8 is selected from hydrogen, halogen, unsubstituted C1-C6 alkyl or substituted C1-C6 alkyl; m is selected from 1, 2, 3, and 4; in a case of multiple R.sup.8, all the R.sup.8 can be the same or different; R.sup.9 is selected from CH.sub.2OH or (C?O)R.sup.2, and R.sup.2 is as defined in any one of claims 1-6.

    12. The compound, or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the compound, metabolite forms thereof, or any combination or mixture thereof according to claim 11; wherein, Q is selected from 6- to 10-membered aryl, 5- to 8-membered monocyclic heteroaryl, 8- to 14-membered fused heteroaryl, 5- to 6-membered cycloalkyl, and 5- to 6-membered heterocyclyl; optionally, the 6- to 10-membered aryl, the 5- to 8-membered monocyclic heteroaryl, the 8- to 14-membered fused heteroaryl, the 5- to 6-membered cycloalkyl, and the 5- to 6-membered heterocyclyl are substituted with one or more M. preferably, Q is selected from 6- to 10-membered aryl, 5- to 8-membered monocyclic heteroaryl, and 5- to 6-membered cycloalkyl; preferably, Q is selected from phenyl, thienyl, and cyclohexyl; preferably, Q is phenyl.

    13. The compound, or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the compound, metabolite forms thereof, or any combination or mixture thereof according to claim 11 or 12; wherein, L.sup.1 is absent or selected from (CH.sub.2).sub.n, wherein n is 1, 2 or 3; preferably, L.sup.1 is (CH.sub.2).sub.2.

    14. The compound, or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the compound, metabolite forms thereof, or any combination or mixture thereof according to any one of claims 11-13; wherein, R.sup.1 is phenyl substituted with one or more groups selected from Group A; preferably, A is heterocycloalkyl that is unsubstituted or substituted with one or more groups selected from Group B; preferably, the heterocyclyl is 5- to 7-membered monoheterocyclyl, 9- to 10-membered spiroheterocyclyl, or 6- to 8-membered bridged heterocyclyl; preferably, the heterocyclyl is 5- to 7-membered nitrogen-containing monoheterocyclyl, 9- to 10-membered nitrogen-containing spiroheterocyclyl, or 6- to 8-membered nitrogen-containing bridged heterocyclyl; preferably, the heterocyclyl is piperazinyl; preferably, B is selected from: (C?O)-phenyl, (C?O)-5- to 6-membered heteroaryl, (C?O)-propenyl, (C?O)-5- to 6-membered cycloalkyl, (C?O)-5- to 6-membered heterocyclyl, and (C?O)C.sub.1-C.sub.6 alkyl; optionally, the phenyl, the 5- to 6-membered heteroaryl, the 5- to 6-membered cycloalkyl, 5- to 6-membered heterocyclyl are substituted with 1, 2 or 3 substituents selected from the following: C.sub.1-C.sub.6 alkyl (e.g., methyl), formamido, acetamido, C.sub.1-C.sub.6 haloalkyl (e.g., trifluoromethyl), cyano, halogen (e.g., fluorine, chlorine, bromine), amino, nitro, C.sub.1-C.sub.6 alkanoyl (e.g., acetyl), C.sub.1-C.sub.6 alkoxy (e.g., methoxy), benzyl, and ethinyl phenyl; preferably, the 5- to 6-membered heteroaryl is selected from pyridyl, thienyl, furyl, pyrrolyl, imidazolyl, oxazolyl, thiazolyl, and pyrazolyl; optionally, the 5- to 6-membered heteroaryl is substituted with one or more C.sub.1-C.sub.6 alkyls (e.g., methyl) or halogen (e.g., bromine); preferably, the 5- to 6-membered heterocyclyl is tetrahydrothiophenyl; preferably, B is selected from (C?O)-phenyl and (C?O)-thienyl.

    15. The compound, or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the compound, metabolite forms thereof, or any combination or mixture thereof according to any one of claims 11-14, the compound is as re resented by formula (2), (3), (4), or (5), ##STR00469## wherein, X is O, S, or NR.sup.8, and R.sup.8 is hydrogen or unsubstituted C1-C6 alkyl; preferably, in formula (2), (3), (4), or (5), R.sup.8 is methyl; preferably, in formula (2), (3), (4), or (5), R.sup.2 is hydroxyl or unsubstituted C1-C6 alkoxy.

    16. The compound, or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the compound, metabolite forms thereof, or any combination or mixture thereof according to any one of claims 11-15, the compound is selected from: ##STR00470## ##STR00471## ##STR00472## ##STR00473## ##STR00474## ##STR00475## ##STR00476## ##STR00477## ##STR00478## ##STR00479## ##STR00480## ##STR00481## ##STR00482##

    17. A pharmaceutical composition, comprising the compound, or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the compound, metabolite forms thereof according to any one of claims 11-16, or any combination or mixture thereof;

    18. Use of the compound, or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the compound, metabolite forms thereof, or any combination or mixture thereof according to any one of claims 1-7 or 11-16 in preparation of a medicament, wherein the medicament is used for treating an FXR-related disease; preferably, the compound, or a pharmaceutically acceptable salt or ester, stereoisomer, tautomer, geometric isomer, prodrug, hydrate, solvate and crystal form of the compound, metabolite forms thereof, or any combination or mixture thereof is used as an FXR agonist or FXR antagonist; preferably, the FXR-related disease is selected from metabolism-related diseases, cardiovascular diseases, liver diseases, cancers, kidney diseases, enteropathies, inflammation or any combination thereof; preferably, the metabolism-related diseases are selected from glycolipid metabolism diseases, cholesterol metabolism diseases, lipid metabolism diseases, bile acid metabolism diseases or any combination thereof; preferably, the glycolipid metabolism diseases are selected from obesity, diabetes (such as type 2 diabetes), dyslipidemia, hyperlipidemia, hypercholesterolemia, cholestasis, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis or any combination thereof; preferably, the cardiovascular diseases are selected from atherosclerosis, myocardial ischemia-reperfusion injury, or combinations thereof; preferably, the liver diseases are selected from liver resection, liver injury, or combinations thereof; preferably, the cancer is selected from breast cancer, melanoma, meningioma, soft tissue sarcoma, salivary gland tumor, primary liver cancer, intraspinal tumor, mediastinal tumor, brain cancer, bone cancer, penile cancer, osteosarcoma, intracranial tumor, tongue cancer, maxillary sinus cancer, thyroid cancer, malignant lymphoma, multiple myeloma, pituitary adenoma, testicular tumor, non-Hodgkin's lymphoma, bladder cancer, leukemia, gastric cancer, nasopharyngeal cancer, laryngeal cancer, oral cancer, esophageal cancer, lung cancer, kidney cancer, cervical cancer, choriocarcinoma, vulvar cancer, skin cancer, endometrial cancer, ovarian cancer, prostate cancer, pancreatic cancer, colon cancer, rectum cancer, colorectal cancer, Kaposi's sarcoma, non-melanoma skin cancer (including squamous cell carcinoma and basal cell carcinoma), hemangioma, glioma, and secondary complications of these diseases; preferably, the kidney diseases are selected from nephritis, nephrotic syndrome, atheroembolic renal disease, or any combination thereof.

    Description

    BRIEF DESCRIPTION OF THE DRAWINGS

    [0525] The accompanying drawings are provided for better understanding of the technical solution of this application, and constitute a part of the specification. Together with the embodiments of this application, they are used to explain the technical solution of this application, and do not constitute a limitation on the technical solution of this application.

    [0526] FIG. 1 shows the activity on decreasing TG (triglyceride) (A) and TC (total cholesterol) (B) of the FXR antagonist compound F27-S96 of the present invention. #### p<0.001 Comparison between model groups and solvent groups; *** p<0.005, **** p<0.001, comparison between treated groups and model groups. The data in the FIGURE are the results of three independent repeated experiments.

    DETAILED DESCRIPTION

    [0527] In order to make the objective, technical solutions and advantages of this application more clear, the embodiments of the invention will be described in detail below. It should be noted that embodiments described herein and the features in the embodiments may be combined in any way with each other without conflict.

    [0528] MS was measured using Agilent (ESI) mass spectrometer (produced by Agilent, model: Agilent 6120B)

    [0529] A high-resolution mass spectrum was prepared, and the mass spectrum was recorded using a PE SCLEX QSTAR spectrometer.

    [0530] The H NMR and C NMR spectra were recorded using a Bruker AVIII-400 spectrometer.

    [0531] Thin-layer chromatography purification was performed by using GF254 (0.4-0.5 nm) silica gel plates.

    [0532] The reaction was monitored by thin layer chromatography (TLC). The developing solvent system used includes but is not limited to: a dichloromethane and methanol system, an n-hexane and ethyl acetate system, and a petroleum ether and ethyl acetate system. The volume ratio of the solvent was adjusted according to the compound, but a small amount of triethylamine and the like may be added for adjustment.

    [0533] Unless otherwise specified in the embodiments, reaction temperature is room temperature (20-30? C.).

    [0534] The reagents used in the examples were purchased from companies such as Acros oRganmes, Aldrich Chemical Company, or J&K Chemical.

    [0535] Abbreviations as used herein have the following meanings: [0536] EA: ethyl acetate; DCM: dichloromethane; MeOH: methanol; EtOH: ethanol; PE: petroleum ether; THF: tetrahydrofuran; DMF: N,N-dimethylformamide; AcCl: acetyl chloride; Ac.sub.2O: acetic anhydride; DMSO: dimethyl sulfoxide; NaOH: sodium hydroxide; LiOH: lithium hydroxide.

    Example 1

    Ethyl 3-methylbenzofuran-2-carboxylate (M1)

    [0537] ##STR00075##

    [0538] 2-hydroxyacetophenone (2.72 g, 20 mmol), ethyl bromoacetate (5.01 g, 30 mmol), and potassium carbonate (5.52 g, 40 mmol) were added to N,N-dimethylformamide (25 mL), and the resulting solution was then heated to 160? C. to react for 3 h. After the reaction was found to be completed from the monitoring of the TLC, the reaction system was cooled to room temperature. The solid was filtered out with suction under reduced pressure, and the filter cake was washed three times with ethyl acetate (25 mL). Filtrates were combined, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (100 mL) and then extracted three times with ether (100 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (PE/EA=15/1?10/1) to obtain 1.54 g of white solid, with a yield of 38%.

    Example 2

    ethyl 3-methyl-5-(chlorosulfonyl)benzofuran-2-carboxylate (M2)

    [0539] ##STR00076##

    [0540] Ethyl 3-methylbenzofuran-2-carboxylate (3.06 g, 15 mmol) was added to chloroform (45 mL) and the resulting solution was stirred at 0? C. for 10 min. The chloroform (45 mL) solution of chlorosulfonic acid (8.70 g, 75 mmol) was then added dropwise, and the mixed solution was stirred at room temperature for 4 h. After the reaction was found to be completed from the monitoring of the TLC, the reaction solution was poured into ice water and then extracted three times with dichloromethane (150 mL). The organic phase was combined and then washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was recrystallized with petroleum ether/ethyl acetate to obtain 2.07 g of white solid, with a yield of 46%.

    Example 3

    ethyl 3-methyl-5-(N-phenethylsulfamoyl)benzofuran-2-carboxylate (M3)

    [0541] ##STR00077##

    [0542] Ethyl 5-(chlorosulfonyl)-3-methylbenzofuran-2-carboxylate (2.07 g, 6.86 mmol) and potassium carbonate (1.89 g, 13.72 mmol) were dissolved in anhydrous dichloromethane (80 mL), anhydrous dichloromethane (20 mL) solution of phenethylamine (0.97 g, 8.23 mmol) was then added dropwise at room temperature, and the mixed solution was stirred for 3 h at room temperature. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (100 mL) and then extracted three times with ethyl acetate (100 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (PE/EA=10/1?5/1) to obtain 2.33 g of white solid, with a yield of 88%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.8 Hz, 1H), 7.84 (dd, J=8.8, 1.9 Hz, 1H), 7.59 (d, J=8.8 Hz, 1H), 7.25-7.13 (m, 3H), 7.10-6.99 (m, 2H), 4.77 (t, J=6.2 Hz, 1H), 4.47 (q, J=7.1 Hz, 2H), 3.24 (q, J=6.9 Hz, 2H), 2.77 (t, J=7.0 Hz, 2H), 2.59 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 137.6, 135.2, 129.4, 128.7, 126.8, 126.2, 125.6, 121.6, 113.0, 61.6, 44.3, 35.8, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.20H.sub.22NO.sub.5S: 388.1219, found 388.1213.

    Example 5

    ethyl 3-methyl-5-(N-benzyl-N-phenethylsulfamoyl)benzofuran-2-carboxylate (F27-S8)

    [0543] ##STR00078##

    [0544] Ethyl 3-methyl-5-(N-phenethylsulfamoyl)benzofuran-2-carboxylate (195 mg, 0.5 mmol), benzyl bromide (171 mg, 1.0 mmol) and potassium carbonate (276 mg, 2.0 mmol) were dissolved in anhydrous dichloromethane (10 mL), and the mixed solution was stirred at 60? C. overnight. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (20 mL) and then extracted three times with dichloromethane (20 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (PE/EA=20/1?2/1) to obtain 229 mg of white solid, with a yield of 96%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.5 Hz, 1H), 7.87 (dd, J=8.8, 1.7 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.39-7.23 (m, 5H), 7.22-7.09 (m, 3H), 6.95 (d, J=6.8 Hz, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.40 (s, 2H), 3.45-3.28 (m, 2H), 2.71-2.62 (m, 2H), 2.60 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 138.3, 136.0, 135.6, 129.4, 128.7, 128.7, 128.5, 128.5, 128.0, 126.5, 126.2, 125.6, 121.5, 113.1, 61.6, 52.2, 49.5, 35.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.28NO.sub.5S: 478.1688, found 478.1680.

    Example 6

    ethyl 3-methyl-5-(N-(2-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-14)

    [0545] ##STR00079##

    [0546] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-fluorobenzyl bromide was used instead of benzyl bromide. 219 mg of white solid was obtained, with a yield of 88%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.10 (s, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.60 (d, J=8.8 Hz, 1H), 7.44 (t, J=7.0 Hz, 1H), 7.19 (ddp, J=28.7, 21.6, 7.4 Hz, 5H), 7.00 (dd, J=12.4, 8.1 Hz, 3H), 4.50 (s, 2H), 4.49-4.42 (m, 2H), 3.44-3.36 (m, 2H), 2.79-2.68 (m, 2H), 2.59 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 160.9 (d, J=247.5 Hz, 1C), 159.9, 155.8, 142.9, 138.1, 135.4, 131.2 (d, J=3.7 Hz, 1C), 129.8 (d, J=8.2 Hz, 1C), 129.4, 128.7, 128.5, 126.5, 126.2, 125.6, 124.5 (d, J=3.6 Hz, 1C), 123.2 (d, J=14.2 Hz, 1C), 121.5, 115.4 (d, J=21.8 Hz, 1C), 113.0, 61.6, 50.0, 45.1 (d, J=3.8 Hz, 1C), 35.2, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?118.62. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.27NO.sub.5FS: 496.1594, found 496.1595.

    Example 7

    ethyl 3-methyl-5-(N-(2-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-15)

    [0547] ##STR00080##

    [0548] ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-chlorobenzyl bromide was used instead of benzyl bromide. 204 mg of white solid was obtained, with a yield of 80%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (s, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.58-7.46 (m, 1H), 7.32 (dd, J=7.3, 1.6 Hz, 1H), 7.28-7.09 (m, 5H), 7.01 (d, J=7.0 Hz, 2H), 4.57 (s, 2H), 4.47 (q, J=7.1 Hz, 2H), 3.49-3.36 (m, 2H), 2.75-2.65 (m, 2H), 2.61 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 138.1, 135.3, 133.9, 133.3, 130.5, 129.5, 129.4, 129.1, 128.7, 128.5, 127.2, 126.5, 126.2, 125.6, 121.6, 113.1, 61.6, 50.5, 49.3, 35.3, 14.4, 9.4. HR-MS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.27NO.sub.5SCl: 512.1298, found 512.1292.

    Example 8

    ethyl 3-methyl-5-(N-(2-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-16)

    [0549] ##STR00081##

    [0550] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-bromobenzyl bromide was used instead of benzyl bromide. 267 mg of white solid was obtained, with a yield of 96%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (s, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.52 (t, J=7.5 Hz, 2H), 7.29 (t, J=7.6 Hz, 1H), 7.23-7.10 (m, 4H), 7.01 (d, J=7.0 Hz, 2H), 4.56 (s, 2H), 4.47 (q, J=7.1 Hz, 2H), 3.52-3.36 (m, 2H), 2.76-2.65 (m, 2H), 2.61 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 138.0, 135.5, 135.3, 132.8, 130.5, 129.4, 129.4, 128.7, 128.5, 127.8, 126.5, 126.2, 125.6, 123.3, 121.6, 113.1, 61.6, 51.8, 50.5, 35.2, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.27NO.sub.5SBr: 556.0793, found 556.0785.

    Example 9

    ethyl 3-methyl-5-(N-(2-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-17)

    [0551] ##STR00082##

    [0552] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-methylbenzyl bromide was used instead of benzyl bromide. 208 mg of white solid was obtained, with a yield of 85%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.17 (s, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.65 (d, J=8.7 Hz, 1H), 7.18 (tt, J=13.3, 7.4 Hz, 7H), 6.88 (d, J=6.8 Hz, 2H), 4.47 (q, J=7.1 Hz, 2H), 4.38 (s, 2H), 3.31-3.19 (m, 2H), 2.61 (s, 3H), 2.57-2.49 (m, 2H), 2.36 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 138.3, 137.6, 134.8, 133.3, 130.8, 129.7, 129.5, 128.6, 128.5, 128.3, 126.4, 126.4, 126.0, 125.6, 121.6, 113.1, 61.6, 51.2, 49.8, 35.7, 19.2, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.30NO.sub.5S: 492.1845, found 492.1835.

    Example 10

    ethyl 3-methyl-5-(N-(2-trifluoromethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-18)

    [0553] ##STR00083##

    [0554] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-trifluoromethyl benzyl bromide was used instead of benzyl bromide. 238 mg of white solid was obtained, with a yield of 87%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.20 (s, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.81 (d, J=7.9 Hz, 1H), 7.65 (t, J=8.1 Hz, 2H), 7.54 (t, J=7.6 Hz, 1H), 7.38 (t, J=7.6 Hz, 1H), 7.15 (dq, J=14.1, 6.9 Hz, 3H), 6.97 (d, J=7.1 Hz, 2H), 4.65 (s, 2H), 4.48 (q, J=7.1 Hz, 2H), 3.51-3.37 (m, 2H), 2.67-2.59 (m, 5H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.9, 143.1, 137.8, 135.7 (d, J=1.3 Hz, 1C), 135.0, 132.3, 129.7, 129.6, 128.6, 128.5, 127.6 (d, J=30.5 Hz, 1C), 127.6, 126.6, 126.1, 125.8 (t, J=6.0 Hz, 1C), 125.6, 121.6, 113.3, 61.6, 50.7, 48.3 (d, J=2.2 Hz, 1C), 34.9, 14.3, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?59.19. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.27NO.sub.5F.sub.3S: 546.1562, found 546.1562.

    Example 11

    ethyl 3-methyl-5-(N-(2-nitrobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-19)

    [0555] ##STR00084##

    [0556] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-nitrobenzyl bromide was used instead of benzyl bromide. 238 mg of white solid was obtained, with a yield of 91%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.98 (d, J=8.1 Hz, 1H), 7.89 (d, J=8.8 Hz, 1H), 7.84 (d, J=7.9 Hz, 1H), 7.64 (dd, J=19.1, 8.2 Hz, 2H), 7.43 (t, J=7.8 Hz, 1H), 7.18 (q, J=9.4, 8.3 Hz, 3H), 6.99 (d, J=7.3 Hz, 2H), 4.79 (s, 2H), 4.48 (q, J=7.1 Hz, 2H), 3.57-3.42 (m, 2H), 2.75-2.65 (m, 2H), 2.62 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.9, 148.2, 143.1, 137.7, 134.8, 133.6, 132.9, 130.2, 129.6, 128.5, 128.4, 126.6, 126.2, 125.5, 124.8, 121.6, 113.3, 61.6, 51.1, 49.3, 34.9, 14.3, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.27N.sub.2O.sub.7S: 523.1539, found 523.1534.

    Example 12

    ethyl 3-methyl-5-(N-(3-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-20)

    [0557] ##STR00085##

    [0558] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 3-fluorobenzyl bromide was used instead of benzyl bromide. 257 mg of white solid was obtained, with a yield of 99%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (s, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.27 (q, J=7.7 Hz, 1H), 7.18 (dt, J=11.6, 6.8 Hz, 3H), 7.04 (d, J=7.7 Hz, 1H), 6.97 (t, J=8.1 Hz, 4H), 4.47 (q, J=7.1 Hz, 2H), 4.38 (s, 2H), 3.46-3.30 (m, 2H), 2.74-2.64 (m, 2H), 2.61 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 163.0 (d, J=247.9 Hz, 1C), 159.9, 155.8, 143.0, 138.8 (d, J=7.1 Hz, 1C), 138.1, 135.4, 130.2 (d, J=8.3 Hz, 1C), 129.5, 128.6, 128.5, 126.6, 126.2, 125.5, 123.8 (d, J=2.9 Hz, 1C), 121.5, 115.2 (d, J=22.0 Hz, 1C), 114.9 (d, J=21.2 Hz, 1C), 113.1, 61.6, 51.7 (d, J=1.6 Hz, 1C), 49.7, 35.2, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?112.36. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.27NO.sub.5FS: 496.1594, found 496.1593.

    Example 13

    ethyl 3-methyl-5-(N-(3-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-21)

    [0559] ##STR00086##

    [0560] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 3-chlorobenzyl bromide was used instead of benzyl bromide. 230 mg of white solid was obtained, with a yield of 90%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.61 (d, J=8.8 Hz, 1H), 7.25-7.08 (m, 7H), 6.96 (d, J=7.1 Hz, 2H), 4.46 (q, J=7.1 Hz, 2H), 4.36 (s, 2H), 3.46-3.31 (m, 2H), 2.72-2.63 (m, 2H), 2.59 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 143.0, 138.4, 138.1, 135.3, 134.5, 130.0, 129.5, 128.6, 128.5, 128.3, 128.1, 126.6, 126.4, 126.2, 125.5, 121.5, 113.1, 61.6, 51.6, 49.7, 35.2, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.27NO.sub.5SCl: 512.1298, found 512.1298.

    Example 14

    ethyl 3-methyl-5-(N-(3-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-22)

    [0561] ##STR00087##

    [0562] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 3-bromobenzyl bromide was used instead of benzyl bromide. 265 mg of white solid was obtained, with a yield of 92%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.12 (s, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.63 (d, J=8.7 Hz, 1H), 7.39 (d, J=7.0 Hz, 1H), 7.31 (s, 1H), 7.18 (dq, J=14.9, 7.1 Hz, 5H), 6.98 (d, J=7.0 Hz, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.35 (s, 2H), 3.48-3.26 (m, 2H), 2.74-2.64 (m, 2H), 2.60 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 138.5, 138.1, 135.4, 131.3, 131.1, 130.2, 129.5, 128.7, 128.6, 126.9, 126.6, 126.2, 125.6, 122.7, 121.5, 113.2, 61.6, 51.5, 49.7, 35.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.27NO.sub.5SBr: 556.0793, found 556.0792.

    Example 15

    ethyl 3-methyl-5-(N-(3-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-23)

    [0563] ##STR00088##

    [0564] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 3-methylbenzyl bromide was used instead of benzyl bromide. 243 mg of white solid was obtained, with a yield of 99%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (s, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.18 (ddd, J=13.0, 8.4, 5.8 Hz, 4H), 7.08 (d, J=7.6 Hz, 1H), 7.03 (s, 2H), 6.96 (d, J=6.9 Hz, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.36 (s, 2H), 3.43-3.30 (m, 2H), 2.72-2.63 (m, 2H), 2.60 (s, 3H), 2.28 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 142.9, 138.4, 135.8, 135.7, 129.4, 129.2, 128.7, 128.7, 128.5, 128.5, 126.5, 126.3, 125.6, 125.5, 121.5, 113.0, 61.6, 52.1, 49.4, 35.2, 21.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.30NO.sub.5S: 492.1845, found 492.1844.

    Example 16

    ethyl 3-methyl-5-(N-(3-trifluoromethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-24)

    [0565] ##STR00089##

    [0566] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 3-trifluoromethyl benzyl bromide was used instead of benzyl bromide. 248 mg of white solid was obtained, with a yield of 90%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.63 (d, J=10.2 Hz, 1H), 7.51 (dd, J=13.2, 7.7 Hz, 2H), 7.44 (d, J=7.4 Hz, 2H), 7.17 (q, J=8.5, 7.5 Hz, 3H), 6.96 (d, J=7.4 Hz, 2H), 4.54-4.40 (m, 4H), 3.53-3.34 (m, 2H), 2.69 (t, J=7.6 Hz, 2H), 2.60 (s, 3H), 1.46 (t, J=6.3 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 143.1, 138.0, 137.4, 135.3, 131.7, 130.9 (d, J=32.0 Hz, 1C), 129.5, 129.2, 128.6, 128.5, 126.6, 126.2, 125.5, 124.9 (t, J=3.8 Hz, 1C), 124.7 (d, J=3.7 Hz, 1C), 123.9 (d, J=273.3 Hz, 1C), 121.5, 113.1, 61.6, 51.7, 49.8, 35.2, 14.3, 9.3. .sup.19F NMR (376 MHz, Chloroform-d) ? ?62.67. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.27NO.sub.5F.sub.3S: 546.1562, found 546.1556.

    Example 17

    ethyl 3-methyl-5-(N-(3-nitrobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-25)

    [0567] ##STR00090##

    [0568] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 3-nitrobenzyl bromide was used instead of benzyl bromide. 259 mg of white solid was obtained, with a yield of 99%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.19 (s, 1H), 8.05 (d, J=8.7 Hz, 2H), 7.90 (d, J=8.7 Hz, 1H), 7.64 (dd, J=15.4, 8.2 Hz, 2H), 7.46 (t, J=7.8 Hz, 1H), 7.12 (q, J=10.2, 8.3 Hz, 3H), 6.95 (d, J=6.9 Hz, 2H), 4.46 (dd, J=15.3, 8.2 Hz, 4H), 3.55-3.39 (m, 2H), 2.81-2.67 (m, 2H), 2.60 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.7, 155.8, 148.2, 143.0, 138.9, 137.9, 134.8, 134.2, 129.6, 129.5, 128.5, 128.5, 126.5, 126.2, 125.4, 122.8, 122.7, 121.6, 113.1, 61.5, 51.5, 50.0, 35.1, 14.3, 9.3. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.27N.sub.2O.sub.7S: 523.1539, found 523.1531.

    Example 18

    ethyl 3-methyl-5-(N-([1,1-biphenyl]-3-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-26)

    [0569] ##STR00091##

    [0570] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 3-phenylbenzyl bromide was used instead of benzyl bromide. 211 mg of white solid was obtained, with a yield of 76%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.20 (s, 1H), 7.93 (d, J=10.6 Hz, 1H), 7.61 (d, J=8.8 Hz, 1H), 7.52 (d, J=7.8 Hz, 1H), 7.47 (d, J=7.1 Hz, 2H), 7.44-7.37 (m, 4H), 7.34 (t, J=7.2 Hz, 1H), 7.28 (d, J=7.6 Hz, 1H), 7.18 (dd, J=13.4, 7.2 Hz, 3H), 7.03 (d, J=6.7 Hz, 2H), 4.53 (s, 2H), 4.49 (t, J=7.1 Hz, 2H), 3.57-3.44 (m, 2H), 2.85-2.73 (m, 2H), 2.58 (s, 3H), 1.49 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 141.5, 140.4, 138.4, 136.6, 135.8, 129.5, 129.2, 128.8, 128.7, 128.6, 127.5, 127.4, 127.0, 127.0, 126.7, 126.5, 126.3, 125.6, 121.5, 113.1, 61.6, 52.1, 49.5, 35.4, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.32NO.sub.5S: 554.2001, found 554.2007.

    Example 19

    ethyl 3-methyl-5-(N-3-phenoxybenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-27)

    [0571] ##STR00092##

    [0572] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 3-phenoxybenzyl bromide was used instead of benzyl bromide. 213 mg of white solid was obtained, with a yield of 75%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (s, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.57 (d, J=8.8 Hz, 1H), 7.27 (dt, J=10.8, 7.7 Hz, 3H), 7.16 (dq, J=14.3, 7.1 Hz, 3H), 7.10-7.00 (m, 2H), 6.97 (d, J=6.7 Hz, 2H), 6.90 (dd, J=18.7, 8.4 Hz, 4H), 4.45 (q, J=7.1 Hz, 2H), 4.36 (s, 2H), 3.46-3.31 (m, 2H), 2.76-2.64 (m, 2H), 2.58 (s, 3H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 157.6, 156.9, 155.8, 143.0, 138.3, 138.2, 135.5, 130.1, 129.8, 129.4, 128.7, 128.6, 126.6, 126.2, 125.6, 123.5, 123.3, 121.5, 118.8, 118.8, 118.3, 113.1, 61.6, 51.8, 49.5, 35.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.32NO.sub.6S: 570.1950, found 570.1948.

    Example 20

    ethyl 3-methyl-5-(N-(4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-28)

    [0573] ##STR00093##

    [0574] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-fluorobenzylbromide was used instead of benzyl bromide. 220 mg of white solid was obtained, with a yield of 89%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.25 (dd, J=8.4, 5.4 Hz, 2H), 7.21-7.11 (m, 3H), 7.04-6.90 (m, 4H), 4.47 (q, J=7.1 Hz, 2H), 4.35 (s, 2H), 3.43-3.29 (m, 2H), 2.63 (d, J=16.1 Hz, 5H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.5 (d, J=247.6 Hz, 1C), 159.9, 155.8, 143.0, 138.2, 135.4, 131.9 (d, J=3.2 Hz, 1C), 130.1 (d, J=8.2 Hz, 1C), 129.5, 128.6, 128.5, 126.5, 126.2, 125.5, 121.5, 115.6 (d, J=21.6 Hz, 1C), 113.1, 61.6, 51.5, 49.5, 35.2, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?114.08. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.27NO.sub.5FS: 496.1594, found 496.1593.

    Example 21

    ethyl 3-methyl-5-(N-(4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-29)

    [0575] ##STR00094##

    [0576] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-chlorobenzyl bromide was used instead of benzyl bromide. 222 mg of white solid was obtained, with a yield of 87%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.12 (s, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.30-7.23 (m, 2H), 7.22-7.11 (m, 5H), 6.95 (d, J=6.5 Hz, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.34 (s, 2H), 3.43-3.29 (m, 2H), 2.69-2.62 (m, 2H), 2.60 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 138.1, 135.4, 134.7, 133.8, 129.7, 129.5, 128.8, 128.6, 128.6, 126.6, 126.2, 125.5, 121.5, 113.1, 61.6, 51.6, 49.6, 35.2, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.27NO.sub.5SCl: 512.1298, found 512.1299.

    Example 22

    ethyl 3-methyl-5-(N-(4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-30)

    [0577] ##STR00095##

    [0578] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-bromobenzyl bromide was used instead of benzyl bromide. 193 mg of white solid was obtained, with a yield of 70%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.8 Hz, 1H), 7.87 (dd, J=8.8, 1.9 Hz, 1H), 7.64 (d, J=8.7 Hz, 1H), 7.42 (d, J=8.3 Hz, 2H), 7.17 (dd, J=17.6, 7.7 Hz, 5H), 6.96 (d, J=6.5 Hz, 2H), 4.49 (q, J=7.1 Hz, 2H), 4.34 (s, 2H), 3.48-3.30 (m, 2H), 2.70-2.64 (m, 2H), 2.62 (s, 3H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 143.0, 138.1, 135.3, 135.2, 131.8, 130.0, 129.4, 128.6, 128.5, 126.6, 126.2, 125.5, 121.9, 121.5, 113.1, 61.6, 51.6, 49.6, 35.2, 14.4, 9.4.

    Example 23

    ethyl 3-methyl-5-(N-(4-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-31)

    [0579] ##STR00096##

    [0580] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-methylbenzyl bromide was used instead of benzyl bromide. 101 mg of white solid was obtained, with a yield of 69%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (s, 1H), 7.88 (dd, J=8.7, 1.5 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.24-7.07 (m, 7H), 6.97 (d, J=7.0 Hz, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.37 (s, 2H), 3.42-3.31 (m, 2H), 2.73-2.64 (m, 2H), 2.60 (s, 3H), 2.33 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 142.9, 138.4, 137.7, 135.7, 132.9, 129.4, 129.4, 128.7, 128.5, 128.5, 126.5, 126.3, 125.6, 121.5, 113.0, 61.6, 51.8, 49.3, 35.2, 21.1, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.30NO.sub.5S: 492.1845, found 492.1837.

    Example 24

    ethyl 3-methyl-5-(N-(4-trifluoromethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-32)

    [0581] ##STR00097##

    [0582] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-trifluoromethyl benzyl bromide was used instead of benzyl bromide. 132 mg of white solid was obtained, with a yield of 80%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.19-8.12 (m, 1H), 7.87 (dd, J=8.8, 1.6 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.55 (d, J=8.1 Hz, 2H), 7.38 (d, J=8.0 Hz, 2H), 7.16 (t, J=7.7 Hz, 3H), 6.94 (d, J=6.5 Hz, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.43 (s, 2H), 3.48-3.32 (m, 2H), 2.74-2.64 (m, 2H), 2.60 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 143.1, 140.4, 138.0, 135.2, 129.5, 128.6, 128.6, 128.5, 126.6, 126.1, 125.6 (d, J=3.7 Hz, 1C), 125.5, 121.6, 113.2, 61.6, 51.8, 49.9, 35.1, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?62.51. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.27NO.sub.5F.sub.3S: 546.1562, found 546.1567.

    Example 25

    ethyl 3-methyl-5-(N-(4-cyanobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-33)

    [0583] ##STR00098##

    [0584] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-cyanobenzyl bromide was used instead of benzyl bromide. 189 mg of white solid was obtained, with a yield of 75%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.9 Hz, 1H), 7.86 (dd, J=8.8, 1.9 Hz, 1H), 7.63 (dd, J=22.4, 8.5 Hz, 3H), 7.39 (d, J=8.0 Hz, 2H), 7.18 (q, J=5.7 Hz, 3H), 6.98-6.89 (m, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.41 (s, 2H), 3.44-3.33 (m, 2H), 2.63 (d, J=14.3 Hz, 5H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.9, 143.2, 141.9, 137.8, 135.0, 132.5, 129.6, 128.7, 128.6, 128.6, 126.7, 126.1, 125.4, 121.6, 118.5, 113.3, 111.9, 61.7, 52.0, 50.0, 35.1, 14.4, 9.4.

    Example 26

    ethyl 3-methyl-5-(N-(4-(trifluoromethoxy)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-34)

    [0585] ##STR00099##

    [0586] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-(trifluoromethoxy) benzyl bromide was used instead of benzyl bromide. 289 mg of white solid was obtained, with a yield of 99%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.17 (d, J=1.9 Hz, 1H), 7.87 (dd, J=8.8, 1.9 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.31 (d, J=8.6 Hz, 2H), 7.18 (q, J=8.9, 7.7 Hz, 5H), 6.95 (d, J=6.6 Hz, 2H), 4.49 (q, J=7.1 Hz, 2H), 4.40 (s, 2H), 3.47-3.33 (m, 2H), 2.72-2.65 (m, 2H), 2.62 (s, 3H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 148.8, 143.0, 138.1, 135.3, 135.0, 129.7, 129.5, 128.6, 128.5, 126.5, 126.1, 125.5, 121.5, 121.1, 113.1, 61.6, 51.5, 49.6, 35.2, 14.3, 9.3.

    Example 27

    ethyl 3-methyl-5-(N-(4-(trifluoromethylthio)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-35)

    [0587] ##STR00100##

    [0588] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-(trifluoromethylthio)benzyl bromide was used instead of benzyl bromide. 237 mg of white solid was obtained, with a yield of 82%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.8 Hz, 1H), 7.85 (dd, J=8.7, 1.9 Hz, 1H), 7.59 (dd, J=17.7, 8.4 Hz, 3H), 7.32 (d, J=8.1 Hz, 2H), 7.22-7.08 (m, 3H), 6.92 (dd, J=7.6, 1.5 Hz, 2H), 4.57-4.29 (m, 4H), 3.47-3.31 (m, 2H), 2.62 (d, J=25.5 Hz, 5H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 143.1, 139.7, 138.0, 136.5, 135.2, 129.6 (d, J=309.4 Hz, 1C), 129.5, 129.3, 128.6, 128.5, 126.6, 126.2, 125.5, 123.8 (d, J=2.4 Hz, 1C), 121.6, 113.2, 61.6, 51.8, 49.9, 35.2, 14.3, 9.3. .sup.19F NMR (376 MHz, Chloroform-d) ? ?42.65.

    Example 28

    ethyl 3-methyl-5-(N-(4-isopropylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-36)

    [0589] ##STR00101##

    [0590] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-isopropyl benzyl bromide was used instead of benzyl bromide. 234 mg of white solid was obtained, with a yield of 90%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.17 (d, J=1.9 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.23-7.11 (m, 7H), 6.96 (d, J=6.8 Hz, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.39 (s, 2H), 3.45-3.32 (m, 2H), 2.89 (hept, J=6.8 Hz, 1H), 2.74-2.64 (m, 2H), 2.61 (s, 3H), 1.46 (t, J=7.1 Hz, 3H), 1.24 (d, J=6.9 Hz, 6H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 148.7, 142.9, 138.4, 135.7, 133.2, 129.4, 128.7, 128.6, 128.5, 126.7, 126.5, 126.3, 125.6, 121.5, 113.0, 61.6, 51.8, 49.3, 35.3, 33.8, 24.0, 14.4, 9.4.

    Example 29

    ethyl 3-methyl-5-(N-(4-(tert-butyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-37)

    [0591] ##STR00102##

    [0592] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-(tert-butyl)benzyl bromide was used instead of benzyl bromide. 236 mg of white solid was obtained, with a yield of 89%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.18 (d, J=1.9 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.33 (d, J=8.4 Hz, 2H), 7.23-7.11 (m, 5H), 7.00-6.92 (m, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.40 (s, 2H), 3.50-3.26 (m, 2H), 2.75-2.65 (m, 2H), 2.61 (s, 3H), 1.46 (t, J=7.1 Hz, 3H), 1.31 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 151.0, 142.9, 138.4, 135.7, 132.9, 129.4, 128.7, 128.5, 128.3, 126.5, 126.3, 125.6, 125.6, 121.6, 113.0, 61.6, 51.7, 49.3, 35.3, 34.6, 31.4, 14.4, 9.4.

    Example 30

    ethyl 3-methyl-5-(N-(4-acetylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-38)

    [0593] ##STR00103##

    [0594] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-(acetyl)benzyl bromide was used instead of benzyl bromide. 256 mg of white solid was obtained, with a yield of 98%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.11 (d, J=1.9 Hz, 1H), 7.95-7.76 (m, 3H), 7.57 (d, J=8.7 Hz, 1H), 7.33 (d, J=8.1 Hz, 2H), 7.20-7.02 (m, 3H), 6.97-6.84 (m, 2H), 4.50-4.33 (m, 4H), 3.42-3.28 (m, 2H), 2.67-2.49 (m, 8H), 1.40 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 198.8, 159.9, 155.8, 142.9, 142.2, 138.0, 136.3, 135.1, 129.4, 128.8, 128.6, 128.5, 128.4, 126.5, 126.2, 125.5, 121.5, 113.2, 61.6, 51.9, 49.9, 35.1, 26.5, 14.3, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.29H.sub.30NO.sub.6S: 520.1794, found 520.1786.

    Example 31

    ethyl 3-methyl-5-(N-(4-(methoxycarbonyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-39)

    [0595] ##STR00104##

    [0596] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-(methoxycarbonyl)benzyl bromide was used instead of benzyl bromide. 188 mg of white solid was obtained, with a yield of 70%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.12 (d, J=1.9 Hz, 1H), 7.94 (d, J=7.9 Hz, 2H), 7.85 (dd, J=8.8, 1.9 Hz, 1H), 7.61 (d, J=8.8 Hz, 1H), 7.32 (d, J=8.0 Hz, 2H), 7.14 (dq, J=14.2, 6.9 Hz, 3H), 6.92 (d, J=6.7 Hz, 2H), 4.57-4.34 (m, 4H), 3.88 (s, 3H), 3.48-3.29 (m, 2H), 2.61 (d, J=25.1 Hz, 5H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 166.6, 159.8, 155.8, 143.0, 141.4, 138.0, 135.3, 129.9, 129.8, 129.5, 128.6, 128.5, 128.2, 126.6, 126.2, 125.5, 121.5, 113.1, 61.6, 52.1, 52.0, 49.9, 35.2, 14.4, 9.4.

    Example 32

    ethyl 3-methyl-5-(N-(4-(tert-butoxycarbonyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-40)

    [0597] ##STR00105##

    [0598] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-(tert-butoxycarbonyl)benzyl bromide was used instead of benzyl bromide. 273 mg of white solid was obtained, with a yield of 94%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.12 (d, J=1.6 Hz, 1H), 7.92 (d, J=8.2 Hz, 2H), 7.87 (dd, J=8.8, 1.8 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.31 (d, J=8.2 Hz, 2H), 7.16 (p, J=6.8 Hz, 3H), 6.95 (d, J=6.7 Hz, 2H), 4.43 (s, 4H), 3.43-3.31 (m, 2H), 2.70-2.61 (m, 2H), 2.59 (s, 3H), 1.59 (s, 9H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 165.3, 159.8, 155.8, 143.0, 140.8, 138.1, 135.3, 131.7, 129.7, 129.4, 128.6, 128.5, 128.1, 126.5, 126.2, 125.5, 121.5, 113.1, 81.1, 61.5, 51.9, 49.8, 35.2, 28.2, 14.4, 9.4.

    Example 33

    ethyl 3-methyl-5-(N-(4-(2-methoxy-2-oxoethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-41)

    [0599] ##STR00106##

    [0600] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that methyl 2-(4-(bromomethyl)phenyl) acetate was used instead of benzyl bromide. 150 mg of white solid was obtained, with a yield of 55%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.9 Hz, 1H), 7.85 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.25-7.10 (m, 7H), 6.94 (d, J=6.8 Hz, 2H), 4.47 (q, J=7.1 Hz, 2H), 4.37 (s, 2H), 3.67 (s, 3H), 3.60 (s, 2H), 3.41-3.29 (m, 2H), 2.62 (d, J=20.1 Hz, 5H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 171.8, 159.9, 155.8, 143.0, 138.3, 135.5, 134.9, 133.8, 129.6, 129.4, 128.7, 128.5, 126.5, 126.2, 125.6, 121.5, 113.1, 61.6, 52.1, 51.7, 49.4, 40.8, 35.2, 14.4, 9.4.

    Example 34

    (E)ethyl-3-methyl-5-(N-(4-(3-methoxy-3-oxoprop-1-en-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-42)

    [0601] ##STR00107##

    [0602] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that methyl [0603] (E)-3-(4-(bromomethyl)phenyl) acrylate was used instead of benzyl bromide. 134 mg of white solid was obtained, with a yield of 48%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.9 Hz, 1H), 7.87 (dd, J=8.8, 1.9 Hz, 1H), 7.69-7.59 (m, 2H), 7.44 (d, J=8.1 Hz, 2H), 7.29 (d, J=8.0 Hz, 2H), 7.22-7.10 (m, 3H), 6.95 (dd, J=7.9, 1.6 Hz, 2H), 6.42 (d, J=16.0 Hz, 1H), 4.47 (q, J=7.1 Hz, 2H), 4.41 (s, 2H), 3.80 (s, 3H), 3.44-3.34 (m, 2H), 2.73-2.64 (m, 2H), 2.59 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 167.2, 159.8, 155.8, 144.0, 143.0, 138.6, 138.1, 135.4, 134.1, 129.4, 128.8, 128.6, 128.5, 128.3, 126.5, 126.2, 125.5, 121.5, 118.1, 113.1, 61.6, 51.9, 51.7, 49.7, 35.2, 14.4, 9.4.

    Example 35

    ethyl 3-methyl-5-(N-(naphthalen-1-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-43)

    [0604] ##STR00108##

    [0605] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 1-(bromomethyl) naphthalene was used instead of benzyl bromide. 220 mg of white solid was obtained, with a yield of 84%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.28 (d, J=8.1 Hz, 1H), 8.20 (s, 1H), 7.95 (d, J=8.5 Hz, 1H), 7.81 (t, J=6.7 Hz, 2H), 7.62 (d, J=8.7 Hz, 1H), 7.50 (dt, J=15.2, 6.7 Hz, 2H), 7.36 (d, J=8.8 Hz, 2H), 7.08 (d, J=7.3 Hz, 3H), 6.75 (d, J=6.7 Hz, 2H), 4.80 (s, 2H), 4.46 (q, J=6.9 Hz, 2H), 3.40-3.10 (m, 2H), 2.58 (s, 3H), 2.46-2.29 (m, 2H), 1.44 (t, J=7.0 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.9, 143.0, 138.3, 134.5, 133.9, 132.0, 130.9, 129.5, 129.4, 128.7, 128.6, 128.4, 127.9, 126.8, 126.5, 126.4, 126.2, 125.6, 125.0, 124.0, 121.7, 113.1, 61.6, 51.4, 49.9, 35.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.31H.sub.30NO.sub.5S: 528.1845, found 528.1837.

    Example 36

    ethyl 3-methyl-5-(N-(quinolin-8-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-44)

    [0606] ##STR00109##

    [0607] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 8-(bromomethyl)quinoline was used instead of benzyl bromide. 222 mg of white solid was obtained, with a yield of 84%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.83 (d, J=2.6 Hz, 1H), 8.19-8.07 (m, 2H), 7.95 (d, J=7.1 Hz, 1H), 7.88 (d, J=10.3 Hz, 1H), 7.71 (d, J=8.0 Hz, 1H), 7.61-7.47 (m, 2H), 7.36 (dd, J=8.2, 4.2 Hz, 1H), 7.11 (dq, J=14.2, 7.0 Hz, 3H), 6.94 (d, J=7.0 Hz, 2H), 5.22 (s, 2H), 4.46 (q, J=7.1 Hz, 2H), 3.71-3.50 (m, 2H), 2.91-2.66 (m, 2H), 2.56 (s, 3H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.6, 149.5, 146.2, 142.8, 138.4, 136.4, 135.7, 134.8, 129.7, 129.2, 128.7, 128.4, 128.1, 127.7, 126.5, 126.3, 126.3, 125.6, 121.4, 121.2, 112.8, 61.5, 50.8, 47.5, 35.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.30H.sub.29N.sub.2O.sub.5S: 529.1797, found 529.1790.

    Example 37

    ethyl 3-methyl-5-(N-(naphthalen-2-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-45)

    [0608] ##STR00110##

    [0609] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-(bromomethyl)naphthalene was used instead of benzyl bromide. 214 mg of white solid was obtained, with a yield of 81%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (s, 1H), 7.92 (d, J=8.8 Hz, 1H), 7.82-7.69 (m, 3H), 7.66-7.57 (m, 2H), 7.50-7.38 (m, 3H), 7.14 (t, J=7.5 Hz, 3H), 6.95 (d, J=6.2 Hz, 2H), 4.58 (s, 2H), 4.48 (q, J=7.1 Hz, 2H), 3.53-3.41 (m, 2H), 2.79-2.68 (m, 2H), 2.52 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.7, 142.9, 138.3, 135.6, 133.5, 133.2, 133.0, 129.4, 128.7, 128.6, 128.5, 127.8, 127.7, 127.4, 126.5, 126.4, 126.3, 126.2, 126.1, 125.6, 121.6, 113.1, 61.6, 52.4, 49.7, 35.3, 14.4, 9.3. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.31H.sub.30NO.sub.5S: 528.1845, found 528.1853.

    Example 38

    ethyl 3-methyl-5-(N-(2,6-difluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-46)

    [0610] ##STR00111##

    [0611] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2,6-difluorobenzyl bromide was used instead of benzyl bromide. 203 mg of white solid was obtained, with a yield of 79%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.6 Hz, 1H), 7.87 (dd, J=8.8, 1.9 Hz, 1H), 7.59 (d, J=8.8 Hz, 1H), 7.31-7.21 (m, 3H), 7.20-7.13 (m, 1H), 7.12-7.05 (m, 2H), 6.85 (t, J=7.9 Hz, 2H), 4.56 (s, 2H), 4.48 (q, J=7.1 Hz, 2H), 3.49-3.35 (m, 2H), 2.94-2.80 (m, 2H), 2.61 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 161.8 (dd, J=251.5, 7.8 Hz, 1C), 159.9, 155.8, 142.9, 138.3, 135.2, 130.5 (t, J=10.5 Hz, 1C), 129.2, 128.7 (d, J=20.6 Hz, 1C), 126.4 (d, J=10.4 Hz, 1C), 125.6, 121.6, 112.9, 111.9, 111.6 (dd, J=19.5, 6.1 Hz, 1C), 61.5, 49.9, 39.4 (t, J=2.9 Hz, 1C), 35.5, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?112.91. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.26NO.sub.5F.sub.2S: 514.1500, found 514.1494.

    Example 39

    ethyl 3-methyl-5-(N-(2-fluoro-6-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-47)

    [0612] ##STR00112##

    [0613] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-fluoro-6-chlorobenzyl bromide was used instead of benzyl bromide. 240 mg of white solid was obtained, with a yield of 91%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (d, J=1.7 Hz, 1H), 7.91 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.25-7.13 (m, 5H), 7.04-6.94 (m, 3H), 4.63 (s, 2H), 4.48 (q, J=7.1 Hz, 2H), 3.40-3.28 (m, 2H), 2.78-2.70 (m, 2H), 2.62 (s, 3H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.2 (d, J=252.6 Hz, 1C), 159.9, 155.8, 142.9, 138.3, 136.3 (d, J=5.2. Hz, 1C), 134.9, 130.5 (d, J=10.0 Hz, 1C), 129.3, 128.7, 128.5, 126.5, 126.4, 125.8 (d, J=3.4 Hz, 1C), 125.6, 121.7, 121.5 (d, J=17.0 Hz, 1C), 114.3 (d, J=22.8 Hz, 1C), 112.9, 61.6, 50.1, 43.6 (d, J=2.7 Hz, 1C), 35.9, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?110.75. HRMS (ESI) [M+H]+, theoretically calculated for C.sub.27H.sub.26NO.sub.5FSCl: 530.1204, found 530.1207.

    Example 40

    ethyl 3-methyl-5-(N-(2-fluoro-6-(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-48)

    [0614] ##STR00113##

    [0615] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-fluoro-6-(trifluoromethyl)benzyl bromide was used instead of benzyl bromide. 260 mg of white solid was obtained, with a yield of 92%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.22-8.13 (m, 1H), 7.91 (dd, J=8.8, 1.5 Hz, 1H), 7.61 (d, J=8.8 Hz, 1H), 7.47 (d, J=7.7 Hz, 1H), 7.41 (q, J=7.9 Hz, 1H), 7.14 (tt, J=22.7, 8.2 Hz, 4H), 6.88 (d, J=7.1 Hz, 2H), 4.66 (s, 2H), 4.44 (q, J=7.1 Hz, 2H), 3.35-3.18 (m, 2H), 2.58 (d, J=7.2 Hz, 5H), 1.42 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.4 (d, J=252.4 Hz, 1C), 159.8, 155.8, 142.9, 138.2, 134.4, 130.5 (d, J=9.5 Hz, 1C), 129.4, 128.5 (d, J=6.8 Hz, 1C), 126.5 (d, J=13.2 Hz, 1C), 125.5, 122.4, 122.0, 121.8, 119.9 (d, J=22.9 Hz, 1C), 113.0, 61.5, 50.0, 43.3, 35.9, 14.3, 9.3. .sup.19F NMR (376 MHz, Chloroform-d) ? ?57.85, ?109.39. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.26NO.sub.5F.sub.4S: 564.1468, found 564.1466.

    Example 41

    ethyl 3-methyl-5-(N-(2,6-dichlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-49)

    [0616] ##STR00114##

    [0617] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2,6-dichloro benzyl bromide was used instead of benzyl bromide. 254 mg of white solid was obtained, with a yield of 93%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.17 (d, J=1.5 Hz, 1H), 7.93 (dd, J=8.8, 1.8 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.27 (d, J=7.7 Hz, 2H), 7.24-7.08 (m, 4H), 6.92 (d, J=6.9 Hz, 2H), 4.70 (s, 2H), 4.47 (q, J=7.1 Hz, 2H), 3.41-3.21 (m, 2H), 2.62 (d, J=5.8 Hz, 5H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 142.9, 138.3, 137.2, 134.3, 130.8, 130.3, 129.3, 128.8, 128.7, 128.5, 126.6, 126.4, 125.6, 121.8, 112.9, 61.6, 50.2, 48.0, 36.6, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.26NO.sub.5SCl.sub.2: 546.0909, found 546.0917.

    Example 42

    ethyl 3-methyl-5-(N-(2,6-dimethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-50)

    [0618] ##STR00115##

    [0619] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2,6-dimethylbenzyl bromide was used instead of benzyl bromide. 122 mg of white solid was obtained, with a yield of 80%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.21-8.11 (m, 1H), 7.93 (dd, J=8.7, 1.6 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H), 7.23-7.09 (m, 4H), 7.04 (d, J=7.5 Hz, 2H), 6.79 (d, J=6.8 Hz, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.42 (s, 2H), 3.15-3.04 (m, 2H), 2.63 (s, 3H), 2.55-2.45 (m, 2H), 2.34 (s, 6H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 138.5, 138.5, 133.9, 130.9, 129.5, 128.8, 128.6, 128.5, 126.4, 126.3, 125.6, 121.7, 113.0, 61.6, 49.9, 47.6, 37.0, 20.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.29H.sub.32NO.sub.5S: 506.2001, found 506.1993.

    Example 43

    ethyl 3-methyl-5-(N-(2,4-difluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-51)

    [0620] ##STR00116##

    [0621] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2,4-difluorobenzyl bromide was used instead of benzyl bromide. 252 mg of white solid was obtained, with a yield of 98%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.10 (s, 1H), 7.83 (d, J=8.7 Hz, 1H), 7.61 (d, J=8.8 Hz, 1H), 7.44 (q, J=8.4 Hz, 1H), 7.17 (dq, J=14.1, 7.0 Hz, 3H), 7.01 (d, J=6.9 Hz, 2H), 6.85 (t, J=8.1 Hz, 1H), 6.80-6.70 (m, 1H), 4.47 (dd, J=15.5, 8.3 Hz, 4H), 3.46-3.33 (m, 2H), 2.78-2.67 (m, 2H), 2.60 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 163.0 (dd, J=250.8, 12.2 Hz, 1C), 160.8 (dd, J=249.8, 11.9 Hz, 1C), 159.9, 155.8, 143.0, 138.0, 135.3, 132.1 (dd, J=9.7, 5.4 Hz, 1C), 129.4, 128.6 (d, J=11.1 Hz, 1C), 126.6, 126.2, 125.5, 121.5, 119.3 (dd, J=14.3, 3.7 Hz, 1C), 113.1, 111.8 (dd, J=21.3, 3.7 Hz, 1C), 103.7 (t, J=25.6 Hz, 1C), 61.6, 50.0, 44.8 (d, J=3.1 Hz, 1C), 35.1, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?109.80, ?114.40. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.26NO.sub.5F.sub.2S: 514.1500, found 514.1497.

    Example 44

    ethyl 3-methyl-5-(N-(2-fluoro-4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-52)

    [0622] ##STR00117##

    [0623] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-fluoro-4-chlorobenzyl bromide was used instead of benzyl bromide. 252 mg of white solid was obtained, with a yield of 95%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.08 (d, J=1.5 Hz, 1H), 7.83 (dd, J=8.8, 1.8 Hz, 1H), 7.60 (d, J=8.8 Hz, 1H), 7.38 (t, J=8.2 Hz, 1H), 7.17 (dq, J=14.3, 7.1 Hz, 3H), 7.11-7.06 (m, 1H), 7.05-6.96 (m, 3H), 4.54-4.38 (m, 4H), 3.47-3.34 (m, 2H), 2.80-2.66 (m, 2H), 2.59 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 160.9 (d, J=250.9 Hz, 1C), 159.8, 155.8, 143.0, 137.9, 135.2, 134.6 (d, J=10.2 Hz, 1C), 131.9 (d, J=4.6 Hz, 1C), 129.4, 128.6 (d, J=10.8 Hz, 1C), 126.6, 126.2, 125.5, 124.9 (d, J=3.5 Hz, 1C), 122.1 (d, J=14.4 Hz, 1C), 121.5, 116.1 (d, J=25.5 Hz, 1C), 113.1, 61.6, 50.2, 44.9 (d, J=3.3 Hz, 1C), 35.1, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?115.97. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.26NO.sub.5FSCl: 530.1204, found 530.1215.

    Example 45

    ethyl 3-methyl-5-(N-(2-fluoro-4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-53)

    [0624] ##STR00118##

    [0625] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-fluoro-4-bromobenzyl bromide was used instead of benzyl bromide. 280 mg of white solid was obtained, with a yield of 98%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.07 (d, J=1.6 Hz, 1H), 7.82 (dd, J=8.8, 1.8 Hz, 1H), 7.60 (d, J=8.8 Hz, 1H), 7.31 (t, J=8.1 Hz, 1H), 7.25-7.11 (m, 5H), 7.05-6.97 (m, 2H), 4.52-4.38 (m, 4H), 3.45-3.36 (m, 2H), 2.78-2.68 (m, 2H), 2.59 (s, 3H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 160.5 (d, J=251.9 Hz, 1C), 159.8, 155.8, 143.0, 137.9, 135.2, 132.2 (d, J=4.4 Hz, 1C), 129.4, 128.6 (d, J=10.6 Hz, 1C), 127.8 (d, J=3.5 Hz, 1C), 126.6, 126.1, 125.5, 122.6 (d, J=14.3 Hz, 1C), 122.1 (d, J=9.5 Hz, 1C), 121.5, 119.0 (d, J=25.1 Hz, 1C), 113.1, 61.6, 50.2, 44.9 (d, J=3.5 Hz, 1C), 35.1, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?115.76. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.26NO.sub.5FSBr: 574.0699, found 574.0704.

    Example 46

    ethyl 3-methyl-5-(N-(2-fluoro-4-cyanobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-54)

    [0626] ##STR00119##

    [0627] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-fluoro-4-cyanobenzyl bromide was used instead of benzyl bromide. 230 mg of white solid was obtained, with a yield of 92%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.12 (s, 1H), 7.84 (d, J=8.7 Hz, 1H), 7.62 (dd, J=11.9, 8.0 Hz, 2H), 7.40 (d, J=8.0 Hz, 1H), 7.28 (d, J=9.1 Hz, 1H), 7.16 (t, J=8.0 Hz, 3H), 6.99 (d, J=7.1 Hz, 2H), 4.47 (d, J=9.5 Hz, 4H), 3.43 (t, J=7.7 Hz, 2H), 2.80-2.48 (m, 5H), 1.45 (t, J=7.1 Hz, 3H). 13C NMR (101 MHz, Chloroform-d) ? 159.9 (d, J=251.0 Hz, 1C), 159.8, 155.9, 143.1, 137.6, 134.6, 131.7 (d, J=4.3 Hz, 1C), 129.8 (d, J=14.2 Hz, 1C), 129.5, 128.6, 128.4 (d, J=3.4 Hz, 1C), 126.7, 126.1, 125.4, 121.6, 119.0 (d, J=25.4 Hz, 1C), 117.3 (d, J=2.4 Hz, 1C), 113.3, 113.1 (d, J=9.7 Hz, 1C), 61.6, 50.6, 45.3 (d, J=3.4 Hz, 1C), 35.0, 14.3, 9.1106-4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?115.58. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.26N.sub.2O.sub.5FS: 521.1546, found 521.1552.

    Example 47

    ethyl 3-methyl-5-(N-(2-fluoro-4-(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-55)

    [0628] ##STR00120##

    [0629] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-fluoro-4-(trifluoromethyl) benzyl bromide was used instead of benzyl bromide. 266 mg of white solid was obtained, with a yield of 95%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.02 (s, 1H), 7.82-7.70 (m, 1H), 7.51 (dd, J=14.2, 8.1 Hz, 2H), 7.27 (d, J=7.9 Hz, 1H), 7.21-7.00 (m, 4H), 6.91 (d, J=6.8 Hz, 2H), 4.56-4.28 (m, 4H), 3.47-3.24 (m, 2H), 2.75-2.59 (m, 2H), 2.51 (s, 3H), 1.36 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 160.2 (d, J=249.7 Hz, 1H), 159.8, 155.9, 143.1, 137.8, 134.9, 131.5 (d, J=3.9 Hz, 1C), 129.5, 128.6, 128.6, 127.8 (d, J=14.2 Hz, 1C), 126.6, 126.1, 125.5, 121.6, 121.4 (t, J=3.4 Hz, 1C), 113.2, 112.9 (d, J=3.9 Hz, 1C), 112.6 (d, J=3.7 Hz, 1C), 61.6, 50.4, 45.1 (d, J=3.7 Hz, 1C), 35.1, 14.3, 9.3. .sup.19F NMR (376 MHz, Chloroform-d) ? ?62.76, ?116.40. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.26NO.sub.5F.sub.4S: 564.1468, found 564.1464.

    Example 48

    ethyl 3-methyl-5-(N-(2-chloro-4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-56)

    [0630] ##STR00121##

    [0631] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-chloro-4-fluorobenzylbromide was used instead of benzyl bromide. 268 mg of white solid was obtained, with a yield of 99%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.23-8.07 (m, 1H), 7.87 (d, J=8.7 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.52 (dd, J=8.5, 6.2 Hz, 1H), 7.17 (dq, J=14.2, 7.0 Hz, 3H), 7.10-6.93 (m, 4H), 4.47 (dd, J=14.5, 7.3 Hz, 4H), 3.54-3.31 (m, 2H), 2.83-2.65 (m, 2H), 2.61 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 161.9 (d, J=251.4 Hz, 1C), 159.9, 155.8, 143.1, 137.9, 135.1, 133.8 (d, J=10.2, 1C), 131.8 (d, J=8.7, 1C), 130.0 (d, J=3.5, 1C), 129.5, 128.6 (d, J=8.5, 1C), 126.6, 126.2, 125.5, 121.5, 116.7 (d, J=24.8, 1C), 114.6 (d, J=21.1, 1C), 113.2, 61.6, 50.5, 48.8, 35.2, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?111.97. HRMS (ESI) [M+H]+, theoretically calculated for C.sub.27H.sub.26NO.sub.5FSCl: 530.1204, found 530.1206.

    Example 49

    ethyl 3-methyl-5-(N-(2-(trifluoromethyl)-4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-57)

    [0632] ##STR00122##

    [0633] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-(trifluoromethyl)-4-fluorobenzylbromide was used instead of benzyl bromide. 238 mg of white solid was obtained, with a yield of 84%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.33-8.13 (m, 1H), 7.91 (dd, J=8.8, 1.6 Hz, 1H), 7.81 (dt, J=11.6, 5.8 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.31 (dd, J=8.8, 2.3 Hz, 1H), 7.27-7.06 (m, 4H), 6.96 (d, J=6.8 Hz, 2H), 4.59 (s, 2H), 4.46 (q, J=7.1 Hz, 2H), 3.63-3.34 (m, 2H), 2.63 (d, J=14.7 Hz, 5H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 161.3 (d, J=249.9 Hz, 1H), 159.7, 155.9, 143.1, 137.7, 134.8, 132.2 (d, J=7.9 Hz, 1C), 131.6 (d, J=2.8 Hz, 1C), 129.6, 128.5 (d, J=2.2 Hz, 1C), 126.6, 126.1, 125.5, 121.6, 119.2 (d, J=21.2 Hz, 1C), 113.3, 61.5, 50.7, 47.9, 34.8, 14.3, 9.3. .sup.19F NMR (376 MHz, Chloroform-d) ? ?59.60, ?112.86. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.26NO.sub.5F.sub.4S: 564.1468, found 564.1465.

    Example 50

    ethyl 3-methyl-5-(N-(2,4-bis(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-58)

    [0634] ##STR00123##

    [0635] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2,4-bis (trifluoromethyl)benzyl bromide was used instead of benzyl bromide. 270 mg of white solid was obtained, with a yield of 88%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.28-8.17 (m, 1H), 8.03-7.85 (m, 3H), 7.74 (d, J=8.1 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.13 (q, J=8.4, 7.3 Hz, 3H), 6.96 (d, J=6.5 Hz, 2H), 4.67 (s, 2H), 4.47 (q, J=7.1 Hz, 2H), 3.67-3.37 (m, 2H), 2.64 (d, J=22.4 Hz, 5H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.7, 155.9, 143.1, 140.4, 137.5, 134.4, 130.5, 130.0 (d, J=33.8 Hz, 1C), 129.6, 129.0, 128.5, 128.1 (d, J=31.5 Hz, 1C), 126.6, 126.1, 125.4, 124.8 (d, J=26.8 Hz, 1C), 122.9, 122.1 (d, J=25.1 Hz, 1C), 121.7, 113.3, 61.5, 51.0, 48.4, 34.7, 14.2, 9.2. .sup.19F NMR (376 MHz, Chloroform-d) ? ?59.95, ?62.92. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.29H.sub.26NO.sub.5F.sub.6S: 613.1358, found 614.1436.

    Example 51

    ethyl 3-methyl-5-(N-(2-trifluoromethyl-4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-59)

    [0636] ##STR00124##

    [0637] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-trifluoromethyl-4-bromobenzyl bromide was used instead of benzyl bromide. 311 mg of white solid was obtained, with a yield of 99%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.18 (d, J=1.5 Hz, 1H), 7.89 (dd, J=8.8, 1.8 Hz, 1H), 7.77-7.73 (m, 1H), 7.71-7.59 (m, 3H), 7.23-7.10 (m, 3H), 6.96 (d, J=6.4 Hz, 2H), 4.54 (s, 2H), 4.47 (q, J=7.1 Hz, 2H), 3.50-3.35 (m, 2H), 2.71-2.56 (m, 5H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.9, 143.1, 137.6, 135.4, 135.0, 134.6, 131.6, 129.6, 129.2, 128.8 (t, J=6.3 Hz, 1C), 128.6 (d, J=1.5 Hz, 1C), 126.6, 126.1, 125.5, 121.6, 121.4, 113.4, 61.6, 50.9, 48.1 (d, J=2.4 Hz, 1C), 34.9, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?59.55. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.26NO.sub.5F.sub.3SBr: 624.0667, found 624.0663.

    Example 52

    ethyl 3-methyl-5-(N-(2,4-dichlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-60)

    [0638] ##STR00125##

    [0639] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2,4-dichloro-benzyl bromide was used instead of benzyl bromide. 113 mg of white solid was obtained, with a yield of 69%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (d, J=1.6 Hz, 1H), 7.86 (dd, J=8.8, 1.9 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.47 (d, J=8.4 Hz, 1H), 7.31 (d, J=2.1 Hz, 1H), 7.24-7.13 (m, 4H), 7.05-6.98 (m, 2H), 4.60-4.37 (m, 4H), 3.54-3.34 (m, 2H), 2.76-2.66 (m, 2H), 2.61 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.9, 143.1, 137.8, 135.0, 134.2, 133.7, 132.7, 131.3, 129.5, 129.2, 128.7, 128.6, 127.5, 126.6, 126.2, 125.5, 121.6, 113.2, 61.6, 50.7, 48.9, 35.2, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.26NO.sub.5SCl.sub.2: 546.0909, found 546.0912.

    Example 53

    ethyl 3-methyl-5-(N-(2-methyl-5-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-61)

    [0640] ##STR00126##

    [0641] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2-methyl-5-fluorobenzyl bromide was used instead of benzyl bromide. 134 mg of white solid was obtained, with a yield of 87%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.17 (d, J=1.6 Hz, 1H), 7.90 (dd, J=8.8, 1.8 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.17 (m, 3H), 7.09 (dd, J=8.2, 5.8 Hz, 1H), 6.99-6.84 (m, 4H), 4.47 (q, J=7.1 Hz, 2H), 4.34 (s, 2H), 3.40-3.25 (m, 2H), 2.61 (d, J=6.1 Hz, 5H), 2.27 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.4, 160.0, 159.9, 155.9, 143.0, 138.1, 135.7 (d, J=6.8 Hz, 1C), 134.7, 132.5 (d, J=3.3 Hz, 1C), 132.0 (d, J=7.7 Hz, 1C), 129.5, 128.6 (d, J=4.8 Hz, 1C), 126.5, 126.3, 125.6, 121.6, 115.9 (d, J=22.2 Hz, 1C), 114.6 (d, J=20.7 Hz, 1C), 113.1, 61.6, 50.6, 50.1, 35.5, 18.5, 14.4, 9.4. .sup.19F NMR (376 MHz, Chloroform-d) ? ?116.96. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.29NO.sub.5FS: 510.1750, found 510.1758.

    Example 54

    ethyl 3-methyl-5-(N-(2,6-difluoro-4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-62)

    [0642] ##STR00127##

    [0643] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 2,6-difluoro-4-chlorobenzyl bromide was used instead of benzyl bromide. 243 mg of white solid was obtained, with a yield of 89%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.09 (d, J=1.5 Hz, 1H), 7.84 (dd, J=8.8, 1.8 Hz, 1H), 7.59 (d, J=8.8 Hz, 1H), 7.25-7.12 (m, 3H), 7.06 (d, J=6.9 Hz, 2H), 6.83 (d, J=7.2 Hz, 2H), 4.46 (d, J=7.2 Hz, 4H), 3.48-3.32 (m, 2H), 2.90-2.78 (m, 2H), 2.59 (s, 3H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 161.5 (dd, J=254.1, 9.4 Hz, 1C), 159.8, 155.8, 143.0, 138.1, 135.5 (t, J=14.2 Hz, 1C), 134.9, 129.3, 128.7, 128.6, 126.5, 126.3, 125.5, 121.6, 112.6 (dd, J=29.8, 1.8 Hz, 1C), 110.9 (t, J=18.9 Hz, 1C), 61.6, 50.2, 39.5, 35.4, 14.4, 9.3. .sup.19F NMR (376 MHz, Chloroform-d) ? ?110.99. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.27H.sub.25NO.sub.5F.sub.2SCl: 548.1110, found 548.1105.

    Example 55

    ethyl 3-methyl-5-(N-([1,1-biphenyl]-4-ylmethyl-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-82)

    [0644] ##STR00128##

    [0645] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-phenylbenzyl bromide was used instead of benzyl bromide. 191 mg of white solid was obtained, with a yield of 69%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (s, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.54 (dd, J=13.2, 7.7 Hz, 4H), 7.43 (t, J=7.5 Hz, 2H), 7.33 (dd, J=17.2, 7.7 Hz, 3H), 7.18 (dt, J=12.5, 6.8 Hz, 3H), 6.98 (d, J=6.7 Hz, 2H), 4.47 (dd, J=15.6, 8.5 Hz, 4H), 3.49-3.34 (m, 2H), 2.80-2.67 (m, 2H), 2.58 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 140.9, 140.5, 138.3, 135.6, 134.9, 129.4, 128.9, 128.8, 128.7, 128.5, 127.5, 127.3, 127.0, 126.5, 126.2, 125.6, 121.6, 113.1, 61.6, 51.9, 49.6, 35.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.32NO.sub.5S: 554.2001, found 546.1562. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.32NO.sub.5S: 5554.2001, found 554.2001.

    Example 56

    ethyl 3-methyl-5-(N-((2-cyano-[1,1-biphenyl]-4-yl)methyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-83)

    [0646] ##STR00129##

    [0647] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that 4-(bromomethyl)-[1,1-biphenyl]-2-carbonitrile was used instead of benzyl bromide. 270 mg of white solid was obtained, with a yield of 93%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.19 (d, J=1.5 Hz, 1H), 7.88 (dd, J=8.8, 1.8 Hz, 1H), 7.72 (d, J=7.7 Hz, 1H), 7.62 (dd, J=8.1, 6.0 Hz, 2H), 7.53-7.35 (m, 6H), 7.17 (t, J=7.2 Hz, 2H), 7.12 (d, J=7.1 Hz, 1H), 7.02-6.95 (m, 2H), 4.45 (q, J=7.2 Hz, 4H), 3.51-3.38 (m, 2H), 2.75-2.67 (m, 2H), 2.60 (s, 3H), 1.43 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 144.7, 143.0, 138.2, 137.8, 136.8, 135.4, 133.8, 132.9, 130.0, 129.4, 129.1, 128.7, 128.5, 127.8, 126.5, 126.3, 125.6, 121.6, 118.6, 113.1, 111.2, 61.6, 51.8, 49.7, 35.2, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31N.sub.2O.sub.5S: 579.1954, found 579.1950.

    Example 57

    ethyl 3-methyl-5-(N-((2-(tert-butoxycarbonyl)-[1,1-biphenyl]-4-yl)methyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-84

    [0648] ##STR00130##

    [0649] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that tert-butyl 4-(bromomethyl)-[1,1-biphenyl]-2-carboxylate was used instead of benzyl bromide. 303 mg of white solid was obtained, with a yield of 93%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.22 (d, J=1.5 Hz, 1H), 7.92 (dd, J=8.8, 1.7 Hz, 1H), 7.79 (dd, J=7.7, 1.4 Hz, 1H), 7.66 (d, J=8.7 Hz, 1H), 7.52-7.44 (m, 1H), 7.43-7.37 (m, 1H), 7.36-7.26 (m, 5H), 7.18 (dq, J=14.3, 7.1 Hz, 3H), 7.01 (d, J=6.9 Hz, 2H), 4.57-4.42 (m, 4H), 3.56-3.34 (m, 2H), 2.82-2.70 (m, 2H), 2.63 (s, 3H), 1.47 (t, J=7.1 Hz, 3H), 1.27 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 167.9, 159.8, 155.8, 143.0, 141.6, 141.4, 138.3, 135.7, 134.9, 132.9, 130.7, 130.5, 129.6, 129.4, 129.0, 128.7, 128.5, 128.1, 127.3, 126.5, 126.3, 125.6, 121.5, 113.1, 81.2, 61.6, 51.7, 49.3, 35.1, 27.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.38H.sub.40NO.sub.7S: 653.2447, found 654.2528.

    Example 58

    ethyl 3-methyl-5-(N-(4-benzoylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M4-85)

    [0650] ##STR00131##

    [0651] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), this example was implemented under the same condition except that (4-(bromomethyl)phenyl)(phenyl)methanone was used instead of benzyl bromide. 142 mg of white solid was obtained, with a yield of 49%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (d, J=1.9 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.78-7.69 (m, 4H), 7.58 (dd, J=27.2, 8.1 Hz, 2H), 7.50-7.35 (m, 4H), 7.14 (dq, J=14.1, 7.0 Hz, 3H), 6.96 (d, J=6.9 Hz, 2H), 4.45 (dd, J=14.9, 7.8 Hz, 4H), 3.52-3.34 (m, 2H), 2.74-2.64 (m, 2H), 2.58 (s, 3H), 1.43 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 196.0, 159.8, 155.8, 143.1, 141.0, 138.1, 137.4, 137.1, 135.3, 132.5, 130.4, 130.0, 129.5, 128.6, 128.6, 128.4, 128.1, 126.6, 126.2, 125.5, 121.6, 113.2, 61.6, 51.9, 49.9, 35.2, 14.4, 9.4.

    Example 59

    3-methyl-5-(N-benzyl-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27)

    [0652] ##STR00132##

    [0653] Ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (95 mg, 0.2 mmol) and sodium hydroxide (40 mg, 1.0 mmol) were dissolved in a mixed solution of ethanol (8 mL) and water (2 mL) and then stirred for 1 h at 100? C. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (10 mL) and the pH value was then adjusted to 3.0 with 1M diluted hydrochloric acid. The resulting solution was set still for 5 h, and then filtered with suction under reduced pressure and dried to obtain 75 mg of white solid, with a yield of 84%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.28 (s, 1H), 7.95 (d, J=8.7 Hz, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.33 (dd, J=16.2, 3.9 Hz, 5H), 7.24-7.05 (m, 3H), 6.97 (d, J=7.1 Hz, 2H), 4.43 (s, 2H), 3.41-3.20 (m, 2H), 2.58 (s, 3H), 2.56-2.51 (m, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.3, 155.5, 144.2, 138.7, 137.3, 135.3, 129.7, 129.0, 128.9, 128.8, 128.8, 128.1, 126.7, 126.5, 124.8, 122.0, 113.5, 51.8, 49.8, 34.8, 9.6. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.25H.sub.24NO.sub.5S: 450.1375, found 450.1378.

    Example 61

    3-methyl-5-(N-(2-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S14)

    [0654] ##STR00133##

    [0655] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-14 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 90 mg of white solid was obtained, with a yield of 96%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.06 (s, 1H), 7.80 (d, J=10.6 Hz, 1H), 7.71 (d, J=8.7 Hz, 1H), 7.43 (t, J=7.7 Hz, 1H), 7.39-7.30 (m, 1H), 7.25-7.11 (m, 5H), 7.01 (d, J=6.9 Hz, 2H), 4.47 (s, 2H), 3.38-3.27 (m, 2H), 2.63-2.54 (m, 2H), 2.52 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.8, 160.9 (d, J=246.5 Hz, 1C), 154.8, 138.6, 133.8, 131.4 (d, J=3.9 Hz, 1C), 130.9, 130.3 (d, J=8.2 Hz, 1C), 128.9, 128.8, 126.8, 124.9 (d, J=3.3 Hz, 1C), 124.5, 124.2 (d, J=14.3 Hz, 1C), 120.7, 117.8, 115.9, 115.7, 112.8, 50.2, 45.8 (d, J=3.3 Hz, 1C), 34.9, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?117.84. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.21NO.sub.5FS: 466.1124, found 466.1128.

    Example 62

    3-methyl-5-(N-(2-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S15)

    [0656] ##STR00134##

    [0657] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-15 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 80 mg of white solid was obtained, with a yield of 83%. M.p. 156-157? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.12 (s, 1H), 7.84 (d, J=8.7 Hz, 1H), 7.75 (d, J=8.7 Hz, 1H), 7.50 (s, 1H), 7.46-7.40 (m, 1H), 7.37-7.29 (m, 2H), 7.20 (t, J=7.2 Hz, 2H), 7.14 (t, J=7.1 Hz, 1H), 7.00 (d, J=7.0 Hz, 2H), 4.50 (s, 2H), 3.41-3.27 (m, 2H), 2.56 (d, J=14.9 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 154.9, 138.5, 134.8, 133.8, 133.0, 130.9, 130.8, 129.8, 129.8, 128.9, 128.8, 127.7, 126.8, 124.8, 121.0, 112.9, 50.5, 49.7, 35.0, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.21NO.sub.5SCl: 482.0829, found 482.0832.

    Example 63

    3-methyl-5-(N-(2-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S16)

    [0658] ##STR00135##

    [0659] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-16 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 104 mg of white solid was obtained, with a yield of 98%. M.p. 170-171? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.27 (d, J=1.7 Hz, 1H), 7.95 (dd, J=8.8, 1.9 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.61 (d, J=7.0 Hz, 1H), 7.48 (d, J=6.3 Hz, 1H), 7.37 (t, J=7.0 Hz, 1H), 7.28-7.17 (m, 3H), 7.14 (t, J=7.2 Hz, 1H), 7.02 (d, J=8.2 Hz, 2H), 4.50 (s, 2H), 3.42-3.34 (m, 2H), 2.58 (s, 5H). .sup.13C NMR (101 MHz, DMSO) ? 161.4, 155.5, 138.5, 136.3, 134.6, 133.1, 130.9, 130.1, 129.8, 129.0, 128.3, 126.8, 126.4, 123.2, 122.0, 113.5, 52.2, 50.6, 35.0, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.21NO.sub.5SBr: 526.0324, found 526.0331.

    Example 64

    3-methyl-5-(N-(2-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S17)

    [0660] ##STR00136##

    [0661] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-17 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 88 mg of white solid was obtained, with a yield of 96%. M.p. 199-200? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.32 (d, J=1.7 Hz, 1H), 8.00 (dd, J=8.8, 1.9 Hz, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.32 (d, J=7.4 Hz, 1H), 7.26-7.14 (m, 5H), 7.14-7.09 (m, 1H), 6.89 (d, J=6.9 Hz, 2H), 4.39 (s, 2H), 3.28-3.18 (m, 2H), 2.59 (s, 3H), 2.45-2.36 (m, 2H), 2.32 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.2, 155.6, 143.8, 138.7, 137.4, 134.6, 134.6, 130.8, 129.8, 129.7, 128.9, 128.8, 128.3, 126.8, 126.7, 126.2, 125.2, 122.2, 113.5, 51.0, 49.9, 35.3, 19.2, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.24NO.sub.5S: 462.1375, found 462.1377.

    Example 65

    3-methyl-5-(N-(2-trifluoromethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S18)

    [0662] ##STR00137##

    [0663] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-18 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 87 mg of white solid was obtained, with a yield of 84%. M.p. 138-139? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.24 (s, 1H), 7.93 (d, J=8.7 Hz, 1H), 7.83 (d, J=8.7 Hz, 1H), 7.72 (d, J=7.8 Hz, 1H), 7.65 (q, J=7.6 Hz, 2H), 7.49 (t, J=7.2 Hz, 1H), 7.16 (dq, J=14.3, 7.1 Hz, 3H), 7.00 (d, J=7.0 Hz, 2H), 4.58 (s, 2H), 3.49-3.35 (m, 2H), 2.58 (d, J=12.8 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.0, 155.4, 146.6, 138.4, 136.4, 134.1, 133.1, 130.2, 130.0, 128.9, 128.8, 128.3, 126.3 (d, J=38.8 Hz, 1C), 126.3 (t, J=5.8 Hz, 1C), 126.1, 125.9, 122.9 (d, J=108.8 Hz, 1C), 121.7, 113.4, 50.9, 48.7, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.21NO.sub.5F.sub.3S: 516.1093, found 516.1095.

    Example 66

    3-methyl-5-(N-(2-nitrobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S19)

    [0664] ##STR00138##

    [0665] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-19 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), and lithium hydroxide was used instead of sodium hydroxide. 31 mg of yellow solid was obtained, with a yield of 63%. M.p. 180-181? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.27 (d, J=1.9 Hz, 1H), 8.02 (d, J=8.1 Hz, 1H), 7.95 (dd, J=8.7, 1.9 Hz, 1H), 7.86 (d, J=8.8 Hz, 1H), 7.71 (q, J=3.6, 3.1 Hz, 2H), 7.55 (td, J=7.0, 5.6, 3.1 Hz, 1H), 7.25-7.10 (m, 3H), 7.05 (d, J=7.0 Hz, 2H), 4.77 (s, 2H), 3.54-3.34 (m, 2H), 2.61 (d, J=21.8 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.5, 155.6, 148.5, 138.5, 134.4, 134.0, 133.2, 130.3, 129.9, 129.1, 129.0, 128.8, 126.8, 126.4, 125.1, 122.1, 113.6, 51.2, 49.3, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.21N.sub.2O.sub.7S: 493.1069, found 493.1070.

    Example 67

    3-methyl-5-(N-(3-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S20)

    [0666] ##STR00139##

    [0667] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-20 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 85 mg of white solid was obtained, with a yield of 91%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.08 (s, 1H), 7.80 (d, J=8.7 Hz, 1H), 7.72 (d, J=8.7 Hz, 1H), 7.44-7.34 (m, 1H), 7.19 (d, J=7.4 Hz, 3H), 7.12 (dt, J=9.0, 6.5 Hz, 3H), 7.00 (d, J=6.9 Hz, 2H), 4.42 (s, 2H), 3.37-3.28 (m, 2H), 2.61-2.54 (m, 2H), 2.52 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.1, 162.6 (d, J=244.6 Hz, 1C), 154.7, 152.0, 140.8 (d, J=7.2 Hz, 1C), 138.7, 133.8, 131.1, 130.8 (d, J=8.4 Hz, 1C), 129.0, 128.8, 126.7, 124.6 (d, J=2.6 Hz, 1C), 124.2, 120.6, 116.9, 115.2 (d, J=21.7 Hz, 1C), 114.7 (d, J=21.0 Hz, 1C), 112.7, 51.3, 50.1, 40.4, 34.7, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) 6-113.23. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.21NO.sub.5FS: 466.1124, found 466.1127.

    Example 68

    3-methyl-5-(N-(3-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S21)

    [0668] ##STR00140##

    [0669] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-21 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 82 mg of white solid was obtained, with a yield of 85%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.07 (d, J=2.0 Hz, 1H), 7.79 (dd, J=8.6, 2.0 Hz, 1H), 7.71 (d, J=8.7 Hz, 1H), 7.43-7.27 (m, 4H), 7.26-7.10 (m, 3H), 7.01 (d, J=6.8 Hz, 2H), 4.41 (s, 2H), 3.40-3.27 (m, 2H), 2.62-2.54 (m, 2H), 2.52 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.2, 154.7, 151.9, 140.4, 138.7, 133.8, 133.5, 131.1, 130.7, 129.0, 128.8, 128.3, 127.9, 127.2, 126.8, 124.2, 120.6, 116.9, 112.8, 51.2, 50.2, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.21NO.sub.5SCl: 482.0829, found 482.0829.

    Example 69

    3-methyl-5-(N-(3-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S22)

    [0670] ##STR00141##

    [0671] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-22 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 93 mg of white solid was obtained, with a yield of 99%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.09 (s, 1H), 7.81 (d, J=8.7 Hz, 1H), 7.72 (d, J=8.7 Hz, 1H), 7.50-7.43 (m, 2H), 7.38-7.27 (m, 2H), 7.20 (t, J=7.2 Hz, 2H), 7.14 (dd, J=8.7, 5.8 Hz, 1H), 7.01 (d, J=6.9 Hz, 2H), 4.41 (s, 2H), 3.37-3.28 (m, 2H), 2.62-2.54 (m, 2H), 2.52 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.5, 154.8, 140.6, 138.7, 133.9, 131.3, 131.0, 131.0, 130.8, 129.0, 128.8, 127.6, 126.8, 124.5, 122.1, 120.7, 112.8, 51.1, 50.2, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.21NO.sub.5SBr: 526.0324, found 526.0326.

    Example 70

    3-methyl-5-(N-(3-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S23)

    [0672] ##STR00142##

    [0673] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-23 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 93 mg of white solid was obtained, with a yield of 99%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.08 (d, J=1.7 Hz, 1H), 7.81 (dd, J=8.7, 1.9 Hz, 1H), 7.73 (d, J=8.7 Hz, 1H), 7.21 (q, J=7.3 Hz, 3H), 7.16-7.06 (m, 3H), 7.04 (s, 1H), 6.98 (d, J=6.9 Hz, 2H), 4.36 (s, 2H), 3.36-3.23 (m, 2H), 2.54 (d, J=9.2 Hz, 5H), 2.23 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.8, 154.8, 138.8, 138.0, 137.2, 134.3, 130.9, 129.3, 129.0, 128.8, 128.8, 128.6, 126.7, 125.9, 124.5, 120.7, 112.8, 51.7, 49.7, 34.7, 21.4, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.24NO.sub.5S: 462.1375, found 462.1376.

    Example 71

    3-methyl-5-(N-(3-trifluoromethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S24)

    [0674] ##STR00143##

    [0675] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-24 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 89 mg of white solid was obtained, with a yield of 86%. M.p. 188-189? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.14 (s, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.75 (d, J=8.7 Hz, 1H), 7.60 (dq, J=15.2, 7.4 Hz, 4H), 7.16 (dq, J=14.3, 7.1 Hz, 3H), 7.00 (d, J=6.8 Hz, 2H), 4.52 (s, 2H), 3.45-3.31 (m, 2H), 2.64-2.56 (m, 2H), 2.54 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.6, 155.0, 139.4, 138.6, 134.0, 132.7, 130.7, 129.9, 129.6 (d, J=31.7 Hz, 1C), 129.0, 128.7, 126.7, 125.9, 125.0 (d, J=4.2 Hz, 1C), 124.9, 124.7, 123.2, 121.0, 113.0, 51.3, 50.4, 34.8, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?61.16. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.21NO.sub.5F.sub.3S: 516.1093, found 516.1095.

    Example 72

    3-methyl-5-(N-(3-nitrobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S25)

    [0676] ##STR00144##

    [0677] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-25 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8), lithium hydroxide was used instead of sodium hydroxide. 51 mg of white solid was obtained, with a yield of 52%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.79 (s, 1H), 8.31 (d, J=1.5 Hz, 1H), 8.16-8.06 (m, 2H), 7.96 (dd, J=8.8, 1.8 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.78 (d, J=7.7 Hz, 1H), 7.62 (t, J=7.9 Hz, 1H), 7.23-7.06 (m, 3H), 7.01 (d, J=6.9 Hz, 2H), 4.57 (s, 2H), 3.52-3.34 (m, 2H), 2.61 (d, J=21.9 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.2, 155.6, 148.2, 144.0, 140.2, 138.5, 135.0, 134.8, 130.3, 129.7, 129.0, 128.7, 126.7, 125.1, 123.0, 122.8, 122.2, 113.6, 51.2, 50.5, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.21N.sub.2O.sub.7S: 493.1069, found 493.1065.

    Example 73

    3-methyl-5-(N-([1,1-biphenyl]-3-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S26)

    [0678] ##STR00145##

    [0679] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-26 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 106 mg of white solid was obtained, with a yield of 95%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.10 (s, 1H), 7.81 (d, J=8.7 Hz, 1H), 7.71 (d, J=8.6 Hz, 1H), 7.57 (d, J=7.8 Hz, 1H), 7.53-7.47 (m, 2H), 7.47-7.39 (m, 4H), 7.34 (dd, J=11.7, 7.4 Hz, 2H), 7.15 (dq, J=14.4, 7.1 Hz, 3H), 7.00 (d, J=6.8 Hz, 2H), 4.48 (s, 2H), 3.39-3.28 (m, 2H), 2.66-2.56 (m, 2H), 2.52 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.1, 154.7, 140.8, 140.3, 138.8, 138.1, 134.2, 131.2, 129.5, 129.4, 129.0, 128.8, 128.0, 127.9, 127.0, 127.0, 126.7, 126.4, 124.2, 120.5, 116.7, 112.7, 51.6, 49.7, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.31H.sub.26NO.sub.5S: 524.1532, found 524.1522.

    Example 74

    3-methyl-5-(N-(3-phenoxybenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S27)

    [0680] ##STR00146##

    [0681] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-27 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 99 mg of white solid was obtained, with a yield of 91%. M.p.>183-184? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.18 (s, 1H), 7.86 (d, J=8.7 Hz, 1H), 7.76 (d, J=8.7 Hz, 1H), 7.36 (td, J=8.0, 3.0 Hz, 3H), 7.16 (dq, J=19.7, 7.0 Hz, 5H), 6.96 (dt, J=21.2, 6.5 Hz, 6H), 4.41 (s, 2H), 3.48-3.22 (m, 2H), 2.56 (d, J=9.0 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.1, 157.1, 157.0, 155.2, 139.9, 138.7, 134.7, 130.6, 130.5, 130.3, 129.0, 128.8, 126.7, 125.5, 123.9, 123.8, 121.4, 118.9, 118.9, 118.3, 113.1, 51.5, 50.0, 34.9, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.31H.sub.26NO.sub.6S: 540.1481, found 540.1477.

    Example 75

    3-methyl-5-(N-(4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S28)

    [0682] ##STR00147##

    [0683] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-28 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 81 mg of white solid was obtained, with a yield of 87%. M.p. 188-189? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.17 (s, 1H), 7.87 (d, J=10.5 Hz, 1H), 7.78 (d, J=8.7 Hz, 1H), 7.38 (dd, J=8.4, 5.7 Hz, 2H), 7.16 (dq, J=13.9, 7.2 Hz, 5H), 6.99 (d, J=7.0 Hz, 2H), 4.40 (s, 2H), 3.38-3.24 (m, 2H), 2.55 (d, J=11.9 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.1 (d, J=244.2 Hz, 1C), 162.1, 155.1, 138.7, 134.6, 133.7 (d, J=2.9 Hz, 1C), 130.8 (d, J=8.3 Hz, 1C), 130.7, 130.4, 129.0, 128.8, 126.7, 125.4, 121.3, 115.8, 115.6, 113.1, 51.1, 49.9, 34.8, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?115.01. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.21NO.sub.5FS: 466.1124, found 466.1123.

    Example 76

    3-methyl-5-(N-(4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S29)

    [0684] ##STR00148##

    [0685] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-29 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 89 mg of white solid was obtained, with a yield of 92%. M.p. 172-173? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25 (s, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.37 (q, J=8.5 Hz, 4H), 7.19 (t, J=7.3 Hz, 2H), 7.13 (t, J=7.2 Hz, 1H), 7.01 (d, J=7.1 Hz, 2H), 4.42 (s, 2H), 3.41-3.26 (m, 2H), 2.58 (d, J=4.6 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.3, 155.5, 144.4, 138.6, 136.6, 135.1, 132.6, 130.5, 129.7, 129.0, 128.9, 128.8, 126.7, 126.5, 124.6, 122.0, 113.5, 51.1, 50.1, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.21NO.sub.5SCl: 482.0829, found 482.0829.

    Example 77

    3-methyl-5-(N-(4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S30)

    [0686] ##STR00149##

    [0687] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-30 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 227 mg of white solid was obtained, with a yield of 85%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.15 (s, 1H), 7.93-7.69 (m, 2H), 7.42 (dd, J=89.8, 8.2 Hz, 4H), 7.23-7.10 (m, 3H), 7.00 (d, J=7.2 Hz, 2H), 4.39 (s, 2H), 3.39-3.27 (m, 2H), 2.56 (s, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.0, 154.6, 148.2, 138.2, 136.7, 133.8, 131.3, 130.4, 130.0, 128.5, 128.3, 126.3, 124.7, 120.7, 120.7, 119.7, 112.6, 50.8, 49.6, 34.3, 9.1. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.28H.sub.21BrNO.sub.5S: 526.0329, found 506.0323.

    Example 78

    3-methyl-5-(N-(4-methylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S31)

    [0688] ##STR00150##

    [0689] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-31 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 63 mg of white solid was obtained, with a yield of 68%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.15 (d, J=1.9 Hz, 1H), 7.86 (dd, J=8.6, 1.9 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.26-7.07 (m, 7H), 6.98 (d, J=7.2 Hz, 2H), 4.36 (s, 2H), 3.28 (t, J=8.0 Hz, 2H), 2.61-2.51 (m, 5H), 2.27 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.4, 155.0, 148.3, 138.8, 137.2, 134.8, 134.2, 130.4, 129.5, 128.9, 128.8, 126.7, 125.3, 121.1, 120.5, 113.1, 51.5, 49.6, 34.8, 21.2, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.24NO.sub.5S: 462.1375, found 462.1378.

    Example 79

    3-methyl-5-(N-(4-(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S32)

    [0690] ##STR00151##

    [0691] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-32 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 72 mg of white solid was obtained, with a yield of 70%. M.p.>192-193? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.33-8.19 (m, 1H), 7.94 (dd, J=8.7, 1.9 Hz, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.68 (d, J=7.9 Hz, 2H), 7.55 (d, J=7.9 Hz, 2H), 7.14 (dq, J=14.1, 7.3 Hz, 3H), 7.00 (d, J=7.3 Hz, 2H), 4.53 (s, 2H), 3.37 (t, J=7.8 Hz, 2H), 2.59 (d, J=10.2 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.6, 155.4, 145.2, 142.7, 138.6, 134.7, 129.9, 129.2, 129.0, 128.7, 126.7, 126.2, 126.1, 125.7 (d, J=3.7 Hz, 1C), 123.5 (d, J=34.9 Hz, 1C), 121.9, 113.4, 51.5, 50.5, 34.8, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?60.94. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.21NO.sub.5SF.sub.3: 516.1093, found 516.1096.

    Example 80

    3-methyl-5-(N-(4-carbamoylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S33)

    [0692] ##STR00152##

    [0693] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-33 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 103 mg of white solid was obtained, with a yield of 43%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.56 (s, 1H), 8.29 (s, 1H), 8.03-7.89 (m, 2H), 7.86 (d, J=8.7 Hz, 2H), 7.50-7.41 (m, 1H), 7.38 (d, J=11.8 Hz, 1H), 7.16 (dq, J=14.1, 7.1, 6.6 Hz, 3H), 7.01 (d, J=7.8 Hz, 2H), 4.50 (d, J=9.7 Hz, 2H), 3.35 (q, J=7.5 Hz, 2H), 2.58 (s, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 168.0, 163.7, 154.9, 149.8, 140.9, 138.7, 134.2, 133.9, 130.7, 128.9, 128.8, 128.4, 128.1, 126.7, 124.9, 121.0, 119.2, 113.0, 51.5, 50.1, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C26H.sub.23N.sub.2O.sub.6S: 491.1282, found 491.1278.

    Example 81

    3-methyl-5-(N-(4-(trifluoromethoxy)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S34)

    [0694] ##STR00153##

    [0695] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-34 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 227 mg of white solid was obtained, with a yield of 85%. M.p. 216-217? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.20 (s, 1H), 7.92-7.74 (m, 2H), 7.40 (dd, J=60.2, 8.2 Hz, 4H), 7.21-7.08 (m, 3H), 6.98 (d, J=7.1 Hz, 2H), 4.45 (s, 2H), 3.34 (t, J=7.8 Hz, 2H), 2.65-2.53 (m, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.4, 155.1, 148.1, 138.6, 137.1, 134.4, 130.5, 130.4, 128.9, 128.7, 126.7, 125.4, 121.8, 121.4, 121.3, 120.8, 113.1, 51.2, 50.2, 34.8, 9.5. .sup.19F NMR (376 MHz, DMSO) ? ?56.83. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.21F.sub.3NO.sub.6S: 532.1047, found 532.1038.

    Example 82

    3-methyl-5-(N-(4-(trifluoromethylthio)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S35)

    [0696] ##STR00154##

    [0697] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-35 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 192 mg of white solid was obtained, with a yield of 70%. M.p. 165-166? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.26 (s, 1H), 7.92 (dd, J=8.7, 1.8 Hz, 1H), 7.82 (d, J=8.8 Hz, 1H), 7.70 (d, J=7.9 Hz, 2H), 7.51 (d, J=7.9 Hz, 2H), 7.17 (dt, J=13.7, 6.9 Hz, 3H), 7.00 (d, J=7.2 Hz, 2H), 4.50 (s, 2H), 3.36 (t, J=7.9 Hz, 2H), 2.65-2.54 (m, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.7, 155.4, 141.8, 138.6, 136.7, 134.5, 131.6, 130.0, 130.0, 129.0, 128.7, 128.5, 126.7, 126.0, 122.3, 121.8, 113.3, 51.4, 50.5, 34.9, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?42.23. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.21F.sub.3NO.sub.5S.sub.2: 548.0819, found 548.0805.

    Example 83

    3-methyl-5-(N-(4-isopropylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S36)

    [0698] ##STR00155##

    [0699] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-36 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 220 mg of white solid was obtained, with a yield of 88%. M.p. 206-207? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.74 (s, 1H), 8.26 (d, J=1.9 Hz, 1H), 7.93 (dd, J=8.8, 1.9 Hz, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.19 (dq, J=16.2, 9.2, 8.7 Hz, 7H), 7.02-6.94 (m, 2H), 4.38 (s, 2H), 3.34-3.27 (m, 2H), 2.85 (h, J=6.8 Hz, 1H), 2.58 (s, 5H), 1.17 (d, J=6.9 Hz, 6H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.1, 155.5, 148.3, 143.8, 138.8, 135.5, 134.5, 129.6, 129.0, 128.8, 128.8, 126.8, 126.7, 126.6, 125.2, 122.0, 113.5, 51.4, 49.6, 34.8, 33.6, 24.3, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.28H.sub.28NO.sub.5S: 490.1694, found 490.1684.

    Example 84

    3-methyl-5-(N-(4-tert-butylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S37)

    [0700] ##STR00156##

    [0701] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-37 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 212 mg of white solid was obtained, with a yield of 84%. M.p. 206-207? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25 (s, 1H), 7.97-7.77 (m, 2H), 7.34 (d, J=8.0 Hz, 2H), 7.18 (ddd, J=22.9, 15.8, 7.5 Hz, 5H), 6.97 (d, J=6.6 Hz, 2H), 4.39 (s, 2H), 3.36-3.27 (m, 2H), 2.58 (s, 5H), 1.25 (s, 9H). .sup.13C NMR (101 MHz, DMSO) ? 161.4, 155.4, 150.5, 138.8, 135.4, 134.1, 129.7, 129.0, 128.7, 128.5, 126.7, 126.4, 125.6, 124.5, 121.9, 113.4, 107.1, 51.3, 49.6, 34.8, 34.7, 31.6, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.29H.sub.30NO.sub.5S: 504.1850, found 504.1838.

    Example 85

    3-methyl-5-(N-(4-acetylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S38)

    [0702] ##STR00157##

    [0703] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-38 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 48 mg of white solid was obtained, with a yield of 49%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.75 (s, 1H), 8.28 (d, J=1.9 Hz, 1H), 8.00-7.80 (m, 4H), 7.47 (d, J=8.0 Hz, 2H), 7.21-7.09 (m, 3H), 7.05-6.98 (m, 2H), 4.52 (s, 2H), 3.40-3.31 (m, 2H), 2.57 (t, J=5.6 Hz, 8H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 197.9, 161.1, 155.6, 143.7, 143.1, 138.6, 136.5, 135.1, 129.6, 129.0, 128.8, 128.8, 128.7, 126.7, 126.7, 125.3, 122.1, 113.6, 51.6, 50.3, 34.8, 27.2, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.27H.sub.24NO.sub.6S: 490.1324, found 490.1322.

    Example 86

    3-methyl-5-(N-(4-carboxybenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S39)

    [0704] ##STR00158##

    [0705] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-39 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 105 mg of white solid was obtained, with a yield of 43%. M.p. 254-255? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.36 (s, 2H), 8.27 (d, J=1.9 Hz, 1H), 8.01-7.81 (m, 4H), 7.46 (d, J=8.0 Hz, 2H), 7.22-7.09 (m, 3H), 7.00 (d, J=7.2 Hz, 2H), 4.51 (s, 2H), 3.42-3.28 (m, 2H), 2.57 (s, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 167.5, 161.2, 155.5, 144.0, 142.7, 138.6, 135.1, 130.4, 129.9, 129.7, 129.0, 128.8, 128.6, 126.7, 126.6, 125.0, 122.1, 113.5, 51.6, 50.4, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.22NO.sub.7S: 492.1122, found 491.1115.

    Example 87

    3-methyl-5-(N-(4-(tert-butoxycarbonyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S40)

    [0706] ##STR00159##

    [0707] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-40 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 200 mg of white solid was obtained, with a yield of 77%. M.p. 188-189? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.61 (s, 1H), 8.21 (s, 1H), 7.88 (dd, J=47.6, 7.6 Hz, 4H), 7.42 (d, J=8.1 Hz, 2H), 7.15 (dt, J=16.9, 7.1 Hz, 3H), 7.01 (d, J=6.2 Hz, 2H), 4.50 (s, 2H), 3.37 (s, 2H), 2.58 (d, J=19.8 Hz, 5H), 1.52 (s, 9H). .sup.13C NMR (101 MHz, DMSO) ? 165.1, 161.1, 155.5, 143.8, 142.5, 138.6, 135.2, 131.0, 129.9, 129.5, 129.0, 128.7, 128.6, 126.7, 126.6, 125.1, 122.0, 113.5, 81.1, 51.6, 50.3, 34.9, 28.2, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.30H.sub.30NO.sub.7S: 548.1748, found 548.1738.

    Example 88

    3-methyl-5-(N-(4-(carboxymethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S41)

    [0708] ##STR00160##

    [0709] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-41 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 95 mg of white solid was obtained, with a yield of 34%. M.p. 182-183? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 12.92 (s, 2H), 8.29 (d, J=1.9 Hz, 1H), 7.94 (dd, J=8.8, 1.9 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.20 (ddd, J=42.8, 17.3, 7.5 Hz, 7H), 7.03-6.94 (m, 2H), 4.40 (s, 2H), 3.56 (s, 2H), 3.30 (t, J=8.0 Hz, 2H), 2.57 (d, J=14.7 Hz, 5H). .sup.13C NMR (101 MHz, DMSO) ? 173.1, 161.1, 155.5, 143.7, 138.7, 135.6, 135.4, 134.9, 130.0, 129.6, 129.0, 128.8, 128.7, 126.7, 125.4, 122.0, 113.5, 51.5, 49.7, 34.8, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.27H.sub.24NO.sub.7S: 507.1352, found 506.1267.

    Example 89

    (E)-3-methyl-5-(N-(4-(2-carboxyvinyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S42)

    [0710] ##STR00161##

    [0711] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-42 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 87 mg of white solid was obtained, with a yield of 83%. M.p. 270-271? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.03 (s, 2H), 8.28 (d, J=1.9 Hz, 1H), 7.96 (dd, J=8.8, 1.9 Hz, 1H), 7.85 (d, J=8.7 Hz, 1H), 7.66 (d, J=7.8 Hz, 2H), 7.57 (d, J=16.0 Hz, 1H), 7.37 (d, J=7.8 Hz, 2H), 7.26-7.10 (m, 3H), 7.06-6.94 (m, 2H), 6.52 (d, J=16.0 Hz, 1H), 4.46 (s, 2H), 3.48-3.23 (m, 3H), 2.58 (s, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 168.0, 161.1, 155.6, 143.9, 143.7, 139.7, 138.7, 135.3, 134.0, 129.6, 129.1, 129.0, 128.8, 126.7, 126.7, 125.3, 122.1, 119.7, 113.6, 51.5, 50.1, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.28H.sub.24NO.sub.7S: 518.1273, found 518.1268.

    Example 90

    3-methyl-5-(N-(naphthalen-2-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S43)

    [0712] ##STR00162##

    [0713] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-43 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 94 mg of white solid was obtained, with a yield of 89%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.48-8.30 (m, 2H), 8.06 (dd, J=8.7, 1.9 Hz, 1H), 8.01-7.86 (m, 3H), 7.67-7.53 (m, 3H), 7.49 (t, J=7.6 Hz, 1H), 7.09 (dq, J=14.0, 7.1 Hz, 3H), 6.86-6.70 (m, 2H), 4.86 (s, 2H), 3.24 (t, J=8.2 Hz, 2H), 2.60 (s, 3H), 2.22 (t, J=8.2 Hz, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.4, 155.6, 144.4, 138.5, 134.3, 133.9, 132.0, 131.9, 129.8, 129.3, 129.0, 128.8, 128.7, 128.4, 126.9, 126.8, 126.7, 126.5, 125.7, 124.3, 122.2, 113.5, 51.1, 49.9, 35.3, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.29H.sub.24NO.sub.5S: 498.1375, found 498.1376.

    Example 91

    3-methyl-5-(N-(quinolin-8-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S44)

    [0714] ##STR00163##

    [0715] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-44 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 103 mg of white solid was obtained, with a yield of 99%. M.p. 190-191? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.88 (s, 1H), 8.36 (d, J=7.9 Hz, 1H), 8.20 (s, 1H), 7.91 (t, J=9.1 Hz, 2H), 7.80 (d, J=5.6 Hz, 2H), 7.68-7.48 (m, 2H), 7.12 (dd, J=15.3, 6.9 Hz, 3H), 6.95 (d, J=7.0 Hz, 2H), 5.10 (s, 2H), 3.60-3.38 (m, 2H), 2.73-2.60 (m, 2H), 2.54 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.1, 155.4, 150.2, 145.8, 143.6, 138.7, 137.2, 135.4, 135.0, 129.8, 129.4, 129.0, 128.7, 128.2, 126.8, 126.7, 125.2, 122.0, 121.9, 113.4, 50.8, 47.7, 35.1, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.28H.sub.23N.sub.2O.sub.5S: 499.1328, found 499.1321.

    Example 92

    3-methyl-5-(N-(naphthalen-2-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S45)

    [0716] ##STR00164##

    [0717] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-45 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 101 mg of white solid was obtained, with a yield of 99%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.09 (s, 1H), 7.89 (d, J=8.1 Hz, 2H), 7.84 (d, J=8.8 Hz, 3H), 7.73 (d, J=8.6 Hz, 1H), 7.58-7.43 (m, 3H), 7.13 (dq, J=14.2, 6.9 Hz, 3H), 6.95 (d, J=6.7 Hz, 2H), 4.57 (s, 2H), 3.46 (s, 3H), 3.38-3.29 (m, 2H), 2.62-2.54 (m, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.2, 154.7, 152.3, 138.8, 135.0, 134.0, 133.2, 132.9, 131.2, 128.9, 128.8, 128.6, 128.1, 128.1, 127.4, 126.8, 126.7, 126.7, 126.5, 124.2, 120.5, 116.6, 112.7, 52.0, 49.9, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.29H.sub.24NO.sub.5S: 498.1375, found 498.1379.

    Example 93

    3-methyl-5-(N-(2,6-difluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S46)

    [0718] ##STR00165##

    [0719] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-46 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 89 mg of white solid was obtained, with a yield of 92%. M.p. 180-181. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.09 (d, J=1.9 Hz, 1H), 7.85 (dd, J=8.8, 1.9 Hz, 1H), 7.78 (d, J=8.8 Hz, 1H), 7.40 (ddd, J=15.0, 8.5, 6.6 Hz, 1H), 7.24 (t, J=7.3 Hz, 2H), 7.16 (ddd, J=7.3, 5.1, 1.3 Hz, 1H), 7.12-7.00 (m, 4H), 4.49 (s, 2H), 3.37-3.26 (m, 2H), 2.72-2.63 (m, 2H), 2.55 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.0, 161.6 (dd, J=249.6, 8.0 Hz, 1C), 155.3, 146.0, 134.4, 131.5 (t, J=10.6 Hz, 1C), 129.9, 128.9, 128.9, 126.8, 125.9, 122.8, 121.5, 113.2, 112.5, 112.2 (dd, J=18.9, 12.0 Hz, 1C), 112.1 (d, J=25.1 Hz, 1C), 50.4, 35.2, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?113.36. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.20NO.sub.5F.sub.2S: 484.1030, found 484.1036.

    Example 94

    3-methyl-5-(N-(2-fluoro-6-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S47)

    [0720] ##STR00166##

    [0721] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-47 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 93 mg of white solid was obtained, with a yield of 94%. M.p. 195-196. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.18 (d, J=1.9 Hz, 1H), 7.92 (dd, J=8.8, 2.0 Hz, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.39 (td, J=8.2, 6.1 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H), 7.26-7.12 (m, 4H), 6.98 (d, J=7.0 Hz, 2H), 4.55 (s, 2H), 3.35-3.23 (m, 2H), 2.56 (s, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.1 (d, J=250.9 Hz, 1C), 161.2, 155.5, 143.9, 138.5, 135.6 (d, J=5.3 Hz, 1C), 134.5, 131.6 (d, J=10.0 Hz, 1C), 129.5, 128.9 (d, J=2.2 Hz, 1C), 126.8, 126.7, 126.3 (d, J=3.1 Hz, 1C), 125.0, 122.0, 121.8 (d, J=16.9 Hz, 1C), 115.2 (d, J=22.6 Hz, 1C), 113.5, 50.5, 44.3 (d, J=1.9 Hz, 1C), 35.7, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?111.00. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.20NO.sub.5FSCl: 500.0735, found 500.0743.

    Example 95

    3-methyl-5-(N-(2-fluoro-6-(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S48)

    [0722] ##STR00167##

    [0723] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-48 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 98 mg of white solid was obtained, with a yield of 91%. M.p. 99-100. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.17 (s, 1H), 7.99-7.76 (m, 2H), 7.57 (dd, J=40.4, 6.1 Hz, 3H), 7.17 (dt, J=17.0, 7.2 Hz, 3H), 6.90 (d, J=7.5 Hz, 2H), 4.60 (s, 2H), 3.20 (t, J=8.1 Hz, 2H), 2.56 (s, 3H), 2.50-2.36 (m, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.3 (d, J=250.0 Hz, 1C), 161.8, 155.4, 146.1, 138.4, 133.8, 131.6 (d, J=9.7 Hz, 1C), 130.2 (d, J=33.4 Hz, 1C), 130.0, 128.9, 128.7, 126.8, 126.1, 125.2, 122.9 (d, J=41.2 Hz, 1C), 122.5, 122.1 (d, J=14.6 Hz, 1C), 121.8, 120.8 (d, J=23.3 Hz, 1C), 113.3, 50.3, 43.7, 35.7, 9.4. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?56.89, ?110.29. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.20NO.sub.5F.sub.4S: 534.0998, found 534.0999.

    Example 96

    3-methyl-5-(N-(2,6-dichlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S49)

    [0724] ##STR00168##

    [0725] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-49 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 84 mg of white solid was obtained, with a yield of 81%. M.p. 176-177? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.21 (s, 1H), 7.94 (d, J=8.6 Hz, 1H), 7.84 (d, J=8.7 Hz, 1H), 7.46 (d, J=7.9 Hz, 2H), 7.42-7.32 (m, 1H), 7.16 (dt, J=23.5, 6.4 Hz, 3H), 6.89 (d, J=7.0 Hz, 2H), 4.62 (s, 2H), 3.33-3.13 (m, 2H), 2.57 (s, 3H), 2.46 (d, J=7.9 Hz, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.5, 155.5, 145.0, 138.4, 136.7, 133.8, 131.5, 131.0, 129.7, 129.5, 128.9, 128.8, 126.8, 126.5, 124.0, 122.0, 113.4, 50.3, 48.5, 36.3, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.20NO.sub.5SCl.sub.2: 516.0439, found 516.0431.

    Example 97

    3-methyl-5-(N-(2,6-dimethylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S5

    [0726] ##STR00169##

    [0727] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-50 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 62 mg of white solid was obtained, with a yield of 65%. M.p. 211-212? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.76 (s, 1H), 8.22 (s, 1H), 7.96 (d, J=8.7 Hz, 1H), 7.86 (d, J=8.7 Hz, 1H), 7.15 (dt, J=14.1, 6.9 Hz, 4H), 7.02 (d, J=7.4 Hz, 2H), 6.77 (d, J=7.0 Hz, 2H), 4.37 (s, 2H), 3.15-2.98 (m, 2H), 2.58 (s, 3H), 2.41-2.31 (m, 2H), 2.26 (s, 6H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.2, 155.6, 143.7, 138.6, 133.8, 131.6, 129.6, 128.9, 128.8, 128.8, 128.6, 126.8, 126.7, 125.2, 122.2, 113.5, 49.9, 47.9, 40.4, 36.6, 20.2, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.27H.sub.26NO.sub.5S: 476.1532, found 476.1533.

    Example 98

    3-methyl-5-(N-(2,4-difluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S51)

    [0728] ##STR00170##

    [0729] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-51 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 92 mg of white solid was obtained, with a yield of 95%. M.p. 155-156? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.15 (d, J=1.9 Hz, 1H), 7.87 (dd, J=8.7, 2.0 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.47 (q, J=8.5 Hz, 1H), 7.28-7.11 (m, 4H), 7.11-6.99 (m, 3H), 4.44 (s, 2H), 3.41-3.28 (m, 2H), 2.58 (d, J=20.0 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.1, 155.2, 138.6, 134.4, 132.7 (dd, J=9.7, 5.1 Hz, 1C), 130.2, 129.0, 128.8, 126.8, 125.7, 121.7 (d, J=2.8 Hz, 1C), 121.4, 120.6 (dd, J=14.8, 3.7 Hz, 1C), 113.2, 112.0 (dd, J=21.1, 3.2 Hz, 1C), 104.3 (t, J=26.2 Hz, 1C), 50.3, 45.5 (d, J=1.4 Hz, 1C), 35.0, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?110.70, ?113.08. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.20NO.sub.5SF.sub.2: 484.1030, found 484.1037.

    Example 99

    3-methyl-5-(N-(2-fluoro-4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S52)

    [0730] ##STR00171##

    [0731] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-52 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 90 mg of white solid was obtained, with a yield of 90%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.03 (d, J=1.9 Hz, 1H), 7.79 (dd, J=8.6, 2.0 Hz, 1H), 7.71 (d, J=8.7 Hz, 1H), 7.44 (t, J=8.3 Hz, 1H), 7.37 (dd, J=10.0, 2.1 Hz, 1H), 7.26 (dd, J=8.3, 2.1 Hz, 1H), 7.24-7.11 (m, 3H), 7.03 (d, J=6.9 Hz, 2H), 4.43 (s, 2H), 3.39-3.28 (m, 2H), 2.67-2.58 (m, 2H), 2.52 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.1, 160.6 (d, J=250.7 Hz, 1C), 154.7, 151.5, 138.6, 133.7, 133.6, 132.6 (d, J=4.8 Hz, 1C), 131.0, 129.0, 128.8, 126.8, 125.1 (d, J=3.5 Hz, 1C), 124.4, 123.7 (d, J=14.4 Hz, 1C), 120.6, 117.3, 116.4 (d, J=25.5 Hz, 1C), 112.8, 50.4, 45.5 (d, J=2.2 Hz, 1C), 34.9, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?114.61. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.20NO.sub.5FSCl: 500.0735, found 500.0736.

    Example 100

    3-methyl-5-(N-(2-fluoro-4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S53)

    [0732] ##STR00172##

    [0733] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-53 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 98 mg of white solid was obtained, with a yield of 90%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.03 (d, J=1.9 Hz, 1H), 7.79 (dd, J=8.7, 2.0 Hz, 1H), 7.71 (d, J=8.7 Hz, 1H), 7.53-7.46 (m, 1H), 7.38 (d, J=5.0 Hz, 2H), 7.26-7.11 (m, 3H), 7.03 (d, J=6.7 Hz, 2H), 4.42 (s, 2H), 3.38-3.28 (m, 2H), 2.67-2.58 (m, 2H), 2.52 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.1, 160.6 (d, J=251.6 Hz, 1C), 154.7, 151.8, 138.6, 133.5, 132.9 (d, J=4.7 Hz, 1C), 131.0, 129.0, 128.8, 128.1 (d, J=3.4 Hz, 1C), 126.8, 124.3, 124.2 (d, J=14.4 Hz, 1C), 121.6 (d, J=9.7 Hz, 1C), 120.6, 119.2 (d, J=25.0 Hz, 1C), 117.1, 112.8, 50.4, 45.6 (d, J=1.7 Hz, 1C), 34.9, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?114.52. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.20NO.sub.5FSBr: 544.0230, found 544.0230.

    Example 102

    3-methyl-5-(N-(2-fluoro-4-(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S55)

    [0734] ##STR00173##

    [0735] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-55 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 82 mg of white solid was obtained, with a yield of 77%. M.p. 174-175? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.23 (d, J=1.9 Hz, 1H), 7.93 (dd, J=8.7, 1.9 Hz, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.62 (q, J=10.7, 9.2 Hz, 2H), 7.54 (d, J=8.0 Hz, 1H), 7.24-7.11 (m, 3H), 7.05 (d, J=7.0 Hz, 2H), 4.55 (s, 2H), 3.49-3.36 (m, 2H), 2.72-2.63 (m, 2H), 2.56 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.3, 160.3 (d, J=248.9 Hz, 1C), 155.5, 144.8, 138.5, 134.6, 132.2 (d, J=4.1 Hz, 1C), 129.8, 129.6 (d, J=14.3 Hz, 1C), 129.0, 128.8, 126.7, 126.4, 124.6 (d, J=99.9 Hz, 1C), 121.9, 121.7 (t, J=3.5 Hz, 1C), 113.4, 113.2 (d, J=25.6 Hz, 1C), 50.8, 45.8 (d, J=3.3 Hz, 1C), 35.0, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?61.16, ?114.91. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.20NO.sub.5SF.sub.4: 534.0998, found 534.0992.

    Example 103

    3-methyl-5-(N-(2-chloro-4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S56)

    [0736] ##STR00174##

    [0737] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-56 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 65 mg of white solid was obtained, with a yield of 65%. M.p. 145-146? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.82 (s, 1H), 8.27 (s, 1H), 8.10-7.72 (m, 2H), 7.53 (t, J=7.5 Hz, 1H), 7.40 (d, J=8.9 Hz, 1H), 7.30-7.09 (m, 4H), 7.02 (d, J=7.3 Hz, 2H), 4.48 (s, 2H), 3.37 (t, J=8.0 Hz, 2H), 2.58 (s, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.8 (d, J=248.6 Hz, 1C), 161.2, 155.6, 144.1, 138.5, 134.7, 133.8 (d, J=10.7 Hz, 1C), 132.4 (d, J=8.9 Hz, 1C), 131.2 (d, J=3.4 Hz, 1C), 129.7, 129.0, 128.8, 126.8, 126.7, 124.9, 122.1, 117.1 (d, J=25.1 Hz, 1C), 114.9 (d, J=21.3 Hz, 1C), 113.6, 50.6, 49.3, 35.1, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?112.54. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.20NO.sub.5FSCl: 500.0735, found 500.0732.

    Example 104

    3-methyl-5-(N-(2-(trifluoromethyl)-4-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S57)

    [0738] ##STR00175##

    [0739] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-57 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 109 mg of white solid was obtained, with a yield of 99%. M.p. 156-157? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.29 (s, 1H), 7.91 (dd, J=36.9, 8.4 Hz, 2H), 7.70 (s, 1H), 7.60 (d, J=8.1 Hz, 1H), 7.55-7.44 (m, 1H), 7.16, 7.00 (d, J=6.0 Hz, 2H), 4.54 (s, 2H), 3.42 (s, 2H), 2.58 (s, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.3, 161.2 (d, J=247.6, 1C), 160.0, 155.6, 144.4, 138.3, 134.3, 132.8, 132.7, 129.8, 128.8 (d, J=13.3, 1C), 126.8, 126.5, 124.6, 122.2, 120.0 (d, J=20.9, 1C), 114.0 (d, J=6.2, 1C), 113.6, 50.9, 48.3, 34.8, 9.5. .sup.19F NMR (376 MHz, DMSO) ? ?58.58, ?113.37. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.20NO.sub.5F.sub.4S: 534.0998, found 534.0988.

    Example 105

    3-methyl-5-(N-(2,4-bis(trifluoromethyl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S58)

    [0740] ##STR00176##

    [0741] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-58 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 62 mg of white solid was obtained, with a yield of 53%. M.p. 155-156? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.26 (s, 1H), 8.05-7.92 (m, 3H), 7.90-7.83 (m, 2H), 7.15 (dq, J=14.1, 7.0 Hz, 3H), 7.04 (d, J=6.9 Hz, 2H), 4.64 (s, 2H), 3.58-3.41 (m, 2H), 2.74-2.61 (m, 2H). 2.57 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.6, 155.6, 141.9, 138.3, 133.9, 131.1, 129.9, 129.0, 128.8, 127.4 (d, J=31.4 Hz, 1C), 126.8, 126.4, 125.2 (d, J=5.5 Hz, 1C), 123.8 (d, J=3.6 Hz, 1C), 123.1, 122.5 (d, J=3.1 Hz, 1C), 122.1, 113.6, 51.3, 48.7, 34.8, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?58.84, ?61.35. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.27H.sub.20NO.sub.5F.sub.6S: 584.0966, found 584.0955.

    Example 106

    3-methyl-5-(N-(2-(trifluoromethyl)-4-bromobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S59)

    [0742] ##STR00177##

    [0743] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-59 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 75 mg of white solid was obtained, with a yield of 63%. M.p. 150-151? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.82 (s, 1H), 8.28 (s, 1H), 8.10-7.72 (m, 4H), 7.57 (d, J=8.5 Hz, 1H), 7.38-6.87 (m, 5H), 4.53 (s, 2H), 3.44 (t, J=7.8 Hz, 2H), 2.59 (d, J=15.7 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.2, 155.7, 144.0, 138.3, 136.1 (d, J=14.9 Hz, 1C), 134.3, 132.2, 129.7, 129.0, 128.9, 128.8, 128.4 (d, J=31.4 Hz, 1C), 126.7 (d, J=10.7 Hz, 1C), 125.0 (d, J=4.3 Hz, 1C), 122.3, 121.0, 113.7, 51.1, 48.4, 34.8, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?58.57. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.20NO.sub.5F.sub.3SBr: 594.0198, found 594.0205.

    Example 107

    3-methyl-5-(N-(2,4-dichlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S60)

    [0744] ##STR00178##

    [0745] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-60 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 48 mg of white solid was obtained, with a yield of 46%. M.p. 177-178? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.77 (s, 1H), 8.27 (s, 1H), 7.96 (d, J=8.5 Hz, 1H), 7.85 (d, J=8.6 Hz, 1H), 7.55 (s, 1H), 7.48 (d, J=8.2 Hz, 1H), 7.39 (d, J=7.9 Hz, 1H), 7.17 (dt, J=16.7, 6.5 Hz, 3H), 7.03 (d, J=6.8 Hz, 2H), 4.49 (s, 2H), 3.50-3.32 (m, 2H), 2.59 (d, J=12.3 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.1, 155.6, 143.8, 138.5, 134.7, 134.1, 133.8, 133.4, 132.1, 129.6, 129.2, 129.0, 128.8, 127.9, 126.8, 126.7, 125.2, 122.2, 113.6, 50.8, 49.4, 35.1, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.20NO.sub.5SCl.sub.2: 516.0439, found 516.0430.

    Example 108

    3-methyl-5-(N-(2-methyl-5-fluorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S61)

    [0746] ##STR00179##

    [0747] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-61 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 72 mg of white solid was obtained, with a yield of 75%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.19 (d, J=2.0 Hz, 1H), 7.89 (dd, J=8.7, 2.0 Hz, 1H), 7.79 (d, J=8.7 Hz, 1H), 7.28-7.09 (m, 5H), 7.02 (td, J=8.5, 2.9 Hz, 1H), 6.95 (d, J=6.8 Hz, 2H), 4.37 (s, 2H), 3.37-3.22 (m, 2H), 2.56 (s, 3H), 2.46 (d, J=7.7 Hz, 2H), 2.26 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.5, 161.0 (d, J=242.1 Hz, 1C), 155.0, 138.6, 137.6 (d, J=6.9 Hz, 1C), 133.6, 133.0 (d, J=2.8 Hz, 1C), 132.2 (d, J=7.9 Hz, 1C), 130.7, 128.8 (d, J=9.0 Hz, 1C), 126.7, 125.1, 121.2, 115.9 (d, J=22.3 Hz, 1C), 114.4 (d, J=20.8 Hz, 1C), 113.0, 50.5, 50.2, 35.1, 18.4, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?117.53. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.23NO.sub.5SF: 480.1281, found 480.1284.

    Example 109

    3-methyl-5-(N-(2,6-difluoro-4-chlorobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S62)

    [0748] ##STR00180##

    [0749] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-62 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 102 mg of white solid was obtained, with a yield of 98%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.08 (d, J=1.9 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.81 (d, J=8.8 Hz, 1H), 7.24 (t, J=7.7 Hz, 4H), 7.17 (t, J=7.3 Hz, 1H), 7.09 (d, J=7.0 Hz, 2H), 4.43 (s, 2H), 3.42-3.32 (m, 2H), 2.77-2.69 (m, 2H), 2.55 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.4 (dd, J=252.4, 9.9 Hz, 1C), 161.2, 155.5, 144.1, 138.6, 134.7 (t, J=14.2 Hz, 1C), 134.7, 129.5, 129.0, 128.9, 126.8, 126.5, 124.7, 121.7, 113.4, 113.2 (d, J=29.6 Hz, 1C), 111.8 (t, J=19.3 Hz, 1C), 50.8, 35.3, 9.5. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?111.06. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.25H.sub.19NO.sub.5F.sub.2SCl: 518.0641, found 518.0642.

    Example 110

    3-methyl-5-(N-([1,1-biphenyl]-4-ylmethyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S82)

    [0750] ##STR00181##

    [0751] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-82 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 93 mg of white solid was obtained, with a yield of 84%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.26 (s, 1H), 7.96 (d, J=8.8 Hz, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.63 (dd, J=7.6, 5.2 Hz, 4H), 7.50-7.39 (m, 4H), 7.35 (t, J=7.3 Hz, 1H), 7.18 (t, J=7.2 Hz, 2H), 7.12 (t, J=7.2 Hz, 1H), 7.02 (d, J=6.9 Hz, 2H), 4.48 (s, 2H), 3.41-3.34 (m, 2H), 2.67-2.58 (m, 2H), 2.56 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.3, 155.5, 144.1, 140.1, 139.9, 138.7, 136.5, 135.4, 129.7, 129.4, 129.3, 129.0, 128.8, 127.9, 127.1, 127.1, 126.7, 126.6, 124.9, 122.0, 113.5, 51.4, 49.9, 34.8, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.31H.sub.26NO.sub.5S: 524.1532, found 524.1528.

    Example 111

    3-methyl-5-(N-(2-cyano-[1,1-biphenyl]-4-yl)methyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S83)

    [0752] ##STR00182##

    [0753] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-83 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 96 mg of white solid was obtained, with a yield of 86%. M.p. 197-198? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25 (d, J=1.9 Hz, 1H), 8.00-7.89 (m, 2H), 7.79 (dd, J=15.5, 8.1 Hz, 2H), 7.58 (dd, J=14.5, 7.9 Hz, 4H), 7.50 (d, J=8.2 Hz, 2H), 7.24-7.08 (m, 3H), 7.02 (d, J=7.0 Hz, 2H), 4.51 (s, 2H), 3.45-3.32 (m, 2H), 2.60 (d, J=14.5 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 155.2, 144.6, 138.7, 138.3, 137.5, 134.7, 134.3, 134.0, 130.5, 130.2, 129.3, 129.0, 129.0, 128.8, 128.7, 126.7, 125.8, 121.6, 119.0, 113.3, 110.7, 51.6, 50.2, 34.9, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.32H.sub.25N.sub.2O.sub.5S: 549.1484, found 549.1487.

    Example 112

    3-methyl-5-(N-((2-(tert-butoxycarbonyl)-[1,1-biphenyl]-4-yl)methyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S84

    [0754] ##STR00183##

    [0755] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-84 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 52 mg of white solid was obtained, with a yield of 42%. M.p. 197-198? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.35-8.23 (m, 1H), 7.95 (dd, J=8.8, 1.7 Hz, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.66 (d, J=7.6 Hz, 1H), 7.56 (t, J=7.4 Hz, 1H), 7.43 (dd, J=22.4, 7.8 Hz, 3H), 7.34 (d, J=7.5 Hz, 1H), 7.27 (d, J=8.0 Hz, 2H), 7.20 (t, J=7.2 Hz, 2H), 7.13 (t, J=7.2 Hz, 1H), 7.03 (d, J=7.1 Hz, 2H), 4.51 (s, 2H), 3.43-3.28 (m, 2H), 2.60 (d, J=12.8 Hz, 5H), 1.17 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 167.9, 161.8, 155.4, 141.0, 140.7, 138.7, 136.4, 135.2, 133.2, 131.3, 130.8, 130.0, 129.5, 129.0, 128.9, 128.8, 128.4, 127.8, 126.7, 126.2, 121.7, 113.4, 81.2, 51.2, 49.7, 34.7, 27.6, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.36H.sub.34NO.sub.7S: 624.2056, found 624.2044.

    Example 113

    3-methyl-5-(N-(4-benzoylbenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S85)

    [0756] ##STR00184##

    [0757] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M4-85 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 70 mg of white solid was obtained, with a yield of 63%. M.p. 192-193? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.70 (s, 1H), 8.30 (d, J=1.9 Hz, 1H), 7.97 (dd, J=8.8, 2.0 Hz, 1H), 7.86 (d, J=8.7 Hz, 1H), 7.69 (d, J=8.0 Hz, 5H), 7.60-7.48 (m, 4H), 7.19 (t, J=7.3 Hz, 2H), 7.13 (t, J=7.2 Hz, 1H), 7.08-6.99 (m, 2H), 4.55 (s, 2H), 3.41 (t, J=7.9 Hz, 2H), 2.64 (t, J=7.9 Hz, 2H), 2.58 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 195.8, 161.1, 155.6, 143.8, 142.6, 138.7, 137.5, 136.6, 135.1, 133.1, 130.3, 130.0, 129.6, 129.0, 129.0, 128.8, 128.6, 126.7, 126.7, 125.3, 122.2, 113.6, 51.6, 50.4, 34.8, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.32H.sub.26NO.sub.6S: 552.1481, found 552.1484.

    Example 114

    3,3-dimethyl-1-(4-(4-nitrophenyl)piperazin-1-yl)butan-1-one (M5-1)

    [0758] ##STR00185##

    [0759] 4-nitrophenylpiperazine (2.07 g, 10 mmol) and triethylamine (1.22 g, 12 mmol) were added to anhydrous tetrahydrofuran (30 mL), and the solution was stirred at 0? C. for 10 min. Anhydrous tetrahydrofuran (10 mL) solution of 3, 3-dimethylbutyrylchloride (1.62 g, 12 mmol) was slowly added dropwise and the resulting solution was then heated to room temperature to react for 10 h. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (100 mL) and then extracted three times with ethyl acetate (100 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (DCM/MeOH=150/1) to obtain 2.82 g of orange red solid, with a yield of 92%.

    Example 115

    propyl-4-(4-nitrophenyl)piperazin-1-carboxylate (M5-2)

    [0760] ##STR00186##

    [0761] In accordance with the preparation method of 3,3-dimethyl-1-(4-(4-nitrophenyl)piperazin-1-yl)butan-1-one (M5-1), this example was implemented under the same condition except that propyl chlorocarbonate was used instead of 3,3-dimethylbutyrylchloride. 1.35 of yellow solid was obtained, with a yield of 92%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.22-7.95 (m, 2H), 6.87-6.71 (m, 2H), 4.06 (t, J=6.7 Hz, 2H), 3.71-3.58 (m, 4H), 3.49-3.35 (m, 4H), 1.66 (h, J=7.2 Hz, 2H), 0.94 (t, J=7.4 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 155.4, 154.6, 138.9, 125.9, 112.9, 67.3, 46.9, 43.0, 22.3, 10.4.

    Example 116

    1-(4-(4-nitrophenyl)piperazin-1-yl)ethan-1-one (M5-3)

    [0762] ##STR00187##

    [0763] In accordance with the preparation method of 3,3-dimethyl-1-(4-(4-nitrophenyl)piperazin-1-yl)butan-1-one (M5-1), this example was implemented under the same condition except that acetyl chloride was used instead of 3,3-dimethylbutyrylchloride. 1.08 of yellow solid was obtained, with a yield of 87%.

    Example 117

    (4-(4-nitrophenyl)piperazin-1-yl)(phenyl)methanone (M5-4)

    [0764] ##STR00188##

    [0765] In accordance with the preparation method of 3,3-dimethyl-1-(4-(4-nitrophenyl)piperazin-1-yl)butan-1-one (M5-1), this example was implemented under the same condition except that benzoyl chloride was used instead of 3,3-dimethylbutyrylchloride. 1.45 of yellow solid was obtained, with a yield of 93%.

    Example 118

    N,N-dimethyl-4-(4-nitrophenyl)piperazine-1-carboxamide (M5-5)

    [0766] ##STR00189##

    [0767] In accordance with the preparation method of 3,3-dimethyl-1-(4-(4-nitrophenyl)piperazin-1-yl)butan-1-one (M5-1), this example was implemented under the same condition except that dimethylcarbamoyl chloride was used instead of 3,3-dimethylbutyrylchloride. 2.47 of yellow solid was obtained, with a yield of 88%.

    Example 119

    3,3-dimethyl-1-(4-(4-aminophenyl)piperazin-1-yl)butan-1-one (M6-1)

    [0768] ##STR00190##

    [0769] 3,3-dimethyl-1-(4-(4-nitrophenyl)piperazin-1-yl)butan-1-one (94 mg, 0.3 mmol) and 38% concentrated hydrochloric acid (0.5 mL, 6 mmol) were mixed and stirred, zinc powder (0.14 g, 2.1 mmol) was then added step by step, the reaction was performed at room temperature for 11 h. After the reaction was found to be completed from the monitoring of the TLC, ammonia water was then slowly added dropwise until PH=5?6. The reaction product was dissolved in water (5 mL) and then extracted three times with dichloromethane (15 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 90 mg of white solid, with a yield of 99%.

    Example 120

    Propyl-4-(4-aminophenyl)piperazine-1-carboxylate (M6-2)

    [0770] ##STR00191##

    [0771] In accordance with the preparation method of 3,3-dimethyl-1-(4-(4-aminophenyl)piperazin-1-yl)butan-1-one (M6-1), this example was implemented under the same condition except that propyl-4-(4-nitrophenyl)piperazin-1-carboxylate was used instead of 3,3-dimethyl-1-(4-(4-nitrophenyl)piperazin-1-yl)butan-1-one. 0.50 g of white solid was obtained, with a yield of 64%. .sup.1H NMR (400 MHz, Chloroform-d) ? 6.80 (d, J=8.8 Hz, 2H), 6.69-6.59 (m, 2H), 4.06 (t, J=6.7 Hz, 2H), 3.69-3.57 (m, 4H), 3.51 (s, 2H), 2.96 (t, J=5.1 Hz, 4H), 1.66 (h, J=7.1 Hz, 2H), 0.95 (t, J=7.4 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 155.6, 144.2, 140.8, 119.3, 116.1, 67.1, 51.2, 43.9, 22.4, 10.4.

    Example 121

    1-(4-(4-aminophenyl)piperazin-1-yl)ethan-1-one (M6-3)

    [0772] ##STR00192##

    [0773] In accordance with the preparation method of 3,3-dimethyl-1-(4-(4-aminophenyl)piperazin-1-yl)butan-1-one (M6-1), this example was implemented under the same condition except that 1-(4-(4-nitrophenyl)piperazin-1-yl)ethan-1-one was used instead of 3,3-dimethyl-1-(4-(4-nitrophenyl)piperazin-1-yl)butan-1-one. 0.39 of yellow solid was obtained, with a yield of 60%.

    Example 122

    (4-(4-aminophenyl)piperazin-1-yl) (phenyl)methanone (M6-4)

    [0774] ##STR00193##

    [0775] In accordance with the preparation method of 3,3-dimethyl-1-(4-(4-aminophenyl)piperazin-1-yl)butan-1-one (M6-4), this example was implemented under the same condition except that (4-(4-nitrophenyl)piperazin-1-yl)phenylmethyl ketone was used instead of 3,3-dimethyl-1-(4-(4-nitrophenyl)piperazin-1-yl)butan-1-one. 0.62 of yellow solid was obtained, with a yield of 74%.

    Example 123

    N,N-dimethyl-4-(4-aminophenyl)piperazine-1-carboxamide (M6-5)

    [0776] ##STR00194##

    [0777] In accordance with the preparation method of 3,3-dimethyl-1-(4-(4-aminophenyl)piperazin-1-yl)butan-1-one (M6-1), this example was implemented under the same condition except that N,N-dimethyl-4-(4-nitrophenyl)piperazine-1-amide was used instead of 3,3-dimethyl-1-(4-(4-nitro phenyl)piperazin-1-yl)butan-1-one. 0.55 g of white solid was obtained, with a yield of 74%.

    Example 124

    General Synthesis Method of Intermediate M7

    [0778] Method A: Substituted aniline or phenethylamine (1.8 mmol), 2-iodoethylbenzene (1.2 mmol), and potassium carbonate (0.25 g, 2.7 mmol) were dissolved in acetonitrile (8 mL), and the resulting solution was then heated to 60? C. to react for 24 h. After the reaction was found to be completed from the monitoring of the TLC, the reaction system was cooled to room temperature. The solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (10 mL) and then extracted three times with ethyl acetate (10 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography to obtain the intermediate M7. [0779] Method B: Substituted benzaldehyde or phenylacetaldehyde (0.5 mmol), substituted aniline or phenethylamine (0.5 mmol), and trimethyl orthoformate (85 mg, 0.8 mmol) were dissolved in methanol (10 mL), and the resulting solution was stirred at 0? C. Sodium cyanoborohydride (38 mg, 0.6 mmol) was added step by step and the reaction was performed at room temperature for 10 h. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (10 mL) and then extracted three times with ethyl acetate (10 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography to obtain the intermediate M7.

    Example 125

    N-phenethylaniline (M7-10)

    [0780] ##STR00195##

    [0781] Method A was performed to obtain 32 mg of yellow oil product, with a yield of 32%.

    Example 126

    4-benzyl-N-phenethylaniline (M7-11)

    [0782] ##STR00196##

    [0783] Method B was performed to obtain 190 mg of yellow oil product, with a yield of 79%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.79-7.51 (m, 10H), 7.43 (d, J=8.4 Hz, 2H), 6.91 (d, J=8.5 Hz, 2H), 4.30 (s, 2H), 3.88 (s, 1H), 3.70 (t, J=7.1 Hz, 2H), 3.21 (t, J=7.1 Hz, 2H). .sup.13C NMR (101 MHz, Chloroform-d) ? 146.2, 142.0, 139.3, 129.8, 129.7, 128.7, 128.7, 128.5, 128.3, 126.3, 125.7, 113.0, 45.1, 41.0, 35.4.

    Example 127

    N-phenethyl-4-phenoxyaniline (M7-12)

    [0784] ##STR00197##

    [0785] Method B was performed to obtain 140 mg of yellow solid product, with a yield of 65%.

    Example 128

    Diphenylethylamine (M7-13)

    [0786] ##STR00198##

    [0787] Method A was performed to obtain 89 mg of yellow oil product, with a yield of 80%.

    Example 129

    4-morpholine-N-phenethylaniline (M7-63)

    [0788] ##STR00199##

    [0789] Method A was performed to obtain 120 mg of yellow solid product, with a yield of 43%.

    Example 130

    4-(4-methylpiperazin-1-yl)-N-phenethylaniline (M7-64)

    [0790] ##STR00200##

    [0791] Method A was performed to obtain 39 mg of yellow oil product, with a yield of 13%.

    Example 131

    Tert-butyl 4-(4-(phenylethylamino)phenyl)piperazine-1-carboxylate (M7-65)

    [0792] ##STR00201##

    [0793] Method A was performed to obtain 340 mg of yellow solid product, with a yield of 45%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.36 (t, J=7.3 Hz, 2H), 7.31-7.22 (m, 3H), 6.89 (d, J=8.0 Hz, 2H), 6.63 (s, 2H), 3.68-3.58 (m, 4H), 3.39 (s, 2H), 3.14-2.83 (m, 6H), 1.56 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 154.8, 143.6, 142.9, 139.5, 128.8, 128.6, 126.4, 119.4, 114.0, 79.7, 60.4, 51.4, 45.8, 35.7, 28.5.

    Example 132

    3,3-dimethyl-1-(4-(phenethylamino)phenyl)piperazine-1-yl)butanone (M7-66)

    [0794] ##STR00202##

    [0795] Method A was performed to obtain 245 mg of yellow solid product, with a yield of 53%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.30 (t, J=7.3 Hz, 2H), 7.21 (t, J=8.4 Hz, 3H), 6.83 (d, J=8.7 Hz, 2H), 6.58 (d, J=8.6 Hz, 2H), 3.77 (t, J=5.1 Hz, 2H), 3.69-3.60 (m, 2H), 3.50 (s, 1H), 3.34 (t, J=7.0 Hz, 2H), 2.98 (q, J=5.8 Hz, 4H), 2.88 (t, J=7.0 Hz, 2H), 2.29 (s, 2H), 1.07 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.4, 143.2, 143.0, 139.4, 128.8, 128.6, 126.4, 119.4, 114.1, 51.7, 51.4, 46.9, 45.7, 44.7, 41.6, 35.6, 31.5, 30.2.

    Example 133

    Propyl 4-(4-(phenethylamino)phenyl)piperazine-1-carboxylate (M7-67)

    [0796] ##STR00203##

    [0797] Method A was performed to obtain 328 mg of yellow solid product, with a yield of 56%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.32-7.10 (m, 5H), 6.79 (d, J=8.3 Hz, 2H), 6.53 (d, J=8.3 Hz, 2H), 4.05 (t, J=6.6 Hz, 2H), 3.57 (q, J=11.4, 8.2 Hz, 5H), 3.29 (t, J=7.1 Hz, 2H), 2.87 (dt, J=36.4, 6.0 Hz, 6H), 1.64 (h, J=7.1 Hz, 2H), 0.93 (t, J=7.4 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 155.6, 143.5, 143.1, 139.5, 128.9, 128.6, 126.4, 119.5, 114.0, 67.1, 51.3, 45.8, 44.0, 35.7, 22.5, 10.6.

    Example 134

    1-(4-(4-(phenethylamino)phenyl)piperazin-1-yl)ethan-1-one (M7-68)

    [0798] ##STR00204##

    [0799] Method A was performed to obtain 23 mg of yellow solid product, with a yield of 6%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.34 (t, J=7.4 Hz, 2H), 7.25 (t, J=8.1 Hz, 3H), 6.87 (s, 2H), 6.62 (s, 2H), 3.78 (t, J=5.1 Hz, 2H), 3.62 (t, J=5.1 Hz, 2H), 3.39 (s, 2H), 3.15-2.84 (m, 6H), 2.15 (s, 3H).

    Example 135

    (4-(4-(phenethylamino)phenyl)piperazin-1-yl)(phenyl)methanone (M7-69)

    [0800] ##STR00205##

    [0801] Method A was performed to obtain 257 mg of yellow solid product, with a yield of 33%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.54-7.40 (m, 5H), 7.35 (t, J=7.3 Hz, 2H), 7.30-7.18 (m, 3H), 6.88 (d, J=8.6 Hz, 2H), 6.61 (d, J=8.5 Hz, 2H), 3.96 (s, 2H), 3.62 (d, J=41.1 Hz, 3H), 3.36 (t, J=7.1 Hz, 2H), 3.19-2.82 (m, 6H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.3, 143.2, 143.1, 139.6, 136.0, 129.8, 128.9, 128.7, 128.6, 127.3, 126.4, 119.5, 114.0, 51.7, 48.0, 45.8, 42.5, 35.7.

    Example 136

    4-(4-benzylpiperazin-1-yl)-N-phenethylaniline (M7-70)

    [0802] ##STR00206##

    [0803] Method A was performed to obtain 138 mg of yellow solid product, with a yield of 37%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.53-7.28 (m, 10H), 6.95 (s, 2H), 6.68 (s, 2H), 3.69 (s, 2H), 3.44 (s, 2H), 3.18 (s, 4H), 2.97 (t, J=6.9 Hz, 2H), 2.73 (t, J=5.0 Hz, 4H). .sup.13C NMR (101 MHz, Chloroform-d) ? 143.9, 142.4, 139.6, 138.0, 129.4, 129.0, 128.7, 128.5, 127.3, 126.5, 118.9, 114.2, 63.2, 53.4, 51.0, 46.0, 35.7.

    Example 137

    N,N-dimethyl-4-(4-(phenylethylamino)phenyl)piperazine-1-carboxamide (M7-71)

    [0804] ##STR00207##

    [0805] Method A was performed to obtain 120 mg of yellow solid product, with a yield of 34%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.34 (t, J=7.3 Hz, 2H), 7.29-7.21 (m, 3H), 6.89 (d, J=7.4 Hz, 2H), 6.62 (s, 2H), 3.42 (t, J=5.0 Hz, 6H), 3.05 (s, 4H), 2.93 (t, J=7.0 Hz, 2H), 2.88 (s, 6H). .sup.13C NMR (101 MHz, Chloroform-d) ? 164.9, 139.5, 128.9, 128.7, 126.5, 119.3, 114.2, 51.3, 47.0, 38.7.

    Example 138

    4-(4-(methylsulfonyl)piperazin-1-yl)-N-phenethylaniline (M7-72)

    [0806] ##STR00208##

    [0807] Method A was performed to obtain 258 mg of yellow solid product, with a yield of 36%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.26 (dt, J=35.0, 7.5 Hz, 5H), 6.83 (d, J=7.5 Hz, 2H), 6.57 (d, J=8.3 Hz, 2H), 3.54-3.23 (m, 7H), 3.09 (s, 4H), 2.88 (t, J=6.9 Hz, 2H), 2.79 (s, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 143.4, 142.8, 139.4, 128.8, 128.6, 126.5, 119.7, 114.0, 51.1, 46.1, 45.7, 35.6, 34.2.

    Example 139

    Tert-butyl 4-(4-(phenethylamino)phenyl)piperidine-1-carboxylate (M7-73)

    [0808] ##STR00209##

    [0809] Method A was performed to obtain 212 mg of yellow solid product, with a yield of 20%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.37 (t, J=7.4 Hz, 2H), 7.29 (t, J=7.1 Hz, 3H), 7.08 (d, J=8.4 Hz, 2H), 6.64 (d, J=8.4 Hz, 2H), 4.29 (s, 2H), 3.70 (s, 1H), 3.43 (t, J=7.0 Hz, 2H), 2.96 (t, J=7.0 Hz, 2H), 2.84 (t, J=11.0 Hz, 2H), 2.59 (t, J=12.1 Hz, 1H), 1.84 (d, J=12.6 Hz, 2H), 1.63 (dt, J=12.6, 6.2 Hz, 2H), 1.55 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 155.0, 146.5, 139.4, 135.0, 128.8, 128.6, 127.6, 126.5, 113.2, 79.4, 45.4, 41.8, 35.6, 33.5, 28.6.

    Example 140

    Tert-butyl 4-(4-(phenylethylamino)-2-(trifluoromethyl)phenyl)piperazine-1-carboxylate (M7-74)

    [0810] ##STR00210##

    [0811] Method A was performed to obtain 288 mg of yellow oil product, with a yield of 64%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.36 (t, J=7.3 Hz, 2H), 7.28 (t, J=8.6 Hz, 3H), 7.20 (d, J=8.6 Hz, 1H), 6.88 (d, J=2.3 Hz, 1H), 6.79-6.70 (m, 1H), 4.06 (s, 1H), 3.59 (s, 4H), 3.41 (t, J=7.0 Hz, 2H), 2.94 (t, J=6.9 Hz, 2H), 2.82 (t, J=5.0 Hz, 4H), 1.57 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 155.0, 145.7, 141.6, 139.1, 128.8, 128.7, 127.0 (q, J=295.3 Hz, 1C), 126.6, 125.4, 116.0, 110.6 (q, J=4.9 Hz, 1C), 79.6, 53.6, 45.1, 35.4, 28.5. .sup.19F NMR (376 MHz, Chloroform-d) ? ?60.46.

    Example 141

    Tert-butyl 4-(5-(phenylethylamino)pyridin-2-yl)piperazine-1-carboxylate (M7-75)

    [0812] ##STR00211##

    [0813] Method A was performed to obtain 340 mg of brown oil product, with a yield of 45%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.71 (d, J=2.7 Hz, 1H), 7.29 (t, J=7.4 Hz, 2H), 7.24-7.15 (m, 3H), 6.90 (dd, J=8.9, 2.8 Hz, 1H), 6.59 (d, J=8.9 Hz, 1H), 3.61-3.47 (m, 5H), 3.32 (q, J=5.6, 4.7 Hz, 6H), 2.86 (t, J=6.9 Hz, 2H), 1.48 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 154.8, 153.4, 139.2, 137.5, 133.3, 128.8, 128.6, 126.5, 124.1, 109.1, 79.7, 46.9, 45.9, 35.5, 28.5.

    Example 142

    Tert-butyl 4-(4-(phenylethylamino)benzyl)piperazine-1-carboxylate (M7-76)

    [0814] ##STR00212##

    [0815] Method A was performed to obtain 230 mg of yellow oil product, with a yield of 29%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.30 (dd, J=34.6, 6.5 Hz, 5H), 7.16 (d, J=7.3 Hz, 2H), 6.61 (d, J=7.3 Hz, 2H), 3.89 (s, 1H), 3.65-3.32 (m, 8H), 2.93 (s, 2H), 2.41 (s, 4H), 1.53 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 154.8, 147.4, 139.4, 130.5, 128.9, 128.7, 126.5, 126.2, 112.7, 79.4, 62.8, 52.8, 45.2, 35.6, 28.6.

    Example 143

    Tert-butyl 4-(2-(phenylethylamino)phenyl)piperazine-1-carboxylate (M7-77)

    [0816] ##STR00213##

    [0817] Method A was performed to obtain 314 mg of colourless oil product, with a yield of 82%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.29 (d, J=14.8 Hz, 2H), 7.25-7.18 (m, 3H), 7.03 (td, J=7.8, 1.4 Hz, 1H), 6.92 (dd, J=8.0, 1.4 Hz, 1H), 6.65 (ddt, J=7.8, 4.0, 1.5 Hz, 2H), 4.67 (s, 1H), 3.71-2.44 (m, 12H), 1.48 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 154.8, 143.0, 139.5, 138.6, 128.9, 128.6, 126.5, 125.5, 119.8, 116.7, 110.3, 79.8, 51.2, 44.5, 35.4, 28.5.

    Example 144

    3-(4-methylpiperazin-1-yl)-N-phenethylaniline (M7-78)

    [0818] ##STR00214##

    [0819] Method A was performed to obtain 33 mg of yellow oil product, with a yield of 11%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.36 (dd, J=10.8, 4.4 Hz, 2H), 7.27 (t, J=6.7 Hz, 3H), 7.11 (td, J=8.4, 1.6 Hz, 1H), 6.37 (d, J=8.4 Hz, 1H), 6.21 (d, J=5.8 Hz, 2H), 3.77 (s, 1H), 3.43 (t, J=7.0 Hz, 2H), 3.31-3.15 (m, 4H), 2.95 (t, J=7.0 Hz, 2H), 2.68-2.54 (m, 4H), 2.39 (s, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 152.5, 149.0, 139.4, 129.9, 128.8, 128.6, 126.4, 106.0, 105.1, 101.0, 55.2, 49.2, 46.1, 45.2, 35.7.

    Example 145

    N-(4-morpholinobenzyl)-2-phenylethane-1-amine (M7-79)

    [0820] ##STR00215##

    [0821] Method B was performed to obtain 132 mg of white solid product, with a yield of 44%.

    Example 146

    N-(4-(4-methylpiperazin-1-yl)benzyl)-2-phenylethane (M7-80)

    [0822] ##STR00216##

    [0823] Method B was performed to obtain 270 mg of white solid product, with a yield of 87%.

    Example 147

    Tert-butyl 4-(4-((phenethylamino)methyl)phenyl)piperazine-1-carboxylate (M7-81)

    [0824] ##STR00217##

    [0825] Method B was performed to obtain 185 mg of white solid product, with a yield of 94%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.23-7.15 (m, 2H), 7.10 (dd, J=7.1, 5.0 Hz, 5H), 6.78 (d, J=8.6 Hz, 2H), 3.63 (s, 2H), 3.55-3.42 (m, 4H), 3.12-2.93 (m, 4H), 2.80 (t, J=6.8 Hz, 2H), 2.72 (t, J=6.5 Hz, 2H), 1.52 (s, 1H), 1.40 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 154.7, 150.3, 140.1, 132.1, 129.1, 128.7, 128.5, 126.1, 116.6, 79.9, 53.3, 50.5, 49.6, 36.4, 28.5.

    Example 148

    N-(4-phenoxybenzyl)-2-phenylethane-1-amine (M7-86)

    [0826] ##STR00218##

    [0827] Method B was performed to obtain 497 mg of light yellow liquid product, with a yield of 82%.

    Example 149

    Tert-butyl 4-(2-((phenethylamino)methyl)phenyl)piperazine-1-carboxylate (M7-87)

    [0828] ##STR00219##

    [0829] Method B was performed to obtain 326 mg of white solid product, with a yield of 83%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.37-7.31 (m, 2H), 7.29 (d, J=6.8 Hz, 1H), 7.25-7.14 (m, 5H), 7.14-7.08 (m, 1H), 5.28 (s, 1H), 4.18 (s, 2H), 3.28 (s, 4H), 3.16 (t, J=6.9 Hz, 2H), 3.00 (t, J=6.8 Hz, 2H), 2.66 (s, 4H), 1.47 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 154.6, 151.1, 136.7, 131.5, 130.5, 129.1, 128.8, 127.6, 127.3, 125.8, 121.3, 80.0, 53.5, 52.7, 49.5, 48.9, 33.1, 28.4.

    Example 150

    Tert-butyl 4-(3-((phenethylamino)methyl)phenyl)piperazine-1-carboxylate (M7-88)

    [0830] ##STR00220##

    [0831] Method B was performed to obtain 200 mg of white solid product, with a yield of 50%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.63 (s, 2H), 7.30-7.13 (m, 5H), 6.84 (dd, J=18.3, 6.7 Hz, 2H), 3.99 (s, 2H), 3.61-3.34 (m, 4H), 3.20-2.72 (m, 8H), 1.95 (s, 1H), 1.47 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 154.8, 151.6, 136.5, 132.0, 129.9, 128.8, 128.8, 127.1, 120.9, 117.3, 116.7, 80.1, 51.8, 48.6, 48.3, 32.5, 28.4.

    Example 151

    ethyl 3-methyl-5-N-phenyl-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-10)

    [0832] ##STR00221##

    [0833] Ethyl 3-methyl-5-(chlorosulfonyl)benzofuran-2-carboxylate (91 mg, 0.3 mmol), N-phenethylaniline (59 mg, 0.3 mmol) and potassium carbonate (46 mg, 0.33 mmol) were dissolved in anhydrous dichloromethane (10 mL), and the resulting solution was stirred at 60? C. overnight. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (10 mL) and then extracted three times with dichloromethane (20 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (PE/EA=10/1?5/1) to obtain 90 mg of yellow solid, with a yield of 65%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.88 (s, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.56 (d, J=8.7 Hz, 1H), 7.39-7.31 (m, 3H), 7.30-7.24 (m, 2H), 7.23-7.18 (m, 1H), 7.17-7.10 (m, 2H), 7.09-7.00 (m, 2H), 4.48 (q, J=7.1 Hz, 2H), 3.90-3.77 (m, 2H), 2.89-2.76 (m, 2H), 2.54 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.9, 142.9, 139.0, 138.0, 133.6, 129.2, 128.9, 128.8, 128.5, 128.2, 126.8, 126.6, 125.6, 122.0, 112.6, 61.5, 52.2, 35.2, 14.4, 9.3. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.26H.sub.26NO.sub.5S: 464.1532, found 464.1525.

    Example 152

    ethyl 3-methyl-5-(N-(4-benzylphenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-11)

    [0834] ##STR00222##

    [0835] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-11 was used instead of N-phenethylaniline. 193 mg of white solid was obtained, with a yield of 70%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.85 (d, J=1.8 Hz, 1H), 7.64 (dd, J=8.8, 1.9 Hz, 1H), 7.53 (d, J=8.8 Hz, 1H), 7.31 (t, J=7.3 Hz, 2H), 7.26-7.08 (m, 10H), 7.03-6.93 (m, 2H), 4.46 (q, J=7.1 Hz, 2H), 3.99 (s, 2H), 3.89-3.72 (m, 2H), 2.88-2.73 (m, 2H), 2.49 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 142.9, 141.4, 140.5, 138.1, 137.0, 133.6, 129.6, 129.1, 129.0, 128.9, 128.9, 128.8, 128.6, 128.5, 126.8, 126.6, 126.4, 125.6, 122.1, 112.6, 61.5, 52.2, 41.5, 35.2, 14.4, 9.3.

    Example 153

    ethyl 3-methyl-5-(N-(4-phenoxyphenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-12)

    [0836] ##STR00223##

    [0837] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-12 was used instead of N-phenethylaniline. 123 mg of white solid was obtained, with a yield of 44%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.92 (d, J=1.9 Hz, 1H), 7.67 (dd, J=8.8, 1.9 Hz, 1H), 7.58 (d, J=8.8 Hz, 1H), 7.39 (t, J=7.9 Hz, 2H), 7.28 (t, J=7.2 Hz, 2H), 7.18 (dt, J=22.1, 7.0 Hz, 4H), 7.07 (t, J=7.8 Hz, 2H), 7.02-6.97 (m, 2H), 6.93 (d, J=9.0 Hz, 2H), 4.49 (q, J=7.1 Hz, 2H), 3.93-3.65 (m, 2H), 2.94-2.79 (m, 2H), 2.57 (s, 3H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 157.3, 156.3, 155.9, 142.9, 138.0, 133.6, 133.6, 130.4, 129.9, 129.2, 128.8, 128.5, 126.8, 126.6, 125.6, 124.1, 122.0, 119.5, 118.6, 112.7, 61.6, 52.3, 35.2, 14.4, 9.3.

    Example 154

    ethyl 3-methyl-5-(N,N-diphenylethylsulfamoyl)benzofuran-2-carboxylate (M8-13)

    [0838] ##STR00224##

    [0839] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-13 was used instead of N-phenethylaniline. 112 mg of white oil product was obtained, with a yield of 76%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.84 (d, J=8.7 Hz, 1H), 7.60 (d, J=8.7 Hz, 1H), 7.29 (t, J=7.2 Hz, 4H), 7.22 (t, J=7.3 Hz, 2H), 7.16 (d, J=7.0 Hz, 4H), 4.49 (q, J=7.1 Hz, 2H), 3.56-3.40 (m, 4H), 2.96-2.82 (m, 4H), 2.63 (s, 3H), 1.48 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.7, 142.9, 138.4, 135.4, 129.4, 128.8, 128.6, 126.6, 126.3, 125.6, 121.5, 113.0, 61.6, 50.0, 35.6, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.28H.sub.30NO.sub.5S: 492.1845, found 492.1836.

    Example 155

    ethyl 3-methyl-5-(N-(4-morpholinophenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-63)

    [0840] ##STR00225##

    [0841] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-63 was used instead of N-phenethylaniline. 158 mg of white solid was obtained, with a yield of 96%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.90 (s, 1H), 7.65-7.57 (m, 1H), 7.54 (d, J=8.7 Hz, 1H), 7.21 (dd, J=18.1, 7.2 Hz, 3H), 7.11 (d, J=7.1 Hz, 2H), 6.90 (d, J=8.8 Hz, 2H), 6.81 (d, J=8.8 Hz, 2H), 4.46 (q, J=7.1 Hz, 2H), 3.92-3.81 (m, 4H), 3.79-3.69 (m, 2H), 3.22-3.12 (m, 4H), 2.83-2.72 (m, 2H), 2.53 (s, 3H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 150.8, 142.8, 138.2, 133.9, 130.2, 129.8, 129.1, 128.8, 128.5, 126.9, 126.5, 125.6, 122.0, 115.4, 112.6, 66.8, 61.5, 52.3, 48.8, 35.1, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.30H.sub.33N.sub.2O.sub.6S: 549.2059, found 549.2054.

    Example 156

    ethyl 3-methyl-5-(N-(4-(4-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-64)

    [0842] ##STR00226##

    [0843] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-64 was used instead of N-phenethylaniline. 56 mg of white oil product was obtained, with a yield of 84%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.90 (s, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.55 (d, J=8.7 Hz, 1H), 7.31-7.22 (m, 2H), 7.22-7.16 (m, 1H), 7.15-7.07 (m, 2H), 6.89 (d, J=9.0 Hz, 2H), 6.82 (d, J=9.1 Hz, 2H), 4.47 (q, J=7.1 Hz, 2H), 3.86-3.69 (m, 2H), 3.33-3.18 (m, 4H), 2.84-2.74 (m, 2H), 2.63-2.55 (m, 4H), 2.54 (s, 3H), 2.36 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 150.7, 142.8, 138.2, 133.9, 129.8, 129.7, 129.7, 129.1, 128.8, 128.5, 126.9, 126.5, 125.6, 122.0, 115.7, 112.5, 61.5, 55.0, 52.3, 48.5, 46.1, 35.1, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.31H.sub.36N.sub.3O.sub.5S: 562.2376, found 562.2380.

    Example 157

    ethyl 3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-65)

    [0844] ##STR00227##

    [0845] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-65 was used instead of N-phenethylaniline. 288 mg of white oil product was obtained, with a yield of 74%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.88 (s, 1H), 7.60 (d, J=8.8 Hz, 1H), 7.51 (d, J=8.8 Hz, 1H), 7.25-7.11 (m, 3H), 7.08 (d, J=6.9 Hz, 2H), 6.89 (d, J=8.9 Hz, 2H), 6.80 (d, J=9.0 Hz, 2H), 4.43 (q, J=7.1 Hz, 2H), 3.84-3.68 (m, 2H), 3.61-3.50 (m, 4H), 3.22-3.02 (m, 4H), 2.80-2.70 (m, 2H), 2.51 (s, 3H), 1.48 (s, 9H), 1.41 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 154.6, 150.7, 142.8, 138.2, 133.9, 130.3, 129.8, 129.1, 128.8, 128.4, 126.9, 126.5, 125.6, 122.0, 116.2, 112.5, 79.9, 79.6, 61.5, 52.3, 48.7, 35.1, 28.4, 14.4, 9.3. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.35H.sub.42N.sub.3O.sub.7S: 648.2743, found 648.2745.

    Example 158

    ethyl 3-methyl-5-(N-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-66)

    [0846] ##STR00228##

    [0847] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-66 was used instead of N-phenethylaniline. 308 mg of white solid was obtained, with a yield of 95%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.85 (d, J=1.8 Hz, 1H), 7.56 (dd, J=8.7, 1.9 Hz, 1H), 7.48 (d, J=8.8 Hz, 1H), 7.22-7.01 (m, 5H), 6.95-6.71 (m, 4H), 4.40 (q, J=7.1 Hz, 2H), 3.82-3.58 (m, 6H), 3.23-3.07 (m, 4H), 2.83-2.64 (m, 2H), 2.48 (s, 3H), 2.27 (s, 2H), 1.38 (t, J=7.1 Hz, 3H), 1.03 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.4, 159.8, 155.8, 150.4, 142.8, 138.1, 133.8, 130.4, 129.8, 129.1, 128.8, 128.4, 126.9, 126.5, 125.5, 121.9, 116.1, 112.5, 61.5, 52.2, 49.0, 48.8, 46.3, 44.6, 41.1, 35.1, 31.4, 30.1, 14.4, 9.4.

    Example 159

    ethyl 3-methyl-5-(N-(4-(4-(propoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzo furan-2-carboxylate (M8-67)

    [0848] ##STR00229##

    [0849] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-67 was used instead of N-phenethylaniline. 308 mg of white solid was obtained, with a yield of 97%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.88 (d, J=1.8 Hz, 1H), 7.60 (dd, J=8.8, 1.8 Hz, 1H), 7.52 (d, J=8.7 Hz, 1H), 7.23 (dd, J=8.0, 6.4 Hz, 2H), 7.19-7.14 (m, 1H), 7.12-7.05 (m, 2H), 6.93-6.86 (m, 2H), 6.84-6.77 (m, 2H), 4.44 (q, J=7.1 Hz, 2H), 4.07 (t, J=6.7 Hz, 2H), 3.81-3.70 (m, 2H), 3.66-3.58 (m, 4H), 3.22-3.09 (m, 4H), 2.82-2.68 (m, 2H), 2.52 (s, 3H), 1.67 (h, J=7.2 Hz, 2H), 1.43 (t, J=7.1 Hz, 3H), 0.95 (t, J=7.4 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 155.5, 150.7, 142.8, 138.2, 133.9, 130.5, 129.8, 129.1, 128.8, 128.5, 126.9, 126.5, 125.6, 122.0, 116.3, 112.6, 67.2, 61.5, 52.3, 48.8, 43.5, 35.1, 22.4, 14.4, 10.4, 9.4.

    Example 160

    ethyl 3-methyl-5-(N-(4-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-68)

    [0850] ##STR00230##

    [0851] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-68 was used instead of N-phenethylaniline. 254 mg of white solid was obtained, with a yield of 86%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.82 (d, J=1.8 Hz, 1H), 7.58-7.42 (m, 2H), 7.21-7.08 (m, 3H), 7.07-6.99 (m, 2H), 6.89-6.70 (m, 4H), 4.38 (q, J=7.1 Hz, 2H), 3.77-3.62 (m, 4H), 3.56 (t, J=5.1 Hz, 2H), 3.12 (dt, J=16.2, 5.3 Hz, 4H), 2.76-2.63 (m, 2H), 2.46 (s, 3H), 2.07 (s, 3H), 1.37 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 169.1, 159.9, 155.8, 150.4, 142.9, 138.1, 133.9, 130.7, 129.9, 129.2, 128.9, 128.5, 126.9, 126.6, 125.6, 122.0, 116.3, 112.6, 61.6, 52.3, 49.1, 48.8, 46.1, 41.2, 35.1, 21.4, 14.4, 9.4.

    Example 161

    ethyl 3-methyl-5-(N-(4-(4-benzoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-69)

    [0852] ##STR00231##

    [0853] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-69 was used instead of N-phenethylaniline. 282 mg of white solid was obtained, with a yield of 86%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.91 (d, J=1.7 Hz, 1H), 7.61 (dd, J=8.8, 1.9 Hz, 1H), 7.54 (d, J=8.7 Hz, 1H), 7.44 (s, 5H), 7.28-7.15 (m, 3H), 7.15-7.07 (m, 2H), 6.97-6.89 (m, 2H), 6.87-6.79 (m, 2H), 4.46 (q, J=7.1 Hz, 2H), 3.92 (s, 2H), 3.79-3.73 (m, 2H), 3.61 (s, 2H), 3.22 (d, J=22.6 Hz, 4H), 2.84-2.70 (m, 2H), 2.54 (s, 3H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.4, 159.9, 155.8, 150.4, 142.8, 138.1, 135.5, 133.9, 130.7, 130.0, 129.9, 129.1, 128.8, 128.6, 128.5, 127.1, 126.9, 126.5, 125.6, 122.0, 116.4, 112.6, 61.6, 52.3, 49.1, 35.1, 14.4, 9.4.

    Example 162

    ethyl 3-methyl-5-(N-(4-(4-benzylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-70)

    [0854] ##STR00232##

    [0855] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-70 was used instead of N-phenethylaniline. 251 mg of white solid was obtained, with a yield of 79%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.93 (d, J=1.3 Hz, 1H), 7.65 (dd, J=8.8, 1.6 Hz, 1H), 7.57 (d, J=8.7 Hz, 1H), 7.37 (q, J=7.4 Hz, 4H), 7.29 (dd, J=14.7, 7.4 Hz, 3H), 7.21 (t, J=7.2 Hz, 1H), 7.15 (d, J=7.0 Hz, 2H), 6.91 (d, J=8.9 Hz, 2H), 6.84 (d, J=9.0 Hz, 2H), 4.49 (q, J=7.1 Hz, 2H), 3.84-3.75 (m, 2H), 3.61 (s, 2H), 3.31-3.21 (m, 4H), 2.85-2.78 (m, 2H), 2.68-2.61 (m, 4H), 2.56 (s, 3H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 150.9, 142.8, 138.3, 137.8, 133.9, 129.7, 129.7, 129.2, 129.1, 128.9, 128.5, 128.3, 127.2, 127.0, 126.5, 125.7, 122.1, 115.7, 112.5, 63.0, 61.5, 53.0, 52.4, 48.5, 35.2, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.37H.sub.40N.sub.3O.sub.5S: 638.2689, found 638.2697.

    Example 163

    ethyl 3-methyl-5-(N-(4-(4-(dimethylcarbamoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-71)

    [0856] ##STR00233##

    [0857] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-71 was used instead of N-phenethylaniline. 143 mg of white solid was obtained, with a yield of 92%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.87 (d, J=1.8 Hz, 1H), 7.58 (dd, J=8.7, 1.9 Hz, 1H), 7.51 (d, J=8.7 Hz, 1H), 7.21 (t, J=7.2 Hz, 2H), 7.14 (dd, J=8.6, 5.9 Hz, 1H), 7.11-7.03 (m, 2H), 6.87 (d, J=9.0 Hz, 2H), 6.79 (d, J=9.0 Hz, 2H), 4.43 (q, J=7.1 Hz, 2H), 3.82-3.67 (m, 2H), 3.46-3.29 (m, 4H), 3.25-3.14 (m, 4H), 2.85 (s, 6H), 2.80-2.70 (m, 2H), 2.51 (s, 3H), 1.41 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 164.6, 159.9, 155.8, 150.7, 142.8, 138.2, 133.9, 130.2, 129.8, 129.1, 128.8, 128.4, 126.9, 126.5, 125.6, 122.0, 116.0, 112.5, 61.5, 52.3, 48.5, 46.6, 38.4, 35.1, 14.4, 9.4.

    Example 164

    ethyl 3-methyl-5-(N-(4-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-72)

    [0858] ##STR00234##

    [0859] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-72 was used instead of N-phenethylaniline. 275 mg of yellow oil product with a yield of 87%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.87 (d, J=1.8 Hz, 1H), 7.58 (dd, J=8.8, 1.9 Hz, 1H), 7.50 (d, J=8.8 Hz, 1H), 7.20 (t, J=7.2 Hz, 2H), 7.13 (dd, J=8.6, 5.9 Hz, 1H), 7.07 (d, J=6.9 Hz, 2H), 6.89 (d, J=9.0 Hz, 2H), 6.81 (d, J=9.0 Hz, 2H), 4.41 (q, J=7.1 Hz, 2H), 3.79-3.69 (m, 2H), 3.39-3.31 (m, 4H), 3.30-3.22 (m, 4H), 2.80 (s, 3H), 2.77-2.68 (m, 2H), 2.50 (s, 3H), 1.40 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 150.2, 142.8, 138.1, 133.8, 130.9, 129.9, 129.1, 128.8, 128.5, 126.9, 126.5, 125.5, 122.0, 116.6, 112.6, 61.5, 52.2, 48.7, 45.7, 35.0, 34.5, 14.4, 9.4.

    Example 165

    ethyl 3-methyl-5-(N-(4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-73)

    [0860] ##STR00235##

    [0861] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-73 was used instead of N-phenethylaniline. 309 mg of white solid was obtained, with a yield of 95%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.84 (d, J=1.5 Hz, 1H), 7.61 (dd, J=8.8, 1.8 Hz, 1H), 7.54 (d, J=8.7 Hz, 1H), 7.16 (ddd, J=35.7, 17.1, 7.2 Hz, 7H), 6.96 (d, J=8.4 Hz, 2H), 4.46 (q, J=7.1 Hz, 2H), 4.25 (s, 2H), 3.81-3.72 (m, 2H), 2.79 (q, J=10.4, 7.5 Hz, 4H), 2.65 (ddd, J=15.1, 7.6, 3.6 Hz, 1H), 2.51 (s, 3H), 1.82 (d, J=12.4 Hz, 2H), 1.65-1.55 (m, 2H), 1.46 (d, J=16.9 Hz, 12H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 154.8, 145.9, 142.9, 138.1, 137.1, 133.7, 129.1, 128.9, 128.8, 128.5, 127.5, 126.8, 126.5, 125.5, 122.0, 112.6, 79.5, 61.6, 52.2, 42.3, 35.2, 33.1, 28.5, 14.4, 9.3.

    Example 166

    ethyl 3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-74)

    [0862] ##STR00236##

    [0863] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-74 was used instead of N-phenethylaniline. 175 mg of white solid was obtained, with a yield of 48%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.82 (d, J=1.8 Hz, 1H), 7.65-7.54 (m, 2H), 7.25-7.09 (m, 6H), 7.08-7.00 (m, 2H), 4.44 (q, J=7.1 Hz, 2H), 3.83-3.71 (m, 2H), 3.55 (t, J=4.8 Hz, 4H), 2.86 (t, J=4.8 Hz, 4H), 2.81-2.73 (m, 2H), 2.50 (s, 3H), 1.45 (d, J=17.8 Hz, 12H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.9, 154.8, 151.8, 143.1, 137.6, 135.8, 133.9, 133.2, 129.3, 128.8, 128.5, 127.5 (t, J=29.6 Hz, 1C), 127.5 (d, J=5.3 Hz, 1C), 126.6, 126.6, 125.4, 124.5, 123.2 (d, J=274.9 Hz, 1C), 122.0, 112.8, 79.8, 61.6, 53.3, 52.1, 35.2, 28.4, 14.3, 9.2. .sup.19F NMR (376 MHz, Chloroform-d) ? ?60.46.

    Example 167

    ethyl 3-methyl-5-(N-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl) pyridin-3-yl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-75)

    [0864] ##STR00237##

    [0865] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-75 was used instead of N-phenethylaniline. 294 mg of white solid was obtained, with a yield of 75%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.90 (d, J=1.4 Hz, 1H), 7.72 (d, J=2.5 Hz, 1H), 7.61 (dd, J=8.8, 1.7 Hz, 1H), 7.53 (d, J=8.7 Hz, 1H), 7.21 (t, J=7.2 Hz, 2H), 7.18-7.11 (m, 2H), 7.08 (d, J=6.9 Hz, 2H), 6.54 (d, J=9.0 Hz, 1H), 4.43 (q, J=7.1 Hz, 2H), 3.81-3.71 (m, 2H), 3.52 (s, 8H), 2.81-2.73 (m, 2H), 2.51 (s, 3H), 1.46 (s, 9H), 1.41 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 158.1, 155.8, 154.7, 148.2, 142.9, 138.4, 137.8, 133.8, 129.2, 128.8, 128.5, 126.7, 126.6, 125.5, 125.5, 121.9, 112.8, 106.7, 80.0, 61.5, 52.4, 44.8, 35.1, 28.4, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.41N.sub.4O.sub.7S: 649.2696, found 649.2701.

    Example 168

    ethyl 3-methyl-5-(N-(4-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-76)

    [0866] ##STR00238##

    [0867] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-76 was used instead of N-phenethylaniline. 247 mg of white solid was obtained, with a yield of 74%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.83 (d, J=1.4 Hz, 1H), 7.58 (dd, J=8.8, 1.7 Hz, 1H), 7.51 (d, J=8.8 Hz, 1H), 7.26-7.11 (m, 5H), 7.07 (d, J=7.0 Hz, 2H), 6.96 (d, J=8.3 Hz, 2H), 4.43 (q, J=7.1 Hz, 2H), 3.84-3.71 (m, 2H), 3.48 (s, 2H), 3.42 (t, J=5.0 Hz, 4H), 2.83-2.72 (m, 2H), 2.49 (s, 3H), 2.36 (t, J=5.0 Hz, 4H), 1.43 (d, J=9.5 Hz, 12H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 154.8, 142.9, 138.1, 138.0, 137.9, 133.6, 129.6, 129.1, 128.8, 128.7, 128.5, 126.8, 126.5, 125.5, 122.0, 112.6, 79.6, 62.4, 61.5, 52.9, 52.2, 35.2, 28.4, 14.4, 9.3. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.44N.sub.3O.sub.7S: 662.2900, found 662.2896.

    Example 169

    ethyl 3-methyl-5-(N-(2-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-77

    [0868] ##STR00239##

    [0869] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-77 was used instead of N-phenethylaniline. 102 mg of white solid was obtained, with a yield of 31%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.6 Hz, 1H), 7.89 (dd, J=8.8, 1.8 Hz, 1H), 7.61 (d, J=8.8 Hz, 1H), 7.36-7.26 (m, 1H), 7.20-6.98 (m, 6H), 6.93 (d, J=6.6 Hz, 2H), 4.46 (q, J=7.1 Hz, 2H), 4.23-3.76 (m, 2H), 3.48 (s, 4H), 3.16 (s, 2H), 2.79 (dd, J=40.6, 17.5 Hz, 2H), 2.68-2.45 (m, 5H), 1.46 (d, J=12.3 Hz, 12H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 154.8, 151.2, 143.0, 138.2, 136.1, 133.8, 130.5, 129.4, 129.3, 128.5, 128.4, 126.8, 126.4, 125.5, 124.3, 122.6, 122.0, 112.9, 79.7, 61.5, 51.2, 34.7, 28.4, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.35H.sub.42N.sub.3O.sub.7S: 648.2743, found 648.2736.

    Example 170

    ethyl 3-methyl-5-(N-(3-(4-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-78)

    [0870] ##STR00240##

    [0871] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-78 was used instead of N-phenethylaniline. 42 mg of white solid was obtained, with a yield of 76%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.92 (d, J=1.8 Hz, 1H), 7.65 (dd, J=8.7, 1.9 Hz, 1H), 7.56 (d, J=8.7 Hz, 1H), 7.31-7.09 (m, 6H), 6.87 (dd, J=8.3, 2.5 Hz, 1H), 6.65 (t, J=2.2 Hz, 1H), 6.39 (dd, J=7.7, 1.9 Hz, 1H), 4.48 (q, J=7.1 Hz, 2H), 3.88-3.71 (m, 2H), 3.26-3.09 (m, 4H), 2.89-2.77 (m, 2H), 2.62 (t, J=4.8 Hz, 4H), 2.55 (s, 3H), 2.41 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 151.7, 142.9, 139.9, 138.1, 133.8, 129.4, 129.1, 128.9, 128.5, 126.9, 126.5, 125.6, 122.1, 118.9, 117.4, 115.4, 112.5, 61.5, 54.8, 52.2, 48.3, 45.8, 35.2, 14.3, 9.3. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.31H.sub.36N.sub.3O.sub.5S: 562.2376, found 562.2380.

    Example 171

    ethyl 3-methyl-5-(N-(4-morpholinobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-79)

    [0872] ##STR00241##

    [0873] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-79 was used instead of N-phenethylaniline. 142 mg of white solid was obtained, with a yield of 63%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.23-8.04 (m, 1H), 7.93-7.78 (m, 1H), 7.60 (d, J=8.8 Hz, 1H), 7.15 (dq, J=16.9, 8.2, 7.5 Hz, 5H), 6.96 (d, J=7.1 Hz, 2H), 6.81 (d, J=8.0 Hz, 2H), 4.46 (q, J=7.0 Hz, 2H), 4.32 (s, 2H), 3.83 (s, 4H), 3.43-3.28 (m, 2H), 3.11 (s, 4H), 2.74-2.53 (m, 5H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.7, 150.9, 142.9, 138.5, 135.8, 129.6, 129.3, 128.7, 128.5, 126.9, 126.4, 126.3, 125.6, 121.5, 115.5, 113.0, 66.8, 61.5, 51.5, 49.2, 49.1, 35.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.31H.sub.35N.sub.2O.sub.6S: 563.2216, found 563.2211.

    Example 172

    ethyl 3-methyl-5-(N-(4-(4-methylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-80)

    [0874] ##STR00242##

    [0875] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-80 was used instead of N-phenethylaniline. 129 mg of white solid was obtained, with a yield of 75%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.10 (s, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.59 (d, J=8.8 Hz, 1H), 7.13 (dt, J=22.9, 7.7 Hz, 5H), 6.95 (d, J=6.9 Hz, 2H), 6.81 (d, J=8.6 Hz, 2H), 4.44 (q, J=7.1 Hz, 2H), 4.30 (s, 2H), 3.42-3.27 (m, 2H), 3.23-3.08 (m, 4H), 2.71-2.61 (m, 2H), 2.57 (s, 3H), 2.56-2.49 (m, 4H), 2.32 (s, 3H), 1.43 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.7, 151.0, 142.9, 138.5, 135.8, 129.6, 129.3, 128.7, 128.5, 126.4, 126.3, 126.3, 125.6, 121.5, 115.8, 113.0, 61.5, 55.0, 51.5, 49.1, 48.8, 46.1, 35.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.38N.sub.3O.sub.5S: 576.2532, found 576.2535.

    Example 173

    ethyl 3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-81)

    [0876] ##STR00243##

    [0877] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-81 was used instead of N-phenethylaniline. 223 mg of white solid was obtained, with a yield of 85%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.11 (s, 1H), 7.84 (d, J=8.8 Hz, 1H), 7.60 (d, J=8.8 Hz, 1H), 7.15 (dt, J=15.3, 7.7 Hz, 5H), 6.95 (d, J=6.8 Hz, 2H), 6.82 (d, J=8.6 Hz, 2H), 4.45 (q, J=7.1 Hz, 2H), 4.31 (s, 2H), 3.69-3.46 (m, 4H), 3.42-3.28 (m, 2H), 3.21-3.04 (m, 4H), 2.72-2.61 (m, 2H), 2.58 (s, 3H), 1.47 (s, 9H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.7, 154.7, 151.0, 142.9, 138.4, 135.8, 129.6, 129.3, 128.7, 128.5, 127.0, 126.4, 126.2, 125.6, 121.5, 116.4, 113.0, 79.9, 61.5, 51.5, 49.1, 35.3, 28.4, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.44N.sub.3O.sub.7S: 662.2900, found 662.2891.

    Example 174

    ethyl 3-methyl-5-(N-phenethyl-N-(4-phenoxybenzyl)sulfamoyl)benzofuran-2-carboxylate (M8-86)

    [0878] ##STR00244##

    [0879] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-86 was used instead of N-phenethylaniline. 70 mg of white solid was obtained, with a yield of 25%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (d, J=1.9 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.64 (d, J=8.7 Hz, 1H), 7.34 (dd, J=8.6, 7.3 Hz, 2H), 7.26-7.08 (m, 6H), 7.03-6.91 (m, 6H), 4.48 (q, J=7.1 Hz, 2H), 4.38 (s, 2H), 3.47-3.34 (m, 2H), 2.75-2.66 (m, 2H), 2.62 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 157.2, 156.9, 155.8, 143.0, 138.3, 135.6, 130.6, 130.0, 129.8, 129.4, 128.7, 128.5, 126.5, 126.2, 125.6, 123.6, 121.5, 119.0, 118.8, 113.1, 61.6, 51.6, 49.4, 35.3, 14.4, 9.4.

    Example 175

    ethyl 3-methyl-5-(N-(2-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-87)

    [0880] ##STR00245##

    [0881] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-87 was used instead of N-phenethylaniline. 250 mg of white solid was obtained, with a yield of 75%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.07 (d, J=1.5 Hz, 1H), 7.80 (dd, J=8.8, 1.8 Hz, 1H), 7.55 (d, J=8.8 Hz, 1H), 7.33 (d, J=7.7 Hz, 1H), 7.23-7.16 (m, 1H), 7.12-6.98 (m, 5H), 6.88-6.78 (m, 2H), 4.49 (s, 2H), 4.39 (q, J=7.1 Hz, 2H), 3.45 (s, 4H), 3.29-3.20 (m, 2H), 2.78-2.67 (m, 4H), 2.53 (d, J=4.4 Hz, 5H), 1.39 (d, J=9.6 Hz, 12H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 154.8, 151.4, 143.0, 138.4, 135.5, 130.8, 130.0, 129.4, 128.7, 128.5, 128.5, 126.4, 126.2, 125.5, 124.7, 121.5, 120.2, 113.0, 79.9, 61.6, 52.9, 49.5, 46.4, 34.8, 28.4, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.44N.sub.3OS: 662.2900, found 662.2896.

    Example 176

    ethyl 3-methyl-5-(N-(3-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M8-88)

    [0882] ##STR00246##

    [0883] In accordance with the preparation method of ethyl 5-(N-phenyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M8-10), this example was implemented under the same condition except that M7-88 was used instead of N-phenethylaniline. 129 mg of white solid was obtained, with a yield of 49%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.9 Hz, 1H), 7.86 (dd, J=8.7, 1.9 Hz, 1H), 7.62 (d, J=8.7 Hz, 1H), 7.17 (dddt, J=14.2, 9.9, 7.3, 3.3 Hz, 4H), 6.96 (d, J=6.7 Hz, 2H), 6.84 (d, J=6.1 Hz, 2H), 6.74 (d, J=7.2 Hz, 1H), 4.47 (q, J=7.1 Hz, 2H), 4.35 (s, 2H), 3.62-3.50 (m, 4H), 3.42-3.32 (m, 2H), 3.07 (t, J=5.2 Hz, 4H), 2.63 (d, J=25.7 Hz, 5H), 1.47 (d, J=11.5 Hz, 12H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 154.7, 143.0, 138.4, 137.0, 135.6, 129.4, 128.7, 128.5, 126.5, 126.2, 125.6, 121.5, 120.1, 116.3, 116.0, 113.0, 80.0, 61.6, 52.3, 49.4, 49.2, 35.2, 28.4, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.44N.sub.3O.sub.7S: 662.2900, found 662.2904.

    Example 177

    3-methyl-5-(N-phenethyl-N-phenylsulfamoyl)benzofuran-2-carboxylic acid (F27-S10)

    [0884] ##STR00247##

    [0885] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-10 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 50 mg of white solid was obtained, with a yield of 76%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.73 (s, 1H), 7.67 (d, J=8.7 Hz, 1H), 7.44 (d, J=8.6 Hz, 1H), 7.35 (d, J=6.8 Hz, 3H), 7.21 (dt, J=27.5, 7.2 Hz, 3H), 7.12 (d, J=7.1 Hz, 2H), 7.04 (d, J=7.8 Hz, 2H), 3.82 (t, J=7.2 Hz, 2H), 2.64 (t, J=7.2 Hz, 2H), 2.45 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 154.9, 139.2, 138.7, 132.2, 130.6, 129.4, 129.2, 129.0, 128.7, 128.3, 126.8, 124.9, 121.0, 112.5, 51.5, 34.6, 9.4. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.24H.sub.20NO.sub.5S: 434.1062, found 434.1054.

    Example 178

    3-methyl-5-(N-(4-benzylphenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S11)

    [0886] ##STR00248##

    [0887] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-11 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 92 mg of white solid was obtained, with a yield of 88%. M.p. 301-302? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.90-7.66 (m, 2H), 7.56 (dd, J=8.6, 1.9 Hz, 1H), 7.34 (tq, J=15.6, 6.5, 5.5 Hz, 10H), 7.21 (d, J=7.4 Hz, 2H), 7.05 (d, J=8.0 Hz, 2H), 4.04 (s, 2H), 3.87 (t, J=7.3 Hz, 2H), 2.72 (t, J=7.3 Hz, 2H), 2.60 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.6, 154.9, 141.4, 141.4, 138.7, 137.1, 132.2, 130.5, 129.7, 129.2, 129.2, 129.2, 129.0, 128.9, 128.7, 126.7, 126.5, 124.9, 121.1, 112.5, 51.5, 41.0, 34.6, 9.3. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.31H.sub.26NO.sub.5S: 524.1532, found 524.1533.

    Example 179

    3-methyl-5-(N-(4-phenoxyphenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S12)

    [0888] ##STR00249##

    [0889] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-12 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 85 mg of white solid was obtained, with a yield of 81%. M.p. 285-286? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.85 (d, J=1.9 Hz, 1H), 7.75 (d, J=8.8 Hz, 1H), 7.54 (dd, J=8.7, 1.9 Hz, 1H), 7.46-7.38 (m, 2H), 7.25 (t, J=7.1 Hz, 2H), 7.22-7.11 (m, 4H), 7.07-6.99 (m, 4H), 6.97-6.91 (m, 2H), 3.81 (t, J=7.2 Hz, 2H), 2.67 (t, J=7.2 Hz, 2H), 2.51 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.0, 156.7, 156.6, 155.3, 138.7, 134.1, 132.6, 130.8, 130.6, 130.0, 129.2, 128.7, 126.7, 126.0, 124.3, 121.7, 119.4, 119.1, 112.9, 51.6, 34.6, 9.4. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.30H.sub.24NO.sub.6S: 526.1324, found 526.1316.

    Example 180

    3-methyl-5-(N,N-diphenylethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S13)

    [0890] ##STR00250##

    [0891] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-13 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 54 mg of white solid was obtained, with a yield of 78%. M.p. 212-213? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.75 (s, 1H), 8.25 (s, 1H), 7.96-7.86 (m, 1H), 7.82 (d, J=8.8 Hz, 1H), 7.32-7.22 (m, 4H), 7.18 (d, J=7.4 Hz, 6H), 3.49-3.29 (m, 4H), 2.86-2.66 (m, 4H), 2.58 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.2, 155.5, 143.8, 139.0, 135.3, 129.6, 129.2, 128.8, 126.8, 126.6, 125.2, 121.8, 113.5, 49.8, 35.2, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.24NO.sub.5S: 462.1375, found 462.1377.

    Example 181

    3-methyl-5-(N-(4-morpholinophenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxyli acid (F27-S63)

    [0892] ##STR00251##

    [0893] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-63 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 81 mg of white solid was obtained, with a yield of 78%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.74-7.58 (m, 2H), 7.43 (d, J=8.4 Hz, 1H), 7.26 (t, J=7.1 Hz, 2H), 7.16 (dd, J=24.8, 7.0 Hz, 3H), 6.85 (q, J=8.8 Hz, 4H), 3.73 (d, J=9.7 Hz, 6H), 3.11 (s, 4H), 2.63 (t, J=6.9 Hz, 2H), 2.44 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.1, 154.7, 150.7, 138.8, 132.3, 130.8, 129.9, 129.7, 129.2, 128.7, 126.7, 124.4, 120.7, 116.3, 115.1, 112.3, 66.5, 51.7, 48.4, 34.6, 9.4. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.28H.sub.27N.sub.2O.sub.6S: 519.1590, found 519.1584.

    Example 182

    3-methyl-5-(N-(4-(4-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S64)

    [0894] ##STR00252##

    [0895] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-64 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 40 mg of white solid was obtained, with a yield of 94%. M.p. 152-153? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 11.66 (s, 1H), 7.96 (d, J=1.7 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.52 (dd, J=8.8, 1.9 Hz, 1H), 7.24 (t, J=7.2 Hz, 2H), 7.17 (td, J=7.3, 6.2, 3.0 Hz, 1H), 7.14-7.08 (m, 2H), 6.94 (d, J=9.1 Hz, 2H), 6.87 (d, J=9.0 Hz, 2H), 3.90-3.71 (m, 4H), 3.45 (d, J=10.8 Hz, 2H), 3.15 (dq, J=21.9, 11.6, 10.7 Hz, 4H), 2.78 (d, J=4.0 Hz, 3H), 2.62 (t, J=7.2 Hz, 2H), 2.51 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.0, 155.6, 149.4, 143.7, 138.7, 133.6, 130.3, 129.9, 129.4, 129.2, 128.7, 127.1, 126.7, 125.2, 122.2, 116.1, 113.2, 52.4, 51.7, 45.3, 42.2, 34.5, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.29H.sub.30N.sub.3O.sub.5S: 532.1906, found 532.1904.

    Example 183

    3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S65)

    [0896] ##STR00253##

    [0897] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-65 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 205 mg of white solid was obtained, with a yield of 83%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.68 (s, 1H), 7.63 (d, J=8.6 Hz, 1H), 7.42 (d, J=8.6 Hz, 1H), 7.26 (t, J=7.2 Hz, 2H), 7.19 (t, J=7.2 Hz, 1H), 7.13 (d, J=7.0 Hz, 2H), 6.94-6.79 (m, 4H), 3.74 (t, J=7.2 Hz, 2H), 3.44 (s, 4H), 3.22-3.03 (m, 4H), 2.62 (t, J=7.2 Hz, 2H), 2.43 (s, 3H), 1.42 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.0, 154.6, 154.4, 152.3, 150.5, 138.8, 132.2, 130.8, 129.9, 129.8, 129.2, 128.7, 126.7, 124.5, 120.7, 116.3, 115.9, 112.3, 79.5, 51.7, 48.1, 34.6, 28.5, 9.4. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.33H.sub.36N.sub.3O.sub.7S: 618.2274, found 618.2267.

    Example 184

    3-methyl-5-(N-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S66)

    [0898] ##STR00254##

    [0899] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-66 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 108 mg of white solid was obtained, with a yield of 87%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.82-7.56 (m, 2H), 7.44 (d, J=8.6 Hz, 1H), 7.31-7.10 (m, 5H), 6.87 (q, J=8.6 Hz, 4H), 3.75 (t, J=7.3 Hz, 2H), 3.63 (p, J=4.8 Hz, 4H), 3.14 (dt, J=10.7, 4.9 Hz, 4H), 2.63 (t, J=7.3 Hz, 2H), 2.45 (s, 3H), 2.28 (s, 2H), 1.00 (s, 9H). .sup.13C NMR (101 MHz, DMSO) ? 169.9, 162.8, 154.7, 150.4, 138.8, 132.3, 130.7, 129.8, 129.8, 129.2, 128.7, 126.7, 124.7, 120.9, 115.7, 112.4, 51.7, 48.6, 48.3, 46.0, 44.1, 41.1, 34.6, 31.5, 30.2, 9.4. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.34H.sub.38N.sub.3O.sub.6S: 616.2481, found 616.2490.

    Example 185

    3-methyl-5-(N-(4-(4-(propoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S67)

    [0900] ##STR00255##

    [0901] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-67 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 130 mg of light yellow solid was obtained, with a yield of 99%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.70 (d, J=1.9 Hz, 1H), 7.65 (d, J=8.7 Hz, 1H), 7.43 (dd, J=8.6, 1.9 Hz, 1H), 7.26 (dd, J=7.9, 6.5 Hz, 2H), 7.22-7.11 (m, 3H), 6.91-6.80 (m, 4H), 3.98 (t, J=6.6 Hz, 2H), 3.74 (t, J=7.2 Hz, 2H), 3.49 (t, J=5.2 Hz, 4H), 3.15 (t, J=5.2 Hz, 4H), 2.62 (t, J=7.2 Hz, 2H), 2.44 (s, 3H), 1.59 (h, J=7.1 Hz, 2H), 0.90 (t, J=7.4 Hz, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.9, 155.1, 154.7, 151.6, 150.4, 138.8, 132.3, 130.7, 129.9, 129.8, 129.2, 128.7, 126.7, 124.7, 120.8, 117.1, 115.9, 112.4, 66.8, 51.7, 48.1, 43.6, 34.6, 22.4, 10.8, 9.4. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.32H.sub.34N.sub.3O.sub.7S: 604.2117, found 604.2109.

    Example 186

    3-methyl-5-(N-(4-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S68)

    [0902] ##STR00256##

    [0903] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-68 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 72 mg of white solid was obtained, with a yield of 64%. M.p. 183-184? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.83 (d, J=8.2 Hz, 1H), 7.70 (d, J=8.6 Hz, 1H), 7.54-7.39 (m, 1H), 7.26-7.04 (m, 5H), 6.94-6.76 (m, 4H), 3.72 (t, J=7.1 Hz, 2H), 3.59-3.30 (m, 4H), 3.14 (tt, J=25.5, 5.2 Hz, 4H), 2.59 (t, J=7.3 Hz, 2H), 2.46 (s, 3H), 1.99 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 168.8, 161.8, 155.4, 150.4, 149.8, 138.7, 133.4, 130.4, 129.8, 129.6, 129.2, 128.7, 126.7, 121.9, 116.1, 115.8, 112.9, 51.7, 48.4, 48.0, 45.8, 41.0, 34.6, 21.6, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.30H.sub.30N.sub.3O.sub.6S: 560.1855, found 560.1852.

    Example 187

    3-methyl-5-(N-(4-(4-benzoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S69)

    [0904] ##STR00257##

    [0905] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-69 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 90 mg of white solid was obtained, with a yield of 72%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.78-7.61 (m, 2H), 7.45 (q, J=9.0, 6.4 Hz, 6H), 7.31-7.10 (m, 5H), 6.95-6.79 (m, 4H), 3.75 (t, J=7.4 Hz, 4H), 3.47 (s, 2H), 3.19 (s, 4H), 2.63 (t, J=7.3 Hz, 2H), 2.45 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 169.5, 163.0, 154.7, 151.8, 150.3, 138.8, 136.3, 132.3, 130.7, 130.1, 129.9, 129.8, 129.2, 128.9, 128.7, 127.4, 126.7, 124.6, 120.8, 116.9, 115.9, 112.3, 51.7, 48.3, 34.6, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.35H.sub.32N.sub.3O.sub.6S: 622.2012, found 622.2010.

    Example 188

    3-methyl-5-(N-(4-(4-benzylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S70)

    [0906] ##STR00258##

    [0907] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-70 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 62 mg of white solid was obtained, with a yield of 51%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.77 (s, 1H), 7.69 (d, J=8.6 Hz, 1H), 7.48 (d, J=8.2 Hz, 1H), 7.33 (d, J=4.1 Hz, 4H), 7.25 (t, J=6.6 Hz, 3H), 7.16 (dd, J=24.4, 7.1 Hz, 3H), 6.83 (q, J=9.0 Hz, 4H), 3.74 (t, J=7.4 Hz, 2H), 3.53 (s, 2H), 3.15 (s, 4H), 2.62 (t, J=7.4 Hz, 2H), 2.50 (s, 4H), 2.47 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.5, 155.0, 150.6, 149.2, 138.8, 138.3, 132.9, 130.3, 129.7, 129.4, 129.2, 128.7, 128.7, 127.5, 126.7, 125.4, 121.3, 119.5, 115.4, 112.6, 62.4, 52.9, 51.8, 48.1, 34.6, 9.4. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.35H.sub.34N.sub.3O.sub.5S: 608.2219, found 608.2211.

    Example 189

    3-methyl-5-(N-(4-(4-(dimethylcarbamoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S71)

    [0908] ##STR00259##

    [0909] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-71 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 69 mg of white solid was obtained, with a yield of 58%. M.p. 192-193? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.75 (s, 1H), 7.96 (s, 1H), 7.78 (d, J=8.8 Hz, 1H), 7.55 (d, J=8.7 Hz, 1H), 7.32-7.06 (m, 5H), 6.87 (q, J=9.0 Hz, 4H), 3.76 (t, J=7.3 Hz, 2H), 3.36-3.00 (m, 8H), 2.76 (s, 6H), 2.62 (t, J=7.3 Hz, 2H), 2.51 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.1, 161.1, 155.6, 150.6, 143.6, 138.7, 133.7, 129.8, 129.5, 129.3, 129.2, 128.7, 127.1, 126.7, 125.2, 122.2, 115.7, 113.2, 51.8, 48.0, 46.7, 38.5, 34.6, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.31H.sub.33N.sub.4O.sub.6S: 589.2121, found 589.2115.

    Example 190

    3-methyl-5-(N-(4-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S72)

    [0910] ##STR00260##

    [0911] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-72 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 126 mg of white solid was obtained, with a yield of 99%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.75 (d, J=1.9 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H), 7.46 (dd, J=8.7, 1.9 Hz, 1H), 7.26 (dd, J=8.0, 6.5 Hz, 2H), 7.22-7.10 (m, 3H), 6.96-6.82 (m, 4H), 3.75 (t, J=7.3 Hz, 2H), 3.25 (q, J=5.7 Hz, 8H), 2.93 (s, 3H), 2.63 (t, J=7.3 Hz, 2H), 2.46 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.7, 154.9, 150.1, 138.8, 132.5, 130.5, 130.2, 129.8, 129.2, 128.7, 126.7, 125.0, 121.1, 118.3, 116.1, 112.5, 51.7, 48.0, 45.7, 34.6, 34.4, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.29H.sub.30N.sub.3O.sub.7S.sub.2: 596.1525, found 596.1525.

    Example 191

    3-methyl-5-(N-(4-(1-(tert-butoxycarbonyl)piperidin-4-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S73)

    [0912] ##STR00261##

    [0913] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-73 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 96 mg of white solid was obtained, with a yield of 38%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.71-7.55 (m, 2H), 7.44 (d, J=8.5 Hz, 1H), 7.21 (tt, J=14.6, 7.2 Hz, 5H), 7.12 (d, J=7.3 Hz, 2H), 6.95 (d, J=8.2 Hz, 2H), 4.06 (d, J=12.4 Hz, 2H), 3.77 (t, J=7.3 Hz, 2H), 3.02-2.66 (m, 3H), 2.63 (t, J=7.4 Hz, 2H), 2.41 (s, 3H), 1.75 (d, J=12.2 Hz, 2H), 1.54-1.44 (m, 2H), 1.41 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.1, 154.7, 154.4, 152.2, 145.9, 138.7, 137.2, 132.0, 130.8, 129.2, 129.0, 128.7, 127.7, 126.7, 124.4, 120.8, 116.5, 112.4, 79.0, 51.5, 41.6, 34.7, 33.1, 28.6, 9.4. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.34H.sub.37N.sub.2O.sub.7S: 617.2321, found 617.2318.

    Example 192

    3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-(trifluoromethyl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S74)

    [0914] ##STR00262##

    [0915] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-74 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 114 mg of light yellow solid was obtained, with a yield of 83%. M.p. 215-216? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.86-7.70 (m, 2H), 7.60-7.43 (m, 2H), 7.31-7.05 (m, 7H), 3.85 (t, J=7.1 Hz, 2H), 3.43 (t, J=4.8 Hz, 4H), 2.81 (t, J=4.8 Hz, 4H), 2.68 (t, J=7.1 Hz, 2H), 2.48 (s, 3H), 1.42 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.2, 155.4, 154.3, 151.6, 138.5, 136.0, 133.9, 132.3, 130.1, 129.2, 128.6, 126.7, 126.2, 125.8, 125.7, 125.2, 122.5, 121.7, 113.0, 79.5, 53.2, 51.4, 34.8, 28.5, 9.3. .sup.19F NMR (376 MHz, DMSO-d.sub.6) ? ?59.16. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.34H.sub.35N.sub.3O.sub.7SF.sub.3: 686.2148, found 686.2136.

    Example 193

    3-methyl-5-(N-(6-(4-(tert-butoxycarbonyl)piperazin-1-yl)pyridin-3-yl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S75)

    [0916] ##STR00263##

    [0917] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-75 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 207 mg of white solid was obtained, with a yield of 83%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.71 (d, J=31.0 Hz, 3H), 7.44 (d, J=8.7 Hz, 1H), 7.35-6.96 (m, 6H), 6.86-6.63 (m, 1H), 3.76 (s, 2H), 3.49 (s, 4H), 3.41 (s, 4H), 2.65 (s, 2H), 2.45 (s, 3H), 1.42 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.9, 158.0, 154.8, 154.4, 152.3, 148.7, 138.6, 137.8, 132.2, 131.0, 129.2, 128.7, 126.7, 125.5, 124.4, 120.7, 116.4, 112.5, 107.1, 79.5, 51.6, 44.7, 34.7, 28.5, 9.4. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.32H.sub.35N.sub.4O.sub.7S: 619.2226, found 619.2230.

    Example 194

    3-methyl-5-(N-(4-((4-(tert-butoxycarbonyl)piperazin-1-yl)methyl)phenyl)-N-phenethylsulfonamide)benzofuran-2-carboxylic acid (F27-S76)

    [0918] ##STR00264##

    [0919] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-76 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 185 mg of white solid was obtained, with a yield of 97%. M.p. 234-235? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.77 (d, J=1.9 Hz, 1H), 7.73 (d, J=8.7 Hz, 1H), 7.51 (dd, J=8.7, 1.9 Hz, 1H), 7.24 (dd, J=13.8, 7.7 Hz, 4H), 7.18 (d, J=7.1 Hz, 1H), 7.11 (d, J=7.1 Hz, 2H), 6.99 (d, J=8.2 Hz, 2H), 3.81 (t, J=7.3 Hz, 2H), 3.49 (s, 2H), 3.32 (t, J=5.1 Hz, 4H), 2.64 (t, J=7.3 Hz, 2H), 2.46 (s, 3H), 2.30 (t, J=4.9 Hz, 4H), 1.38 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.0, 155.3, 154.3, 147.5, 138.7, 138.0, 137.9, 132.7, 130.0, 129.8, 129.2, 128.8, 128.7, 126.7, 125.8, 121.6, 121.1, 112.8, 79.2, 61.7, 52.7, 51.5, 34.7, 28.5, 9.3. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.34H.sub.38N.sub.3O.sub.7S: 632.2430, found 632.2432.

    Example 195

    3-methyl-5-(N-(2-(4-(tert-butoxycarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S77)

    [0920] ##STR00265##

    [0921] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-77 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 63 mg of white solid was obtained, with a yield of 67%. M.p. 168-169? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25 (d, J=1.8 Hz, 1H), 7.97-7.77 (m, 2H), 7.38-7.29 (m, 1H), 7.22 (d, J=8.0 Hz, 1H), 7.18-7.03 (m, 5H), 6.95 (d, J=7.0 Hz, 2H), 3.96 (d, J=74.5 Hz, 2H), 3.28 (d, J=24.7 Hz, 4H), 2.94 (s, 2H), 2.58 (s, 7H), 1.39 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.3, 155.6, 154.4, 151.0, 144.3, 138.6, 135.9, 133.6, 131.3, 129.7, 129.6, 128.9, 128.7, 127.0, 126.6, 124.7, 123.1, 122.2, 113.5, 79.4, 52.1, 50.6, 34.4, 28.5, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.33H.sub.36N.sub.3O.sub.7S: 618.2274, found 618.2280.

    Example 196

    3-methyl-5-(N-(3-(4-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S78)

    [0922] ##STR00266##

    [0923] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-78 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 112 mg of white solid was obtained, with a yield of 99%. M.p. 232-233? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 7.90 (s, 1H), 7.71 (d, J=8.7 Hz, 1H), 7.50 (d, J=8.7 Hz, 1H), 7.25-7.03 (m, 6H), 6.95-6.86 (m, 1H), 6.57 (s, 1H), 6.44 (d, J=7.9 Hz, 1H), 3.76 (t, J=7.2 Hz, 2H), 3.27 (d, J=6.3 Hz, 4H), 3.08 (t, J=5.0 Hz, 4H), 2.63 (d, J=21.3 Hz, 5H), 2.47 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.1, 155.4, 150.8, 145.9, 140.1, 138.7, 133.2, 129.9, 129.8, 129.2, 128.7, 126.7, 126.5, 122.9, 122.0, 120.0, 116.7, 115.6, 112.9, 52.7, 51.6, 46.1, 43.0, 34.7, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.29H.sub.30N.sub.3O.sub.5S: 532.1906, found 532.1906.

    Example 197

    3-methyl-5-(N-(4-(4-morpholinobenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S79)

    [0924] ##STR00267##

    [0925] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-79 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 73 mg of white solid was obtained, with a yield of 68%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.27-8.13 (m, 1H), 7.91 (dd, J=8.8, 1.6 Hz, 1H), 7.82 (d, J=8.8 Hz, 1H), 7.16 (dq, J=15.5, 7.1 Hz, 5H), 7.00 (d, J=7.0 Hz, 2H), 6.87 (d, J=8.5 Hz, 2H), 4.32 (s, 2H), 3.76-3.67 (m, 4H), 3.34-3.24 (m, 2H), 3.12-3.00 (m, 4H), 2.55 (d, J=10.5 Hz, 5H). .sup.13C NMR (101 MHz, DMSO) ? 161.4, 155.4, 151.0, 138.8, 135.6, 129.8, 129.6, 129.0, 128.8, 127.1, 126.7, 126.4, 121.8, 115.3, 113.4, 66.5, 51.2, 49.4, 48.7, 34.9, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.29H.sub.29N.sub.2O.sub.6S: 533.1746, found 533.1737.

    Example 198

    3-methyl-5-(N-(4-(4-methylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S80)

    [0926] ##STR00268##

    [0927] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-80 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 77 mg of white solid was obtained, with a yield of 94%. M.p.>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.22 (s, 1H), 7.90 (d, J=8.8 Hz, 1H), 7.82 (d, J=8.8 Hz, 1H), 7.23-7.14 (m, 4H), 7.11 (t, J=7.2 Hz, 1H), 7.05-6.88 (m, 4H), 4.32 (s, 2H), 3.45 (s, 4H), 3.25 (d, J=7.8 Hz, 6H), 2.75 (s, 3H), 2.61-2.51 (m, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 155.4, 149.6, 138.8, 135.4, 129.9, 129.7, 129.0, 128.8, 128.0, 126.7, 126.4, 121.7, 116.2, 113.4, 52.4, 51.1, 49.3, 45.8, 42.4, 34.8, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.30H.sub.32N.sub.3O.sub.5S: 546.2063, found 546.2056.

    Example 198

    3-methyl-5-(N-(4-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S81)

    [0928] ##STR00269##

    [0929] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-81 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 160 mg of white solid was obtained, with a yield of 84%. M.p. 166-167? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.21 (s, 1H), 7.91 (d, J=8.6 Hz, 1H), 7.82 (d, J=8.7 Hz, 1H), 7.17 (p, J=9.8, 8.4 Hz, 5H), 6.99 (d, J=7.0 Hz, 2H), 6.89 (d, J=8.3 Hz, 2H), 4.31 (s, 2H), 3.43 (s, 4H), 3.34-3.22 (m, 2H), 3.07 (s, 4H), 2.55 (d, J=12.9 Hz, 5H), 1.41 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.4, 155.4, 154.3, 150.8, 138.8, 135.6, 129.8, 129.7, 129.0, 128.8, 127.3, 126.7, 126.4, 121.8, 116.1, 113.4, 79.4, 51.2, 49.3, 48.6, 34.8, 28.5, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.34H.sub.38N.sub.3O.sub.7S: 632.2430, found 632.2438.

    Example 199

    3-methyl-5-(N-(4-(4-phenoxybenzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S86)

    [0930] ##STR00270##

    [0931] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-86 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 30 mg of white solid was obtained, with a yield of 55%. M.p. 302-303? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.06 (d, J=1.9 Hz, 1H), 7.89-7.59 (m, 2H), 7.45-7.30 (m, 4H), 7.26-7.09 (m, 4H), 7.06-6.91 (m, 6H), 4.38 (s, 2H), 3.35-3.26 (m, 2H), 2.54 (d, J=19.3 Hz, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.9, 157.1, 156.5, 154.6, 152.1, 138.8, 134.0, 132.4, 131.1, 130.6, 130.5, 129.0, 128.8, 126.7, 124.1, 123.9, 120.5, 119.1, 119.0, 116.8, 112.7, 51.2, 49.8, 34.9, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.31H.sub.26NO.sub.6S: 540.1481, found 540.1477.

    Example 200

    3-methyl-5-(N-(2-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S87)

    [0932] ##STR00271##

    [0933] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-87 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 144 mg of white solid was obtained, with a yield of 75%. M.p. 158-159? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.29 (d, J=1.9 Hz, 1H), 7.97 (dd, J=8.8, 1.9 Hz, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.42 (d, J=7.0 Hz, 1H), 7.30 (t, J=7.6 Hz, 1H), 7.23-7.09 (m, 5H), 6.95 (d, J=7.0 Hz, 2H), 4.53 (s, 2H), 3.41 (s, 4H), 3.33-3.23 (m, 2H), 2.78 (t, J=4.8 Hz, 4H), 2.61 (s, 3H), 2.56-2.52 (m, 2H), 1.43 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.6, 155.4, 154.4, 151.7, 138.8, 135.0, 131.6, 129.9, 128.8, 128.8, 126.7, 126.3, 124.4, 121.7, 120.6, 113.3, 79.4, 52.8, 49.9, 46.8, 34.5, 28.5, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.34H.sub.38N.sub.3O.sub.7S: 632.2430, found 632.2423.

    Example 201

    3-methyl-5-(N-(3-(4-(tert-butoxycarbonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S88)

    [0934] ##STR00272##

    [0935] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M8-88 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 53 mg of white solid was obtained, with a yield of 42%. M.p. 104-105? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.26 (d, J=1.6 Hz, 1H), 7.94 (dd, J=8.8, 1.8 Hz, 1H), 7.83 (d, J=8.8 Hz, 1H), 7.25-7.09 (m, 4H), 7.01 (d, J=7.0 Hz, 2H), 6.89-6.81 (m, 1H), 6.77 (d, J=7.5 Hz, 1H), 6.72 (s, 1H), 4.36 (s, 2H), 3.47-3.36 (m, 4H), 3.35-3.28 (m, 2H), 2.94 (s, 4H), 2.59 (d, J=10.7 Hz, 5H), 1.41 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.2, 155.5, 154.3, 151.4, 144.0, 138.9, 137.8, 135.6, 129.6, 129.6, 129.0, 128.8, 126.7, 126.6, 125.0, 121.9, 119.9, 116.1, 115.6, 113.5, 79.4, 51.9, 49.5, 48.6, 34.8, 28.5, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.34H.sub.38N.sub.3O.sub.7S: 632.2430, found 632.2421.

    Example 202

    ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M9-1)

    [0936] ##STR00273##

    [0937] Tert-butyl 4-(2-(((2-(ethoxycarbonyl)-3-methyl-N-phenethylbenzofuran)-5-sulfonylamino)phenyl)piperazine-1-carboxylate (96 mg, 0.15 mmol) and trifluoroacetic acid (85.5 mg, 0.75 mmol) were added to dichloromethane (5 mL), and the resulting solution was then stirred at room temperature for 2 h. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (20 mL). A proper amount of sodium bicarbonate was added to adjust the pH value to 7-8, and extraction with dichloromethane (20 mL) was carried out three times. The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (DCM/CH.sub.3OH=15/1?10/1)) to obtain 85 mg of light yellow solid, with a yield of 99%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.17 (d, J=1.5 Hz, 1H), 7.91 (dd, J=8.8, 1.8 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.34 (dt, J=8.5, 4.5 Hz, 1H), 7.23-7.13 (m, 4H), 7.04 (d, J=4.1 Hz, 2H), 6.97 (d, J=6.6 Hz, 2H), 4.49 (q, J=7.1 Hz, 2H), 4.17 (s, 1H), 3.88 (s, 1H), 3.26-2.75 (m, 8H), 2.61 (s, 5H), 1.47 (t, J=7.1 Hz, 3H), 1.27 (s, 1H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 151.5, 143.0, 138.4, 136.3, 133.6, 130.7, 129.3, 129.3, 128.6, 128.4, 126.8, 126.4, 125.6, 124.0, 122.6, 122.0, 112.9, 61.6, 51.1, 34.7, 29.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.30H.sub.34N.sub.3O.sub.5S: 548.2219, found 548.2230.

    Example 203

    ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)benzyl)sulfamoyl)benzofuran-2-carboxylate (M9-2)

    [0938] ##STR00274##

    [0939] Ethyl 5-(N-(2-(4-(tert-butoxycarbonyl)piperazine)benzyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (1.981 g, 3.0 mmol) was dissolved in dichloromethane (20 mL), trifluoroacetic acid (1.337 mL, 18.0 mmol) was then added, and the resulting solution was stirred for 1 h. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure and the product was dried with a vacuum pump to obtain 1.65 g of white solid, with a yield of 98%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.17 (d, J=2.0 Hz, 1H), 7.90 (dd, J=8.7, 2.0 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H), 7.47-7.08 (m, 7H), 6.98-6.86 (m, 2H), 4.61-4.42 (m, 4H), 3.83 (d, J=41.7 Hz, 2H), 3.31 (t, J=8.1 Hz, 2H), 2.61 (d, J=23.8 Hz, 5H), 1.48 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 143.0, 138.3, 135.3, 131.0, 130.2, 129.5, 129.0, 128.5, 128.5, 126.5, 126.2, 125.5, 121.5, 120.8, 113.1, 61.6, 49.4, 47.1, 47.1, 45.2, 35.0, 14.4, 9.4.

    Example 204

    4-(2-((2-(ethoxycarbonyl)-3-methyl-N-phenethylbenzofuran)-5-sulfonylamino)phenyl)-1,1-dimethylpiperazin-1-ium (M10-90)

    [0940] ##STR00275##

    [0941] Ethyl 3-methyl-5-N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (200 mg, 0.36 mmol), methyl iodide (102 mg, 0.72 mmol) and potassium carbonate (100 mg, 0.72 mmol) were added to acetonitrile (2 mL), and the reaction was performed overnight at room temperature. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (10 mL) and then extracted three times with dichloromethane (10 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (DCM/CH.sub.3OH=20/1?10/1) to obtain 163 mg of white solid, with a yield of 79%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25 (s, 1H), 7.91 (d, J=8.8 Hz, 2H), 7.53 (d, J=7.2 Hz, 1H), 7.42 (t, J=8.2 Hz, 1H), 7.14 (dt, J=13.9, 7.5 Hz, 4H), 6.98 (t, J=6.3 Hz, 3H), 4.39 (q, J=7.1 Hz, 2H), 4.00 (s, 1H), 3.85 (s, 1H), 3.48 (s, 4H), 3.36 (s, 4H), 3.24 (s, 6H), 3.15 (s, 2H), 2.60 (s, 3H), 1.36 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 159.6, 155.7, 149.9, 142.8, 138.6, 135.7, 134.1, 131.0, 129.8, 129.4, 129.0, 128.7, 127.5, 126.7, 126.1, 125.8, 124.3, 122.6, 113.8, 61.7, 51.4, 45.9, 34.3, 14.6, 9.6. HRMS (ESI) [M].sup.+, theoretically calculated for C.sub.32H.sub.38N.sub.3O.sub.5S.sup.+: 576.2532, found 576.2535.

    Example 205

    ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-91)

    [0942] ##STR00276##

    [0943] Ethyl 3-methyl-5-N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (150 mg, 0.27 mmol), N, N-diisopropylethylamine (70 mg, 0.54 mmol) and 4-dimethylaminopyridine (4 mg, 0.03 mmol) were added to dichloromethane (1 mL), and the solution was stirred at 0? C. for 30 min. Dichloromethane (1 mL) solution of acetic anhydride (37 mg, 0.32 mmol) was then added dropwise and the resulting solution was then stirred at room temperature for 5 h. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (10 mL) and then extracted three times with dichloromethane (10 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (PE/EA=1/2) to obtain 129 mg of white solid, with a yield of 81%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.8 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.63 (d, J=8.7 Hz, 1H), 7.35 (td, J=7.7, 1.6 Hz, 1H), 7.21-7.12 (m, 4H), 7.07 (td, J=7.6, 1.4 Hz, 1H), 6.94 (ddd, J=7.6, 3.6, 1.5 Hz, 3H), 4.48 (q, J=7.1 Hz, 2H), 4.17-3.93 (m, 2H), 3.81 (s, 1H), 3.59 (s, 2H), 3.44 (d, J=18.9 Hz, 2H), 3.10 (s, 1H), 2.84 (s, 2H), 2.68 (s, 1H), 2.60 (s, 4H), 2.12 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 169.2, 159.8, 155.8, 151.1, 143.1, 138.1, 136.0, 134.1, 130.3, 129.5, 129.4, 128.5, 126.8, 126.5, 125.5, 124.6, 122.9, 122.1, 112.9, 61.6, 53.0, 51.8, 51.5, 46.9, 42.0, 34.6, 21.4, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.36N.sub.3O.sub.6S: 590.2325, found 590.2331.

    Example 206

    ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-92)

    [0944] ##STR00277##

    [0945] Ethyl 3-methyl-5-N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (168 mg, 0.3 mmol) and triethylamine (50 ?L, 0.36 mmol) were added to dichloromethane (1 mL), and the resulting solution was then stirred at 0? C. for 30 min. Dichloromethane (1 mL) solution of N,N-dimethylcarbamoyl chloride (53 ?L, 0.36 mmol) was then added dropwise and the resulting solution was stirred at room temperature for 5 h. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (10 mL) and then extracted three times with dichloromethane (10 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (DCM/MeOH=50/1) to obtain 141 mg of white solid, with a yield of 76%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.6 Hz, 1H), 7.89 (dd, J=8.8, 1.8 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.32 (t, J=7.0 Hz, 1H), 7.22-7.09 (m, 4H), 7.06-6.96 (m, 2H), 6.93 (d, J=6.6 Hz, 2H), 4.47 (q, J=7.1 Hz, 2H), 3.97 (d, J=113.4 Hz, 2H), 3.34 (d, J=46.4 Hz, 6H), ? 2.90-2.78 (m, 8H), 2.70-2.50 (m, 5H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 164.7, 159.8, 155.8, 151.0, 143.0, 138.2, 136.2, 133.8, 130.5, 129.3, 129.3, 128.5, 128.4, 126.8, 126.4, 125.5, 124.2, 122.6, 122.0, 112.9, 61.5, 52.2, 51.2, 47.2, 38.5, 34.7, 14.3, 9.3.

    Example 207

    ethyl 3-methyl-5-(N-(2-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate M10-93)

    [0946] ##STR00278##

    [0947] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-92), this example was implemented under the same condition except that methanesulfonyl chloride was used instead of N, N-dimethylcarbamoyl chloride. 158 mg of light yellow liquid product was obtained, with a yield of 94%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.12 (d, J=1.9 Hz, 1H), 7.86 (dd, J=8.8, 1.9 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.37 (td, J=7.7, 1.6 Hz, 1H), 7.29-7.23 (m, 1H), 7.22-7.05 (m, 4H), 7.00-6.93 (m, 2H), 6.90 (dd, J=7.9, 1.4 Hz, 1H), 4.48 (q, J=7.1 Hz, 2H), 4.01 (s, 1H), 3.78 (s, 1H), 3.36 (d, J=12.9 Hz, 6H), 2.97 (s, 2H), 2.83 (s, 3H), 2.69 (s, 1H), 2.60 (s, 3H), 2.54 (s, 1H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.9, 151.3, 143.1, 138.0, 135.7, 134.5, 130.0, 129.6, 129.4, 128.5, 126.8, 126.6, 125.5, 125.1, 123.4, 122.1, 113.0, 61.6, 52.0, 51.7, 46.4, 34.6, 34.5, 31.6, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.31H.sub.36N.sub.3O.sub.7S.sub.2: 626.1995, found 626.1990.

    Example 208

    ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94)

    [0948] ##STR00279##

    [0949] Ethyl 3-methyl-5-N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (200 mg, 0.36 mmol), 3,3-dimethyl-1-butanoic acid (92 mg, 0.79 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (152 mg, 0.79 mmol), 1-hydroxybenzotriazole (107 mg, 0.79 mmol), N, N-diisopropylethylamine (150 mg, 1.08 mmol), and 4-dimethylaminopyridine (5 mg, 0.04 mmol) were added to dichloromethane (2 mL), and the resulting solution was then stirred at room temperature overnight. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (10 mL) and then extracted three times with dichloromethane (10 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (PE/EA=8/1?6/1) to obtain 120 mg of white solid, with a yield of 52%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.8 Hz, 1H), 7.89 (dd, J=8.8, 1.9 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.38-7.31 (m, 1H), 7.23-7.12 (m, 4H), 7.10-7.04 (m, 1H), 6.99-6.92 (m, 3H), 4.49 (q, J=7.1 Hz, 2H), 4.25-3.94 (m, 2H), 3.88-3.76 (m, 1H), 3.75-3.30 (m, 4H), 3.10 (s, 1H), 2.84 (s, 2H), 2.74-2.65 (m, 1H), 2.61 (s, 4H), 2.30 (s, 2H), 1.47 (t, J=7.1 Hz, 3H), 1.08 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.6, 159.8, 155.8, 150.9, 143.1, 138.1, 136.0, 134.0, 130.4, 129.5, 129.4, 128.5, 128.5, 126.8, 126.5, 125.5, 124.6, 122.8, 122.1, 112.9, 61.6, 51.4, 44.7, 34.6, 31.5, 30.1, 29.6, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.44N.sub.3O.sub.6S: 646.2951, found 646.2958.

    Example 209

    ethyl 3-methyl-5-(N-(2-(4-(4-(benzylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-95)

    [0950] ##STR00280##

    [0951] Ethyl 3-methyl-5-N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (164 mg, 0.3 mmol) and potassium carbonate (83 mg, 0.6 mmol) were dissolved in acetonitrile (2 mL), benzyl bromide (54 ?L, 0.45 mmol) was then added, and the reaction was performed at 60? C. overnight. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the obtained product was dissolved in water (20 mL) and then extracted three times with ethyl acetate (20 mL). The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (DCM/MeOH=50/1) to obtain 129 mg of white solid, with a yield of 67%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.19 (d, J=1.6 Hz, 1H), 7.93 (dd, J=8.8, 1.9 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.42-7.30 (m, 6H), 7.24-7.14 (m, 4H), 7.06 (qd, J=7.9, 1.7 Hz, 2H), 7.02-6.96 (m, 2H), 4.51 (q, J=7.1 Hz, 2H), 4.29-4.09 (m, 1H), 3.92 (s, 1H), 3.55 (s, 2H), 3.23 (s, 2H), 3.00-2.79 (m, 2H), 2.74-2.63 (m, 2H), 2.56 (dd, J=16.2, 5.9 Hz, 4H), 1.49 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 151.2, 143.0, 138.4, 137.9, 136.4, 133.5, 130.8, 129.3, 129.2, 128.6, 128.5, 128.4, 128.3, 127.5, 127.2, 126.9, 126.9, 126.4, 125.6, 123.8, 122.4, 122.0, 112.8, 63.2, 61.6, 53.6, 52.2, 51.1, 34.8, 14.4, 9.4.

    Example 210

    ethyl 3-methyl-5-(N-(2-(4-(benzoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-96)

    [0952] ##STR00281##

    [0953] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that benzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 148 mg of white solid was obtained, with a yield of 63%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.9 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.43 (dt, J=4.9, 3.4 Hz, 5H), 7.35 (td, J=7.7, 1.6 Hz, 1H), 7.25-7.05 (m, 5H), 6.96 (ddd, J=9.5, 7.8, 1.5 Hz, 3H), 4.48 (q, J=7.1 Hz, 2H), 4.29-3.94 (m, 2H), 3.90-3.45 (m, 4H), 3.27 (s, 2H), 3.04-2.63 (m, 3H), 2.59 (s, 4H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.5, 159.8, 155.8, 151.0, 143.1, 138.1, 135.9, 135.8, 134.1, 130.3, 129.7, 129.5, 129.4, 128.5, 127.1, 126.8, 126.5, 125.5, 124.7, 122.9, 122.1, 112.9, 61.6, 51.5, 34.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.37H.sub.38N.sub.3O.sub.6S: 652.2481, found 652.2487.

    Example 211

    ethyl 3-methyl-5-(N-(2-(4-methylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-98)

    [0954] ##STR00282##

    [0955] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-91), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)benzyl)sulfamoyl)benzofuran-2-carboxylate (M9-2), and methyl iodide (102 mg, 0.36 mmol) were used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M9-1). 113 mg of white solid was obtained, with a yield of 66%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (s, 1H), 7.89 (d, J=8.6 Hz, 1H), 7.65 (d, J=8.7 Hz, 1H), 7.38-7.25 (m, 3H), 7.24-7.04 (m, 5H), 6.87 (d, J=6.8 Hz, 2H), 4.61-4.36 (m, 4H), 3.26 (t, J=8.1 Hz, 2H), 3.00 (d, J=69.2 Hz, 8H), 2.61 (s, 3H), 2.53 (s, 5H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 151.3, 143.0, 138.2, 135.1, 130.9, 130.4, 129.5, 129.2, 128.5, 128.4, 126.4, 126.2, 125.5, 124.9, 121.4, 121.2, 113.1, 61.6, 54.9, 51.6, 49.3, 47.5, 45.1, 34.9, 14.4, 9.4.

    Example 212

    4-(2-((2-(ethoxycarbonyl)-3-methyl-N-benzylethylbenzofuran)-5-sulfonylamino)phenyl)-1,1-dimethylpiperazin-1-ium (M10-99)

    [0956] ##STR00283##

    [0957] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-90), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)benzyl)sulfamoyl)benzofuran-2-carboxylate (M9-2) was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M9-1). 81 mg of yellow solid was obtained, with a yield of 76%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.93 (d, J=8.8 Hz, 1H), 7.68 (d, J=8.8 Hz, 1H), 7.49 (d, J=7.8 Hz, 1H), 7.37 (t, J=7.2 Hz, 1H), 7.26-7.04 (m, 5H), 6.80 (d, J=6.7 Hz, 2H), 4.44 (d, J=7.6 Hz, 4H), 3.94 (s, 4H), 3.63 (s, 6H), 3.30 (s, 4H), 3.22-3.11 (m, 2H), 2.61 (s, 3H), 2.44-2.27 (m, 2H), 1.42 (t, J=7.0 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 150.1, 143.0, 138.0, 134.2, 131.7, 131.2, 130.0, 129.6, 128.5, 128.5, 126.5, 126.4, 126.1, 125.6, 123.3, 121.6, 113.4, 62.6, 61.6, 52.7, 49.9, 49.5, 46.8, 35.5, 14.3, 9.6.

    Example 213

    ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-100)

    [0958] ##STR00284##

    [0959] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-91), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)benzyl)sulfamoyl)benzofuran-2-carboxylate (M9-2) was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M9-1). 154 mg of white solid was obtained, with a yield of 86%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.88 (d, J=10.4 Hz, 1H), 7.63 (d, J=8.7 Hz, 1H), 7.38 (d, J=7.0 Hz, 1H), 7.29 (t, J=7.6 Hz, 1H), 7.18-7.06 (m, 5H), 6.89 (s, 2H), 4.58 (s, 2H), 4.47 (q, J=7.1 Hz, 2H), 3.65 (d, J=56.1 Hz, 4H), 3.37-3.28 (m, 2H), 2.84 (d, J=20.5 Hz, 4H), 2.65-2.53 (m, 5H), 2.12 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 169.1, 159.8, 155.7, 151.0, 143.0, 138.3, 135.3, 130.9, 130.1, 129.4, 128.9, 128.5, 126.5, 126.2, 125.5, 124.9, 121.5, 120.4, 113.0, 61.6, 53.2, 52.8, 49.4, 46.8, 46.6, 41.8, 35.0, 21.4, 14.4, 9.4.

    Example 214

    ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-101)

    [0960] ##STR00285##

    [0961] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-92), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)benzyl)sulfamoyl)benzofuran-2-carboxylate (M9-2) was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M9-1). 162 mg of white solid was obtained, with a yield of 85%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (d, J=1.8 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.64 (d, J=8.7 Hz, 1H), 7.43 (d, J=7.7 Hz, 1H), 7.28 (t, J=8.3 Hz, 1H), 7.20-7.05 (m, 5H), 6.90 (d, J=6.6 Hz, 2H), 4.59 (s, 2H), 4.48 (q, J=7.1 Hz, 2H), 3.35 (d, J=3.9 Hz, 6H), 2.91-2.79 (m, 10H), 2.65-2.56 (m, 5H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 164.7, 159.9, 155.7, 151.2, 142.9, 138.3, 135.4, 130.9, 130.0, 129.4, 128.7, 128.5, 128.5, 126.4, 126.2, 125.5, 124.7, 121.5, 120.2, 113.0, 61.6, 52.9, 49.4, 47.1, 46.4, 38.5, 34.8, 14.4, 9.4.

    Example 215

    ethyl 3-methyl-5-(N-(2-(4-methanesulfonylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-102)

    [0962] ##STR00286##

    [0963] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-methanesulfonylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-93), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)benzyl)sulfamoyl)benzofuran-2-carboxylate (M9-2) was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M9-1). 86 mg of white solid was obtained, with a yield of 83%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.17 (s, 1H), 7.91 (d, J=8.8 Hz, 1H), 7.67 (d, J=8.7 Hz, 1H), 7.38-7.27 (m, 2H), 7.16 (dd, J=18.9, 7.8 Hz, 5H), 6.91 (d, J=7.2 Hz, 2H), 4.56 (s, 2H), 4.49 (q, J=7.1 Hz, 2H), 3.40 (s, 4H), 3.30 (t, J=8.1 Hz, 2H), 2.99 (s, 4H), 2.84 (s, 3H), 2.67-2.52 (m, 5H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 155.8, 151.2, 143.0, 138.3, 135.2, 131.0, 130.4, 129.4, 129.2, 128.5, 126.5, 126.2, 125.5, 125.1, 121.5, 121.1, 113.1, 61.6, 52.5, 49.4, 47.5, 46.2, 35.2, 34.5, 14.4, 9.4.

    Example 216

    ethyl 3-methyl-5-(N-(2-(4-(3,3-dimethylbutyryl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-103)

    [0964] ##STR00287##

    [0965] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-methanesulfonylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-93), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)benzyl)sulfamoyl)benzofuran-2-carboxylate (M9-2) was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M9-1). 197 mg of white solid was obtained, with a yield of 99%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (d, J=1.8 Hz, 1H), 7.88 (dd, J=8.8, 1.8 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.38 (d, J=7.7 Hz, 1H), 7.28 (t, J=7.6 Hz, 1H), 7.19-7.05 (m, 5H), 6.89 (d, J=6.6 Hz, 2H), 4.57 (s, 2H), 4.47 (q, J=7.1 Hz, 2H), 3.70 (d, J=49.1 Hz, 4H), 3.36-3.28 (m, 2H), 2.84 (dt, J=16.4, 4.4 Hz, 4H), 2.61 (d, J=3.8 Hz, 5H), 2.32 (s, 2H), 1.45 (t, J=7.1 Hz, 3H), 1.07 (s, 9H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.8, 159.8, 155.7, 151.0, 143.0, 138.3, 135.3, 130.9, 130.1, 129.4, 128.8, 128.5, 128.5, 126.4, 126.2, 125.5, 124.8, 121.5, 120.4, 113.0, 61.6, 53.3, 52.9, 49.4, 47.8, 46.8, 44.6, 41.9, 35.0, 31.6, 30.1, 14.4, 9.4.

    Example 217

    ethyl 3-methyl-5-(N-(2-(4-benzylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-104)

    [0966] ##STR00288##

    [0967] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-benzylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-95), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)benzyl)sulfamoyl)benzofuran-2-carboxylate (M9-2) was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M9-1). 138 mg of white solid was obtained, with a yield of 71%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.18 (d, J=1.5 Hz, 1H), 7.91 (dd, J=8.8, 1.9 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.44 (dd, J=7.7, 1.6 Hz, 1H), 7.40-7.34 (m, 4H), 7.33-7.25 (m, 2H), 7.22-7.05 (m, 5H), 6.95 (d, J=6.6 Hz, 2H), 4.61 (s, 2H), 4.52 (q, J=7.1 Hz, 2H), 3.58 (s, 2H), 3.42-3.26 (m, 2H), 2.92 (s, 4H), 2.65 (s, 9H), 1.50 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 155.8, 151.7, 142.9, 138.5, 137.8, 135.7, 130.7, 129.9, 129.4, 129.2, 128.6, 128.4, 128.3, 127.2, 127.0, 126.4, 126.3, 125.6, 124.3, 121.5, 120.1, 113.0, 63.1, 61.6, 53.5, 53.0, 49.3, 46.0, 34.7, 14.4, 9.5.

    Example 218

    ethyl 3-methyl-5-(N-(2-(4-benzoylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-105)

    [0968] ##STR00289##

    [0969] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(benzoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-96), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)benzyl)sulfamoyl)benzofuran-2-carboxylate (M9-2) was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M9-1). 181 mg of white solid was obtained, with a yield of 95%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.18 (d, J=1.8 Hz, 1H), 8.12 (dd, J=8.3, 1.2 Hz, 1H), 7.94-7.86 (m, 1H), 7.66 (d, J=8.7 Hz, 1H), 7.45 (s, 6H), 7.22-7.10 (m, 5H), 6.92 (dd, J=7.7, 1.4 Hz, 2H), 4.60 (s, 2H), 4.50 (q, J=7.1 Hz, 2H), ? 3.59 (s, 4H), 3.38-3.29 (m, 2H), 2.91 (s, 4H) 2.63 (s, 5H), 1.48 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.6, 159.9, 155.8, 150.9, 143.0, 138.3, 135.6, 135.3, 133.5, 130.9, 130.2, 130.1, 129.8, 129.4, 129.0, 128.6, 128.5, 128.4, 127.1, 126.5, 126.2, 125.5, 125.0, 121.5, 120.5, 113.1, 61.6, 49.5, 46.9, 35.0, 14.4, 9.4.

    Example 219

    3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylic acid (F27-S89)

    [0970] ##STR00290##

    [0971] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-89 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 49 mg of white solid was obtained, with a yield of 55%. Mp 172-173? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.24 (s, 1H), 7.92-7.81 (m, 2H), 7.39 (t, J=7.3 Hz, 1H), 7.28 (d, J=7.7 Hz, 1H), 7.17-7.04 (m, 4H), 7.01 (d, J=7.7 Hz, 1H), 6.95 (d, J=7.1 Hz, 2H), 3.96 (s, 2H), 3.79 (s, 2H), 3.28 (s, 2H), 3.11 (s, 4H), 3.03 (s, 2H), 2.58 (s, 3H), 2.43 (s, 1H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.1, 155.7, 150.6, 143.8, 138.5, 135.5, 134.1, 131.0, 129.9, 129.6, 128.9, 128.7, 127.1, 126.6, 125.4, 125.3, 123.3, 122.5, 113.6, 51.0, 49.2, 43.7, 34.2, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.28H.sub.28N.sub.3O.sub.5S: 518.1750, found 518.1755.

    Example 220

    4-(2-((2-carboxy-3-methyl-N-phenethylbenzofuran)-5-sulfonylamino)phenyl)-1,1-dimethylpiperazin-1-ium (F27-S90

    [0972] ##STR00291##

    [0973] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-90 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 97 mg of white solid was obtained, with a yield of 74%. Mp 246-247? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.19 (s, 1H), 7.85 (s, 2H), 7.53 (d, J=8.0 Hz, 1H), 7.40 (t, J=7.6 Hz, 1H), 7.12 (dt, J=13.9, 7.4 Hz, 4H), 6.98 (d, J=7.5 Hz, 3H), 4.09-3.92 (m, 1H), 3.89-3.71 (m, 1H), 3.49 (t, J=5.3 Hz, 4H), 3.38 (d, J=13.5 Hz, 2H), 3.26 (s, 6H), 3.12 (d, J=13.9 Hz, 2H), 2.57 (s, 4H), 2.44 (s, 1H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.3, 155.6, 149.9, 145.0, 138.6, 135.4, 134.2, 131.0, 129.8, 129.0, 128.7, 126.8, 126.6, 125.7, 124.2, 124.0, 122.2, 113.5, 61.6, 51.3, 45.9, 34.3, 9.5. HRMS (ESI) [M].sup.+, theoretically calculated for C.sub.30H.sub.34N.sub.3O.sub.5S.sup.+: 548.2219, found 548.2222.

    Example 221

    3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S91)

    [0974] ##STR00292##

    [0975] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-91 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 59 mg of white solid was obtained, with a yield of 75%. Mp 196-197? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.24 (s, 1H), 7.89 (q, J=8.8 Hz, 2H), 7.36 (t, J=7.7 Hz, 1H), 7.24 (d, J=8.0 Hz, 1H), 7.12 (dt, J=12.6, 7.1 Hz, 4H), 7.02 (d, J=7.8 Hz, 1H), 6.95 (d, J=7.2 Hz, 2H), 4.06 (s, 1H), 3.84 (s, 1H), 3.43 (d, J=37.5 Hz, 6H), 3.13 (s, 1H), 2.95 (s, 1H), 2.73 (s, 2H), 2.59 (s, 3H), 2.02 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 168.8, 161.3, 155.6, 151.1, 138.6, 135.9, 133.8, 131.0, 129.7, 129.7, 128.9, 128.7, 126.9, 126.6, 124.7, 123.1, 122.3, 113.5, 52.6, 52.0, 50.8, 46.6, 41.7, 34.3, 21.7, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.30H.sub.30N.sub.3O.sub.6S: 560.1855, found 560.1865.

    Example 222

    3-methyl-5-(N-(2-(4-(dimethylcarbamoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid F27-S92)

    [0976] ##STR00293##

    [0977] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-92 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 97 mg of white solid was obtained, with a yield of 83%. Mp>380? C. (for decomposition). .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.19 (s, 1H), 7.93-7.77 (m, 2H), 7.34 (t, J=7.4 Hz, 1H), 7.22 (d, J=7.9 Hz, 1H), 7.18-7.02 (m, 5H), 6.95 (d, J=7.1 Hz, 2H), 3.86 (s, 2H), 3.17 (s, 2H), 3.13-2.91 (m, 4H), 2.74 (s, 8H), 2.58 (s, 3H), 2.51 (s, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.1, 155.3, 151.0, 138.6, 135.5, 133.6, 131.1, 130.3, 129.5, 128.8, 128.7, 126.6, 126.0, 124.4, 122.8, 121.7, 113.2, 52.0, 50.6, 47.3, 38.5, 34.4, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.31H.sub.33N.sub.4O.sub.6S: 589.2126, found 589.2122.

    Example 223

    3-methyl-5-(N-(2-(4-(methylsulfonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S93)

    [0978] ##STR00294##

    [0979] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-93 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 60 mg of white solid was obtained, with a yield of 72%. Mp 144-145? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.22 (s, 1H), 7.94-7.81 (m, 2H), 7.41-7.27 (m, 2H), 7.11 (dd, J=13.5, 6.9 Hz, 4H), 6.99 (dd, J=19.9, 7.3 Hz, 3H), 3.93 (d, J=62.2 Hz, 4H), 3.13 (s, 6H), 2.87 (d, J=23.0 Hz, 5H), 2.58 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.3, 155.6, 151.0, 144.4, 138.6, 135.8, 134.0, 131.1, 129.7, 129.7, 128.9, 128.7, 127.0, 126.6, 125.1, 124.7, 123.6, 122.3, 113.5, 51.9, 51.0, 46.3, 34.6, 34.3, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.29H.sub.30N.sub.3O.sub.7S.sub.2: 596.1525, found 596.1534.

    Example 224

    3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzo furan-2-carboxylic acid (F27-S94)

    [0980] ##STR00295##

    [0981] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-94 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 66 mg of white solid was obtained, with a yield of 89%. Mp 191-192? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25 (s, 1H), 7.88 (q, J=8.1 Hz, 2H), 7.35 (t, J=6.5 Hz, 1H), 7.23 (d, J=7.6 Hz, 1H), 7.19-7.02 (m, 5H), 6.96 (d, J=6.4 Hz, 2H), 4.06 (s, 1H), 3.87 (s, 1H), 3.71-3.27 (m, 6H), 2.98 (d, J=37.3 Hz, 2H), 2.70 (s, 2H), 2.59 (s, 3H), 2.22 (s, 2H), 0.98 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 170.0, 161.3, 155.6, 151.0, 138.6, 135.9, 133.7, 131.2, 129.7, 129.6, 128.9, 128.7, 126.9, 126.6, 124.7, 123.1, 122.3, 113.5, 52.9, 52.0, 50.8, 46.9, 44.1, 41.7, 34.4, 31.5, 30.2, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.34H.sub.38N.sub.3O.sub.6S: 616.2481, found 616.2470.

    Example 225

    3-methyl-5-(N-(2-(4-(4-(benzylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S95)

    [0982] ##STR00296##

    [0983] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-95 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 90 mg of white solid was obtained, with a yield of 74%. Mp 161-162? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.24 (s, 1H), 7.95-7.79 (m, 2H), 7.66-7.52 (m, 2H), 7.48-7.33 (m, 4H), 7.26 (d, J=7.9 Hz, 1H), 7.15 (dt, J=13.8, 6.2 Hz, 4H), 7.05-6.92 (m, 3H), 4.16 (d, J=8.5 Hz, 2H), 4.00 (s, 1H), 3.88-3.72 (m, 1H), 3.27 (s, 2H), 3.00 (d, J=37.0 Hz, 6H), 2.59 (s, 3H), 2.51 (s, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.2, 155.6, 150.3, 144.0, 138.6, 135.5, 133.8, 131.3, 131.1, 129.8, 129.6, 129.3, 129.0, 128.9, 128.7, 127.1, 126.7, 125.1, 125.0, 123.0, 122.4, 113.5, 59.8, 51.9, 51.0, 49.6, 34.3, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.35H.sub.34N.sub.3O.sub.5S: 608.2225, found 608.2216.

    Example 226

    3-methyl-5-(N-(2-(4-(benzoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S96)

    [0984] ##STR00297##

    [0985] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-96 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 68 mg of white solid was obtained, with a yield of 73%. Mp 128-129? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.23 (s, 1H), 7.87 (q, J=9.0 Hz, 2H), 7.52-7.21 (m, 7H), 7.09 (dt, J=22.3, 7.0 Hz, 5H), 6.97 (d, J=6.3 Hz, 2H), 4.06 (s, 1H), 3.86 (s, 1H), 3.44 (d, J=120.0 Hz, 6H), 2.99 (d, J=26.6 Hz, 2H), 2.76 (d, J=26.4 Hz, 2H), 2.56 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 169.5, 161.3, 155.6, 150.9, 138.6, 136.3, 135.8, 133.7, 131.3, 130.0, 129.7, 129.6, 128.9, 128.8, 128.7, 127.3, 127.0, 126.6, 124.8, 124.6, 123.2, 122.2, 113.5, 50.8, 34.4, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.35H.sub.32N.sub.3O.sub.6S: 622.2012, found 622.2005.

    Example 227

    3-methyl-5-(N-(2-(piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S97)

    [0986] ##STR00298##

    [0987] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-97 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 80 mg of white solid was obtained, with a yield of 75%. Mp 223-224? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 9.83 (s, 1H), 8.25 (s, 1H), 7.95 (d, J=8.8 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.41 (d, J=7.6 Hz, 1H), 7.30 (d, J=7.8 Hz, 1H), 7.14 (dt, J=15.6, 7.0 Hz, 5H), 6.91 (d, J=7.2 Hz, 2H), 4.51 (s, 2H), 3.23 (d, J=21.6 Hz, 6H), 3.07 (s, 4H), 2.58 (s, 3H), 2.46 (s, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.2, 155.5, 151.0, 138.7, 136.3, 135.0, 131.9, 130.2, 129.7, 129.1, 128.9, 128.8, 126.7, 125.0, 122.0, 120.7, 113.5, 110.0, 49.9, 49.7, 47.4, 43.6, 34.7, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.29H.sub.30N.sub.3O.sub.5S: 532.1912, found 532.1896.

    Example 228

    3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S98)

    [0988] ##STR00299##

    [0989] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-98 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 77 mg of white solid was obtained, with a yield of 71%. Mp 190-191? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.34 (s, 1H), 8.01 (d, J=8.7 Hz, 1H), 7.89 (d, J=8.7 Hz, 1H), 7.41 (d, J=7.4 Hz, 1H), 7.32 (t, J=7.6 Hz, 1H), 7.16 (dt, J=15.7, 6.6 Hz, 5H), 6.93 (d, J=7.0 Hz, 2H), 4.53 (s, 2H), 3.42 (s, 4H), 3.13 (s, 6H), 2.78 (s, 3H), 2.60 (s, 3H), 2.49-2.40 (m, 2H). .sup.13C NMR (101 MHz, DMSO) ? 161.1, 155.6, 150.4, 138.7, 135.1, 131.9, 130.0, 129.7, 129.0, 128.9, 128.8, 126.8, 126.7, 125.3, 125.0, 122.1, 120.6, 113.6, 110.0, 53.3, 50.1, 49.7, 47.1, 42.5, 34.7, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.30H.sub.32N.sub.3O.sub.5S: 546.2068, found 546.2057.

    Example 229

    4-(2-(((2-carboxy-3-methyl-N-phenethylbenzofuran)-5-sulfonamido)methyl)phenyl)-1,1-dimethylpiperazin-1-ium (F27-S99)

    [0990] ##STR00300##

    [0991] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-99 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 81 mg of white solid was obtained, with a yield of 76%. Mp 143-144? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.36 (s, 1H), 8.03 (d, J=8.7 Hz, 1H), 7.90 (d, J=8.7 Hz, 1H), 7.46-7.31 (m, 3H), 7.16 (dt, J=15.7, 7.1 Hz, 4H), 6.93 (d, J=7.1 Hz, 2H), 4.56 (s, 2H), 3.61-3.53 (m, 4H), 3.25 (d, J=7.5 Hz, 8H), 3.21 (d, J=5.5 Hz, 4H), 2.60 (s, 3H), 2.45 (t, J=8.1 Hz, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.1, 155.6, 150.1, 143.7, 138.7, 135.1, 132.3, 129.9, 129.7, 128.9, 128.9, 128.8, 126.9, 126.7, 125.3, 125.3, 122.1, 121.6, 113.6, 61.6, 56.5, 50.3, 47.4, 46.4, 34.8, 9.6. HRMS (ESI) [M]+, theoretically calculated for C.sub.31H.sub.36N.sub.3O.sub.5S: 562.2370, found 562.2383.

    Example 230

    3-methyl-5-(N-(2-(4-acetylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S100)

    [0992] ##STR00301##

    [0993] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-100 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 92 mg of white solid was obtained, with a yield of 61%. Mp 236-237? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.74 (s, 1H), ? 8.30 (s, 1H), 8.03-7.82 (m, 2H), 7.39 (d, J=7.3 Hz, 1H), 7.29 (t, J=7.6 Hz, 1H), 7.14 (dq, J=15.0, 8.0, 7.3 Hz, 5H), 6.94 (d, J=7.2 Hz, 2H), 4.54 (s, 3H), 3.51 (s, 4H), 3.37-3.23 (m, 4H), 2.78 (dt, J=28.9, 4.9 Hz, 4H), 2.59 (s, 3H), 2.54-2.49 (m, 2H), 2.02 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 168.8, 161.1, 155.5, 151.6, 143.7, 138.7, 135.2, 131.7, 129.9, 129.6, 128.9, 128.8, 128.8, 126.8, 126.7, 125.3, 124.5, 122.0, 120.7, 113.5, 56.5, 53.1, 52.9, 49.8, 46.7, 46.5, 41.7, 34.5, 21.7, 19.0, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.31H.sub.32N.sub.3O.sub.6S: 574.2017, found 574.2017.

    Example 231

    3-methyl-5-(N-(2-(4-(dimethylcarbamoyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S101)

    [0994] ##STR00302##

    [0995] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-101 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 45 mg of white solid was obtained, with a yield of 28%. Mp 118-119? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.29 (s, 1H), 7.90 (dd, J=53.2, 8.7 Hz, 2H), 7.41 (d, J=7.5 Hz, 1H), 7.24 (dd, J=26.0, 7.5 Hz, 3H), 7.10 (dd, J=17.5, 7.1 Hz, 4H), 6.92 (d, J=7.3 Hz, 2H), 4.60 (s, 2H), 3.33-3.15 (m, 6H), 2.87 (s, 4H), 2.73 (s, 6H), 2.49 (s, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.0, 161.0, 155.5, 143.7, 138.7, 135.2, 131.5, 130.0, 129.6, 129.0, 128.8, 128.7, 126.7, 126.6, 125.2, 125.0, 122.0, 120.7, 113.5, 53.0, 49.9, 46.9, 46.8, 38.5, 34.5, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.32H.sub.35N.sub.4O.sub.6S: 603.2283, found 603.2270.

    Example 232

    3-methyl-5-(N-(2-(4-(methylsulfonyl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S102)

    [0996] ##STR00303##

    [0997] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-102 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 52 mg of white solid was obtained, with a yield of 57%. Mp 150-151? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.29 (s, 1H), 7.92 (dd, J=41.7, 9.3 Hz, 2H), 7.38 (d, J=7.4 Hz, 1H), 7.29 (t, J=7.4 Hz, 1H), 7.15 (ddd, J=29.1, 12.9, 7.2 Hz, 5H), 6.94 (d, J=7.1 Hz, 2H), 4.54 (s, 2H), 3.29 (t, J=7.9 Hz, 2H), 3.21 (s, 4H), 2.97-2.84 (m, 7H), 2.59 (s, 3H), 2.54 (t, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.3, 155.5, 151.3, 144.1, 138.7, 135.2, 131.7, 129.8, 129.7, 128.9, 128.8, 126.7, 126.6, 124.8, 124.7, 122.0, 120.8, 113.5, 52.4, 49.9, 46.8, 46.3, 34.6, 34.5, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.30H.sub.32N.sub.3O.sub.7S.sub.2: 610.1687, found 610.1687.

    Example 233

    3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzo furan-2-carboxylic acid (F27-S103)

    [0998] ##STR00304##

    [0999] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-94 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 75 mg of white solid was obtained, with a yield of 39%. Mp 190-191? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.29 (s, 1H), 7.98 (d, J=10.5 Hz, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.40 (d, J=7.3 Hz, 1H), 7.28 (t, J=7.5 Hz, 1H), 7.14 (dq, J=15.0, 7.4 Hz, 5H), 6.94 (d, J=7.0 Hz, 2H), 4.54 (s, 2H), 3.56 (s, 4H), 3.32-3.24 (m, 2H), 2.76 (dt, J=17.5, 4.9 Hz, 4H), 2.59 (s, 3H), 2.52 (d, J=10.3 Hz, 2H), 2.25 (s, 2H), 0.99 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 170.0, 161.1, 155.5, 151.5, 143.7, 138.7, 135.2, 131.6, 129.9, 129.6, 128.9, 128.8, 128.8, 126.8, 126.7, 125.3, 124.5, 122.0, 120.6, 113.5, 53.3, 53.0, 49.8, 46.8, 44.1, 41.6, 34.5, 31.5, 30.2, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.35H.sub.42N.sub.3O.sub.6S: 632.2789, found 632.2802.

    Example 234

    3-methyl-5-(N-(2-(4-benzylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S104)

    [1000] ##STR00305##

    [1001] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-104 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 107 mg of white solid was obtained, with a yield of 82%. Mp 154-155? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.30 (s, 1H), 7.98 (d, J=10.4 Hz, 1H), 7.87 (d, J=8.8 Hz, 1H), 7.59 (d, J=5.7 Hz, 2H), 7.46-7.25 (m, 5H), 7.20-7.05 (m, 5H), 6.91 (d, J=7.1 Hz, 2H), 4.50 (s, 2H), 4.14 (s, 2H), 3.25 (s, 2H), 3.07 (d, J=23.3 Hz, 8H), 2.59 (s, 3H), 2.51-2.43 (m, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.2, 155.5, 150.7, 144.2, 138.7, 135.1, 132.0, 131.6, 131.4, 129.8, 129.7, 129.3, 129.0, 128.9, 128.8, 128.8, 126.7, 126.6, 124.8, 124.8, 121.9, 120.5, 113.5, 59.8, 51.8, 50.2, 50.0, 46.9, 34.6, 9.6. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.36H.sub.36N.sub.3O.sub.5S: 622.2381, found 622.2374.

    Example 235

    3-methyl-5-(N-(2-(4-benzoylpiperazin-1-yl)benzyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S105)

    [1002] ##STR00306##

    [1003] In accordance with the preparation method of 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27), this example was implemented under the same condition except that M10-105 was used instead of ethyl 5-(N-benzyl-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S8). 133 mg of white solid was obtained, with a yield of 78%. Mp 163-164? C. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.18 (d, J=1.8 Hz, 1H), 7.93-7.76 (m, 2H), 7.51-7.36 (m, 6H), 7.28 (t, J=8.1 Hz, 1H), 7.14 (dt, J=25.5, 7.5 Hz, 5H), 6.92 (d, J=7.0 Hz, 2H), 4.53 (s, 2H), 3.56 (d, J=124.8 Hz, 4H), 3.30-3.20 (m, 2H), 2.82 (s, 4H), 2.59-2.47 (m, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 169.5, 162.8, 155.0, 151.5, 149.0, 138.8, 136.3, 134.3, 131.7, 130.5, 130.0, 129.9, 129.7, 128.9, 128.8, 128.8, 127.4, 126.7, 125.2, 124.5, 121.1, 120.7, 119.9, 113.0, 52.8, 49.9, 46.9, 34.5, 9.5. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.36H.sub.34N.sub.3O.sub.6S: 636.2174, found 636.2177.

    Example 236

    ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-106)

    [1004] ##STR00307##

    [1005] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 4-methylbenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 170 mg of white solid was obtained, with a yield of 100%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.5 Hz, 1H), 7.89 (dd, J=8.8, 1.9 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.36 (d, J=8.0 Hz, 3H), 7.29-7.13 (m, 6H), 7.11-7.04 (m, 1H), 7.00-6.93 (m, 3H), 4.50 (q, J=7.1 Hz, 2H), 4.24-2.51 (m, 15H), 2.40 (s, 3H), 1.48 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.8, 159.9, 155.8, 151.1, 143.0, 139.9, 138.1, 135.9, 134.1, 132.7, 130.3, 130.1, 129.5, 129.4, 129.1, 128.5, 127.3, 126.8, 126.5, 125.5, 124.6, 122.9, 122.1, 112.9, 61.6, 51.5, 34.7, 21.4, 14.4, 9.4.

    Example 237

    Ethyl 3-methyl-5-(N-(2-(4-(2-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-107)

    [1006] ##STR00308##

    [1007] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that O-methylbenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 122.2 mg of white solid was obtained, with a yield of 92%. 1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.5 Hz, 1H), 7.88 (dd, J=8.8, 1.8 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.37 (t, J=7.0 Hz, 1H), 7.32-7.13 (m, 8H), 7.08 (t, J=7.6 Hz, 1H), 6.95 (d, J=7.9 Hz, 3H), 4.50 (q, J=7.1 Hz, 2H), 4.31-4.02 (m, 2H), 3.88-3.61 (m, 2H), 3.45-3.16 (m, 4H), 3.00 (s, 1H), 2.81-2.48 (m, 6H), 2.36 (s, 3H), 1.48 (t, J=7.1 Hz, 3H). 13C NMR (101 MHz, Chloroform-d) ? 170.2, 159.8, 155.8, 151.0, 143.1, 138.1, 136.0, 135.8, 134.1, 132.4, 131.3, 130.4, 130.3, 129.5, 129.4, 128.9, 128.5, 126.8, 126.5, 126.0, 125.9, 125.5, 124.7, 122.8, 122.1, 113.0, 61.6, 53.4, 51.7 (d, J=38.5 Hz), 42.0, 34.6, 19.1, 14.4, 9.4.

    Example 238

    ethyl 3-methyl-5-(N-(2-(4-(3-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-108)

    [1008] ##STR00309##

    [1009] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that M-methyl benzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 119.3 mg of white solid was obtained, with a yield of 90%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.6 Hz, 1H), 7.95-7.86 (m, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.41-7.11 (m, 9H), 7.08 (t, J=8.3 Hz, 1H), 6.96 (d, J=9.5 Hz, 3H), 4.50 (q, J=7.1 Hz, 2H), 4.26-4.04 (m, 2H), 3.92-3.52 (m, 4H), 3.38-3.19 (m, 2H), 3.07-2.55 (m, 7H), 2.40 (s, 3H), 1.48 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.8, 159.9, 155.8, 151.1, 143.1, 138.4, 138.1, 135.9, 135.7, 134.1, 130.5, 130.3, 129.5, 129.4, 128.5, 128.3, 127.7, 127.2, 126.8, 126.5, 125.5, 124.6, 124.0, 122.8, 122.1, 113.0, 61.6, 51.5, 34.7, 21.4, 14.4, 9.4.

    Example 239

    Ethyl 5-(N-(2-(4-(4-Acetylaminobenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylate M10-109)

    [1010] ##STR00310##

    [1011] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that paracetamol benzoic acid was used instead of 3, 3-dimethyl-1-butanoic acid. 72.8 mg of white solid was obtained, with a yield of 51%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.46 (s, 1H), 8.14 (s, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.52 (d, J=8.3 Hz, 2H), 7.41-7.30 (m, 3H), 7.25-7.11 (m, 4H), 7.08 (t, J=7.5 Hz, 1H), 6.99-6.90 (m, 3H), 4.50 (q, J=7.1 Hz, 2H), 4.16-3.96 (m, 2H), 3.88-3.52 (m, 4H), 3.35-3.19 (m, 2H), 3.07-2.66 (m, 3H), 2.64-2.50 (m, 1H), 2.15 (s, 3H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.4, 169.0, 159.9, 155.8, 151.1, 143.1, 139.9, 138.0, 135.8, 134.1, 130.6, 130.2, 129.6, 129.4, 128.5, 128.1, 126.8, 126.5, 125.5, 124.7, 122.9, 122.1, 119.6, 113.0, 61.6, 51.5, 34.6, 29.7, 24.4, 14.4, 9.4.

    Example 240

    Ethyl 5-(N-(2-(4-(4-Acetylaminobenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylate M10-110)

    [1012] ##STR00311##

    [1013] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that para-trifluoromethyl benzoic acid was used instead of 3, 3-dimethyl-1-butanoic acid. 113.1 mg of white solid was obtained, with a yield of 79%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.4 Hz, 1H), 7.93-7.84 (m, 1H), 7.72 (d, J=8.1 Hz, 2H), 7.65 (d, J=8.8 Hz, 1H), 7.57 (d, J=8.1 Hz, 2H), 7.38 (t, J=7.7 Hz, 1H), 7.25-7.06 (m, 5H), 6.94 (dd, J=12.0, 7.3 Hz, 3H), 4.50 (q, J=7.1 Hz, 2H), 4.24-4.03 (m, 2H), 3.88-3.65 (m, 2H), 3.62-3.49 (m, 2H), 3.40-3.21 (m, 2H), 3.08-2.68 (m, 3H), 2.64-2.48 (m, 4H), 1.48 (t, J=7.1 Hz, 3H). HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.38H.sub.37F.sub.3N.sub.3O.sub.6S: 720.2350, found 720.2343.

    Example 241

    Ethyl 5-(N-(2-(4-(4-cyanophenyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-111)

    [1014] ##STR00312##

    [1015] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that para cyanobenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 101.0 mg of white solid was obtained, with a yield of 75%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (d, J=1.6 Hz, 1H), 7.87 (dd, J=8.8, 1.8 Hz, 1H), 7.75 (d, J=8.3 Hz, 2H), 7.65 (d, J=8.8 Hz, 1H), 7.56 (d, J=8.3 Hz, 2H), 7.37 (d, J=8.0 Hz, 1H), 7.25-7.13 (m, 4H), 7.09 (t, J=7.6 Hz, 1H), 6.99-6.87 (m, 3H), 4.50 (q, J=7.1 Hz, 2H), 4.25-4.00 (m, 2H), 3.83-3.65 (m, 2H), 3.60-3.44 (m, 2H), 3.39-3.24 (m, 2H), 3.10-2.94 (m, 1H), 2.87-2.64 (m, 2H), 2.64-2.50 (m, 4H), 1.48 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 168.4, 159.8, 155.9, 151.0, 143.1, 140.1, 138.0, 135.7, 134.3, 132.5, 130.1, 129.6, 129.4, 128.5, 128.5, 127.8, 126.8, 126.6, 125.5, 124.9, 123.0, 122.1, 118.1, 113.6, 113.0, 61.6, 51.7, 34.6, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.38H.sub.37N.sub.4O.sub.6S: 677.2428, found 677.2439.

    Example 242

    Ethyl 5-(N-(2-(4-(4-fluorobenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-12)

    [1016] ##STR00313##

    [1017] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that P-fluorobenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 107.5 mg of white solid was obtained, with a yield of 80%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.6 Hz, 1H), 7.89 (dd, J=8.8, 1.9 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.46 (dd, J=8.7, 5.3 Hz, 2H), 7.41-7.33 (m, 1H), 7.24-7.04 (m, 7H), 6.99-6.91 (m, 3H), 4.51 (q, J=7.1 Hz, 2H), 4.19-2.48 (m, 15H), 1.48 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 169.6, 162.2, 159.9, 155.8, 151.0, 143.1, 138.0, 135.8, 134.2, 130.2, 129.5, 129.5, 129.4, 129.4, 128.5 (d, J=1.7 Hz), 126.8, 126.6, 125.5, 124.7, 122.9, 122.1, 115.7, 115.5, 113.0, 61.6, 51.6, 34.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.37H.sub.37FN.sub.3O.sub.6S: 670.2382, found 670.2396.

    Example 243

    Ethyl-(N-(2-(4-(4-((tert-butoxycarbonyl)amino)benzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-113)

    [1018] ##STR00314##

    [1019] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 4-(N-tert-butoxycarbonyl) aminobenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 121.6 mg of white solid was obtained, with a yield of 79%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (d, J=1.6 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.49-7.32 (m, 5H), 7.23-7.00 (m, 6H), 6.98-6.92 (m, 3H), 4.48 (q, J=7.1 Hz, 2H), 4.16-2.44 (m, 15H), 1.51 (s, 9H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 170.3, 159.9, 155.8, 152.6, 151.1, 143.0, 140.2, 138.1, 135.9, 134.1, 130.3, 129.7, 129.5, 129.3, 128.5, 128.4, 126.8, 126.5, 125.5, 124.6, 122.9, 122.1, 118.0, 112.9, 80.8, 61.6, 60.4, 51.5, 34.7, 28.3, 14.4, 14.2, 9.4.

    Example 244

    Ethyl 3-methyl-5-(N-(2-(4-(4-nitrobenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-114)

    [1020] ##STR00315##

    [1021] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 4-(N-tert-butoxycarbonyl) aminobenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 56.6 mg of white solid was obtained, with a yield of 41%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.30 (d, J=8.8 Hz, 2H), 8.13 (d, J=1.6 Hz, 1H), 7.87 (dd, J=8.8, 1.9 Hz, 1H), 7.63 (t, J=8.8 Hz, 3H), 7.38 (t, J=8.4 Hz, 1H), 7.27-7.04 (m, 5H), 6.99-6.84 (m, 3H), 4.49 (q, J=7.1 Hz, 2H), 4.27-3.97 (m, 2H), 3.86-3.66 (m, 2H), 3.60-3.47 (m, 2H), 3.41-3.25 (m, 2H), 3.08-2.66 (m, 3H), 2.63-2.47 (m, 4H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 168.1, 159.8, 155.8, 151.0, 148.4, 143.1, 142.0, 138.0, 135.7, 134.3, 130.1, 129.6, 129.4, 128.5, 128.5, 128.2, 126.8, 126.6, 125.5, 124.9, 123.9, 123.0, 122.1, 113.0, 61.6, 51.7, 34.6, 14.4, 9.4.

    Example 245

    Ethyl 5-(N-(2-(4-(4-acetylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-115)

    [1022] ##STR00316##

    [1023] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that Para-acetyl benzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 84.2 mg of white solid was obtained, with a yield of 61%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.12 (d, J=1.5 Hz, 1H), 8.01 (d, J=8.3 Hz, 2H), 7.86 (dd, J=8.8, 1.8 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.52 (d, J=8.3 Hz, 2H), 7.36 (t, J=8.2 Hz, 1H), 7.24-7.03 (m, 5H), 6.97-6.90 (m, 3H), 4.47 (q, J=7.1 Hz, 2H), 4.24-3.97 (m, 2H), 3.90-3.63 (m, 2H), 3.59-3.45 (m, 2H), 3.41-3.18 (m, 2H), 3.05-2.64 (m, 3H), 2.63 (s, 3H), 2.61-2.50 (m, 4H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 197.3, 169.3, 159.8, 155.8, 151.0, 143.0, 140.2, 138.0, 137.8, 135.8, 134.2, 130.2, 129.6, 129.3, 1286, 128.5, 128.5, 127.3, 126.8, 126.5, 125.5, 124.8, 122.9, 122.1, 113.0, 61.6, 60.4, 51.6, 34.6, 26.7, 14.4, 14.2, 9.4.

    Example 246

    Ethyl 3-methyl-5-(N-(2-(4-nicotinoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-116)

    [1024] ##STR00317##

    [1025] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that nicotinic acid was used instead of 3,3-dimethyl-1-butanoic acid. 71.1 mg of white solid was obtained, with a yield of 55%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.76-8.62 (m, 2H), 8.12 (s, 1H), 7.82 (dd, J=36.0, 8.3 Hz, 2H), 7.63 (d, J=8.8 Hz, 1H), 7.43-7.32 (m, 2H), 7.14 (ddd, J=36.9, 18.4, 7.5 Hz, 5H), 6.98-6.88 (m, 3H), 4.48 (q, J=7.1 Hz, 2H), 4.23-3.97 (m, 2H), 3.86-3.49 (m, 4H), 3.40-3.20 (m, 2H), 3.07-2.65 (m, 3H), 2.64-2.50 (m, 4H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 167.9, 159.8, 155.8, 151.0, 150.8, 148.1, 143.1, 138.0, 135.7, 135.0, 134.2, 131.6, 130.1, 129.6, 129.4, 128.5, 128.5, 126.8, 126.5, 125.5, 124.8, 123.4, 123.0, 122.1, 113.0, 61.6, 51.6, 34.6, 14.4, 9.4.

    Example 247

    ethyl 3-methyl-5-(N-phenethyl-N-(2-(4-pyridineformylpiperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M10-117)

    [1026] ##STR00318##

    [1027] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 2-pyridinecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 69.5 mg of white solid was obtained, with a yield of 53%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.61 (d, J=4.6 Hz, 1H), 8.15 (s, 1H), 7.89 (d, J=10.5 Hz, 1H), 7.82 (t, J=8.5 Hz, 1H), 7.70-7.59 (m, 2H), 7.36 (t, J=6.8 Hz, 2H), 7.27-7.11 (m, 4H), 7.07 (t, J=7.1 Hz, 1H), 6.97 (t, J=8.7 Hz, 3H), 4.49 (q, J=7.1 Hz, 2H), 4.22-4.04 (m, 2H), 3.92-3.61 (m, 4H), 3.40-3.21 (m, 2H), 3.07-2.66 (m, 3H), 2.64-2.50 (m, 4H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 167.7, 159.9, 155.8, 154.1, 151.0, 148.4, 143.0, 138.1, 137.1, 136.0, 134.0, 130.4, 129.5, 129.3, 128.5, 126.8, 126.5, 125.6, 124.6, 124.5, 123.8, 122.8, 122.1, 112.9, 61.6, 53.1, 51.5, 47.8, 34.7, 14.4, 9.4.

    Example 248

    Ethyl 3-methyl-5-(N-phenethyl-N-(2-(4-(thiophene-2-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M10-118)

    [1028] ##STR00319##

    [1029] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 2-thiophenecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 28.4 mg of white solid was obtained, with a yield of 21%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.90 (dd, J=8.8, 1.8 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.47 (dd, J=5.0, 1.2 Hz, 1H), 7.37 (t, J=8.3 Hz, 1H), 7.32 (d, J=3.5 Hz, 1H), 7.25-7.13 (m, 4H), 7.13-7.04 (m, 2H), 6.97 (d, J=5.9 Hz, 3H), 4.50 (q, J=7.1 Hz, 2H), 4.21-3.68 (m, 6H), 3.41-3.18 (m, 2H), 3.01-2.67 (m, 3H), 2.67-2.49 (m, 4H), 1.48 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 163.7, 159.9, 155.8, 151.0, 138.1, 137.0, 135.9, 134.1, 130.3, 129.5, 129.4, 128.9, 128.6, 128.5, 126.8, 126.7, 126.5, 125.5, 124.7, 122.9, 122.1, 113.0, 61.6, 51.5, 34.7, 14.4, 9.4.

    Example 249

    Ethyl 3-methyl-5-(N-phenethyl-N-(2-(4-(thiophene-3-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M10-119)

    [1030] ##STR00320##

    [1031] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 3-thiophenecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 69.7 mg of white solid was obtained, with a yield of 53%. .sup.13C NMR (101 MHz, Chloroform-d) ? 165.8, 159.8, 155.8, 151.0, 143.1, 138.1, 136.3, 135.9, 134.1, 130.3, 129.5, 129.4, 128.5, 127.1, 126.8, 126.5, 126.0, 125.5, 124.6, 122.9, 122.1, 113.0, 61.6, 51.5, 34.7, 14.4, 9.4.

    Example 250

    (E)ethyl-5-(N-(2-(4-(but-2-enoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-120)

    [1032] ##STR00321##

    [1033] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that Trans-2-butenoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 67.3 mg of white solid was obtained, with a yield of 55%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.90 (dd, J=8.8, 1.7 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.36 (t, J=8.3 Hz, 1H), 7.22-7.12 (m, 4H), 7.08 (t, J=7.6 Hz, 1H), 7.00-6.93 (m, 3H), 6.93-6.86 (m, 1H), 6.33-6.25 (m, 1H), 4.50 (q, J=7.1 Hz, 2H), 4.22-4.00 (m, 2H), 3.89-3.29 (m, 5H), 3.20-3.08 (m, 1H), 2.96-2.66 (m, 3H), 2.66-2.49 (m, 4H), 1.91 (d, J=8.0 Hz, 3H), 1.48 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 165.8, 159.9, 155.8, 151.1, 143.1, 141.7, 138.1, 136.0, 134.1, 130.3, 129.5, 129.4, 128.5, 126.8, 126.5, 125.6, 124.6, 122.8, 122.1, 121.5, 113.0, 61.6, 51.5, 34.7, 18.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.38N.sub.3O.sub.6S: 616.2476, found 616.2479.

    Example 251

    Ethyl 5-(N-(2-(4-(furan-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate M10-121)

    [1034] ##STR00322##

    [1035] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 2-furancarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 106.2 mg of white solid was obtained, with a yield of 83%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.90 (d, J=8.0 Hz, 1H), 7.65 (d, J=8.2 Hz, 1H), 7.51 (s, 1H), 7.43-7.31 (m, 1H), 7.24-6.88 (m, 9H), 6.50 (s, 1H), 4.50 (q, J=7.3 Hz, 2H), 4.22-3.67 (m, 6H), 3.41-3.22 (m, 2H), 3.08-2.84 (m, 2H), 2.78-2.42 (m, 5H), 1.47 (t, J=7.2 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 159.3, 155.8, 151.0, 147.9, 143.7, 143.1, 138.1, 136.0, 134.0, 130.4, 129.5, 129.4, 128.5, 126.8, 126.5, 125.5, 124.6, 122.8, 122.1, 116.4, 113.0, 111.3, 61.6, 51.5, 34.7, 14.4, 9.4.

    Example 252

    Ethyl 5-(N-(2-(4-(cyclopentanecarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-122)

    [1036] ##STR00323##

    [1037] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that cyclopentylcarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 104.5 mg of yellow liquid product was obtained, with a yield of 810%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.6 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.33 (td, J=7.7, 1.6 Hz, 1H), 7.22-7.09 (m, 4H), 7.06 (td, J=7.6, 1.5 Hz, 1H), 6.94 (ddd, J=8.8, 5.5, 1.5 Hz, 2H), 4.47 (q, J=7.1 Hz, 2H), 4.16-3.95 (m, 2H), 3.62-3.52 (m, 2H), 3.46-3.33 (m, 2H), 3.15-3.02 (m, 1H), 2.95-2.64 (m, 4H), 2.62-2.48 (m, 4H), 1.95-1.65 (m, 8H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 174.8, 159.9, 155.8, 151.0, 143.0, 138.1, 136.0, 134.0, 130.3, 129.4, 129.3, 128.4, 128.4, 126.8, 126.4, 125.5, 124.5, 122.7, 122.1, 112.9, 61.6, 58.2, 51.4, 41.1, 34.6, 30.0, 26.0, 18.3, 14.4, 9.4.

    Example 253

    Ethyl 5-(N-(2-(4-(5-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-123)

    [1038] ##STR00324##

    [1039] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 5-bromo-2-thiophenecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 104.7 mg of white solid was obtained, with a yield of 71%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (d, J=1.5 Hz, 1H), 7.90 (d, J=10.5 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.38 (t, J=7.7 Hz, 1H), 7.20 (dd, J=10.4, 7.8 Hz, 4H), 7.09 (d, J=4.0 Hz, 2H), 7.04 (d, J=3.9 Hz, 1H), 6.96 (t, J=8.8 Hz, 3H), 4.51 (q, J=7.1 Hz, 2H), 4.20-3.69 (m, 6H), 3.39-3.23 (m, 2H), 3.03-2.83 (m, 2H), 2.83-2.46 (m, 5H), 1.49 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.4, 159.9, 155.9, 151.0, 143.1, 138.8, 138.0, 135.8, 134.2, 130.2, 129.7, 129.6, 129.4, 128.5, 128.5, 126.8, 126.6, 125.5, 124.8, 122.9, 122.1, 116.7, 113.0, 61.6, 51.6, 34.7, 14.4, 9.4.

    Example 254

    Ethyl 5-(N-(2-(4-(1H-pyrrole-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-124)

    [1040] ##STR00325##

    [1041] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 2-pyrrolecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 125.2 mg of white solid was obtained, with a yield of 98%. .sup.1H NMR (400 MHz, Chloroform-d) ? 9.62 (s, 1H), 8.18 (s, 1H), 7.92 (d, J=10.3 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.37 (t, J=8.0 Hz, 2H), 7.25-7.14 (m, 4H), 7.09 (t, J=7.3 Hz, 1H), 7.02-6.93 (m, 4H), 6.54 (s, 1H), 6.32-6.23 (m, 1H), 4.51 (q, J=7.1 Hz, 2H), 4.25-3.76 (m, 6H), 3.38-3.20 (m, 2H), 2.99-2.87 (m, 2H), 2.80-2.52 (m, 5H), 1.49 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 161.8, 159.9, 155.8, 151.1, 143.1, 138.14, 136.0, 134.1, 130.4, 129.5, 129.4, 128.5, 128.5, 126.8, 126.5, 125.6, 124.6, 122.8, 122.1, 121.0, 113.0, 112.2, 110.0, 109.6, 61.6, 52.5, 51.5, 34.7, 14.4, 9.4.

    Example 255

    ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-125)

    [1042] ##STR00326##

    [1043] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 3-bromo-2-thiophenecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 97.5 mg of white solid was obtained, with a yield of 66%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.5 Hz, 1H), 7.89 (dd, J=8.8, 1.8 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.38 (q, J=5.4, 4.4 Hz, 2H), 7.25-7.14 (m, 4H), 7.10 (t, J=7.6 Hz, 1H), 7.02-6.92 (m, 4H), 4.51 (q, J=7.1 Hz, 2H), 4.21-3.99 (m, 2H), 3.89-3.22 (m, 6H), 3.01-2.85 (m, 2H), 2.81-2.51 (m, 5H), 1.49 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.2, 159.9, 155.8, 151.0, 143.1, 138.1, 135.9, 134.1, 132.0, 130.3, 130.2, 129.5, 129.4, 128.5, 127.3, 126.8, 126.6, 125.5, 124.7, 122.9, 122.1, 113.0, 109.7, 61.6, 51.5, 34.7, 14.4, 9.4.

    Example 256

    Ethyl 5-(N-(2-(4-(3-chlorothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-126)

    [1044] ##STR00327##

    [1045] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 3-chloro-2-thiophenecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 97.5 mg of white solid was obtained, with a yield of 71%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (d, J=1.6 Hz, 1H), 7.89 (dd, J=8.8, 1.9 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.43-7.33 (m, 2H), 7.26-7.13 (m, 4H), 7.09 (d, J=7.7 Hz, 1H), 7.01-6.91 (m, 4H), 4.51 (q, J=7.1 Hz, 2H), 4.21-4.03 (m, 2H), 3.91-3.51 (m, 4H), 3.41-3.23 (m, 2H), 2.99-2.83 (m, 2H), 2.78-2.52 (m, 5H), 1.49 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 161.7, 159.9, 155.8, 151.0, 143.1, 138.1, 135.9, 134.1, 130.3, 130.1, 129.5, 129.4, 128.5, 127.7, 126.8, 126.6, 125.5, 124.7, 124.0, 122.9, 122.1, 113.0, 61.6, 51.5, 34.7, 14.4, 9.4.

    Example 257

    Ethyl 5-(N-(2-(4-(4-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-127)

    [1046] ##STR00328##

    [1047] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 4-bromo-2-thiophenecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 96.6 mg of white solid was obtained, with a yield of 66%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (d, J=1.5 Hz, 1H), 7.90 (dd, J=8.8, 1.8 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.42-7.34 (m, 1H), 7.26-7.14 (m, 5H), 7.12 (s, 1H), 6.96 (d, J=23.0 Hz, 3H), 4.51 (q, J=7.1 Hz, 2H), 4.18-3.68 (m, 6H), 3.40-3.26 (m, 2H), 3.00-2.70 (m, 3H), 2.65-2.53 (m, 4H), 1.49 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.2, 159.9, 155.9, 151.1, 143.1, 138.4, 138.0, 135.8, 134.2, 131.0, 130.1, 129.6, 129.4, 128.5, 128.5, 126.8, 126.6, 126.1, 125.5, 124.7, 122.9, 122.2, 113.0, 109.4, 61.6, 51.6, 34.6, 14.4, 9.4.

    Example 258

    Ethyl 5-(N-(2-(4-(5-chlorothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-128)

    [1048] ##STR00329##

    [1049] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 5-chloro-2-thiophenecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 101.5 mg of white solid was obtained, with a yield of 74%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (d, J=1.6 Hz, 1H), 7.90 (dd, J=8.8, 1.8 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.38 (t, J=8.3 Hz, 1H), 7.26-7.14 (m, 2H), 7.15-7.05 (m, 4H), 6.96 (t, J=8.7 Hz, 3H), 6.90 (d, J=3.9 Hz, 1H), 4.51 (q, J=7.1 Hz, 2H), 4.20-3.68 (m, 6H), 3.41-3.23 (m, 2H), 3.00-2.85 (m, 2H), 2.77-2.54 (m, 5H), 1.49 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.4, 159.9, 155.9, 151.0, 143.1, 138.0, 135.9, 135.8, 134.2, 134.1, 130.2, 129.6, 129.4, 128.6, 128.5, 128.5, 126.8, 126.6, 126.0, 125.5, 124.8, 122.9, 122.1, 113.0, 61.6, 51.6, 34.7, 14.4, 9.4.

    Example 259

    Ethyl 3-methyl-5-(N-phenethyl-N-(2-(4-(thiazole-5-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate (M10-129)

    [1050] ##STR00330##

    [1051] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that thiazole-5-carboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 115.4 mg of white solid was obtained, with a yield of 84%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.91 (s, 1H), 8.15 (d, J=1.6 Hz, 1H), 8.10 (s, 1H), 7.89 (dd, J=8.8, 1.9 Hz, 1H), 7.66 (d, J=8.8 Hz, 1H), 7.38 (t, J=8.4 Hz, 1H), 7.27-7.14 (m, 4H), 7.10 (t, J=7.6 Hz, 1H), 7.02-6.89 (m, 3H), 4.51 (q, J=7.1 Hz, 2H), 4.16-3.69 (m, 6H), 3.42-3.27 (m, 2H), 3.05-2.68 (m, 3H), 2.66-2.52 (m, 4H), 1.48 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 161.4, 159.9, 155.9, 155.1, 151.0, 143.8, 143.1, 138.0, 135.7, 134.3, 130.1, 129.6, 129.4, 128.5, 128.5, 126.8, 126.6, 125.5, 124.9, 123.0, 122.1, 113.0, 61.6, 51.7, 34.6, 14.4, 9.4.

    Example 260

    Ethyl 5-(N-(2-(4-(1H-pyrazole-3-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate M10-130)

    [1052] ##STR00331##

    [1053] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that pyrazole-3-carboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 84.3 mg of white solid was obtained, with a yield of 66%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.90 (d, J=8.7 Hz, 1H), 7.67-7.57 (m, 2H), 7.35 (t, J=7.4 Hz, 1H), 7.24-6.92 (m, 8H), 6.69 (s, 1H), 4.50 (q, J=7.1 Hz, 2H), 4.24-3.55 (m, 6H), 3.39-3.15 (m, 2H), 3.04-2.52 (m, 7H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.7, 160.0, 155.8, 150.9, 143.0, 138.1, 136.0, 133.9, 130.5, 129.5, 129.4, 128.5, 128.5, 126.8, 126.5, 125.6, 124.5, 122.7, 122.1, 113.0, 107.5, 61.7, 51.4, 34.7, 14.4, 9.4.

    Example 261

    Ethyl 3-methyl-5-(N-(2-(4-(oxazole-5-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-131)

    [1054] ##STR00332##

    [1055] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that oxazole-5-carboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 68.6 mg of white solid was obtained, with a yield of 54%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (s, 1H), 7.97 (s, 1H), 7.89 (dd, J=8.8, 1.6 Hz, 1H), 7.68-7.57 (m, 2H), 7.36 (t, J=7.6 Hz, 1H), 7.25-7.03 (m, 5H), 6.95 (t, J=7.4 Hz, 3H), 4.49 (q, J=7.1 Hz, 3H), 4.16-3.67 (m, 6H), 3.52-3.16 (m, 2H), 3.01-2.84 (m, 2H), 2.78-2.52 (m, 5H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.8, 157.4, 155.8, 151.5, 151.0, 145.2, 143.1, 138.02, 135.8, 134.2, 131.6, 130.2, 129.6, 129.4, 128.5, 1285, 126.8, 126.6, 125.5, 124.8, 122.9, 122.1, 113.0, 61.6, 51.6, 34.6, 14.4, 9.4.

    Example 262

    Ethyl 5-(N-(2-(4-(3,4-Dimethylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl) 3-methylbenzofuran-2-carboxylate (M10-132)

    [1056] ##STR00333##

    [1057] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 3,5-dimethylbenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 82.4 mg of white solid was obtained, with a yield of 30%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (d, J=1.9 Hz, 1H), 7.87 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.34 (td, J=7.6, 1.6 Hz, 1H), 7.23-7.02 (m, 8H), 6.98-6.85 (m, 3H), 4.47 (q, J=7.1 Hz, 2H), 4.23-3.11 (m, 8H), 3.07-2.59 (m, 1H), 2.58 (s, 3H), 2.28 (d, J=1.9 Hz, 6H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 170.8, 159.8, 155.8, 151.1, 143.1, 138.5, 138.1, 136.9, 136.0, 134.1, 133.2, 130.3, 129.5, 129.5, 129.4, 128.5, 128.4, 126.8, 126.5, 125.5, 124.6, 122.8, 122.1, 113.0, 61.6, 51.5, 34.7, 19.8, 19.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.39H.sub.42N.sub.3O.sub.6S: 680.2794, found 680.2798.

    Example 263

    Ethyl 5-(N-(2-(4-(2,6-Dimethoxybenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-133)

    [1058] ##STR00334##

    [1059] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 2,6-dimethoxybenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 58.7 mg of white solid was obtained, with a yield of 22%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (d, J=1.9 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.43-6.86 (m, 10H), 6.56 (d, J=8.4 Hz, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.34-4.01 (m, 2H), 3.82 (s, 8H), 3.44-3.11 (m, 4H), 2.58 (s, 7H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 165.5, 159.9, 156.7, 155.9, 151.1, 143.1, 138.2, 136.1, 133.8, 130.5, 130.4, 129.5, 129.4, 128.6, 128.5, 126.9, 126.6, 125.6, 124.4, 122.6, 122.1, 114.3, 113.0, 104.0, 61.6, 55.9, 53.4, 51.6, 51.3, 47.2, 41.9, 34.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.39H.sub.42N.sub.3O.sub.8S: 712.2693, found 712.2689.

    Example 264

    Ethyl 5-(N-(2-(4-(2-benzylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-134)

    [1060] ##STR00335##

    [1061] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 2-benzylbenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 57.5 mg of white solid was obtained, with a yield of 19%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.12 (s, 1H), 7.86 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.43-6.82 (m, 18H), 4.48 (q, J=7.1 Hz, 2H), 4.28-3.89 (m, 4H), 3.84-3.41 (m, 2H), 3.26-2.31 (m, 10H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 169.9, 159.9, 155.9, 143.1, 140.4, 138.4, 138.2, 136.1, 136.1, 131.0, 130.4, 129.4, 129.2, 128.6, 128.5, 126.8, 126.6, 126.5, 126.4, 126.3, 125.6, 122.1, 113.0, 61.7, 52.4, 51.5, 47.3, 41.8, 39.2, 34.8, 14.5, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.44H.sub.44N.sub.3O.sub.6S: 742.2951, found 742.2938.

    Example 265

    Ethyl 5-(N-(2-(4-(2,4,6-trimethylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-135)

    [1062] ##STR00336##

    [1063] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 2,4,6-trimethylbenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 21.2 mg of white solid was obtained, with a yield of 25%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.12 (d, J=1.9 Hz, 1H), 7.86 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.35 (td, J=7.7, 1.6 Hz, 1H), 7.23-7.02 (m, 5H), 6.96-6.90 (m, 3H), 6.85 (s, 2H), 4.48 (q, J=7.1 Hz, 2H), 4.34-3.53 (m, 4H), 3.39-3.09 (m, 4H), 2.58 (s, 7H), 2.26 (d, J=9.8 Hz, 9H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 170.0, 159.9, 155.9, 151.2, 143.1, 138.2, 138.1, 135.9, 134.1, 133.6, 133.2, 130.3, 129.6, 129.4, 128.6, 128.4, 126.9, 126.6, 125.6, 124.7, 122.8, 122.2, 113.0, 61.7, 53.6, 52.0, 51.6, 46.7, 41.7, 34.7, 21.1, 19.2, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.40H.sub.44N.sub.3O.sub.6S: 694.2951, found 694.2955.

    Example 266

    Ethyl 5-(N-(2-(4-(2-methoxybenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzo furan-2-carboxylate (M10-136)

    [1064] ##STR00337##

    [1065] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 2-methoxybenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 76.5 mg of white solid was obtained, with a yield of 56%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (d, J=1.9 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.35 (td, J=8.0, 1.7 Hz, 2H), 7.29-7.22 (m, 1H), 7.22-7.10 (m, 4H), 7.06 (td, J=7.6, 1.4 Hz, 1H), 7.01-6.88 (m, 5H), 4.48 (q, J=7.1 Hz, 2H), 4.25-4.00 (m, 2H), 3.94-3.51 (m, 5H), 3.44-3.10 (m, 4H), 3.07-2.46 (m, 7H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 167.9, 159.8, 155.8, 155.3, 151.1, 143.1, 138.1, 136.0, 133.9, 130.5, 130.4, 129.5, 129.4, 128.5, 128.5, 128.0, 126.8, 126.5, 125.7, 125.5, 124.5, 122.7, 122.1, 120.9, 112.9, 111.0, 61.6, 55.6, 53.2, 51.7, 51.4, 47.5, 42.1, 34.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.38H.sub.40N.sub.3O.sub.7S: 682.2587, found 682.2577.

    Example 267

    Ethyl 5-(N-(2-(4-(2,5-Dimethylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-137)

    [1066] ##STR00338##

    [1067] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 2,5-dimethylbenzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 28.2 mg of white solid was obtained, with a yield of 21%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.12 (d, J=1.9 Hz, 1H), 7.86 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.35 (td, J=7.7, 1.6 Hz, 1H), 7.23-7.02 (m, 7H), 6.99 (s, 1H), 6.93 (dd, J=7.8, 1.7 Hz, 3H), 4.48 (q, J=7.1 Hz, 2H), 4.34-3.51 (m, 4H), 3.48-3.07 (m, 4H), 3.05-2.41 (m, 7H), 2.30 (d, J=14.5 Hz, 6H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 170.5, 160.0, 156.0, 151.2, 143.2, 138.2, 136.1, 136.0, 135.7, 134.2, 130.9, 130.4, 130.4, 129.8, 129.6, 129.5, 128.6, 126.9, 126.7, 126.5, 125.6, 124.7, 122.9, 122.2, 113.1, 61.7, 53.5, 52.0, 51.6, 42.1, 34.7, 21.0, 18.7, 14.5, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.39H.sub.42N.sub.3O.sub.6S: 680.2794, found 680.2795.

    Example 268

    Ethyl 5-(N-(2-(4-(4-(phenylethynyl)benzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-138)

    [1068] ##STR00339##

    [1069] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 4-(phenylethynyl) benzoic acid was used instead of 3,3-dimethyl-1-butanoic acid. 128.3 mg of yellow solid was obtained, with a yield of 85%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (d, J=1.9 Hz, 1H), 7.87 (dd, J=8.8, 1.9 Hz, 1H), 7.64-7.51 (m, 5H), 7.43 (d, J=8.1 Hz, 2H), 7.38-7.28 (m, 4H), 7.23-7.03 (m, 5H), 7.00-6.85 (m, 3H), 4.47 (q, J=7.1 Hz, 2H), 4.26-3.94 (m, 2H), 3.87-3.46 (m, 4H), 3.27 (s, 2H), 2.59 (s, 7H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 169.8, 159.8, 155.8, 151.1, 143.1, 138.1, 135.8, 135.3, 134.2, 131.7, 131.7, 130.2, 129.6, 129.4, 128.6, 128.5, 128.4, 127.3, 126.8, 126.6, 125.5, 124.9, 124.8, 123.0, 122.9, 122.1, 113.0, 90.9, 88.7, 61.6, 51.6, 34.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.45H.sub.42N.sub.3O.sub.6S: 752.2794, found 752.2789.

    Example 269

    Ethyl 5-(N-(2-(4-(5-methylthiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-139)

    [1070] ##STR00340##

    [1071] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 5-methyl-2-thiophenecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 93.9 mg of yellow solid was obtained, with a yield of 23%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (d, J=1.9 Hz, 1H), 7.87 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.34 (td, J=7.6, 1.6 Hz, 1H), 7.22-7.02 (m, 6H), 6.95 (ddd, J=7.6, 5.7, 1.6 Hz, 3H), 6.69 (dd, J=3.7, 1.3 Hz, 1H), 4.47 (q, J=7.1 Hz, 2H), 4.20-3.60 (m, 6H), 3.21 (d, J=45.4 Hz, 2H), 2.99-2.51 (m, 7H), 2.49 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 163.7, 159.8, 155.8, 151.0, 143.9, 143.1, 138.1, 136.0, 134.6, 134.1, 130.3, 129.5, 129.5, 129.4, 128.5, 126.8, 126.5, 125.5, 125.2, 125.1, 124.6, 122.9, 122.1, 113.0, 61.6, 52.5, 51.5, 34.7, 15.3, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.38N.sub.3O.sub.6S.sub.2: 672.2202, found 672.2194.

    Example 270

    Ethyl 5-(N-(2-(4-(4-methylthiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-140)

    [1072] ##STR00341##

    [1073] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 4-methyl-2-thiophenecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 80.4 mg of yellow solid was obtained, with a yield of 20%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.14 (d, J=1.9 Hz, 1H), 7.88 (dd, J=8.7, 1.9 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.35 (td, J=7.7, 1.6 Hz, 1H), 7.22-7.00 (m, 7H), 6.94 (dd, J=7.7, 1.6 Hz, 3H), 4.47 (q, J=7.1 Hz, 2H), 4.27-3.57 (m, 6H), 3.29 (s, 2H), 3.03-2.44 (m, 7H), 2.27 (s, 3H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 163.9, 159.9, 155.9, 151.1, 143.1, 138.1, 137.4, 136.7, 136.0, 134.1, 131.2, 130.3, 129.6, 129.4, 128.6, 126.9, 126.6, 125.6, 124.7, 124.2, 122.9, 122.2, 113.0, 61.6, 52.5, 51.6, 34.7, 15.6, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.38N.sub.3O.sub.6S.sub.2: 672.2202, found 672.2191.

    Example 271

    Ethyl 5-(N-(2-(4-(3-methylthiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-141)

    [1074] ##STR00342##

    [1075] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 3-methyl-2-thiophenecarboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 119.5 mg of yellow solid was obtained, with a yield of 30%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (d, J=1.8 Hz, 1H), 7.87 (dd, J=8.7, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.35 (td, J=7.7, 1.6 Hz, 1H), 7.27 (d, J=4.9 Hz, 1H), 7.22-7.10 (m, 4H), 7.07 (td, J=7.6, 1.5 Hz, 1H), 6.95 (ddd, J=7.8, 4.6, 1.6 Hz, 3H), 6.84 (d, J=5.0 Hz, 1H), 4.48 (q, J=7.1 Hz, 2H), 4.21-3.51 (m, 6H), 3.26 (s, 2H), 2.59 (s, 7H), 2.28 (s, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 164.8, 159.9, 155.9, 151.0, 143.1, 138.1, 137.3, 135.9, 134.1, 130.3, 130.3, 129.8, 129.5, 129.4, 128.5, 126.8, 126.6, 126.0, 125.5, 124.7, 122.9, 122.1, 113.0, 61.6, 52.6, 51.5, 34.7, 14.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.38N.sub.3O.sub.6S.sub.2: 672.2202, found 672.2195.

    Example 272

    Ethyl 5-(N-(2-(4-(1H-imidazole-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-142)

    [1076] ##STR00343##

    [1077] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 1H-imidazole-2-carboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 50.5 mg of white solid was obtained, with a yield of 13%. .sup.1H NMR (400 MHz, Chloroform-d) ? 11.8 (s, 1H), 8.2 (d, J=1.9 Hz, 1H), 7.9 (dd, J=8.8, 1.9 Hz, 1H), 7.6 (d, J=8.8 Hz, 1H), 7.3 (td, J=7.6, 1.7 Hz, 1H), 7.2-7.1 (m, 6H), 7.1 (td, J=7.6, 1.7 Hz, 1H), 7.0-6.9 (m, 3H), 4.8 (d, J=141.8 Hz, 2H), 4.5 (q, J=7.1 Hz, 2H), 4.2-3.7 (m, 4H), 3.5-2.6 (m, 9H), 1.5 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 160.0, 158.1, 155.9, 151.1, 143.1, 141.4, 138.3, 136.1, 134.2, 130.5, 129.8, 129.6, 129.5, 128.6, 128.6, 127.0, 126.6, 125.7, 124.6, 122.9, 122.2, 118.5, 113.0, 61.7, 52.9, 52.5, 51.6, 47.2, 43.5, 34.9, 14.5, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.36N.sub.5O.sub.6S: 642.2386, found 642.2388.

    Example 273

    Ethyl 5-(N-(2-(4-(tetrahydrothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-143

    [1078] ##STR00344##

    [1079] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that tetrahydrothiophene-2-carboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 113.5 mg of white solid was obtained, with a yield of 28%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.9 Hz, 1H), 7.88 (dd, J=8.8, 1.9 Hz, 1H), 7.63 (d, J=8.8 Hz, 1H), 7.34 (td, J=7.6, 1.7 Hz, 1H), 7.23-7.03 (m, 5H), 6.97 (dd, J=17.6, 7.4 Hz, 3H), 4.48 (q, J=7.1 Hz, 2H), 4.16-3.73 (m, 4H), 3.71-3.24 (m, 4H), 3.12 (s, 1H), 3.05-2.75 (m, 4H), 2.74-2.42 (m, 6H), 2.30-2.21 (m, 1H), 2.10-1.87 (m, 2H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 170.8, 159.8, 155.7, 150.9, 142.9, 138.0, 135.8, 133.9, 130.3, 129.4, 129.3, 128.4, 128.4, 126.7, 126.4, 125.5, 124.6, 122.8, 122.0, 112.9, 61.5, 52.7, 51.6, 51.3, 46.3, 45.1, 42.5, 34.6, 33.4, 33.0, 31.3, 14.3, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.35H.sub.40N.sub.3O.sub.6S.sub.2: 662.2359, found 662.2357.

    Example 274

    Ethyl 5-(N-(2-(4-(1H-imidazole-4-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-144)

    [1080] ##STR00345##

    [1081] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 1H-imidazole-4-carboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 118.5 mg of white solid was obtained, with a yield of 31%. .sup.1H NMR (400 MHz, Chloroform-d) ? 11.55 (s, 1H), 8.13 (d, J=1.9 Hz, 1H), 7.87 (dd, J=8.8, 1.9 Hz, 1H), 7.65-7.57 (m, 2H), 7.46 (s, 1H), 7.32 (t, J=7.7 Hz, 1H), 7.21-6.82 (m, 8H), 4.45 (q, J=7.1 Hz, 2H), 4.35-3.59 (m, 6H), 3.30 (s, 2H), 2.91 (d, J=10.6 Hz, 2H), 2.76-2.42 (m, 5H), 1.43 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 163.4, 159.9, 155.8, 151.0, 143.0, 138.1, 135.9, 135.5, 133.9, 130.3, 129.5, 129.3, 128.5, 128.5, 126.8, 126.5, 125.6, 124.5, 122.8, 122.1, 112.9, 61.6, 51.4, 34.6, 29.6, 14.3, 9.4. HRMS (ESI) [M+H]+, theoretically calculated for C.sub.34H.sub.36N.sub.5O.sub.6S: 642.2386, found 642.2394.

    Example 275

    Ethyl 5-(N-(2-(4-(2-ethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-145)

    [1082] ##STR00346##

    [1083] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that 2-ethylbutyric acid was used instead of 3,3-dimethyl-1-butanoic acid. 138.2 mg of white solid was obtained, with a yield of 31%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.89 (d, J=8.8 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.35 (t, J=7.7 Hz, 1H), 7.23-7.03 (m, 5H), 6.95 (t, J=8.2 Hz, 3H), 4.48 (q, J=7.1 Hz, 2H), 4.11 (dd, J=13.4, 7.0 Hz, 2H), 3.92-3.33 (m, 5H), 3.22-2.48 (m, 9H), 1.86-1.39 (m, 7H), 0.89 (t, J=7.4 Hz, 6H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 174.5, 159.8, 155.8, 151.0, 143.1, 138.1, 136.0, 134.0, 130.4, 129.5, 129.4, 128.5, 128.5, 126.8, 126.5, 125.5, 124.6, 122.7, 122.1, 113.0, 61.6, 53.5, 52.1, 51.4, 46.3, 44.0, 42.2, 34.6, 25.6, 14.4, 12.1, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.44N.sub.3O.sub.6S: 646.2951, found 646.2940.

    Example 276

    Ethyl 5-(N-(2-(4-(isoxazole-5-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-146)

    [1084] ##STR00347##

    [1085] In accordance with the preparation method of ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-94), this example was implemented under the same condition except that isoxazole-5-carboxylic acid was used instead of 3,3-dimethyl-1-butanoic acid. 42.1 mg of white solid was obtained, with a yield of 21%.

    Example 277

    ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-147)

    [1086] ##STR00348##

    [1087] P-3-bromothiophene-2-carboxylic acid (223 mg, 1.078 mmol), EDCI (207 mg, 1.078 mmol), HOBt (146 mg, 1.078 mmol), and DIPEA (1.47 mmol, 242 ?L) were dissolved in 4 mL of DCM and stirred at room temperature. When it was found from the monitoring of the TLC that there was no raw material carboxylic acid left, ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (275 mg, 0.49 mmol) was added to the system. The reaction was performed overnight at room temperature. After the reaction was found to be completed from the monitoring of the TLC, the product was dissolved in 20 mL of water and then extracted three times with 20 mL of ethyl acetate. The organic phases were combined and then concentrated under reduced pressure and then separated by column chromatography (PE:EtOAc=3:1) to obtain 366.5 mg of white solid, with a yield of 99%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.90 (dd, J=8.8, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.45 (d, J=5.3 Hz, 2H), 7.34 (ddd, J=8.8, 7.0, 1.9 Hz, 1H), 7.28-7.10 (m, 5H), 7.08-6.92 (m, 6H), 4.48 (q, J=7.1 Hz, 2H), 4.19-2.95 (m, 6H), 2.80-2.48 (m, 6H), 2.28-1.57 (m, 4H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 159.9, 159.7, 155.8, 151.7, 143.0, 138.3, 136.2, 135.1, 133.8, 132.0, 130.6, 130.1, 129.3, 128.6, 128.5, 126.8, 126.5, 125.6, 124.2, 122.9, 122.1, 112.9, 110.0, 108.4, 61.6, 51.3, 47.0, 34.8, 14.4, 9.4.

    Example 278

    Ethyl 5-(N-(2-(3-bromothiophene-2-carbonyl)-2,8-diazospiro[4.5]decan-8-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-148)

    [1088] ##STR00349##

    [1089] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-132), this example was implemented under the same condition except that ethyl 5-(N-(2,8-diazospiro[4.5]decan-8-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate 98.0 mg of white solid was obtained, with a yield of 57%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.17 (s, 1H), 7.91 (t, J=8.1 Hz, 1H), 7.63 (d, J=8.6 Hz, 1H), 7.35 (s, 2H), 7.25-7.10 (m, 4H), 7.08-6.86 (m, 4H), 4.49 (q, J=6.9 Hz, 2H), 3.87 (s, 1H), 3.74 (s, 1H), 3.64-3.45 (m, 2H), 3.32 (s, 1H), 3.28-3.00 (m, 2H), 2.96-2.48 (m, 8H), 1.97-1.80 (m, 2H), 1.80-1.57 (m, 4H), 1.47 (t, J=7.0 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.0, 159.9, 155. 8, 151.8, 143.0, 138.3, 136.2, 133.7, 133.3, 130.5, 130.3, 129.3, 128.5, 128.4, 126.9, 126.8, 126.4, 125.6, 124.0, 122.6, 122.5, 122.1, 112.9, 109.4, 61.6, 58.2, 55.3, 51.1, 50.0, 46.5, 44.5, 39.4, 34.9, 34.7, 21.1, 14.4, 9.4.

    Example 279

    Ethyl 5-(N-(2-(7-(3-bromothiophene-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-149)

    [1090] ##STR00350##

    [1091] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-132), this example was implemented under the same condition except that ethyl 5-(N-(2,7-diazaspiro[3.5]nonan-2-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate. 220.2 mg of white solid was obtained, with a yield of 59%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.04 (s, 1H), 7.83 (d, J=8.6 Hz, 1H), 7.64 (d, J=8.6 Hz, 1H), 7.44-7.04 (m, 7H), 6.99 (s, 1H), 6.51 (s, 2H), 6.34 (d, J=7.6 Hz, 1H), 4.49 (q, J=6.7 Hz, 2H), 4.09-3.26 (m, 10H), 2.93-2.76 (m, 1H), 2.76-2.62 (m, 1H), 2.00-1.81 (m, 4H), 1.47 (t, J=6.9 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.1, 159.9, 156.0, 148.7, 143.0, 138.0, 134.0, 132.3, 130.2, 129.3, 129.3, 128.7, 128.6, 128.5, 127.4, 127.0, 126.7, 125.6, 123.8, 122.7, 116.9, 113.9, 112.7, 109.6, 62.4, 61.6, 52.9, 34.7, 34.2, 14.4, 9.4.

    Example 280

    Ethyl 5-(N-(2-(3-bromothiophene-2-carbonyl)-2,7-diazaspiro[3.5]nonan-7-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-150)

    [1092] ##STR00351##

    [1093] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-132), this example was implemented under the same condition except that ethyl 5-(N-(2,7-diazospiro[3.5]nonan-7-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate. 539.7 mg of white solid was obtained, with a yield of 68%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.15 (d, J=1.9 Hz, 1H), 7.89 (dd, J=8.7, 1.9 Hz, 1H), 7.62 (d, J=8.8 Hz, 1H), 7.38 (d, J=5.2 Hz, 1H), 7.36-7.28 (m, 1H), 7.21-7.09 (m, 4H), 7.09-6.96 (m, 3H), 6.97-6.90 (m, 2H), 4.49 (q, J=7.1 Hz, 2H), 4.15-3.74 (m, 7H), 3.12 (s, 2H), 2.84-2.47 (m, 6H), 1.89 (d, J=21.8 Hz, 4H), 1.47 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 163.2, 159.9, 155.8, 151.6, 143.0, 138.3, 136.2, 133.8, 131.4, 130.5, 130.1, 129.3, 129.3, 128.5, 128.5, 128.1, 126.8, 126.5, 125.6, 124.2, 122.7, 122.1, 112.9, 111.8, 61.6, 51.2, 49.8, 36.0, 34.7, 33.9, 14.4, 14.2, 9.4.

    Example 281

    Ethyl 5-(N-(2-(6-(3-bromothiophene-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-151)

    [1094] ##STR00352##

    [1095] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-132), this example was implemented under the same condition except that ethyl 5-(N-(2-(3,6-diazabicyclo[3.1.1]heptan-3-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate. 291 mg of white solid was obtained, with a yield of 30%. .sup.1H NMR (400 MHz, Chloroform-d) ? 7.94 (s, 1H), 7.73 (d, J=8.8 Hz, 1H), 7.59 (d, J=8.8 Hz, 1H), 7.42-7.10 (m, 6H), 7.02 (d, J=19.6 Hz, 3H), 6.78 (s, 1H), 6.55 (s, 1H), 4.65 (s, 2H), 4.47 (q, J=7.1 Hz, 2H), 4.12-3.90 (m, 2H), 3.74-3.30 (m, 3H), 2.91-2.48 (m, 6H), 1.53-1.34 (m, 5H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.8, 159.8, 155.9, 149.2, 143.0, 137.9, 131.5, 131.1, 129.5, 129.2, 129.0, 128.6, 128.6, 128.1, 127.3, 126.6, 125.6, 122.6, 121.7, 120.9, 112.6, 111.5, 61.6, 52.4, 49.9, 34.3, 26.9, 14.4, 9.3.

    Example 282

    (S)-ethyl-5-(N-(2-(4-(3-bromothiophene-2-carbonyl)-2-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-152)

    [1096] ##STR00353##

    [1097] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-132), this example was implemented under the same condition except that (S)ethyl-3-methyl-5-(N-(2-(2-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate. 398 mg of white solid was obtained, with a yield of 73%.

    Example 283

    (R)-ethyl-5-(N-(2-(4-(3-bromothiophene-2-carbonyl)-2-methylpiperazin-1-yl) phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-153)

    [1098] ##STR00354##

    [1099] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-132), this example was implemented under the same condition except that (R)ethyl-3-methyl-5-(N-(2-(2-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate. 354 mg of white solid was obtained, with a yield of 73%.

    Example 284

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-formyl)-1,4-diazepin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-154)

    [1100] ##STR00355##

    [1101] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-132), this example was implemented under the same condition except that ethyl 5-(N-(2-(1,4-diazepan-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate. 727.1 mg of white solid was obtained, with a yield of 53%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.23 (d, J=26.6 Hz, 1H), 7.88 (d, J=22.2 Hz, 2H), 7.72 (d, J=16.7 Hz, 1H), 7.41-7.05 (m, 6H), 7.03-6.81 (m, 4H), 4.39 (q, J=7.1 Hz, 2H), 4.17-2.93 (m, 12H), 2.58 (s, 3H), 2.09-1.63 (m, 2H), 1.36 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, DMSO) ? 162.3, 159.1, 155.2, 151.4, 142.3, 138.0, 135.3, 132.5, 132.0, 130.0, 129.7, 129.1, 128.9, 128.5, 128.3, 127.0, 126.2, 125.7, 122.8, 122.1, 113.2, 108.4, 61.2, 54.8, 50.5, 49.9, 46.7, 44.3, 33.7, 27.3, 14.1, 9.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.37N.sub.3O.sub.6S.sub.2Br: 750.1307, found 750.1295.

    Example 285

    Ethyl 5-(N-(2-(3-(3-bromothiophene-2-formyl)-3,8-diazepine[3.2.1]cyclooctan-8-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-155)

    [1102] ##STR00356##

    [1103] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-132), this example was implemented under the same condition except that ethyl 5-(N-(2-(3,8-diazabicyclo[3.2.1]oct-8-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate. 149.0 mg of white solid was obtained, with a yield of 43.4%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.16 (s, 1H), 7.90 (t, J=8.9 Hz, 1H), 7.65 (d, J=8.8 Hz, 1H), 7.35 (d, J=5.2 Hz, 1H), 7.21 (ddd, J=21.5, 14.9, 6.7 Hz, 4H), 7.06-6.66 (m, 6H), 4.73-3.98 (m, 6H), 3.89-3.58 (m, 2H), 3.55-3.08 (m, 2H), 2.86-2.46 (m, 5H), 2.14 (s, 1H), 2.02-1.74 (m, 3H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 163.9, 159.9, 156.0, 143.2, 138.1, 132.1, 130.4, 129.5, 129.0, 128.6, 127.2, 127.0, 126.7, 125.6, 125.3, 122.4, 120.4, 119.2, 113.1, 109.7, 109.4, 61.7, 34.4, 26.8, 14.4, 9.4, 1.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.37H.sub.37N.sub.3O.sub.6S.sub.2Br: 762.1307, found 762.1312.

    Example 286

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-formyl)-3-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-156)

    [1104] ##STR00357##

    [1105] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-132), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-(2-(3-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate. 1.751 mg of white solid was obtained, with a yield of 54.5%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.13 (d, J=1.8 Hz, 1H), 7.87 (dd, J=8.8, 1.9 Hz, 1H), 7.64 (t, J=8.4 Hz, 1H), 7.42-7.29 (m, 2H), 7.28-7.12 (m, 4H), 7.10-6.69 (m, 5H), 4.49 (qd, J=7.1, 1.9 Hz, 2H), 4.07 (dtd, J=13.3, 10.6, 5.8 Hz, 1H), 3.83 (tdd, J=13.3, 10.6, 5.8 Hz, 1H), 3.71-3.31 (m, 2H), 3.29-2.40 (m, 9H), 1.61 (d, J=7.2 Hz, 2H), 1.46 (td, J=7.1, 2.9 Hz, 5H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 162.2, 160.0, 156.0, 151.9, 151.4, 143.2, 134.5, 134.2, 130.3, 129.7, 128.7, 128.7, 128.6, 128.6, 127.1, 126.9, 126.8, 126.7, 124.8, 124.5, 122.4, 122.2, 113.1, 109.6, 61.7, 52.6, 51.5, 34.7, 34.4, 14.5, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.37N.sub.3O.sub.6S.sub.2Br: 750.1307, found 750.1309.

    Example 287

    Ethyl 5-(N-(2-(5-(3-bromothiophene-2-formyl)-2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate (M10-157)

    [1106] ##STR00358##

    [1107] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-132), this example was implemented under the same condition except that ethyl 5-(N-(2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 5-(N-(2-(4-aminopiperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate. 782 mg of white solid was obtained, with a yield of 40%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.19-7.52 (m, 3H), 7.41-7.15 (m, 5H), 7.10-6.69 (m, 4H), 6.65-6.27 (m, 2H), 5.37-4.34 (m, 4H), 4.27-3.31 (m, 6H), 3.06-2.40 (m, 5H), 2.21-1.89 (m, 2H), 1.45 (td, J=8.4, 7.2, 2.5 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 159.9, 156.1, 146.1, 143.0, 138.0, 130.7, 130.5, 129.9, 129.5, 128.8, 128.7, 128.7, 127.5, 127.2, 126.8, 126.7, 126.1, 125.7, 123.0, 122.8, 116.6, 113.0, 112.7, 110.0, 61.7, 58.6, 53.4, 33.9, 14.5, 9.5, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.35N.sub.3O.sub.6S.sub.2Br: 748.1151, found 748.1147.

    Example 288

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-toluothiophene-2-carboxylate (M10-158)

    [1108] ##STR00359##

    [1109] P-3-bromothiophene-2-carboxylic acid (167 mg, 0.814 mmol), EDCI (156 mg, 0.814 mmol), HOBt (110 mg, 0.814 mmol) and DIPEA (1.14 mmol, 183 ?L) were dissolved in 4 mL of DCM and stirred at room temperature. When it was found from the monitoring of the TLC that there was no raw material carboxylic acid left, ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzo[b]thiophene-2-carboxylate (206.7 mg, 0.37 mmol) was added to the system. The reaction was performed overnight at room temperature. After the reaction was found to be completed from the monitoring of the TLC, the product was dissolved in 20 mL of water and then extracted three times with 20 mL of ethyl acetate. The organic phases were combined and then concentrated under reduced pressure and then separated by column chromatography (PE:EtOAc=3:1) to obtain 203.3 mg of white solid, with a yield of 73%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.28 (s, 1H), 7.99-7.79 (m, 2H), 7.44-7.33 (m, 2H), 7.25-7.05 (m, 5H), 7.03-6.89 (m, 4H), 4.44 (q, J=7.0 Hz, 2H), 4.16-2.83 (m, 10H), 2.77 (s, 3H), 2.73-2.52 (m, 2H), 1.45 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.7, 162.2, 150.9, 144.1, 140.8, 139.9, 138.1, 137.0, 134.1, 132.0, 130.4, 130.2, 129.8, 129.5, 128.5, 127.3, 126.5, 124.9, 124.7, 123.7, 123.5, 122.8, 109.7, 61.6, 51.5, 34.7, 14.4, 13.2. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.35H.sub.35BrN.sub.3O.sub.5S.sub.3: 752.0917, found 752.0921.

    Example 289

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzo[b]thiophene-2-carboxylate (M10-159)

    [1110] ##STR00360##

    [1111] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-toluothiophene-2-carboxylate (M10-158), this example was implemented under the same condition except that ethyl 5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzo[b]thiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzo[b]thiophene-2-carboxylate. 79.4 mg of white solid was obtained, with a yield of 57%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.34 (s, 1H), 8.12 (s, 1H), 7.97 (d, J=8.5 Hz, 1H), 7.84 (d, J=8.5 Hz, 1H), 7.49-6.89 (m, 11H), 4.47 (q, J=7.0 Hz, 2H), 4.16-2.48 (m, 12H), 1.46 (t, J=7.0 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.2, 162.0, 150.9, 145.6, 138.3, 138.0, 137.7, 136.8, 134.1, 132.0, 130.4, 130.2, 129.5, 129.2, 128.6, 128.5, 127.3, 126.6, 125.4, 124.8, 124.8, 123.6, 122.9, 109.7, 62.1, 51.6, 34.7, 14.3. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.33BrN.sub.3O.sub.5S.sub.3: 738.0760, found 738.0760.

    Example 290

    Ethyl 6-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzo[b]thiophene-2-carboxylate (M10-160)

    [1112] ##STR00361##

    [1113] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-toluothiophene-2-carboxylate (M10-158), this example was implemented under the same condition except that ethyl 6-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzo[b]thiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzo[b]thiophene-2-carboxylate. 45.7 mg of white solid was obtained, with a yield of 62%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.34 (s, 1H), 8.12 (s, 1H), 7.98 (d, J=8.5 Hz, 1H), 7.81 (d, J=8.5 Hz, 1H), 7.37 (d, J=5.3 Hz, 2H), 7.19 (d, J=7.8 Hz, 4H), 7.10 (t, J=7.7 Hz, 1H), 6.99 (d, J=5.1 Hz, 4H), 4.47 (q, J=7.2 Hz, 2H), 4.11 (dd, J=21.1, 11.4 Hz, 2H), 3.88 (s, 1H), 3.56 (s, 3H), 3.26 (s, 2H), 3.02-2.49 (m, 4H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.2, 162.0, 150.9, 150.7, 141.7, 141.3, 138.8, 138.4, 138.0, 134.0, 132.0, 130.6, 130.2, 129.6, 129.4, 128.5, 127.2, 126.6, 126.0, 124.9, 123.5, 123.0, 122.9, 109.7, 62.1, 60.4, 51.6, 34.8, 14.3, 14.2. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.33BrN.sub.3O.sub.5S.sub.3: 738.0760, found 738.0770.

    Example 291

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-chloro-1H-indole-2-carboxylate (M10-161)

    [1114] ##STR00362##

    [1115] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-toluothiophene-2-carboxylate (M10-158), this example was implemented under the same condition except that ethyl 3-chloro-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)-1H-indole-2-carboxylate was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzo[b]thiophene-2-carboxylate. 179.5 mg of white solid was obtained, with a yield of 70%. .sup.1H NMR (400 MHz, Chloroform-d) ? 10.15 (s, 1H), 8.50-8.09 (m, 1H), 7.87-7.65 (m, 1H), 7.56-6.75 (m, 11H), 4.50 (q, J=8.2, 7.7 Hz, 2H), 4.09-2.46 (m, 12H), 1.48 (t, J=8.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.4, 160.5, 150.7, 138.1, 136.3, 134.2, 133.4, 131.9, 130.5, 130.2, 129.4, 128.5, 127.4, 126.5, 125.6, 124.9, 124.8, 124.7, 122.5, 121.6, 113.3, 113.2, 109.7, 61.9, 51.5, 34.6, 14.4. HR-MS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.33BrClN.sub.4O.sub.5S.sub.2: 755.0759, found 755.0770.

    Example 292

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-162)

    [1116] ##STR00363##

    [1117] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-toluothiophene-2-carboxylate (M10-158), this example was implemented under the same condition except that ethyl 5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzo[b]thiophene-2-carboxylate. 183.0 mg of white solid was obtained, with a yield of 47%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.17 (d, J=1.9 Hz, 1H), 7.85 (dd, J=8.8, 1.9 Hz, 1H), 7.64 (d, J=8.8 Hz, 1H), 7.56 (s, 1H), 7.32 (t, J=6.7 Hz, 2H), 7.20-7.01 (m, 5H), 6.93 (dd, J=6.5, 4.2 Hz, 4H), 4.44 (q, J=7.1 Hz, 2H), 4.28-3.43 (m, 6H), 3.25 (d, J=11.6 Hz, 2H), 2.97-2.44 (m, 4H), 1.42 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 162.1, 158.7, 156.9, 150.8, 147.8, 138.0, 136.5, 134.0, 131.9, 130.3, 130.1, 129.4, 128.4, 128.4, 127.3, 127.1, 126.6, 126.5, 124.7, 123.5, 122.8, 113.6, 113.0, 109.5, 61.9, 51.4, 34.5, 14.2. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.33N.sub.3O.sub.6S.sub.2Br: 722.0994, found 722.0997.

    Example 293

    Ethyl 6-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (M10-163)

    [1118] ##STR00364##

    [1119] In accordance with the preparation method of Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-toluothiophene-2-carboxylate (M10-158), this example was implemented under the same condition except that ethyl 3-methyl-6-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzo[b]thiophene-2-carboxylate. 92.2 mg of white solid was obtained, with a yield of 22%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.07-8.00 (m, 1H), 7.76 (dq, J=12.8, 8.1, 6.2 Hz, 2H), 7.35 (h, J=4.9 Hz, 2H), 7.24-7.04 (m, 5H), 7.02-6.80 (m, 4H), 4.51-4.43 (m, 2H), 4.34-3.11 (m, 9H), 2.89 (s, 2H), 2.71-2.40 (m, 5H), 1.50-1.42 (m, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 162.2, 159.9, 153.2, 150.9, 144.0, 139.9, 138.1, 134.2, 132.7, 132.1, 130.3, 130.2, 129.6, 128.6, 128.6, 127.3, 126.6, 124.9, 122.9, 122.3, 121.9, 112.4, 109.7, 61.7, 51.7, 34.7, 14.4, 9.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.35H.sub.35N.sub.3O.sub.6S.sub.2Br: 736.1151, found 736.1158.

    Example 294

    Ethyl 6-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-164)

    [1120] ##STR00365##

    [1121] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-toluothiophene-2-carboxylate (M10-158), this example was implemented under the same condition except that ethyl 6-(N-phenethyl-N-(2-(piperazin-1-yl) phenyl)sulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzo[b]thiophene-2-carboxylate. 386.9 mg of white solid was obtained, with a yield of 30%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.06 (d, J=1.4 Hz, 1H), 7.83-7.72 (m, 2H), 7.57 (d, J=1.4 Hz, 1H), 7.39-7.30 (m, 2H), 7.23-7.03 (m, 5H), 7.00-6.91 (m, 4H), 4.47 (q, J=7.1 Hz, 2H), 4.21-3.10 (m, 8H), 3.04-2.45 (m, 4H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 162.2, 158.9, 154.4, 150.9, 148.9, 139.7, 138.0, 134.1, 132.0, 130.7, 130.3, 130.2, 129.6, 128.6, 128.5, 127.3, 126.5, 125.0, 123.5, 122.9, 122.9, 113.1, 112.6, 109.7, 62.1, 51.7, 34.7, 14.3. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.33N.sub.3O.sub.6S.sub.2Br: 722.0994, found 722.0992.

    Example 295

    ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165)

    [1122] ##STR00366##

    [1123] P-(3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone (119.4 mg, 0.24 mmol), ethyl 5-(chlorosulfonyl)-3-methylbenzo[b]thiophene-2-carboxylate (90 mg, 0.29 mmol) and DIPEA (0.6 mmol, 99 ?L) were dissolved in 4 mL of DCM. The resulting solution was stirred at 40? C. to react until there was no raw material left under the monitoring of the TLC. After the reaction was found to be completed from the monitoring of the TLC, the product was dissolved in 20 mL of water and then extracted three times with 20 mL of ethyl acetate. The organic phases were combined and then concentrated under reduced pressure and then separated by column chromatography (PE:EtOAc=5:1) to obtain 33.0 mg of white solid, with a yield of 18%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.24 (s, 1H), 7.96-7.76 (m, 2H), 7.36 (d, J=5.1 Hz, 2H), 7.21 (d, J=7.3 Hz, 1H), 7.08 (d, J=8.3 Hz, 3H), 7.02-6.93 (m, 2H), 6.84 (d, J=8.3 Hz, 2H), 4.44 (q, J=7.1 Hz, 2H), 4.14-2.80 (m, 10H), 2.76 (s, 3H), 2.71-2.46 (m, 2H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.9, 162.4, 151.0, 144.3, 140.9, 140.0, 137.0, 136.6, 134.1, 132.5, 132.10, 130.7, 130.3, 130.1, 129.9, 129.7, 128.7, 127.4, 124.9, 123.8, 123.6, 123.0, 109.8, 61.8, 51.3, 34.1, 14.5, 13.3.

    Example 296

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-methylphenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-166)

    [1124] ##STR00367##

    [1125] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-((4-methylphenylethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 76.6 mg of white solid was obtained, with a yield of 29%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.26 (s, 1H), 7.95-7.76 (m, 2H), 7.35 (d, J=5.0 Hz, 2H), 7.20 (d, J=7.9 Hz, 1H), 7.08 (t, J=7.4 Hz, 1H), 7.03-6.91 (m, 4H), 6.82 (d, J=7.7 Hz, 2H), 4.43 (q, J=7.1 Hz, 2H), 4.13-2.85 (m, 10H), 2.76 (s, 3H), 2.69-2.45 (m, 2H), 2.24 (s, 3H), 1.44 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.8, 162.2, 150.9, 144.1, 140.9, 139.9, 137.0, 136.1, 134.9, 134.1, 132.0, 130.4, 130.2, 129.8, 129.5, 129.2, 128.4, 127.3, 125.0, 124.7, 123.7, 123.4, 122.8, 109.7, 61.6, 51.6, 34.2, 21.0, 14.4, 13.2.

    Example 297

    ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-(methoxycarbonyl)phenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-167)

    [1126] ##STR00368##

    [1127] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that methyl 4-(2-(4-(3-bromothiophene-2-carbonyl) piperazin-1-yl) phenyl)amino)ethyl)benzoate was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 79.8 mg of white solid was obtained, with a yield of 25%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.23 (d, J=1.7 Hz, 1H), 7.92 (d, J=8.5 Hz, 1H), 7.84 (dd, J=8.6, 1.8 Hz, 1H), 7.80-7.75 (m, 2H), 7.40-7.34 (m, 2H), 7.23 (dd, J=8.1, 1.5 Hz, 1H), 7.12 (d, J=1.5 Hz, 1H), 7.06-6.95 (m, 4H), 4.45 (q, J=7.1 Hz, 2H), 4.22-4.08 (m, 2H), 3.96-3.83 (m, 4H), 3.69-3.07 (m, 5H), 2.97-2.84 (m, 2H), 2.78-2.73 (m, 4H), 2.63 (q, J=7.8 Hz, 1H). .sup.13C NMR (101 MHz, Chloroform-d) ? 166.6, 162.7, 162.2, 150.9, 144.1, 143.5, 140.7, 139.9, 136.9, 133.9, 132.0, 130.7, 130.2, 130.0, 129.7, 128.5, 128.4, 127.3, 124.9, 124.8, 123.6, 123.4, 122.9, 109.7, 61.6, 52.0, 50.9, 34.6, 14.3, 13.2.

    Example 298

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-cyanophenyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-168)

    [1128] ##STR00369##

    [1129] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that 4-(2-((2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)amino)ethyl)benzonitrile was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 43.0 mg of white solid was obtained, with a yield of 14%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.24 (d, J=1.6 Hz, 1H), 7.94 (d, J=8.5 Hz, 1H), 7.83 (dd, J=8.6, 1.7 Hz, 1H), 7.47-7.34 (m, 4H), 7.22 (d, J=7.6 Hz, 1H), 7.14-6.96 (m, 5H), 4.45 (q, J=7.2 Hz, 2H), 4.12-3.00 (m, 8H), 2.91-2.57 (m, 7H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.7, 162.2, 150.8, 144.2, 143.7, 140.6, 139.9, 136.7, 133.8, 132.2, 131.9, 130.6, 130.2, 129.8, 129.3, 127.3, 124.9, 124.7, 123.7, 123.5, 123.0, 118.5, 110.5, 109.7, 61.7, 50.69, 34.9, 14.3, 13.2.

    Example 299

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-(trifluoromethyl)phenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-169)

    [1130] ##STR00370##

    [1131] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-((4-(trifluoromethyl)phenethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 51 mg of white solid was obtained, with a yield of 18%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.29 (d, J=1.7 Hz, 1H), 7.98-7.76 (m, 2H), 7.40 (dd, J=16.5, 6.8 Hz, 4H), 7.23 (dd, J=8.1, 1.5 Hz, 1H), 7.13-6.93 (m, 5H), 4.46 (q, J=7.1 Hz, 2H), 4.17-3.11 (m, 7H), 2.98-2.54 (m, 8H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.7, 162.2, 150.8, 144.2, 142.2, 140.7, 139.9, 136.8, 133.9, 132.0, 130.5, 130.2, 130.1, 129.7, 128.8, 127.3, 125.4, 125.4, 124.9, 124.7, 123.7, 123.5, 122.9, 109.7, 61.7, 51.0, 34.6, 14.3, 13.2.

    Example 300

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(3-methoxyphenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-170)

    [1132] ##STR00371##

    [1133] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-((3-methoxyphenethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 81 mg of white solid was obtained, with a yield of 36%.

    Example 301

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(3-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-171)

    [1134] ##STR00372##

    [1135] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-((3-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 38.8 mg of white solid was obtained, with a yield of 24%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.38-8.19 (m, 1H), 8.02-7.78 (m, 2H), 7.38 (d, J=4.7 Hz, 2H), 7.22 (d, J=7.9 Hz, 1H), 7.10 (q, J=7.1, 6.5 Hz, 3H), 7.01 (t, J=6.7 Hz, 2H), 6.91 (s, 1H), 6.84 (d, J=6.9 Hz, 1H), 4.46 (q, J=7.1 Hz, 2H), 4.18-3.14 (m, 8H), 2.98-2.47 (m, 7H), 1.47 (t, J=7.0 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.8, 162.2, 150.8, 144.2, 140.8, 140.1, 139.9, 136.9, 134.2, 134.0, 132.0, 130.5, 130.2, 129.7, 129.6, 128.7, 127.3, 126.6, 124.8, 123.7, 123.5, 122.8, 109.7, 61.7, 51.1, 34.3, 29.7, 14.3, 13.2.

    Example 302

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-chlorophenylethyl) sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-172)

    [1136] ##STR00373##

    [1137] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-((2-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 15 mg of white solid was obtained, with a yield of 13%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.36 (d, J=1.6 Hz, 1H), 8.03-7.86 (m, 2H), 7.37 (d, J=5.2 Hz, 2H), 7.25-7.15 (m, 2H), 7.14-7.06 (m, 4H), 6.99 (d, J=5.0 Hz, 2H), 4.46 (q, J=7.1 Hz, 2H), 4.17-3.18 (m, 8H), 2.96-2.60 (m, 7H), 1.47 (t, J=7.2 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.8, 162.2, 150.7, 144.1, 140.9, 139.9, 137.2, 135.7, 134.0, 133.9, 132.0, 130.8, 130.6, 130.2, 129.5, 128.1, 127.2, 126.9, 124.8, 124.7, 123.8, 123.5, 122.7, 109.7, 61.6, 49.2, 32.9, 14.3, 13.2.

    Example 303

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-methoxyphenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-173)

    [1138] ##STR00374##

    [1139] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-((2-methoxyphenethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 70.7 mg of white solid was obtained, with a yield of 28%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.32 (s, 1H), 7.98-7.83 (m, 2H), 7.37 (d, J=4.9 Hz, 2H), 7.22 (d, J=7.9 Hz, 1H), 7.16-7.05 (m, 2H), 7.05-6.96 (m, 2H), 6.87 (dd, J=7.4, 1.7 Hz, 1H), 6.78 (t, J=7.3 Hz, 1H), 6.69 (d, J=8.2 Hz, 1H), 4.45 (q, J=7.1 Hz, 2H), 4.16-3.77 (m, 2H), 3.72-3.43 (m, 6H), 3.37-2.75 (m, 8H), 2.69-2.53 (m, 2H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.8, 162.2, 157.4, 150.9, 144.0, 141.0, 139.8, 137.4, 134.2, 132.1, 130.6, 130.2, 130.2, 129.7, 129.3, 127.9, 127.2, 126.3, 125.0, 124.6, 123.8, 123.3, 122.7, 120.4, 110.2, 109.7, 61.6, 55.0, 49.5, 29.9, 14.3, 13.2.

    Example 304

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-nitrophenylethyl)sulfamoyl-3-toluothiophene-2-carboxylate (M10-174)

    [1140] ##STR00375##

    [1141] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-((2-nitrophenylethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 27.6 mg of white solid was obtained, with a yield of 15%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.37 (d, J=1.6 Hz, 1H), 8.04-7.90 (m, 2H), 7.83 (d, J=8.2 Hz, 1H), 7.53-7.43 (m, 1H), 7.39-7.30 (m, 3H), 7.23-7.15 (m, 2H), 7.10 (d, J=4.4 Hz, 2H), 6.98 (d, J=5.2 Hz, 1H), 4.46 (q, J=7.1 Hz, 2H), 4.30-3.11 (m, 7H), 3.05-2.68 (m, 8H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.7, 162.2, 150.4, 144.2, 140.9, 140.0, 137.2, 133.7, 133.3, 132.5, 132.0, 130.6, 130.2, 130.0, 129.6, 127.9, 127.2, 124.9, 124.8, 124.7, 123.7, 123.6, 122.7, 109.7, 61.7, 50.0, 32.9, 14.3, 13.2.

    Example 305

    ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(3-phenylpropyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-175)

    [1142] ##STR00376##

    [1143] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that ((3-bromothien-2-yl)(4-(2-((3-phenylpropyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 62.5 mg of white solid was obtained, with a yield of 30%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.28 (s, 1H), 8.01-7.80 (m, 2H), 7.42-7.31 (m, 2H), 7.23-6.90 (m, 9H), 4.45 (q, J=7.1 Hz, 2H), 3.90-3.02 (m, 8H), 2.89-2.61 (m, 5H), 2.62-2.38 (m, 2H), 1.46 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.8, 162.1, 150.8, 144.0, 140.7, 139.9, 137.3, 134.2, 132.0, 130.4, 130.2, 129.9, 129.4, 128.4, 128.1, 127.2, 126.1, 124.9, 124.8, 123.7, 123.5, 122.8, 109.6, 61.6, 49.4, 32.8, 29.4, 14.4, 13.2.

    Example 306

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)-3-toluothiophene-2-carboxylate (M10-176)

    [1144] ##STR00377##

    [1145] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (4-(2-aminophenyl)piperazin-1-yl)(3-bromothien-2-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 180.0 mg of white solid was obtained, with a yield of 93%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.31 (d, J=1.4 Hz, 1H), 8.03 (s, 1H), 7.91-7.81 (m, 2H), 7.66 (d, J=8.1 Hz, 1H), 7.38 (d, J=5.2 Hz, 1H), 7.21-6.92 (m, 4H), 4.42 (p, J=7.1 Hz, 2H), 3.92-3.24 (m, 4H), 2.80-2.68 (m, 3H), 2.53 (t, J=5.1 Hz, 4H), 1.42 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.6, 162.2, 144.4, 141.4, 140.6, 139.8, 136.0, 132.9, 131.7, 130.3, 130.1, 127.6, 126.7, 125.0, 123.9, 123.5, 123.0, 122.1, 119.4, 109., 61.7, 52.6, 14.3, 13.1.

    Example 307

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-(4-methoxyphenethyl)sulfamoyl)3-methylbenzothiophene-2-carboxylate (M10-177)

    [1146] ##STR00378##

    [1147] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-((4-methoxyphenethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 112.3 mg of white solid was obtained, with a yield of 31%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.25 (d, J=1.7 Hz, 1H), 7.90 (d, J=8.6 Hz, 1H), 7.83 (dd, J=8.5, 1.7 Hz, 1H), 7.39-7.30 (m, 2H), 7.20 (dd, J=8.2, 1.5 Hz, 1H), 7.08 (td, J=7.6, 1.5 Hz, 1H), 7.03-6.93 (m, 2H), 6.87-6.81 (m, 2H), 6.70-6.64 (m, 2H), 4.42 (q, J=7.1 Hz, 2H), 4.20-3.75 (m, 3H), 3.71 (s, 3H), 3.42 (d, J=122.1 Hz, 5H), 2.90 (s, 2H), 2.75 (s, 3H), 2.69-2.40 (m, 2H), 1.43 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 162.8, 162.2, 158.2, 150.9, 144.0, 140.8, 139.9, 137.1, 134.1, 132.1, 130.5, 130.2, 130.0, 129.9, 129.5, 129.4, 127.3, 125.0, 124.7, 123.7, 123.4, 122.8, 113.9, 109.7, 61.6, 55.2, 51.7, 33.7, 29.7, 14.4, 13.2, 1.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.37N.sub.3O.sub.6S.sub.3Br: 782.1028, found 782.1033.

    Example 308

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-(3-methoxyphenethyl)sulfamoyl)3-methylbenzothiophene-2-carboxylate (M10-178)

    [1148] ##STR00379##

    [1149] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-((3-methoxyphenethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 81.0 mg of white solid was obtained, with a yield of 36%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.26 (d, J=1.8 Hz, 1H), 7.91 (d, J=8.5 Hz, 1H), 7.83 (dd, J=8.5, 1.8 Hz, 1H), 7.40-7.31 (m, 2H), 7.20 (dd, J=8.1, 1.4 Hz, 1H), 7.12-6.91 (m, 4H), 6.64 (dd, J=8.5, 2.9 Hz, 1H), 6.58-6.46 (m, 2H), 4.43 (q, J=7.1 Hz, 2H), 4.18-3.74 (m, 3H), 3.70 (s, 3H), 3.66-2.81 (m, 7H), 2.76 (s, 3H), 2.60 (dt, J=35.8, 8.0 Hz, 2H), 1.43 (t, J=7.1 Hz, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 162.8, 162.3, 159.7, 151.0, 144.2, 141.0, 139.9, 139.7, 137.1, 134.2, 132.1, 130.5, 130.3, 129.9, 129.6, 129.6, 127.3, 125.0, 124.8, 123.8, 123.5, 122.9, 120.8, 114.6, 111.5, 109.7, 61.7, 55.2, 51.5, 34.7, 14.4, 13.3. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.37N.sub.3O.sub.6S.sub.3Br: 782.1028, found 782.1046.

    Example 309

    3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106)

    [1150] ##STR00380##

    [1151] Ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (170 mg, 0.26 mmol) was dissolved in a mixed solvent of ethanol (3 mL) and water (1 mL), and NaOH (31 mg, 0.78 mmol) was then added. The resulting solution was refluxed and stirred until it was found from the monitoring of the TLC that there was no raw material left. The reaction system was concentrated under reduced pressure to remove the ethanol out of the system. 5 mL of water was added to the system, and 1M diluted hydrochloric acid was then added dropwise until the pH showed acidity. The system was then stirred rapidly for 10 min, during which solid precipitated. The system was filtered by using a suction funnel and washed with water to obtain 168.6 mg of white solid, with a yield of 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.26 (s, 1H), 7.96-7.79 (m, 2H), 7.43-7.20 (m, 6H), 7.18-7.05 (m, 5H), 6.98 (d, J=7.1 Hz, 2H), 4.17-2.54 (m, 15H), 2.35 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 169.1, 160.7, 155.1, 150.4, 143.6, 139.2, 138.2, 135.4, 133.2, 132.8, 130.8, 129.3, 129.2, 129.1, 128.8, 128.5, 128.2, 127.0, 126.6, 126.2, 124.3, 122.8, 121.8, 113.0, 50.3, 34.0, 20.9, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.34N.sub.3O.sub.6S: 636.2174, found 636.2170.

    Example 310

    3-methyl-5-(N-(2-(4-(2-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S107)

    [1152] ##STR00381##

    [1153] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-(2-(4-(2-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 99.5 mg of white solid was obtained, with a yield of 87%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.23 (s, 1H), 7.96-7.74 (m, 2H), 7.43-7.21 (m, 5H), 7.17-7.04 (m, 6H), 6.97 (d, J=7.1 Hz, 2H), 4.14-2.53 (m, 15H), 2.21 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 169.0, 161.3, 155.5, 150.8, 138.6, 136.7, 135.7, 134.0, 133.7, 131.3, 130.6, 129.7, 129.6, 129.1, 128.9, 128.7, 126.9, 126.6, 126.2, 126.1, 124.8, 124.4, 123.2, 122.2, 113.4, 52.7, 51.4 (d, J=122.5 Hz), 41.7, 34.4, 19.0, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.34N.sub.3O.sub.6S: 636.2174, found 636.2155.

    Example 311

    3-methyl-5-(N-(2-(4-(3-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S108)

    [1154] ##STR00382##

    [1155] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-(2-(4-(3-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 50.3 mg of white solid was obtained, with a yield of 44%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.73 (s, 1H), 8.25 (s, 1H), 7.94-7.81 (m, 2H), 7.40-7.23 (m, 4H), 7.21-7.04 (m, 7H), 6.97 (s, 2H), 4.14-2.53 (m, 15H), 2.34 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 169.6, 161.1, 155.6, 150.9, 143.8, 138.6, 138.3, 136.3, 135.9, 133.7, 131.2, 130.5, 129.6, 128.9, 128.7, 127.8, 127.1, 126.6, 125.2, 124.8, 124.3, 123.2, 122.3, 113.5, 50.8, 34.4, 21.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.34N.sub.3O.sub.6S: 636.2174, found 636.2163.

    Example 312

    5-(N-(2-(4-(4-acetamidobenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S109)

    [1156] ##STR00383##

    [1157] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(4-Acetylaminobenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 127.6 mg of white solid was obtained, with a yield of 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.23 (s, 1H), 7.88 (q, J=8.7 Hz, 2H), 7.65 (d, J=8.0 Hz, 2H), 7.44-7.25 (m, 4H), 7.19-6.90 (m, 7H), 4.16-2.51 (m, 15H), 2.07 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 169.4, 169.1, 161.2, 155.6, 151.0, 141.0, 138.6, 135.7, 133.7, 131.0, 130.4, 129.7, 128.9, 128.7, 128.5, 127.0, 126.6, 124.8, 123.3, 122.3, 118.9, 113.5, 110.0, 52.3, 50.8, 34.3, 24.5, 9.5.

    Example 313

    3-methyl-5-(N-phenethyl-N-(2-(4-(4-(trifluoromethyl)benzoyl)piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylic acid F27-S110)

    [1158] ##STR00384##

    [1159] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(4-(4-(trifluoromethyl)benzoyl)piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 127.6 mg of white solid was obtained, with a yield of 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.26 (s, 1H), 7.87 (dd, J=24.6, 9.0 Hz, 4H), 7.66 (d, J=7.9 Hz, 2H), 7.38 (t, J=7.4 Hz, 1H), 7.29 (d, J=7.7 Hz, 1H), 7.21-7.02 (m, 5H), 6.98 (d, J=7.1 Hz, 2H), 4.21-2.69 (m, 10H), 2.59 (s, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 168.1, 161.3, 155.6, 150.9, 144.37, 140.43, 138.59, 135.70, 133.83, 131.02, 129.68, 129.65, 128.89, 128.66, 128.22, 127.0, 126.6, 125.9, 125.9, 124.8, 124.7, 123.2, 122.3, 113.5, 50.9, 34.3, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.31F.sub.3N.sub.3O.sub.6S: 690.1891, found 690.1889.

    Example 314

    5-(N-(2-(4-(4-cyanophenyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S111)

    [1160] ##STR00385##

    [1161] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(4-cyanophenyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 54.4 mg of white solid was obtained, with a yield of 56%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.19 (s, 1H), 7.95 (d, J=8.2 Hz, 2H), 7.84 (d, J=5.3 Hz, 2H), 7.48 (d, J=8.0 Hz, 2H), 7.31 (dd, J=30.1, 7.1 Hz, 2H), 7.18-7.00 (m, 5H), 6.97 (d, J=7.1 Hz, 2H), 4.14-2.66 (m, 13H), 2.58 (s, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 168.8, 167.8, 162.1, 155.3, 150.9, 138.9, 138.6, 137.9, 135.6, 135.3, 133.8, 133.0, 131.1, 130.1, 129.6, 128.9, 128.7, 128.1, 127.3, 126.6, 126.3, 124.8, 123.3, 121.9, 113.3, 50.8, 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.33N.sub.4O.sub.7S: 665.2075, found 665.2065.

    Example 315

    5-(N-(2-(4-(4-fluorobenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S112)

    [1162] ##STR00386##

    [1163] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(4-fluorobenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 67.1 mg of white solid was obtained, with a yield of 65%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25 (s, 1H), 7.88 (q, J=8.6 Hz, 2H), 7.57-7.43 (m, 2H), 7.42-7.21 (m, 4H), 7.20-7.03 (m, 5H), 6.98 (d, J=6.9 Hz, 2H), 4.13-2.69 (m, 11H), 2.58 (s, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 168.6, 163.0 (d, J=246.6 Hz), 161.4, 155.5, 150.9, 144.7, 138.6, 135.7, 133.8, 132.7, 131.2, 130.0 (d, J=8.4 Hz), 129.7 (d, J=12.0 Hz), 128.9, 128.7, 126.9, 126.6, 124.8, 124.3, 123.2, 122.2, 115.9, 115.7, 113.5, 50.8, 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.35H.sub.31FN.sub.3O.sub.6S: 640.1923, found 640.1909.

    Example 316

    Ethyl-(N-(2-(4-(4-((tert-butoxycarbonyl)amino)benzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate (F27-S113)

    [1164] ##STR00387##

    [1165] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl-(N-(2-(4-(4-((tert-butoxycarbonyl)amino)benzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 83.7 mg of white solid was obtained, with a yield of 72%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 9.59 (s, 1H), 8.23 (d, J=1.8 Hz, 1H), 8.00-7.77 (m, 2H), 7.55 (d, J=8.2 Hz, 2H), 7.40-7.31 (m, 3H), 7.28 (d, J=8.0 Hz, 1H), 7.12 (ddd, J=12.7, 8.2, 4.3 Hz, 4H), 7.03 (dd, J=7.9, 1.5 Hz, 1H), 6.99-6.94 (m, 2H), 4.15-2.70 (m, 12H), 2.59 (s, 3H), 1.49 (s, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 169.4, 161.5, 155.5, 153.1, 151.0, 141.3, 138.6, 135.6, 133.8, 130.9, 129.8, 129.6, 129.4, 128.9, 128.7, 128.6, 126.7, 126.6, 124.7, 123.2, 122.2, 117.9, 113.4, 110.0, 79.8, 52.3, 50.8, 34.3, 28.5, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.40H.sub.41N.sub.4O.sub.8S: 737.2651, found 737.2644.

    Example 317

    3-methyl-5-(N-(2-(4-(4-nitrobenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S114)

    [1166] ##STR00388##

    [1167] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-(2-(4-(4-nitrobenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 29.3 mg of white solid was obtained, with a yield of 53%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 9.38 (s, 1H), 8.31 (t, J=9.0 Hz, 1H), 8.23 (s, 1H), 8.21-8.14 (m, 1H), 7.92-7.84 (m, 2H), 7.71 (d, J=8.6 Hz, 1H), 7.45-7.32 (m, 1H), 7.33-7.23 (m, 1H), 7.19-6.92 (m, 7H), 4.20-2.70 (m, 11H), 2.63-2.54 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 167.6, 161.4, 155.6, 150.9, 150.6, 148.3, 142.7, 138.5, 135.3, 134.1, 133.8, 131.1, 129.9, 129.8, 128.9, 128.7, 126.9, 126.6, 125.3, 124.2, 124.1, 123.2, 122.4, 113.5, 51.1, 49.2, 43.8, 34.2, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.35H.sub.31N.sub.4O.sub.8S: 667.1868, found 667.1864.

    Example 318

    5-(N-(2-(4-(4-acetylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S115)

    [1168] ##STR00389##

    [1169] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(4-acetylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 66.4 mg of white solid was obtained, with a yield of 82%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 9.60 (s, 1H), 8.23 (s, 1H), 8.11-7.98 (m, 2H), 7.86 (t, J=7.7 Hz, 2H), 7.56 (d, J=8.2 Hz, 1H), 7.44-7.34 (m, 1H), 7.29 (t, J=6.6 Hz, 1H), 7.19-6.92 (m, 7H), 4.17-2.69 (m, 11H), 2.66-2.58 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 197.9, 168.6, 161.8, 155.4, 150.9, 140.6, 138.6, 138.5, 137.7, 135.5, 135.4, 134.1, 133.8, 131.1, 129.9, 129.6, 128.9, 128.8, 128.7, 127.6, 126.6, 124.8, 123.2, 122.1, 113.4, 50.8, 49.3, 43.7, 34.4, 27.3, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.37H.sub.34N.sub.3O.sub.7S: 664.2123, found 664.2110.

    Example 319

    3-methyl-5-(N-(2-(4-nicotinoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S116)

    [1170] ##STR00390##

    [1171] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-(2-(4-nicotinoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 37.2 mg of white solid was obtained, with a yield of 54%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.74-8.60 (m, 1H), 8.20 (s, 1H), 7.94-7.78 (m, 3H), 7.54-7.45 (m, 1H), 7.42-7.25 (m, 2H), 7.21-6.80 (m, 8H), 4.19-2.69 (m, 11H), 2.65-2.51 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 167.3, 161., 155.4, 150.9, 148.1, 145.9, 138.6, 135.5, 135.2, 133.8, 132.1, 131.1, 131.0, 129.9, 129.6, 128.9, 128.7, 126.6, 126.5, 124.8, 123.9, 123.2, 122.0, 113.3, 52.2, 50.8, 49.4, 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31N.sub.4O.sub.6S: 623.1970, found 623.1971.

    Example 320

    3-methyl-5-(N-phenethyl-N-(2-(4-pyridinecarbonylpiperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylic acid (F27-S117)

    [1172] ##STR00391##

    [1173] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(4-pyridineformylpiperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 47.1 mg of white solid was obtained, with a yield of 71%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.60 (d, J=4.6 Hz, 1H), 8.26 (s, 1H), 8.04-7.80 (m, 3H), 7.59 (d, J=7.8 Hz, 1H), 7.49 (dd, J=7.5, 4.9 Hz, 1H), 7.36 (t, J=6.8 Hz, 1H), 7.27 (d, J=7.2 Hz, 1H), 7.21-7.03 (m, 5H), 6.98 (d, J=6.9 Hz, 2H), 4.21-2.65 (m, 11H), 2.64-2.55 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 167.2, 161.2, 155.6, 154.3, 150.8, 148.8, 144.2, 139.1, 138.6, 137.8, 135.8, 133.7, 131.3, 129.6 (d, J=3.8 Hz), 128.9, 128.7, 127.0, 126.6, 125.3, 125.0, 124.8, 123.6, 123.2, 122.3, 113.5, 52.3 (d, J=81.1 Hz), 50.7, 44.9 (d, J=511.4 Hz), 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31N.sub.4O.sub.6S: 623.1970, found 623.1961.

    Example 321

    3-methyl-5-(N-phenethyl-N-(2-(4-(thiophene-2-carbonyl)piperazin-1-yl)phenyl) sulfamoyl)benzofuran-2-carboxylic acid (F27-S118)

    [1174] ##STR00392##

    [1175] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-(2-(4-(4-(3,3-dimethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 10.6 mg of white solid was obtained, with a yield of 40%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.20 (d, J=14.9 Hz, 1H), 7.86 (td, J=8.8, 5.7 Hz, 2H), 7.76 (d, J=5.0 Hz, 1H), 7.37 (dd, J=14.1, 5.8 Hz, 2H), 7.27 (d, J=7.8 Hz, 1H), 7.21-6.94 (m, 8H), 4.22-3.50 (m, 7H), 3.09-2.69 (m, 4H), 2.57 (s, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 168.1, 162.8, 155.5, 150.8, 145.5, 138.6, 137.5, 135.6, 133.8, 132.0, 131.2, 129.9, 129.6, 129.6, 128.9, 128.7, 127.5, 126.6, 124.8, 123.2, 122.1, 113.4, 110.0, 52.3, 50.8, 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.30N.sub.3O.sub.6S.sub.2: 628.1582, found 628.1580.

    Example 322

    3-methyl-5-(N-phenethyl-N-(2-(4-(thiophene-3-carbonyl)piperazin-1-yl)phenyl) sulfamoyl)benzofuran-2-carboxylic acid (F27-S119)

    [1176] ##STR00393##

    [1177] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(4-(thiophene-3-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 28.0 mg of white solid was obtained, with a yield of 42%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.22 (d, J=1.8 Hz, 1H), 7.94-7.82 (m, 2H), 7.79 (d, J=2.8 Hz, 1H), 7.62 (dd, J=5.0, 2.9 Hz, 1H), 7.42-7.32 (m, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.21 (d, J=5.0 Hz, 1H), 7.19-7.02 (m, 5H), 7.02-6.94 (m, 2H), 4.15-2.70 (m, 11H), 2.58 (d, J=3.5 Hz, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 165.0, 161.6, 155.5, 150.9, 138.6, 136.7, 135.6, 133.8, 131.1, 129.9, 128.9, 128.7, 127.8, 127.3, 127.0, 126.6, 124.8, 123.6, 123.2, 122.1, 113.4, 103.5, 52.5, 50.8, 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.30N.sub.3O.sub.6S.sub.2: 628.1582, found 628.1579.

    Example 323

    (E)-5-(N-(2-(4-(but-2-enoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S120)

    [1178] ##STR00394##

    [1179] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that (E)ethyl-5-(N-(2-(4-(but-2-enoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 41.5 mg of white solid was obtained, with a yield of 46%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25 (s, 1H), 7.89 (q, J=8.8 Hz, 2H), 7.36 (t, J=7.7 Hz, 1H), 7.25 (d, J=8.0 Hz, 1H), 7.12 (dd, J=13.0, 7.0 Hz, 4H), 7.03 (d, J=7.9 Hz, 1H), 6.97 (d, J=7.3 Hz, 2H), 6.70 (dd, J=14.6, 7.0 Hz, 1H), 6.52 (d, J=15.0 Hz, 1H), 4.16-3.54 (m, 6H), 3.20-2.67 (m, 5H), 2.59 (s, 4H), 1.85 (d, J=6.5 Hz, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.8, 161.4, 155.5, 151.0, 141.2, 138.6, 135.8, 133.8, 131.1, 129.7, 129.6, 128.9, 128.7, 126.8, 126.6, 124.8, 124.7, 124.3, 123.2, 122.4, 122.3, 113.5, 52.9, 50.8, 34.3, 18.2, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.32N.sub.3O.sub.6S: 586.2017, found 586.2007.

    Example 324

    5-(N-(2-(4-(furan-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S121)

    [1180] ##STR00395##

    [1181] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(furan-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 87.2 mg of white solid was obtained, with a yield of 85%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.20 (d, J=12.6 Hz, 1H), 7.89-7.80 (m, 2H), 7.44-7.32 (m, 1H), 7.30-7.24 (m, 1H), 7.19-6.95 (m, 8H), 6.63 (dd, J=3.4, 1.7 Hz, 1H), 4.15-3.52 (m, 6H), 3.19-2.72 (m, 5H), 2.64-2.54 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 167.3, 158.8, 155.4, 150.8, 147.4, 145.2, 138.6, 138.6, 134.1, 133.7, 131.2, 130.0, 129.6, 128.9, 128.7, 126.7, 126.6, 124.8, 123.2, 122.0, 122.0, 116.1, 113.3, 111.7, 50.8, 49.3, 43.8, 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.30N.sub.3O.sub.7S: 612.1810, found 612.1808.

    Example 325

    5-(N-(2-(4-(cyclopentanecarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S122)

    [1182] ##STR00396##

    [1183] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(cyclopentanecarbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 80.7 mg of white solid was obtained, with a yield of 82%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.75 (s, 1H), ? 8.28 (s, 1H), 7.99-7.83 (m, 2H), 7.36 (t, J=7.6 Hz, 1H), 7.25 (d, J=9.0 Hz, 1H), 7.19-7.02 (m, 5H), 6.97 (d, J=6.7 Hz, 2H), 4.20-3.24 (m, 6H), 3.10-2.65 (m, 6H), 2.60 (s, 4H), 1.79-1.43 (m, 8H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 173.9, 161.1, 155.6, 151.0, 143.9, 138.6, 136.0, 133.7, 131.2, 129.6, 128.9, 128.7, 127.1, 126.6, 125.2, 124.7, 123.1, 122.4, 113.5, 52.5 (d, J=87.1 Hz), 50.7, 45.8, 42.1, 34.4, 30.0, 26.1, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.36N.sub.3O.sub.6S: 614.2330, found 614.2326.

    Example 326

    5-(N-(2-(4-(5-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylic acid (F27-S123)

    [1184] ##STR00397##

    [1185] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(5-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 83.3 mg of white solid was obtained, with a yield of 74%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.23 (s, 1H), 7.88 (q, J=9.3, 8.7 Hz, 2H), 7.36 (t, J=7.4 Hz, 1H), 7.30-7.23 (m, 3H), 7.19-6.93 (m, 9H), 4.15-3.52 (m, 7H), 3.16-2.73 (m, 4H), 2.67-2.54 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.5, 161.4, 155.5, 150.9, 139.7, 138.6, 135.7, 133.8, 131.1, 131.0, 130.6, 129.8, 129.7, 128.9, 128.7, 126.8, 126.6, 124.8, 124.1, 123.3, 122.2, 116.1, 113.5, 52.2, 50.9, 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.29BrN.sub.3O.sub.6S.sub.2: 706.0687, found 706.0677.

    Example 327

    5-(N-(2-(4-(1H-pyrrole-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S124)

    [1186] ##STR00398##

    [1187] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(1H-pyrrole-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 58.6 mg of white solid was obtained, with a yield of 48%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 11.47 (s, 1H), 8.19 (s, 1H), 7.85 (q, J=8.8 Hz, 2H), 7.35 (t, J=6.9 Hz, 1H), 7.25 (d, J=7.9 Hz, 1H), 7.20-6.93 (m, 7H), 6.89 (s, 1H), 6.42 (s, 1H), 6.12 (s, 1H), 4.17-3.50 (m, 7H), 3.10-2.69 (m, 4H), 2.64-2.52 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.1, 161.9, 155.3, 150.9, 138.7, 135.4, 133.7, 131.2, 130.2, 129.6, 128.9, 128.7, 126.6, 126.1, 124.6, 124.6, 123.1, 121.8, 121.6, 113.2, 112.3, 108.8, 52.4, 50.7, 45.2, 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.31N.sub.4O.sub.6S: 611.1970, found 611.1971.

    Example 328

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylic acid (F27-S125)

    [1188] ##STR00399##

    [1189] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 74.1 mg of white solid was obtained, with a yield of 80%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.24 (s, 1H), 7.86 (q, J=9.5, 8.8 Hz, 2H), 7.79 (d, J=5.2 Hz, 1H), 7.36 (t, J=7.6 Hz, 1H), 7.26 (d, J=7.7 Hz, 1H), 7.11 (ddt, J=18.4, 12.7, 6.4 Hz, 6H), 6.98 (d, J=7.0 Hz, 2H), 4.10-3.77 (m, 4H), 3.62-2.68 (m, 9H), 2.62-2.52 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.6, 161.4, 155.5, 150.7, 138.6, 135.7, 133.7, 132.4, 131.3, 130.3, 129.7, 129.7, 129.3, 128.9, 128.7, 126.9, 126.6, 124.8, 123.2, 122.2, 113.4, 110.0, 109.2, 50.8, 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.29BrN.sub.3O.sub.6S.sub.2: 706.0687, found 706.0686.

    Example 329

    5-(N-(2-(4-(3-chlorothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylic acid F27-S126)

    [1190] ##STR00400##

    [1191] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-chlorothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 69.6 mg of white solid was obtained, with a yield of 75%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.19 (d, J=5.2 Hz, 1H), 7.89-7.77 (m, 3H), 7.44-7.32 (m, 1H), 7.27 (t, J=8.1 Hz, 1H), 7.18-6.91 (m, 8H), 4.13-2.71 (m, 11H), 2.66-2.53 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.9, 161.0, 155.4, 150.7, 150.6, 138.6, 138.6, 135.4, 135.0, 134.1, 133.8, 131.2, 130.4, 130.1, 130.0, 129.8, 129.6, 128.9, 128.7, 127.9, 126.6, 126.4, 125.3, 124.8, 123.2, 121.9, 50.9 (d, J=26.3 Hz), 49.4, 43.7, 34.3 (d, J=11.4 Hz), 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.29ClN.sub.3O.sub.6S.sub.2: 662.1192, found 662.1185.

    Example 330

    5-(N-(2-(4-(4-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylic acid (F27-S127)

    [1192] ##STR00401##

    [1193] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(4-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 65.3 mg of white solid was obtained, with a yield of 71%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.20 (d, J=7.7 Hz, 1H), 7.87 (dd, J=17.3, 6.4 Hz, 3H), 7.49 (s, 1H), 7.42-7.32 (m, 1H), 7.28 (d, J=7.7 Hz, 1H), 7.12 (dt, J=12.6, 7.1 Hz, 4H), 7.04 (d, J=7.1 Hz, 1H), 6.98 (d, J=6.9 Hz, 2H), 4.22-2.75 (m, 11H), 2.66-2.53 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.8, 161.4, 155.4, 151.0, 150.6, 139.1, 138.6, 138.6, 135.4, 135.1, 134.1, 133.9, 131.3, 130.9, 129.9, 129.6, 128.9, 128.7, 128.7, 127.7, 126.6, 126.6, 126.4, 124.8, 123.2, 122.1, 113.4, 108.8, 52.2, 50.9, 49.4, 43.8, 34.3, 34.24, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.29BrN.sub.3O.sub.6S.sub.2: 706.0687, found 706.0675.

    Example 331

    5-(N-(2-(4-(5-chlorothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylic acid (F27-S128)

    [1194] ##STR00402##

    [1195] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(5-chlorothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 65.2 mg of white solid was obtained, with a yield of 67%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.18 (d, J=7.1 Hz, 1H), 7.84 (d, J=9.1 Hz, 2H), 7.50-7.22 (m, 3H), 7.13 (dq, J=12.2, 7.1, 5.1 Hz, 5H), 7.08-7.00 (m, 1H), 6.98 (t, J=5.7 Hz, 2H), 4.16-3.49 (m, 4H), 3.33-2.95 (m, 6H), 2.87-2.73 (m, 1H), 2.67-2.53 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.2, 161.3, 155.3, 150.7 (d, J=23.0 Hz), 138.6 (d, J=6.8 Hz), 137.0, 135.3, 134.9, 134.1, 133.8, 132.4, 131.0, 130.2, 129.8, 129.6, 128.9, 128.7, 127.6, 126.6, 126.2, 125.3, 123.1, 121.9, 113.2, 51.0 (d, J=18.5 Hz), 49.4, 43.7, 34.3 (d, J=15.0 Hz), 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.29ClN.sub.3O.sub.6S.sub.2: 662.1192, found 662.1184.

    Example 332

    3-methyl-5-(N-phenethyl-N-(2-(4-(thiazole-5-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylic acid (F27-S129)

    [1196] ##STR00403##

    [1197] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-phenethyl-N-(2-(4-(thiazole-5-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 63.8 mg of white solid was obtained, with a yield of 58%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 9.25 (s, 1H), 8.21 (d, J=4.0 Hz, 1H), 7.92-7.81 (m, 2H), 7.43-7.33 (m, 1H), 7.28 (d, J=8.0 Hz, 1H), 7.18-7.07 (m, 4H), 7.03 (t, J=7.3 Hz, 1H), 6.97 (d, J=6.6 Hz, 2H), 4.13-3.58 (m, 4H), 3.35-2.97 (m, 6H), 2.84 (s, 1H), 2.65-2.54 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.7 (d, J=6.3 Hz), 161.0, 157.1, 155.5, 150.6, 144.2, 138.6, 135.5, 135.2, 134.1, 133.8, 132.8, 130.9, 130.0, 129.9, 129.7, 128.9, 128.7, 128.7, 126.6, 125.3, 123.2, 122.2, 113.4, 51.0, 49.3, 43.7, 34.2, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.29N.sub.4O.sub.6S.sub.2: 629.1534, found 629.1536.

    Example 333

    5-(N-(2-(4-(1H-pyrazole-3-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzo furan-2-carboxylic acid (F27-S130)

    [1198] ##STR00404##

    [1199] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(1H-pyrazole-3-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzo furan-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 49.8 mg of white solid was obtained, with a yield of 61%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.28-8.22 (m, 1H), 7.96-7.82 (m, 2H), 7.78 (d, J=1.9 Hz, 1H), 7.35 (t, J=7.6 Hz, 1H), 7.27 (d, J=7.9 Hz, 1H), 7.18-7.01 (m, 5H), 6.97 (d, J=6.8 Hz, 2H), 6.58 (d, J=2.3 Hz, 1H), 4.17-3.49 (m, 7H), 3.18-3.00 (m, 2H), 2.88-2.72 (m, 2H), 2.64-2.53 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.5, 161.3, 155.6, 151.0, 144.4, 138.6, 135.8, 133.7, 131.1, 129.7, 129.6, 128.9, 128.7, 126.9, 126.6, 124.7, 124.6, 123.2, 122.3, 113.5, 107.5, 50.7, 34.3, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.30N.sub.5O.sub.6S: 612.1922, found 612.1919.

    Example 334

    3-methyl-5-(N-(2-(4-(oxazole-5-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S131)

    [1200] ##STR00405##

    [1201] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 3-methyl-5-(N-(2-(4-(oxazole-5-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 60.0 mg of white solid was obtained, with a yield of 91%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.57 (s, 1H), 8.20 (d, J=7.3 Hz, 1H), 7.86 (q, J=9.7, 9.1 Hz, 2H), 7.73 (s, 1H), 7.45-7.32 (m, 1H), 7.30-7.23 (m, 1H), 7.17-6.88 (m, 7H), 4.16-2.92 (m, 10H), 2.87-2.69 (m, 1H), 2.65-2.53 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.8, 160.3, 157.3, 155.4, 153.6, 150.9, 150.6, 138.6, 138.6, 135.4, 135.1, 134.1, 133.9, 133.9, 130.9, 128.9, 128.7, 126.6, 126.4, 122.0, 113.3, 49.4, 43.8, 34.3, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.29N.sub.4O.sub.7S: 613.1762, found 613.1752.

    Example 335

    5-(N-(2-(4-(3,4-dimethylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S132)

    [1202] ##STR00406##

    [1203] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3,4-Dimethylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl) 3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 58.1 mg of white solid was obtained, with a yield of 59%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.22 (d, J=1.8 Hz, 1H), 7.92-7.81 (m, 2H), 7.41-7.30 (m, 1H), 7.26 (dd, J=8.1, 1.5 Hz, 1H), 7.22-7.02 (m, 8H), 7.00-6.94 (m, 2H), 4.26-3.40 (m, 6H), 3.26-2.57 (m, 6H), 2.56 (s, 3H), 2.25 (s, 6H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 169.2, 161.0, 155.1, 150.4, 138.2, 137.9, 136.4, 135.2, 133.2, 130.8, 129.3, 129.2, 129.1, 128.5, 128.2, 128.1, 126.4, 126.2, 124.4, 124.3, 122.8, 121.7, 113.0, 50.3, 33.9, 19.3, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.37H.sub.36N.sub.3O.sub.6S: 650.2325, found 650.2327.

    Example 336

    5-(N-(2-(4-(2,6-dimethoxybenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S133)

    [1204] ##STR00407##

    [1205] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(2,6-Dimethoxybenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 36.4 mg of white solid was obtained, with a yield of 69%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.24 (d, J=1.8 Hz, 1H), 7.92-7.80 (m, 2H), 7.41-7.26 (m, 2H), 7.22 (d, J=8.0 Hz, 1H), 7.17-6.99 (m, 5H), 6.96 (d, J=7.2 Hz, 2H), 6.67 (d, J=8.4 Hz, 2H), 4.23-3.60 (m, 10H), 3.17-2.67 (m, 6H), 2.64-2.51 (m, 5H). .sup.13C NMR (101 MHz, DMSO) ? 163.9, 160.7, 156.0, 155.1, 150.3, 138.2, 135.3, 133.0, 130.9, 130.3, 129.1, 128.4, 128.2, 126.6, 126.1, 124.6, 124.1, 122.5, 121.8, 113.9, 113.0, 104.1, 55.7, 52.4, 51.4, 50.1, 46.2, 41.1, 33.9, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.37H.sub.36N.sub.3O.sub.8S: 682.2223, found 682.2219.

    Example 337

    5-(N-(2-(4-(2-benzylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S134)

    [1206] ##STR00408##

    [1207] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(2-benzylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 38.3 mg of white solid was obtained, with a yield of 80%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.05 (d, J=22.4 Hz, 1H), 7.85-7.67 (m, 2H), 7.42-7.24 (m, 4H), 7.20-7.03 (m, 11H), 6.93 (d, J=29.9 Hz, 3H), 4.07-3.25 (m, 11H), 3.15-2.50 (m, 6H). .sup.13C NMR (101 MHz, DMSO) ? 168.5, 154.4, 140.2, 138.2, 138.0, 135.9, 130.6, 130.5, 129.0, 128.9, 128.4, 128.3, 128.2, 126.2, 126.0, 124.5, 120.5, 112.3, 46.5, 41.0, 34.0, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.42H.sub.38N.sub.3O.sub.6S: 712.2481, found 712.2490.

    Example 338

    5-(N-(2-(4-(2,4,6-trimethylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S135)

    [1208] ##STR00409##

    [1209] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(2-benzylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 39.1 mg of white solid was obtained, with a yield of 74%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.20 (d, J=1.8 Hz, 1H), 7.88-7.77 (m, 2H), 7.34 (td, J=7.6, 7.1, 1.7 Hz, 1H), 7.25 (dd, J=8.1, 1.6 Hz, 1H), 7.18-7.02 (m, 5H), 6.99-6.93 (m, 2H), 6.87 (s, 2H), 4.10-3.49 (m, 5H), 3.18-2.51 (m, 10H), 2.24 (s, 3H), 2.10 (s, 6H). .sup.13C NMR (101 MHz, DMSO) ? 168.3, 154.9, 150.4, 138.2, 137.3, 135.1, 133.3, 133.3, 132.9, 130.9, 129.5, 129.2, 128.4, 128.2, 127.9, 126.1, 124.4, 122.7, 121.5, 112.8, 52.5, 51.6, 50.4, 45.7, 40.8, 33.9, 20.6, 18.6, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.38H.sub.38N.sub.3O.sub.6S: 664.2481, found 664.2471.

    Example 339

    5-(N-(2-(4-(2-methoxybenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S136)

    [1210] ##STR00410##

    [1211] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(2-methoxybenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 46.2 mg of white solid was obtained, with a yield of 73%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.23 (d, J=1.9 Hz, 1H), 7.92-7.80 (m, 2H), 7.43-7.30 (m, 2H), 7.24 (d, J=8.0 Hz, 1H), 7.20-7.03 (m, 7H), 6.98 (q, J=7.2 Hz, 3H), 4.13-3.83 (m, 2H), 3.81-3.33 (m, 7H), 2.93-2.51 (m, 8H). .sup.13C NMR (101 MHz, DMSO) ? 166.5, 160.8, 155.1, 154.8, 150.4, 138.2, 135.3, 133.1, 130.9, 130.4, 129.2, 128.4, 128.2, 127.6, 126.5, 126.1, 125.5, 124.2, 121.8, 120.6, 113.0, 111.3, 55.4, 51.4, 50.2, 41.4, 33.9, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.34N.sub.3O.sub.7S: 652.2117, found 652.2118.

    Example 340

    5-(N-(2-(4-(2,5-Dimethylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S137)

    [1212] ##STR00411##

    [1213] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(2,5-Dimethylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 18.3 mg of white solid was obtained, with a yield of 79%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.03 (d, J=1.9 Hz, 1H), 7.81-7.69 (m, 2H), 7.38-7.30 (m, 1H), 7.28-7.21 (m, 1H), 7.12 (dq, J=13.8, 7.6, 7.0 Hz, 6H), 7.05-6.88 (m, 4H), 4.24-3.49 (m, 4H), 3.36-2.53 (m, 11H), 2.28 (s, 3H), 2.16 (s, 3H). .sup.13C NMR (101 MHz, DMSO) ? 168.7, 154.3, 150.4, 138.2, 136.2, 134.9, 134.0, 130.4, 130.0, 129.2, 129.0, 128.4, 128.2, 126.2, 126.1, 124.1, 120.5, 112.2, 52.0, 51.6, 50.0, 46.6, 41.2, 33.8, 20.4, 18.1, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.37H.sub.36N.sub.3O.sub.6S: 650.2325, found 650.2325.

    Example 341

    5-(N-(2-(4-(4-(phenylethynyl)benzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S138)

    [1214] ##STR00412##

    [1215] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(4-(phenylethynyl)benzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 82.3 mg of white solid was obtained, with a yield of 70%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.20 (d, J=1.9 Hz, 1H), 7.91-7.79 (m, 2H), 7.69-7.54 (m, 4H), 7.50-7.40 (m, 5H), 7.35 (td, J=7.7, 1.6 Hz, 1H), 7.27 (dd, J=8.2, 1.5 Hz, 1H), 7.17-6.93 (m, 7H), 4.29-3.72 (m, 3H), 3.69-3.27 (m, 4H), 3.25-2.53 (m, 8H). .sup.13C NMR (101 MHz, DMSO) ? 168.3, 154.9, 150.5, 138.1, 135.8, 135.0, 133.4, 131.5, 131.4, 130.5, 129.6, 129.2, 129.0, 128.8, 128.4, 128.2, 127.5, 126.2, 125.9, 124.3, 123.4, 122.8, 122.0, 121.5, 112.8, 90.5, 88.7, 50.4, 33.9, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.43H.sub.36N.sub.3O.sub.6S: 722.2325, found 722.2310.

    Example 342

    5-(N-(2-(4-(5-methylthiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S139)

    [1216] ##STR00413##

    [1217] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(5-methylthiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 76.0 mg of white solid was obtained, with a yield of 83%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.24 (d, J=1.9 Hz, 1H), 7.93-7.82 (m, 2H), 7.51-6.89 (m, 10H), 6.81 (d, J=3.6 Hz, 1H), 3.97 (d, J=74.9 Hz, 2H), 3.62 (d, J=30.4 Hz, 4H), 3.37-2.52 (m, 9H), 2.46 (s, 3H). .sup.13C NMR (101 MHz, DMSO) ? 162.2, 160.9, 155.1, 150.4, 143.4, 138.2, 135.3, 134.6, 133.3, 130.8, 129.5, 129.3, 129.1, 128.4, 128.2, 126.4, 126.2, 125.5, 124.3, 122.8, 121.7, 113.0, 51.9, 50.3, 34.0, 14.9, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.32N.sub.3O.sub.6S.sub.2: 642.1733, found 642.1740.

    Example 343

    5-(N-(2-(4-(4-methylthiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S140)

    [1218] ##STR00414##

    [1219] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(4-methylthiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 57.3 mg of white solid was obtained, with a yield of 77%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.21 (d, J=1.9 Hz, 1H), 7.92-7.81 (m, 2H), 7.50-7.01 (m, 10H), 6.98 (d, J=7.3 Hz, 2H), 4.15-3.49 (m, 7H), 3.06 (s, 2H), 2.79 (s, 2H), 2.57 (s, 4H), 2.24 (s, 3H). .sup.13C NMR (101 MHz, DMSO) ? 162.3, 155.0, 150.4, 138.2, 137.1, 136.7, 135.1, 133.3, 131.1, 130.6, 129.4, 129.2, 128.4, 128.2, 126.2, 124.6, 124.3, 122.8, 121.6, 112.9, 51.9, 50.4, 33.9, 15.3, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.32N.sub.3O.sub.6S.sub.2: 642.1733, found 642.1736.

    Example 344

    5-(N-(2-(4-(3-methylthiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S141)

    [1220] ##STR00415##

    [1221] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-methylthiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 78.4 mg of white solid was obtained, with a yield of 68%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.23 (d, J=1.8 Hz, 1H), 7.91-7.80 (m, 2H), 7.56 (d, J=5.0 Hz, 1H), 7.39-7.31 (m, 1H), 7.26 (dd, J=8.1, 1.5 Hz, 1H), 7.19-7.02 (m, 5H), 7.01-6.95 (m, 2H), 6.92 (d, J=5.0 Hz, 1H), 4.27-3.20 (m, 7H), 3.06-2.54 (s, 8H), 2.17 (s, 3H). .sup.13C NMR (101 MHz, DMSO) ? 163.4, 160.9, 155.1, 150.3, 138.2, 136.5, 135.2, 133.2, 130.8, 130.2, 129.7, 129.3, 129.1, 128.4, 128.2, 126.5, 126.4, 126.1, 124.3, 122.8, 121.7, 112.9, 51.9, 50.3, 33.9, 14.3, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.32N.sub.3O.sub.6S.sub.2: 642.1733, found 642.1741.

    Example 345

    5-(N-(2-(4-(1H-imidazole-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S142)

    [1222] ##STR00416##

    [1223] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(1H-imidazole-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 30.3 mg of white solid was obtained, with a yield of 63%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 12.90 (s, 1H), 8.22 (d, J=16.8 Hz, 1H), 7.96-7.79 (m, 2H), 7.74-7.45 (m, 1H), 7.42-6.89 (m, 10H), 4.48 (s, 1H), 4.17-3.58 (m, 3H), 3.54-2.57 (m, 11H). .sup.13C NMR (101 MHz, DMSO) ? 161.0, 157.4, 155.1, 150.4, 150.1, 140.8, 138.2, 138.1, 133.6, 133.2, 129.4, 129.4, 129.1, 128.4, 128.2, 126.3, 126.2, 126.2, 124.9, 124.2, 121.8, 121.7, 113.0, 50.2, 48.8, 43.3, 33.9, 33.8, 9.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.30N.sub.5O.sub.6S: 612.1917, found 612.1924.

    Example 346

    5-(N-(2-(4-(tetrahydrothiophene-2-formyl)piperazin-1-yl) phenyl)-N-phenethylsulfamoyl)3-methyl benzofuran-2-carboxylic acid (F27-S143)

    [1224] ##STR00417##

    [1225] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(tetrahydrothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 81.7 mg of white solid was obtained, with a yield of 75%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.71 (s, 1H), 8.26 (s, 1H), 7.94-7.82 (m, 2H), 7.39-7.31 (m, 1H), 7.26-7.19 (m, 1H), 7.17-7.01 (m, 5H), 7.01-6.93 (m, 2H), 4.19 (t, J=6.1 Hz, 1H), 3.96 (d, J=69.3 Hz, 2H), 3.41 (d, J=61.7 Hz, 5H), 3.13-2.65 (m, 6H), 2.59 (s, 4H), 2.32-1.74 (m, 4H). .sup.13C NMR (101 MHz, DMSO) ? 170.1, 160.7, 155.2, 150.4, 143.4, 138.2, 135.5, 133.3, 129.2, 129.2, 128.4, 128.2, 126.6, 126.1, 124.7, 124.3, 122.7, 121.9, 113.1, 51.4, 50.3, 45.7, 44.4, 41.9, 33.9, 32.6, 30.8, 9.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.34N.sub.3O.sub.6S.sub.2: 632.1889, found 632.1891.

    Example 347

    5-(N-(2-(4-(1H-imidazole-4-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S144)

    [1226] ##STR00418##

    [1227] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(1H-imidazole-4-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 73.5 mg of white solid was obtained, with a yield of 64%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.09 (s, 1H), 8.27 (d, J=1.9 Hz, 1H), 7.96-7.75 (m, 3H), 7.64 (s, 1H), 7.38-7.30 (m, 1H), 7.25 (d, J=8.0 Hz, 1H), 7.17-7.02 (m, 5H), 7.00-6.90 (m, 2H), 4.67-3.31 (m, 7H), 3.06 (s, 2H), 2.76 (d, J=12.8 Hz, 2H), 2.58 (s, 4H). .sup.13C NMR (101 MHz, DMSO) ? 161.7, 160.7, 155.2, 150.5, 143.3, 138.2, 138.1, 135.5, 133.2, 130.7, 129.1, 128.4, 128.2, 126.6, 126.1, 124.8, 124.2, 122.6, 121.9, 113.1, 52.2, 50.2, 33.9, 9.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.30N.sub.5O.sub.6S: 612.1917, found 612.1909.

    Example 348

    5-(N-(2-(4-(2-ethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S145)

    [1228] ##STR00419##

    [1229] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(2-ethylbutyryl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 88.6 mg of white solid was obtained, with a yield of 81%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25 (d, J=1.9 Hz, 1H), 7.93-7.81 (m, 2H), 7.38-7.30 (m, 1H), 7.23 (d, J=8.0 Hz, 1H), 7.17-7.02 (m, 5H), 7.00-6.93 (m, 2H), 4.25-3.28 (m, 7H), 2.98 (d, J=42.7 Hz, 2H), 2.70 (s, 2H), 2.63-2.55 (m, 5H), 1.57-1.42 (m, 2H), 1.41-1.28 (m, 2H), 0.78 (t, J=7.4 Hz, 6H). .sup.13C NMR (101 MHz, DMSO) ? 173.2, 160.9, 155.1, 150.5, 138.2, 135.4, 133.3, 130.7, 129.3, 129.2, 128.4, 128.2, 126.4, 126.1, 124.3, 122.6, 121.8, 113.0, 52.7, 51.8, 50.3, 45.5, 42.5, 41.5, 33.9, 25.1, 11.7, 9.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.38N.sub.3O.sub.6S: 616.2481, found 616.2484.

    Example 349

    5-(N-(2-(4-(isoxazole-5-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S146)

    [1230] ##STR00420##

    [1231] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(isoxazole-5-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 26.0 mg of white solid was obtained, with a yield of 16%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.72 (s, 1H), 8.66 (s, 1H), 8.25 (t, J=5.7 Hz, 1H), 7.86 (td, J=14.4, 12.4, 8.0 Hz, 2H), 7.49-6.78 (m, 10H), 4.18-3.64 (m, 3H), 3.61-3.36 (m, 3H), 3.04 (d, J=32.6 Hz, 2H), 2.76 (d, J=44.1 Hz, 2H), 2.57 (d, J=6.5 Hz, 4H), 2.48-2.30 (m, 1H). .sup.13C NMR (101 MHz, DMSO) ? 167.2, 160.6, 155.2, 155.2, 155.2, 150.0, 143.3, 138.1, 138.1, 135.4, 135.0, 133.6, 133.4, 128.4, 128.4, 128.2, 128.2, 128.1, 126.1, 124.8, 113.1, 50.6, 50.3, 48.8, 43.5, 33.8, 9.0. HRMS (ESI) [M+H]+, theoretically calculated for C.sub.32H.sub.29N.sub.4O.sub.7S: 613.1757, found 613.1747.

    Example 350

    5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S147)

    [1232] ##STR00421##

    [1233] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carboxamido)piperidin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 102.6 mg of white solid was obtained, with a yield of 60%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.24-8.09 (m, 2H), 7.87 (d, J=8.7 Hz, 1H), 7.82-7.76 (m, 2H), 7.39-7.30 (m, 1H), 7.26 (d, J=7.9 Hz, 1H), 7.21-7.01 (m, 5H), 6.95 (d, J=7.0 Hz, 2H), 4.21-2.86 (m, 8H), 2.67-2.52 (m, 4H), 2.02-1.51 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.7, 160.2, 155.0, 151.5, 138.7, 135.2, 134.1, 133.6, 131.7, 130.9, 130.7, 129.8, 129.4, 128.8, 128.8, 126.7, 125.3, 124.1, 122.8, 121.2, 119.1, 113.0, 110.2, 50.5, 47.2, 34.5, 32.3, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31BrN.sub.3O.sub.6S.sub.2: 720.0843, found 720.0836.

    Example 351

    5-(N-(2-(3-bromothiophene-2-carbonyl)-2,8-diazospiro[4.5]decan-8-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S148)

    [1234] ##STR00422##

    [1235] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(3-bromothiophene-2-carbonyl)-2,8-diazospiro[4.5]decan-8-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 51.1 mg of white solid was obtained, with a yield of 54%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.26 (s, 1H), 7.97-7.81 (m, 2H), 7.77 (d, J=5.0 Hz, 1H), 7.38-7.25 (m, 2H), 7.18-7.00 (m, 6H), 6.94 (s, 2H), 3.99 (d, J=68.4 Hz, 2H), 3.53 (s, 1H), 3.38 (s, 3H), 3.26-2.64 (m, 5H), 2.58 (s, 4H), 1.80 (s, 2H), 1.52 (s, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.3, 155.5, 151.8, 151.6, 144.3, 138.7, 136.2, 133.8, 133.5, 131.3, 130.4, 129.7, 129.5, 128.8, 128.7, 126.9, 126.6, 124.7, 124.3, 123.1, 122.2, 113.4, 108.7, 50.5, 49.9, 46.4, 44.5, 35.2, 34.6, 34.4, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.37H.sub.35BrN.sub.3O.sub.6S.sub.2: 760.1156, found 760.1144.

    Example 352

    5-(N-(2-(7-(3-bromothiophene-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S149)

    [1236] ##STR00423##

    [1237] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(7-(3-bromothiophene-2-carbonyl)-2,7-diazaspiro[3.5]nonan-2-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 88.7 mg of white solid was obtained, with a yield of 42%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.09 (d, J=8.6 Hz, 1H), 7.85 (d, J=8.8 Hz, 1H), 7.80-7.69 (m, 2H), 7.30-7.01 (m, 7H), 6.57-6.41 (m, 3H), 3.91-3.76 (m, 3H), 3.73-3.63 (m, 2H), 3.60-3.48 (m, 1H), 2.80-2.68 (m, 1H), 2.66-2.58 (m, 1H), 2.54 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.4, 161.3, 155.6, 148.9, 148.8, 144.5, 138.6, 134.1, 133.9, 133.3, 132.8, 130.3, 129.6, 129.4, 129.1, 128.9, 127.3, 126.8, 123.9, 122.7, 117.1, 114.1, 113.2, 109.0, 62.3, 52.4, 34.5, 34.0, 33.1, 31.8, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.33BrN.sub.3O.sub.6S.sub.2: 746.1000, found 746.0996.

    Example 353

    5-(N-(2-(3-bromothiophene-2-carbonyl)-2,7-diazaspiro[3.5]nonan-7-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S150)

    [1238] ##STR00424##

    [1239] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(3-bromothiophene-2-carbonyl)-2,7-diazaspiro[3.5]nonan-7-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 87.5 mg of white solid was obtained, with a yield of 29%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.26 (s, 1H), 7.99-7.77 (m, 3H), 7.36-7.28 (m, 1H), 7.26-7.00 (m, 7H), 6.92 (d, J=6.3 Hz, 2H), 4.21-3.52 (m, 9H), 3.15-2.83 (m, 2H), 2.71-2.53 (m, 4H), 1.88-1.63 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.5, 161.1, 155.6, 151.7, 143.8, 138.6, 136.2, 133.4, 131.5, 131.1, 130.5, 130.2, 129.6, 129.5, 128.8, 128.7, 127.0, 126.6, 125.2, 124.4, 123.2, 122.3, 113.5, 111.1, 50.6, 49.7, 35.8, 34.4, 33.8, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.36H.sub.33BrN.sub.3O.sub.6S.sub.2: 746.1000, found 746.0992.

    Example 354

    5-(N-(2-(6-(3-bromothiophene-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S151)

    [1240] ##STR00425##

    [1241] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(6-(3-bromothiophene-2-carbonyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 186.2 mg of white solid was obtained, with a yield of 64%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.05 (s, 1H), 7.90-7.66 (m, 3H), 7.37-6.96 (m, 8H), 6.88-6.65 (m, 2H), 4.61-4.40 (m, 2H), 4.03-3.71 (m, 3H), 3.68-3.47 (m, 2H), 2.82-2.44 (m, 6H), 1.90 (d, J=8.4 Hz, 1H), 1.25 (d, J=11.6 Hz, 1H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.9, 161.4, 155.6, 149.0, 144.7, 138.5, 133.9, 131.8, 131.2, 130.4, 129.8, 129.6, 129.0, 128.8, 127.2, 126.8, 124.3, 122.6, 121.1, 113.2, 111.3, 110.0, 63.6, 59.9, 51.7, 33.9, 28.5, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.29BrN.sub.3O.sub.6S.sub.2: 718.0687, found 718.0674.

    Example 355

    (S)-5-(N-(2-(4-(3-bromothiophene-2-carbonyl)-2-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S152)

    [1242] ##STR00426##

    [1243] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that (S) ethyl-5-(N-(2-(4-(3-bromothiophene-2-carbonyl)-2-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 250.7 mg of white solid was obtained, with a yield of 63%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.23 (s, 1H), 8.00-7.71 (m, 3H), 7.52-6.73 (m, 10H), 4.24-2.74 (m, 10H), 2.65-2.53 (m, 4H), 0.99-0.62 (m, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.3, 161.8, 155.4, 148.7, 145.6, 138.5, 138.4, 135.9, 133.1, 132.6, 132.3, 130.3, 129.9, 129.7, 129.3, 128.8 (d, J=6.3 Hz), 128.6 (d, J=6.6 Hz), 126.6, 125.2, 123.4, 122.1, 115.1, 113.4, 109.3, 53.0, 49.0, 43.6, 34.3, 34.1, 16.2, 9.6. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31BrN.sub.3O.sub.6S.sub.2: 720.0843, found 720.0840.

    Example 356

    (R)-5-(N-(2-(4-(3-bromothiophene-2-carbonyl)-2-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylic acid (F27-S153)

    [1244] ##STR00427##

    [1245] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that (R) ethyl-5-(N-(2-(4-(3-bromothiophene-2-carbonyl)-2-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 237.2 mg of white solid was obtained, with a yield of 67%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.21 (s, 1H), 7.95-7.69 (m, 3H), 7.48-6.76 (m, 10H), 4.29-2.70 (m, 10H), 2.66-2.52 (m, 4H), 0.96-0.67 (m, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.0, 161.6, 155.3, 148.7, 146.3, 138.4, 138.3, 134.5, 133.0, 132.1, 130.2, 130.0, 129.3, 128.7, 128.6, 126.5, 126.2, 125.1, 122.6, 121.8 (d, J=18.6 Hz), 113.3, 109.2, 53.0, 50.2, 43.6, 34.3, 34.1, 16.1, 14.9, 9.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31BrN.sub.3O.sub.6S.sub.2: 720.0843, found 720.0829.

    Example 357

    5-(N-(2-(4-(3-bromothiophene-2-formyl)-1,4-diazepin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S154)

    [1246] ##STR00428##

    [1247] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-formyl)-1,4-diazepin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 577.6 mg of white solid was obtained, with a yield of 85%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.19 (d, J=25.8 Hz, 1H), 7.97-7.63 (m, 3H), 7.37-6.80 (m, 10H), 4.23-2.94 (m, 11H), 2.57 (s, 4H), 2.08-1.70 (m, 2H). .sup.13C NMR (101 MHz, DMSO) ? 162.3, 160.9, 155.1, 138.1, 132.5, 129.7, 129.2, 129.1, 128.5, 128.3, 126.5, 126.2, 123.9, 122.8, 121.9, 113.0, 107.8, 54.6, 50.5, 33.7, 9.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31N.sub.3O.sub.6S.sub.2Br: 720.0838, found 720.0832.

    Example 358

    5-(N-(2-(3-(3-bromothiophene-2-formyl)-3,8-diazepine[3.2.1]cyclooctan-8-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S155)

    [1248] ##STR00429##

    [1249] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(3-(3-bromothiophene-2-formyl)-3,8-diazepine[3.2.1]cyclooctan-8-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 99.6 mg of white solid was obtained, with a yield of 69%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.24 (s, 1H), 7.93-7.81 (m, 2H), 7.78 (d, J=5.2 Hz, 1H), 7.30-7.20 (m, 1H), 7.20-7.06 (m, 4H), 7.06-6.97 (m, 3H), 6.91-6.86 (m, 2H), 4.55-3.52 (m, 6H), 3.06 (t, J=59.2 Hz, 3H), 2.55 (s, 4H), 2.03 (s, 1H), 1.85-1.51 (m, 3H). .sup.13C NMR (101 MHz, DMSO) ? 162.8, 161.0, 155.1, 138.1, 134.3, 131.6, 129.9, 129.4, 129.1, 128.7, 128.5, 128.3, 126.4, 126.2, 123.5, 122.2, 119.2, 113.0, 108.6, 56.7, 33.5, 26.3, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.35H.sub.31N.sub.3O.sub.6S.sub.2Br: 732.0838, found 732.0830.

    Example 359

    5-(N-(2-(4-(3-bromothiophene-2-formyl)-3-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S156)

    [1250] ##STR00430##

    [1251] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-formyl)-3-methylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 240.8 mg of white solid was obtained, with a yield of 62%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25-8.19 (m, 1H), 7.89-7.74 (m, 3H), 7.50-7.24 (m, 2H), 7.22-6.76 (m, 8H), 4.93-3.57 (m, 4H), 3.55-3.32 (m, 1H), 3.22-2.71 (m, 4H), 2.56 (d, J=8.8 Hz, 4H), 2.50-2.36 (m, 1H), 1.36 (dd, J=62.4, 6.8 Hz, 3H). .sup.13C NMR (101 MHz, DMSO) ? 161.1, 155.1, 151.1, 150.5, 138.1, 138.0, 135.0, 133.3, 131.9, 129.9, 129.3, 129.2, 128.5, 128.4, 128.3, 128.2, 126.3, 126.2, 124.4, 121.7, 112.9, 108.6, 51.3, 50.3, 33.9, 33.4, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31N.sub.3O.sub.6S.sub.2Br: 720.0838, found 720.0833.

    Example 360

    5-(N-(2-(5-(3-bromothiophene-2-formyl)-2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S157)

    [1252] ##STR00431##

    [1253] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(5-(3-bromothiophene-2-formyl)-2,5-diazabicyclo[2.2.1]hept-2-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 467.0 mg of white solid was obtained, with a yield of 68%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.62 (s, 1H), 8.18 (s, 1H), 7.98-7.57 (m, 3H), 7.31-6.73 (m, 8H), 6.51 (dd, J=34.7, 19.5 Hz, 2H), 4.96-4.10 (m, 2H), 4.04-3.06 (m, 7H), 2.76 (s, 1H), 2.45 (s, 3H), 1.81 (d, J=56.1 Hz, 2H). .sup.13C NMR (101 MHz, DMSO) ? 160.7, 155.3, 145.7, 143.8, 137.9, 130.1, 129.9, 129.2, 129.0, 128.7, 128.6, 128.4, 128.3, 127.0, 126.4, 126.3, 125.6, 122.5, 122.3, 117.8, 116.6, 116.2, 113.0, 112.7, 61.4, 58.6, 57.0, 52.8, 37.1, 34.1, 32.8, 9.0, 9.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.29N.sub.3O.sub.6S.sub.2Br: 718.0681, found 718.0675.

    Example 361

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-toluothiophene-2-carboxylic acid F27-S158)

    [1254] ##STR00432##

    [1255] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-toluothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 127.4 mg of white solid was obtained, with a yield of 65%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.31-8.13 (m, 2H), 7.86 (dd, J=8.5, 1.7 Hz, 1H), 7.80 (d, J=5.2 Hz, 1H), 7.44-7.31 (m, 1H), 7.26 (d, J=8.1 Hz, 1H), 7.18-7.03 (m, 6H), 7.01-6.93 (m, 2H), 4.14-2.91 (m, 9H), 2.85-2.69 (m, 5H), 2.65-2.56 (m, 1H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.6, 161.6, 150.8, 143.7, 140.3, 138.6, 136.9, 133.7, 132.4, 131.2, 130.3, 129.7, 129.3, 128.9, 128.7, 126.6, 124.9, 124.9, 124.6, 123.4, 123.2, 110.0, 109.2, 52.2, 50.8, 34.4, 13.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.29BrN.sub.3O.sub.5S.sub.3: 722.0458, found 722.0453.

    Example 362

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzo[b]thiophene-2-carboxylic acid (F27-S159)

    [1256] ##STR00433##

    [1257] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzo[b]thiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 24.9 mg of white solid was obtained, with a yield of 32%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.54 (s, 1H), 8.25 (d, J=16.5 Hz, 2H), 7.90-7.70 (m, 2H), 7.46-6.87 (m, 10H), 4.11-2.71 (m, 11H), 2.67-2.40 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.8, 161.6, 150.8, 145.4, 139.3, 138.6, 137.2, 133.8, 132.4, 131.3, 130.3, 130.0, 129.7, 129.3, 128.9, 128.7, 126.7, 125.6, 125.0, 124.7, 124.5, 123.3, 109.3, 52.5, 51.0, 34.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.27BrN.sub.3O.sub.5S.sub.3: 708.0302, found 708.0295.

    Example 363

    6-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzo[b]thiophene-2-carboxylic acid (F27-S160

    [1258] ##STR00434##

    [1259] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 6-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzo[b]thiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 23.2 mg of white solid was obtained, with a yield of 51%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.64 (s, 1H), 8.21-8.06 (m, 2H), 7.86-7.69 (m, 2H), 7.42-6.84 (m, 10H), 4.18-2.68 (m, 10H), 2.64-2.43 (m, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.8, 161.6, 154.4, 150.7, 142.4, 141.6, 138.6, 133.7, 132.3, 131.5, 130.3, 129.7, 129.3, 129.0, 128.7, 128.6, 128.6, 126.7, 123.6, 123.5, 123.3, 116.4, 109.2, 53.2, 50.9, 34.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.27BrN.sub.3O.sub.5S.sub.3: 708.0302, found 708.0299.

    Example 364

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-chloro-1H-indole-2-carboxylic acid (F27-S161)

    [1260] ##STR00435##

    [1261] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-chloro-1H-indole-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 98.4 mg of white solid was obtained, with a yield of 57%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 12.48 (s, 1H), 8.01 (s, 1H), 7.86-6.57 (m, 13H), 4.18-2.57 (m, 12H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 162.1, 161.6, 150.7, 138.6, 136.5, 134.0, 132.4, 131.0, 130.3, 129.5, 129.3, 128.9, 128.7, 126.7, 125.1, 124.7, 123.8, 123.0, 120.0, 114.5, 113.7, 109.2, 52.2, 51.0, 34.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.27BrClN.sub.4O.sub.5S.sub.2: 725.0300, found 725.0303.

    Example 365

    5-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S162)

    [1262] ##STR00436##

    [1263] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 336.2 mg of white solid was obtained, with a yield of 24%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.31 (d, J=1.9 Hz, 1H), 7.93-7.83 (m, 2H), 7.79 (d, J=5.2 Hz, 1H), 7.72 (s, 1H), 7.39-7.31 (m, 1H), 7.26 (d, J=8.0 Hz, 1H), 7.20-7.06 (m, 5H), 7.05-6.96 (m, 3H), 4.22-3.35 (m, 6H), 3.18-2.53 (m, 6H). .sup.13C NMR (101 MHz, DMSO) ? 161.2, 159.9, 156.4, 150.3, 138.1, 135.6, 133.3, 131.9, 130.7, 129.8, 129.2, 128.9, 128.5, 128.3, 127.6, 126.2, 126.0, 124.5, 123.5, 122.8, 113.1, 108.8, 50.5, 33.9. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.32H.sub.27N.sub.3O.sub.6S.sub.2Br: 692.0525, found 692.0532.

    Example 366

    6-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylic acid (F27-S163)

    [1264] ##STR00437##

    [1265] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 6-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 71.0 mg of white solid was obtained, with a yield of 80%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.77 (s, 1H), 8.12 (d, J=1.5 Hz, 1H), 7.99 (d, J=8.3 Hz, 1H), 7.82-7.67 (m, 2H), 7.39-7.32 (m, 1H), 7.29-7.21 (m, 1H), 7.13 (h, J=6.9 Hz, 5H), 7.05-6.94 (m, 3H), 3.96 (d, J=64.6 Hz, 2H), 3.34 (s, 3H), 2.84 (dd, J=80.9, 39.5 Hz, 5H), 2.56 (s, 4H). .sup.13C NMR (101 MHz, DMSO) ? 161.1, 160.6, 152.5, 150.3, 144.4, 138.9, 138.1, 133.3, 132.5, 131.9, 130.7, 129.8, 129.2, 128.9, 128.5, 128.2, 126.1, 124.5, 123.9, 122.8, 122.6, 122.0, 111.6, 108.8, 50.4, 33.9, 9.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.29N.sub.3O.sub.6S.sub.2Br: 706.0681, found 706.0682.

    Example 367

    6-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S164)

    [1266] ##STR00438##

    [1267] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 6-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 69.3 mg of white solid was obtained, with a yield of 60%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.17 (s, 1H), 7.98 (d, J=8.3 Hz, 1H), 7.79 (d, J=5.1 Hz, 1H), 7.74 (dd, J=8.4, 1.4 Hz, 2H), 7.35 (td, J=7.6, 1.6 Hz, 1H), 7.26 (dd, J=8.4, 1.6 Hz, 1H), 7.18-7.06 (m, 5H), 7.05-6.95 (m, 3H), 3.96 (d, J=64.4 Hz, 2H), 3.42 (s, 4H), 3.10-2.56 (m, 6H). .sup.13C NMR (101 MHz, DMSO) ? 161.1, 159.8, 153.8, 150.3, 138.4, 138.1, 133.3, 131.9, 131.0, 130.7, 129.8, 129.2, 128.8, 128.5, 128.2, 126.1, 124.5, 124.0, 122.8, 122.4, 112.4, 111.8, 108.8, 50.4, 33.9. HRMS (ESI) [M+H]+, theoretically calculated for C.sub.32H.sub.27N.sub.3O.sub.6S.sub.2Br: 692.0525, found 692.0527.

    Example 368

    5-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-(4-methoxyphenethyl)sulfamoyl)3-methylbenzothiophene-2-carboxylic acid (F27-S165)

    [1268] ##STR00439##

    [1269] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-(4-methoxyphenethyl) sulfamoyl)3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 81.9 mg of white solid was obtained, with a yield of 73%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.25-8.18 (m, 2H), 7.85 (dd, J=8.5, 1.8 Hz, 1H), 7.79 (d, J=5.1 Hz, 1H), 7.40-7.32 (m, 1H), 7.26 (dd, J=8.5, 1.8 Hz, 1H), 7.19-7.02 (m, 3H), 6.90-6.83 (m, 2H), 6.72-6.62 (m, 2H), 3.91 (d, J=66.8 Hz, 3H), 3.64 (s, 3H), 3.57-3.15 (m, 4H), 2.91 (d, J=84.3 Hz, 4H), 2.72 (s, 3H), 2.42 (s, 1H). .sup.13C NMR (101 MHz, DMSO) ? 161.1, 157.6, 150.3, 143.1, 139.8, 136.6, 133.2, 131.9, 130.8, 129.9, 129.8, 129.4, 129.2, 128.8, 124.5, 124.4, 124.1, 122.9, 113.6, 108.8, 54.9, 50.5, 32.9, 12.6. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31N.sub.3O.sub.6S.sub.3Br: 752.0558, found 752.0567.

    Example 369

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic (F27-S166)

    [1270] ##STR00440##

    [1271] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 21.0 mg of white solid was obtained, with a yield of 65%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.28-8.12 (m, 2H), 7.87-7.73 (m, 2H), 7.36 (t, J=7.4 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.18-7.02 (m, 5H), 6.98 (d, J=8.1 Hz, 2H), 4.15-2.90 (m, 9H), 2.85-2.68 (m, 5H), 2.65-2.55 (m, 1H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.5, 161.6, 150.7, 143.7, 140.3, 137.7, 136.8, 133.6, 132.4, 131.4, 131.3, 130.8, 130.3, 129.7, 129.3, 128.4, 124.9, 124.8, 124.5, 123.3, 118.1, 110.0, 109.2, 50.4, 33.6, 13.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.28BrClN.sub.3O.sub.5S: 756.0068, found 756.0070.

    Example 370

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-methylphenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S167)

    [1272] ##STR00441##

    [1273] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-methylphenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 27.1 mg of white solid was obtained, with a yield of 37%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.21 (t, J=4.2 Hz, 2H), 7.94-7.68 (m, 2H), 7.36 (t, J=7.6 Hz, 1H), 7.27 (d, J=8.0 Hz, 1H), 7.20-7.00 (m, 3H), 6.90-6.73 (m, 4H), 4.13-2.92 (m, 8H), 2.87-2.64 (m, 6H), 2.47-2.35 (m, 1H), 2.14 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.4, 161.6, 150.8, 143.7, 140.2, 140.0, 137.1, 135.6, 135.4, 133.7, 132.4, 131.3, 130.3, 129.7, 129.3, 129.2, 128.7, 125.1, 124.9, 124.6, 123.5, 123.3, 109.2, 52.3, 50.8, 33.8, 21.0, 13.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31BrN.sub.3O.sub.5S.sub.3: 736.0615, found 736.0603.

    Example 371

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-carboxyphenethyl)sulfamoyl)-3-toluenothiophene-2-carboxylic acid (F27-S168)

    [1274] ##STR00442##

    [1275] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-(methoxycarbonyl)phenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 58.2 mg of white solid was obtained, with a yield of 76%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.30-8.15 (m, 2H), 7.86 (dd, J=8.6, 1.9 Hz, 1H), 7.78 (d, J=5.1 Hz, 1H), 7.67 (d, J=8.1 Hz, 2H), 7.41-7.32 (m, 1H), 7.30-7.22 (m, 1H), 7.17-6.98 (m, 5H), 4.23-2.90 (m, 8H), 2.86-2.65 (m, 6H), 2.61-2.54 (m, 1H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 167.5, 164.2, 161.6, 150.7, 143.9, 143.7, 140.3, 140.1, 137.0, 133.6, 132.4, 131.4, 131.3, 130.3, 129.8, 129.6, 129.3, 129.1, 129.1, 125.2, 125.0, 124.7, 123.6, 123.3, 109.2, 52.4, 50.3, 34.3, 13.2. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.35H.sub.31BrN.sub.3O.sub.7S.sub.3: 766.0356, found 766.0355.

    Example 372

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-cyanophenyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S169)

    [1276] ##STR00443##

    [1277] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-cyanophenyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 33 mg of white solid was obtained, with a yield of 77%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 13.68 (s, 1H), 8.32 (s, 1H), 8.24-8.12 (m, 1H), 7.79 (d, J=9.1 Hz, 2H), 7.68 (d, J=7.8 Hz, 1H), 7.48 (d, J=7.8 Hz, 1H), 7.42-7.32 (m, 2H), 7.26 (d, J=7.3 Hz, 1H), 7.17-7.06 (m, 4H), 4.21-2.89 (m, 6H), 2.80-2.71 (m, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.2, 161.4, 150.7, 144.9, 143.5, 140.0, 137.6, 132.4, 132.2, 131.2, 130.3, 130.0, 129.2, 128.8, 127.9, 126.3, 125.7, 124.5, 123.5, 122.9, 122.6, 109.2, 109.1, 52.0, 31.7, 25.8, 13.2 (d, J=6.7 Hz). HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.28BrN.sub.4O.sub.5S.sub.3: 747.0411, found 747.0413.

    Example 373

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-(trifluoromethyl)phenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S170)

    [1278] ##STR00444##

    [1279] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-(trifluoromethyl)phenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 36 mg of white solid was obtained, with a yield of 72%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.17-7.95 (m, 2H), 7.72 (dd, J=8.5, 1.8 Hz, 1H), 7.45 (d, J=7.9 Hz, 3H), 7.34 (t, J=7.6 Hz, 1H), 7.25-6.84 (m, 6H), 4.02 (d, J=73.5 Hz, 2H), 3.20-2.76 (m, 9H), 2.74-2.62 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 165.8, 162.0, 150.9, 144.1, 143.6, 143.3, 141.6, 135.8, 133.6, 131.9, 131.0, 129.7, 129.6, 127.6, 127.2, 126.1, 125.4 (q), 124.5, 123.9, 122.92, 122.7, 122.3, 51.2, 49.9, 44.8, 34.2, 12.5. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.28BrF.sub.3N.sub.3O.sub.5S.sub.3: 790.0332, found 790.0336.

    Example 374

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-(trifluoromethyl)phenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S171)

    [1280] ##STR00445##

    [1281] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(3-methoxyphenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 20.4 mg of white solid was obtained, with a yield of 26%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.30-8.12 (m, 2H), 7.84 (dd, J=8.6, 1.7 Hz, 1H), 7.79 (d, J=5.2 Hz, 1H), 7.46-7.31 (m, 1H), 7.28-7.18 (m, 1H), 7.18-6.94 (m, 4H), 6.69-6.45 (m, 3H), 4.20-3.79 (m, 2H), 3.71-3.56 (m, 4H), 3.52-2.90 (m, 6H), 2.84-2.54 (m, 6H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.8, 161.6, 159.6, 150.8, 143.7, 140.4, 140.2, 139.0, 136.9, 133.7, 132.4, 131.2, 130.3, 129.6, 129.3, 124.8, 124.6, 123.4, 123.2, 122.6, 121.1, 114.5, 112.1, 109.2, 55.2, 50.7, 34.7, 13.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31BrN.sub.3O.sub.6S.sub.3: 752.0564, found 752.0564.

    Example 375

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(3-chlorophenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S172)

    [1282] ##STR00446##

    [1283] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(3-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 21.5 mg of white solid was obtained, with a yield of 57%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.23-8.08 (m, 2H), 7.84-7.71 (m, 2H), 7.43-7.29 (m, 1H), 7.28-7.19 (m, 1H), 7.17-7.07 (m, 4H), 7.04-6.84 (m, 3H), 4.19-2.93 (m, 8H), 2.82-2.59 (m, 7H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 165.8, 161.6, 150.7, 143.5, 141.3, 141.0, 136.2, 133.8, 133.3, 132.4, 131.1, 130.3, 129.6, 129.3, 128.8, 127.6, 126.5, 124.7, 124.3, 123.9, 123.1, 122.8, 118.6, 109.2, 50.3, 33.9, 12.7. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.28BrClN.sub.3O.sub.5S.sub.3: 756.0068, found 756.0067.

    Example 376

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-chlorophenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S173)

    [1284] ##STR00447##

    [1285] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-chlorophenylethyl) sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 13.5 mg of white solid was obtained, with a yield of 91%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.28-8.16 (m, 2H), 7.87 (dd, J=8.6, 1.7 Hz, 1H), 7.79 (d, J=5.2 Hz, 1H), 7.41-7.34 (m, 1H), 7.26 (d, J=8.3 Hz, 2H), 7.19-7.09 (m, 6H), 4.18-3.76 (m, 2H), 3.14-2.61 (m, 13H). HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.28BrClN.sub.3O.sub.5S.sub.3: 756.0068, found 756.0070.

    Example 377

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-methoxyphenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S174)

    [1286] ##STR00448##

    [1287] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-methoxyphenethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 59.0 mg of white solid was obtained, with a yield of 88%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.22-8.09 (m, 2H), 7.86-7.75 (m, 2H), 7.36 (ddd, J=8.5, 6.8, 2.0 Hz, 1H), 7.26 (dd, J=8.1, 1.5 Hz, 1H), 7.18-7.01 (m, 4H), 6.88 (dd, J=7.4, 1.8 Hz, 1H), 6.81-6.67 (m, 2H), 4.16-3.72 (m, 2H), 3.59-3.24 (m, 7H), 3.16-2.64 (m, 9H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 161.6, 159.1, 157.5, 150.7, 143.5, 140.8, 136.7, 133.8, 132.4, 131.1, 130.3, 129.6, 129.3, 128.2, 126.3, 124.7, 124.3, 124.1, 123.0, 122.8, 120.7, 111.0, 109.3, 55.5, 49.0, 29.6, 12.8. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31BrN.sub.3O.sub.6S.sub.3: 752.0564, found 752.0566.

    Example 378

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-nitrophenylethyl)sulfamoyl)-3-toluothiophene-2-carboxylic acid (F27-S175)

    [1288] ##STR00449##

    [1289] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-nitrophenylethyl)sulfamoyl)-3-toluothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 17.0 mg of white solid was obtained, with a yield of 64%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.31 (d, J=1.7 Hz, 1H), 8.26 (d, J=8.6 Hz, 1H), 7.91 (dd, J=8.6, 1.8 Hz, 1H), 7.85-7.74 (m, 2H), 7.59-7.51 (m, 1H), 7.47-7.32 (m, 2H), 7.28 (dd, J=12.6, 7.8 Hz, 2H), 7.18-7.07 (m, 3H), 4.29-3.86 (m, 2H), 3.67-2.59 (m, 13H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.3, 161.6, 150.4, 149.4, 143.8, 143.1, 140.2, 137.1, 133.8, 132.9, 132.8, 132.4, 131.2, 130.3, 129.7, 129.3, 128.4, 124.9, 123.5, 123.2, 111.5, 110.0, 109.2, 49.6, 31.9, 13.2. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.28BrN.sub.4O.sub.7S.sub.3: 767.0309, found 767.0310.

    Example 379

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(3-phenylpropyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S176)

    [1290] ##STR00450##

    [1291] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(3-phenylpropyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 17.0 mg of white solid was obtained, with a yield of 28%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.16-7.95 (m, 2H), 7.87-7.58 (m, 2H), 7.40-7.03 (m, 8H), 6.99-6.85 (m, 2H), 3.94-3.49 (m, 3H), 3.18-2.58 (m, 10H), 2.46-2.35 (m, 2H), 1.57-1.38 (m, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 165.7, 165.5, 151.0, 149.8, 143.2, 141.7, 141.5, 140.4, 136.8, 136.3, 136.0, 133.9, 131.5, 131.0, 130.1, 129.5, 128.6, 128.5, 126.2, 123.9, 122.9, 122.7, 122.1, 51.5, 45.1, 32.4, 29.7, 12.4. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.34H.sub.31BrN.sub.3O.sub.5S.sub.3: 736.0615, found 736.0600.

    Example 380

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)-3-toluothiophene-2-carboxylic acid (F27-S177)

    [1292] ##STR00451##

    [1293] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)-3-toluothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 108.0 mg of white solid was obtained, with a yield of 63%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 9.27 (s, 1H), 8.32 (d, J=1.7 Hz, 1H), 8.17 (d, J=8.6 Hz, 1H), 7.84-7.65 (m, 2H), 7.50-7.32 (m, 1H), 7.22-6.98 (m, 4H), 3.89-3.00 (m, 4H), 2.69 (s, 3H), 2.49-2.26 (m, 4H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.2, 161.4, 144.9, 143.5, 140.0, 137.6, 132.5, 132.4, 131.2, 130.3, 129.2, 126.3, 125.7, 124.5, 123.5, 122.9, 122.6, 109.1, 52.5, 13.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.25H.sub.21BrN.sub.3O.sub.5S.sub.3: 617.9832, found 617.9821.

    Example 381

    5-(N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)3-methylbenzofuran-2-carboxamide (F27-S178)

    [1294] ##STR00452##

    [1295] 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-methyl benzofuran-2-carboxylic acid (F27-S125) (0.042 mmol, 30.0 mg) and CDI (0.042 mmol, 7.0 mg) were dissolved in 1 mL of DCM and the resulting solution was then stirred at room temperature for 20 min. 0.5 mL of ammonia water was added and then the system was stirred at room temperature for 3 h. After the reaction was found to be completed from the monitoring of the TLC, the reaction was quenched with 0.5 mL of 1M aqueous solution of hydrochloric acid. The product was dissolved in 20 mL of water and then extracted three times with 20 mL of ethyl acetate. The organic phases were combined and then concentrated and then separated by column chromatography (DCM:MeOH=20:1) to obtain 25.8 mg of white solid, with a yield of 87%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.11 (s, 1H), 7.88 (d, J=8.8 Hz, 1H), 7.55 (d, J=8.8 Hz, 1H), 7.35 (t, J=5.4 Hz, 2H), 7.21-6.87 (m, 7H), 6.57 (s, 1H), 6.11 (s, 1H), 4.30-3.75 (m, 3H), 3.44 (d, J=119.4 Hz, 4H), 2.79 (d, J=86.6 Hz, 3H), 2.62 (s, 2H), 1.26 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 162.3, 161.3, 155.0, 151.0, 144.4, 138.2, 136.0, 134.2, 132.1, 130.4, 130.3, 130.1, 129.6, 128.6, 127.4, 126.7, 126.6, 124.8, 123.7, 122.9, 122.0, 112.5, 109.8, 51.6, 34.8, 29.8, 29.4, 9.1. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.32N.sub.4O.sub.5S.sub.2Br: 707.0997, found 707.1000.

    Example 382

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-1,3-dimethyl-1H-indole-2-carboxylate (M10-179)

    [1296] ##STR00453##

    [1297] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-3-toluothiophene-2-carboxylate (M10-158), this example was implemented under the same condition except that ethyl 5-(chlorosulfonyl)-1,3-dimethyl-1H-indole-2-carboxylate was used instead of ethyl 3-methyl-5-(N-phenethyl-N-(2-(piperazin-1-yl)phenyl)sulfamoyl)benzo[b]thiophene-2-carboxylate. 316.1 mg of white solid was obtained, with a yield of 99%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.23 (d, J=1.8 Hz, 1H), 7.79 (dd, J=8.9, 1.8 Hz, 1H), 7.44 (d, J=8.8 Hz, 1H), 7.36 (dd, J=12.2, 4.6 Hz, 2H), 7.23-7.12 (m, 4H), 7.07 (d, J=4.3 Hz, 2H), 7.01-6.95 (m, 3H), 4.47 (q, J=7.1 Hz, 2H), 4.20-3.95 (m, 5H), 3.91-2.76 (m, 8H), 2.74-2.47 (m, 5H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.5, 162.2, 150.7, 139.9, 138.3, 134.4, 132.1, 131.5, 130.5, 130.2, 129.2, 128.5, 128.5, 127.2, 126.5, 126.4, 124.4, 123.6, 122.3, 122.3, 121.8, 110.6, 109.6, 60.9, 51.4, 34.7, 32.6, 14.4, 10.9.

    Example 383

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-1,3-dimethyl-1H-indole-2-carboxylic acid (F27-S179)

    [1298] ##STR00454##

    [1299] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)-1,3-dimethyl-1H-indole-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 280.5 mg of white solid was obtained, with a yield of 92%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.13 (s, 1H), 7.79-7.60 (m, 3H), 7.39-7.27 (m, 1H), 7.23-7.04 (m, 8H), 6.96 (d, J=7.2 Hz, 2H), 4.00 (s, 3H), 3.34-2.65 (m, 10H), 2.61-2.43 (m, 5H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 163.9, 161.6, 150.5, 139.8, 138.7, 133.9, 132.3, 1312, 131.1, 130.3, 129.4, 129.3, 128.8, 128.7, 126.6, 126.3, 124.5, 123.3, 122.7, 121.6, 120.2, 112.0, 109.2, 52.1, 50.6, 34.4, 32.8, 10.8. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.34H.sub.32BrN.sub.4O.sub.5S.sub.2: 719.1003, found 719.0997.

    Example 384

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-cyclohexylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-180)

    [1300] ##STR00455##

    [1301] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-((2-cyclohexylethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 102 mg of white solid was obtained, with a yield of 47%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.32 (d, J=1.7 Hz, 1H), 8.04-7.84 (m, 2H), 7.38 (d, J=5.3 Hz, 1H), 7.34 (ddd, J=8.7, 7.4, 1.6 Hz, 1H), 7.18 (dd, J=8.1, 1.5 Hz, 1H), 7.06 (td, J=7.6, 1.5 Hz, 1H), 7.01-6.93 (m, 2H), 4.45 (q, J=7.1 Hz, 2H), 4.26-3.39 (m, 6H), 3.01-2.71 (m, 6H), 1.64-1.53 (m, 4H), 1.50-1.40 (m, 4H), 1.16-0.99 (m, 5H), 0.75 (q, J=10.6, 9.8 Hz, 2H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.8, 162.2, 150.94, 144.0, 140.9, 139.9, 137.3, 134.3, 132.0, 130.2, 130.2, 129.8, 129.3, 127.3, 125.0, 124.6, 123.7, 123.4, 122.7, 109.7, 61.6, 48.2, 35.5, 35.2, 33.1, 26.3, 26.1, 14.4, 13.2.

    Example 385

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-cyclohexylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S180)

    [1302] ##STR00456##

    [1303] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-cyclohexylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 73.0 mg of white solid was obtained, with a yield of 72%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.27 (t, J=4.2 Hz, 2H), 7.91 (d, J=8.6 Hz, 1H), 7.80 (d, J=5.2 Hz, 1H), 7.29 (dd, J=33.0, 8.3 Hz, 2H), 7.18-7.00 (m, 3H), 3.94-2.91 (m, 8H), 2.87-2.63 (m, 5H), 1.57-1.28 (m, 4H), 1.15-0.77 (m, 7H), 0.74-0.52 (m, 2H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.7, 161.6, 150.8, 143.6, 140.4, 138.9, 137.1, 133.9, 132.4, 131.1, 130.3, 129.6, 129.3, 124.9, 124.6, 123.3, 123.2, 109.2, 52.4, 47.4, 35.4, 34.6, 32.9, 26.4, 26.1, 13.0. HRMS (ESI) [M+H].sup.+, theoretically calculated for C.sub.33H.sub.35BrN.sub.3O.sub.5S.sub.3: 728.0928, found 728.0918.

    Example 386

    Ethyl 5-(N-benzyl-N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-181)

    [1304] ##STR00457##

    [1305] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that 4-(2-(benzylamino)phenyl)piperazin-1-yl)(3-bromothiophen-2-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 74.0 mg of white solid was obtained, with a yield of 46%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.24 (d, J=1.6 Hz, 1H), 8.00-7.80 (m, 2H), 7.38 (d, J=5.2 Hz, 1H), 7.28 (s, 1H), 7.16 (qd, J=8.0, 7.2, 2.8 Hz, 4H), 7.09-6.97 (m, 4H), 6.87 (dd, J=7.9, 1.5 Hz, 1H), 4.81 (d, J=122.3 Hz, 2H), 4.45 (q, J=7.1 Hz, 2H), 4.00-3.34 (m, 4H), 3.30-2.93 (m, 2H), 2.76 (s, 3H), 2.68-2.24 (m, 2H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.8, 162.1, 151.4, 144.1, 141.0, 139.9, 137.1, 135.7, 135.1, 132.1, 130.2, 129.8, 129.8, 129.4, 129.4, 128.3, 128.0, 127.2, 125.2, 124.9, 123.9, 123.3, 123.3, 109.7, 61.6, 55.0, 14., 13.2.

    Example 387

    5-(N-benzyl-N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S181)

    [1306] ##STR00458##

    [1307] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-benzyl-N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 56.0 mg of white solid was obtained, with a yield of 80%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.35-8.18 (m, 2H), 7.90 (d, J=8.6 Hz, 1H), 7.79 (d, J=5.2 Hz, 1H), 7.40-6.83 (m, 10H), 5.18-4.68 (m, 2H), 4.14-3.07 (m, 6H), 2.95-2.58 (m, 7H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.4, 161.6, 150.9, 143.7, 140.2, 137.2, 136.5, 134.3, 132.4, 131.3, 130.3, 129.6, 129.4, 129.3, 128.5, 128.0, 125.3, 125.0, 124.6, 123.7, 123.5, 110.0, 109.2, 53.8, 52.2, 13.2. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.32H.sub.27BrN.sub.3O.sub.5S.sub.3: 708.0302, found 708.0294.

    Example 388

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-methylsulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-182)

    [1308] ##STR00459##

    [1309] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that (3-bromothien-2-yl)(4-(2-(methylamino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 137.7 mg of white solid was obtained, with a yield of 76%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.24 (s, 1H), 8.07-7.69 (m, 2H), 7.50-7.17 (m, 2H), 7.14-6.66 (m, 4H), 4.43 (q, J=7.2 Hz, 2H), 4.18-3.41 (m, 5H), 3.31-3.15 (m, 3H), 2.77 (s, 3H), 1.44 (t, J=7.2 Hz, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.7, 162.2, 150.3, 144.1, 140.9, 139.9, 135.8, 135.4, 132.1, 130.2, 129.8, 129.3, 128.1, 127.3, 125.1, 123.9, 123.7, 123.4, 121.6, 109.7, 61.6, 51.7, 38.5, 14.4, 13.2.

    Example 389

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-methylsulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S182)

    [1310] ##STR00460##

    [1311] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-methylsulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 78.0 mg of white solid was obtained, with a yield of 58%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.26 (d, J=8.5 Hz, 1H), 8.19 (s, 1H), 7.82 (dd, J=15.7, 7.0 Hz, 2H), 7.29 (t, J=7.9 Hz, 1H), 7.15 (q, J=8.7, 5.5 Hz, 2H), 6.97 (dd, J=26.4, 7.9 Hz, 2H), 3.98-3.10 (m, 8H), 2.98 (s, 3H), 2.74 (s, 3H). .sup.13C NMR (101 MHz, DMSO-d.sub.6) ? 164.7, 161.6, 150.3, 143.7, 140.3, 139.1, 135.8, 132.4, 130.3, 129.5, 129.3, 129.0, 125.1, 124.5, 124.0, 123.5, 122.2, 109.2, 51.7, 38.6, 13.1. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.26H.sub.23BrN.sub.3O.sub.5S.sub.3: 631.9989, found 631.9986.

    Example 390

    Ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-(thiophen-2-yl)ethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-183)

    [1312] ##STR00461##

    [1313] In accordance with the preparation method of ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl) piperazin-1-yl)phenyl)-N-(4-chlorophenylethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate (M10-165), this example was implemented under the same condition except that 3-bromothien-2-yl)(4-(2-(thien-2-yl)ethyl)amino)phenyl)piperazin-1-yl)methanone was used instead of (3-bromothien-2-yl)(4-(2-((4-chlorophenylethyl)amino)phenyl)piperazin-1-yl)methanone. 10.0 mg of white solid was obtained, with a yield of 7%. .sup.1H NMR (400 MHz, Chloroform-d) ? 8.31 (s, 1H), 8.04-7.82 (m, 2H), 7.45-7.33 (m, 2H), 7.26-7.15 (m, 2H), 7.13-6.95 (m, 3H), 6.87-6.78 (m, 1H), 6.65 (s, 1H), 4.46 (q, J=6.6 Hz, 2H), 4.22-3.12 (m, 9H), 3.02-2.69 (m, 6H), 1.45 (t, 3H). .sup.13C NMR (101 MHz, Chloroform-d) ? 162.8, 162.2, 150.8, 140.3, 139.9, 137.1, 134.0, 132.0, 130.5, 130.2, 129.9, 129.6, 127.2, 126.9, 125.2, 124.8, 123.8, 123.7, 123.5, 123.2, 122.9, 109.7, 61.6, 51.6, 29.7, 22.7, 14.3.

    Example 391

    5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-(thiophen-2-yl)ethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylic acid (F27-S183)

    [1314] ##STR00462##

    [1315] 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylic acid (F27-S106), this example was implemented under the same condition except that ethyl 5-(N-(2-(4-(3-bromothiophene-2-carbonyl)piperazin-1-yl)phenyl)-N-(2-(thiophen-2-yl)ethyl)sulfamoyl)-3-methylbenzothiophene-2-carboxylate was used instead of ethyl 3-methyl-5-(N-(2-(4-(4-methylbenzoyl)piperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate. 14.0 mg of white solid was obtained, with a yield of 100%. .sup.1H NMR (400 MHz, DMSO-d.sub.6) ? 8.26 (s, 2H), 7.92-7.73 (m, 2H), 7.36 (s, 1H), 7.30-7.07 (m, 4H), 6.97 (s, 1H), 6.82 (s, 1H), 6.74 (s, 1H), 4.22-3.37 (m, 5H), 3.09-2.67 (m, 10H). HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.31H.sub.27BrN.sub.3O.sub.5S.sub.4: 728.0022, found 728.0023.

    Example 392

    N-(2-(4-(3-bromothiophene-2-formyl)piperazin-1-yl)phenyl)-2-hydroxymethyl-3-methyl-N-phenethylbenzofuran-5-sulfonamide (F27-S184)

    [1316] ##STR00463##

    [1317] Ethyl 3-methyl-5-(N-(2-(4-(benzoylpiperazin-1-yl)phenyl)-N-phenethylsulfamoyl)benzofuran-2-carboxylate (M10-96) (248 mg, 0.34 mmol) was dissolved in anhydrous tetrahydrofuran (0.5 mL), and the resulting solution was then slowly added dropwise to a stirred lithium aluminum hydride-tetrahydrofuran solution (14 mg of lithium aluminum hydride dissolved in 1 mL of anhydrous tetrahydrofuran) at 0? C. to react at room temperature for 2 h, until it was found from the monitoring of the TLC that there was no raw material left. 1.5 mL of saturated potassium carbonate solution was added dropwise to the reaction system and the system was then stirred for 15 min. The reaction system was then poured into 5 mL of ethyl acetate and stirred for 15 min. The product was dissolved in 20 mL of water and then extracted three times, and the organic layer was then dried with anhydrous sodium sulfate. Column chromatography (PE:EA=3:1?1:1) was carried out to obtain 105 mg of the target product, with a yield of 45%. .sup.1H NMR (400 MHz, CDCl.sub.3) ? 8.05 (d, J=2.0 Hz, 1H), 7.81 (dd, J=8.7, 2.0 Hz, 1H), 7.61-7.53 (m, 2H), 7.37 (dd, J=9.7, 6.2 Hz, 2H), 7.24-7.14 (m, 5H), 7.03-6.93 (m, 3H), 5.49 (s, 2H), 4.32-2.48 (m, 14H), 2.39 (s, 3H). .sup.13C NMR (101 MHz, CDCl.sub.3) ? 162.2, 151.0, 149.4, 138.2, 135.0, 134.3, 133.6, 133.2, 132.1, 131.9, 130.2, 129.8, 129.4, 128.5, 127.2, 126.5, 124.8, 124.6, 122.7, 120.8, 116.8, 112.0, 111.9, 109.7, 63.5, 56.9, 51.5, 34.6, 8.0. HRMS (ESI) [M?H].sup.?, theoretically calculated for C.sub.33H.sub.31BrN.sub.3O.sub.5S.sub.2: 692.0894, found 692.0898.

    Preparation Example 1

    5-(2,5-dimethylphenoxy)-N-(2-(4-hydroxyphenyl)-2-oxoethyl)-2,2-dimethylpentanamide (SIPI-7623) (SIPI-7623)

    [1318] ##STR00464##

    [1319] 2-amino-4-hydroxyacetophenone hydrochloride (0.38 g, 2 mmol), 2,2-dimethyl-5-(2,5-dimethylphenoxy)pentanoic acid (0.5 g, 2 mmol), triethylamine (0.6 g, 4 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.77 g, 4 mmol), and 1-hydroxybenzotriazole (0.54 g, 4 mmol) were added to anhydrous dichloromethane (10 mL) and reacted at room temperature for 13 h. After the reaction was found to be completed from the monitoring of the TLC, the system was washed with saturated sodium carbonate solution (10 mL), and extraction with ethyl acetate (30 mL) was carried out three times. The organic phase was washed with saturated aqueous NaCl solution and then dried with anhydrous sodium sulfate. The crude product was separated by column chromatography (PE/EA=1/1) to obtain 0.39 g of white solid, with a yield of 51%. After verification according to NMR and mass spectrometry data, the compound obtained in this preparation example was consistent with the compound reported!

    Preparation Example 2

    1-((3S, 8R, 9S, 10R, 135, 14S)-3-hydroxy-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthren-17-yl)ethan-1-one (Centatin)

    [1320] ##STR00465##

    [1321] (3S, 8R, 9S, 10R, 13S, 14S)-17-acetyl-10,13-dimethyl-2,3,4,7,8,9,10,11,12,13,14,15-dodecahydro-1H-cyclopenta[a]phenanthrene-3-acetate (5.34 g, 15 mmol) was dissolved in tert-butanol (125 mL), and the aqueous solution (5 mL) of potassium hydroxide (4.2 g, 75 mmol) was then added, and the resulting solution was stirred overnight at 30? C. After the reaction was found to be completed from the monitoring of the TLC, the solvent was distilled off under reduced pressure, and the product was washed five times with ice water (25 mL), and then recrystallized with DCM/CH.sub.3OH (9:1) to obtain 4.58 g of white solid, with a yield of 97%. After verification according to NMR and mass spectrometry data, the compound obtained in this preparation example was consistent with the compound reported!

    Bioactivity

    1. Experimental Methods for Bioactivity Evaluation

    1.1 Evaluation on FXR Activity

    [1322] FXR activity was evaluated by time-resolved fluorescence resonance energy transfer (TR-FRET) assay, using LanthaScreen? TR-FRET FXR co-activation assay kit (ThermoFisher, Cat. PV4833). For agonist screening, 10 ?L of Complete Coregulator buffer G containing the corresponding concentration of the compound to be tested, 5 ?L of 20 nM FXR-LBD Complete Coregulator buffer G, and 5 ?L of 2.0 ?M Fluorescein-SRC2-2/20 nM Tb-anti-GST antibody Complete Coregulator buffer G were added to each well of a 384-well black plate (Coring) in sequence. After incubation at room temperature for 1 h, the fluorescence values at 520 nm and 495 nm were detected by a microplate reader, and the obtained values were expressed in 520 nm/495 nm. Three duplicate wells were set up for each compound, with CDCA as the positive compound and DMSO as the solvent control. For antagonist screening, 5 ?L of Complete Coregulator buffer G containing the corresponding concentration of the compound to be tested, 5 ?L of 20 nM FXR-LBD Complete Coregulator buffer G, 5 ?L of 200 ?M CDCA FXR-LBD Complete Coregulator buffer G, and 5 ?L of 2.0 ?M Fluorescein-SRC2-2/20 nM Tb-anti-GST antibody Complete Coregulator buffer G were added to each well of a 384-well black plate (Coring) in sequence and incubated at room temperature for 10 h. Following operations were the same as those for agonist screening

    1.2. Cell Culture and Passaging

    [1323] The human embryonic kidney cell line HEK293A was subcultured in a medium containing penicillin (final concentration: 100 U/mL), streptomycin (final concentration: 100 ?g/mL) and 10% FBS, in a humidified atmosphere of 95% air and 5% carbon dioxide at a constant temperature of 37? C. When the cells were 90% confluent, the old culture medium was discarded and the cells were washed twice with 2 mL of PBS. After the PBS was discarded, 2 mL of 0.25% trypsin-0.25% EDTA mixed digestion solution was added. When it was observed under a microscope that the cells became round, 2 mL of complete culture medium was added quickly to stop the digestion. The cell solution was pipetted gently to collect cells. The cells were centrifuged at 800 rpm, 4? C. for 5 min, the supernatant was discarded, the cells were resuspended in complete culture medium and cultured in bottles, and the medium was changed every other day.

    [1324] The human liver cancer cell line HepG2 was subcultured in a DMEM medium containing penicillin (final concentration: 100 U/mL), streptomycin (final concentration: 100 ?g/mL) and 10% FBS under the same conditions as those in the subculture of HEK293A.

    1.3 Cell Proliferation Inhibition Assay

    [1325] The cell proliferation inhibition ability of compounds was tested by MTT assay. HepG2 and HEK293 cells were inoculated in a 96-well plate at a density of 30%. After incubation for 18 h to allow the cells to adhere, the original culture medium was removed, a given concentration of the compound to be tested was added to each well, and an equal amount of DMSO was added to the control group. Three replicate wells were set up for each compound. 48 hours after administration, cell viability was tested by MTT assay. The blank group was the wells where no cells were added, and then its OD value was read at 490 nm with a microplate reader. Calculation formula for cell viability: cell viability (%)=(OD.sub.to be tested?OD.sub.blank)/(OD.sub.control?OD.sub.blank)?100.

    1.4 Testing of TC/TG in Cells

    [1326] Cell TC/TG was tested using Nanjing Jiancheng TG test kit and TC test kit. HepG2 cells were incubated with 0.5 mmol/L FFA (oleic acid and palmitate mixed at a ratio of 2:1) and a solvent or different concentrations (20 ?M, 40 ?M, 80 ?M) of compounds for 24 h. The culture medium was discarded and the cells were washed once with 0.01 M PBS (pH 7.4). The cells were scraped off with a cell scraper. 2-5 mL of 0.01 M PBS (pH 7.4) was then added. The cell suspension was collected and then centrifuged at 1000?g, 4? C. for 10 min. According to the ratio of 10.sup.6 cells/300-500 ?L of homogenization medium, isopropyl alcohol was added for mechanical homogenization, such that the cells were thoroughly disrupted until there was no obvious cell precipitation. The cell solution was centrifuged at 10000?g, 4? C. for 10 min. The supernatant was taken and placed on ice for testing. 2.5 ?L of distilled water, standard products or samples were well mixed with 250 ?L of distilled water respectively. After incubation at 37? C. for 10 min, the absorbance value of each well was tested with a microplate reader at 510 nm. Calculation formula for TC/TG concentration: sample concentration (mmol/g protein)=(OD.sub.sample?OD.sub.blank)/(OD.sub.standard?OD.sub.blank)?standard product concentration (mmol/L)/protein concentration (g protein/L).

    BCA Protein Quantification

    [1327] Preparation of protein standard: a. 1.2 mL of standard protein solution was added to a tube of protein standard (30 mg BSA), and a 25 mg/mL standard protein solution was obtained after the protein standard was thoroughly dissolved. b. An appropriate amount of 25 mg/mL protein standard was diluted to the final concentration of 0.5 mg/mL. Preparation of BCA working solution: according to the number of samples, reagent A for the BCA working solution and reagent B for BCA working solution (v/v: 50:1) were well mixed to prepare an appropriate amount of BCA working solution. Determination of protein concentration: a. 0, 1, 2, 4, 8, 12, 16, and 20 ?L of the protein standard were respectively added into the standard wells of the 96-well plate, and the diluted standard solution was then added to make up to 20 ?L, which is equivalent to obtaining standard concentrations of 0, 0.025, 0.05, 0.1, 0.2, 0.3, 0.4, and 0.5 mg/mL, respectively. b. An appropriate volume of sample was added to the sample wells of the 96-well plate. If the sample is less than 20 ?L, the diluted standard solution should be added to make up to 20 ?L. c. 20 ?L of BCA working solution was added to each well and the well plate was set still at 37? C. for 20-30 min. d. The absorbance at A562 nm was determined with a microplate reader. e. The protein concentrations of the samples were calculated according to the standard curves and the sample volumes used.

    2 Conclusion and Discussion

    Conclusion and Discussion on FXR Antagonistic Activity

    [1328] A: 0.1 ?M<IC.sub.50<10 ?M [1329] B: 10 ?M<IC.sub.50<50 ?M [1330] C: 50 ?M<IC.sub.50<100 ?M

    TABLE-US-00001 TABLE 1.1 FXR antagonistic activity of compounds Compound FXR IC.sub.50 number (?M) .sup.a Z-GS .sup.a C SIPI-7623 .sup.a B Centatin .sup.a B F27 B F27-S8 C M8-10 C F27-S10 C M8-11 C F27-S11 A M8-12 C F27-S12 A M8-13 C F27-S13 B M4-14 C F27-S14 A M4-15 C F27-S15 B M4-16 C F27-S16 B M4-17 C F27-S17 B M4-18 C F27-S18 B M4-19 C F27-S19 B M4-20 C F27-S20 B M4-21 C F27-S21 B M4-22 C F27-S22 B M4-23 C F27-S23 B M4-24 C F27-S24 C M4-25 C F27-S25 B M4-26 C F27-S26 B M4-27 C F27-S27 B M4-28 C F27-S28 B M4-29 C F27-S29 B M4-30 C F27-S30 B M4-31 C F27-S31 B M4-32 C F27-S32 B M4-33 C F27-S33 C M4-34 C F27-S34 B M4-35 C F27-S35 B M4-36 C F27-S36 B M4-37 C F27-S37 B M4-38 C F27-S38 C M4-39 C F27-S39 C M4-40 C F27-S40 B M4-41 C F27-S41 C M4-42 C F27-S42 C M4-43 C F27-S43 B M4-44 C F27-S44 B M4-45 C F27-S45 B M4-46 C F27-S46 B M4-47 C F27-S47 A M4-48 C F27-S48 B M4-49 C F27-S49 A M4-50 C F27-S50 A M4-51 C F27-S51 B M4-52 C F27-S52 B M4-53 C F27-S53 B M4-54 C M4-55 C F27-S55 C M4-56 C F27-S56 B M4-57 C F27-S57 B M4-58 C F27-S58 C M4-59 C F27-S59 C M4-60 C F27-S60 B M4-61 C F27-S61 B M4-62 C F27-S62 B M8-63 C F27-S63 C M8-64 C F27-S64 C M8-65 C F27-S65 B M8-66 C F27-S66 B M8-67 C F27-S67 B M8-68 C F27-S68 C M8-69 C F27-S69 B M8-70 C F27-S70 B M8-71 C F27-S71 C M8-72 C F27-S72 C M8-73 C F27-S73 A M8-74 C F27-S74 A M8-75 C F27-S75 B M8-76 C F27-S76 B M8-77 C F27-S77 A M8-78 C F27-S78 C M8-79 C F27-S79 C M8-80 C F27-S80 C M8-81 C F27-S81 B M4-82 C F27-S82 C M4-83 C F27-S83 B M4-84 C F27-S84 B M4-85 C F27-S85 B M8-86 C F27-S86 B M8-87 C F27-S87 A M8-88 C F27-S88 A M9-1 C F27-S89 C M10-90 C F27-S90 C M10-91 C F27-S91 C M10-92 C F27-S92 B M10-93 C F27-S93 B M10-94 C F27-S94 A M10-95 C F27-S95 B M10-96 C F27-S96 A M9-2 C F27-S97 C M10-98 C F27-S98 A M10-99 C F27-S99 C M10-100 C F27-S100 B M10-101 C F27-S101 A M10-102 C F27-S102 C M10-103 C F27-S103 B M10-104 C F27-S104 C M10-105 C F27-S105 A

    TABLE-US-00002 TABLE 1.2 FXR antagonistic activity of compounds Compound FXR IC.sub.50 number (?M) .sup.a M10-106 C M10-107 C M10-108 C M10-109 C M10-110 C M10-111 C M10-112 C M10-113 C M10-114 C M10-115 C M10-116 C M10-117 C M10-118 C M10-119 C M10-120 C M10-121 C M10-122 C M10-123 C M10-124 C M10-125 C M10-126 C M10-127 C M10-128 C M10-129 C M10-130 C M10-131 C M10-132 C M10-133 C M10-134 C M10-135 C M10-136 C M10-137 C M10-138 C M10-139 C M10-140 C M10-141 C M10-142 C M10-143 C M10-144 C M10-145 C M10-146 C M10-147 C M10-148 C M10-149 C M10-150 C M10-151 C M10-152 C M10-153 C M10-154 C M10-155 C M10-156 C M10-157 C M10-158 C M10-159 C M10-160 C M10-161 C M10-162 C M10-163 C M10-164 C M10-165 C M10-166 C M10-167 C M10-168 C M10-169 C M10-170 C M10-171 C M10-172 C M10-173 C M10-174 C M10-175 C M10-176 C M10-177 C M10-178 C F27-S106 A F27-S107 A F27-S108 A F27-S109 A F27-S110 A F27-S111 A F27-S112 A F27-S113 A F27-S114 A F27-S115 A F27-S116 A F27-S117 A F27-S118 A F27-S119 A F27-S120 A F27-S121 A F27-S122 A F27-S123 A F27-S124 A F27-S125 A F27-S126 A F27-S127 A F27-S128 A F27-S129 A F27-S130 A F27-S131 A F27-S132 A F27-S133 A F27-S134 A F27-S135 A F27-S136 A F27-S137 A F27-S138 A F27-S139 A F27-S140 A F27-S141 A F27-S142 A F27-S143 A F27-S144 A F27-S145 A F27-S146 A F27-S147 A F27-S148 A F27-S149 A F27-S150 A F27-S151 A F27-S152 A F27-S153 A F27-S154 A F27-S155 A F27-S156 A F27-S157 A F27-S158 A F27-S159 A F27-S160 A F27-S161 A F27-S162 A F27-S163 A F27-S164 A F27-S165 A F27-S166 A F27-S167 A F27-S168 A F27-S169 A F27-S170 A F27-S171 A F27-S172 A F27-S173 A F27-S174 A F27-S175 A F27-S176 A F27-S177 A F27-S178 A M10-179 C F27-S179 A M10-180 C F27-S180 A M10-181 C F27-S181 A M10-182 C F27-S182 A M10-183 C F27-S183 A F27-S184 A .sup.a data are presented as geometric means of at least two independent runs. .sup.b Z-GS, SIPI-7623 and Centatin are positive control. SIPI-7623 was in Phase I clinical research, and Centatin was in Phase III clinical research.

    Conclusion and Discussion on Lipid-Lowering Activity

    [1331] Evaluation on cytotoxicity of compounds in human embryonic kidney cell line HEK293A and human liver cancer cell line HepG2. As shown in Table 1.3, all benzofuran FXR antagonists tested had no significant cytotoxicity (CC.sub.50>160 ?M).

    TABLE-US-00003 TABLE 1.3 Cytotoxicity results of benzofuran FXR antagonists HEK293A HepG2 Compound CC.sub.50 (?M) CC.sub.50 (?M) F27-S11 >160 >160 F27-S12 >160 >160 F27-S96 >160 >160 F27-S101 >160 >160 F27-S105 >160 >160

    [1332] The data in the table are the average of three independent repeated experiments.

    [1333] The inventors selected Centatin in Phase III clinical research and SIPI-7623 and Z-GS in Phase I clinical research as positive control. Analysis of TG and TC results shows (FIG. 1) that 20 ?M Z-GS, SIPI-7623, Centatin, and F27-S96 can significantly reduce the increase in TG and TC levels of HepG2 cell induced by oleic acid and palmitate. Among the positive drugs, Centatin has the greatest effect, followed by SIPI-7623, and Z-GS worst. The compound F27-S96 achieves the similar effect in reducing TG and TC to SIPI-7623, and its inhibitory effect on TG and TC is dose-dependent to some extent.