Fluorinated benzenesulfonamides as inhibitors of carbonic anhydrase

Abstract

Novel fluorinated benzenesulfonamides compounds of general formula (I) ##STR00001##
can be used in biomedicine as active ingredients in pharmaceutical formulations, because they inhibit enzymes which participate in disease progression.

Claims

1. Fluorinated benzenesulfonamides of general formula (I) ##STR00017## where n is 2 or 3, the fluorine atoms are in any position, m is 2 or 3, the A groups are identical or different from each other, n+m must be equal to 5, A is selected from the group consisting of R.sup.1, OH, OR.sup.1, SH, SR.sup.1, S(O)R.sup.1, SO.sub.2R.sup.1, C(O)R.sup.1, C(O)OR.sup.1, OC(O)R.sup.1, NHR.sup.1, N(R.sup.1).sub.2, C(O)N(R.sup.1).sub.2, NHC(O)R.sup.1, NR.sup.1C(O)R.sup.1, NHC(O)OR.sup.1, NR.sup.1C(O)OR.sup.1, NHC(O)NH.sub.2, NHC(O)NHR.sup.1, NHC(O)N(R.sup.1).sub.2, NR.sup.1O(O)NHR.sup.1, NR.sup.1C(O)N(R.sup.1).sub.2, SO.sub.2NHR.sup.1, SO.sub.2N(R.sup.1).sub.2, NR.sup.1SO.sub.2R.sup.1, NHSO.sub.2NHR.sup.1, NHSO.sub.2N(R.sup.1).sub.2, NR.sup.1SO.sub.2NHR.sup.1, NR.sup.1SO.sub.2N(R.sup.1).sub.2, C(O)NHNOH, C(O)NHNOR.sup.1, C(O)NHSO.sub.2R.sup.1, C(NH)NH.sub.2, C(NH)NHR.sup.1, C(NH)N(R.sup.1).sub.2, NHSO.sub.2NHR.sup.1, NHSO.sub.2N(CH.sub.3)R.sup.1, N(CH.sub.3)SO.sub.2N(CH.sub.3)R.sup.1, Cl, Br, I, CN, NO.sub.2, N.sub.3, C(O)H, CHNOH, CH(NOCH.sub.3), CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, and C(O)NH.sub.2, R.sup.1 is R.sup.2, R.sup.3, R.sup.4, R.sup.5, R.sup.6, R.sup.7, R.sup.2 is phenyl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane, R.sup.3 is heteroaryl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane, R.sup.4 is cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloakenyl or heterocycloakynyl, each of which is unfused or fused with benzene, heteroarene, R.sup.5 is alkyl, alkenyl or alkynyl each of which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of R.sup.8, OH, OR.sup.8, SH, SR.sup.8, S(O)R.sup.8, SO.sub.2R.sup.8, C(O)R.sup.8, C(O)OR.sup.8, OC(O)R.sup.8, NHR.sup.8, N(R.sup.8).sub.2, C(O)NHR.sup.8, C(O)N(R.sup.8).sub.2, NHC(O)R.sup.8, NR.sup.8C(O)R.sup.8, NHC(O)OR.sup.8, NR.sup.8C(O)OR.sup.8, NHC(O)NH.sub.2, NHC(O)NHR.sup.8, NHC(O)N(R.sup.8).sub.2, NR.sup.8C(O)NHR.sup.8, NR.sup.8C(O)N(R.sup.8).sub.2, SO.sub.2NHR.sup.8, SO.sub.2N(R.sup.8).sub.2, NR.sup.8SO.sub.2R.sup.8, NHSO.sub.2NHR.sup.8, NHSO.sub.2N(R.sup.8).sub.2, NR.sup.8SO.sub.2NHR.sup.8, NR.sup.8SO.sub.2N(R.sup.8).sub.2, C(O)NHNOH, C(O)NHNOR.sup.8, C(O)NHSO.sub.2R.sup.8, C(NH)NH.sub.2, C(NH)NHR.sup.8, C(NH)N(R.sup.8).sub.2, NHSO.sub.2NHR.sup.8, NHSO.sub.2N(CH.sub.3)R.sup.8, N(CH.sub.3)SO.sub.2N(CH.sub.3)R.sup.8, F, Cl, Br, I, CN, NO.sub.2, N.sub.3, C(O)H, CHNOH, CH(NOCH.sub.3), CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)OH, and C(O)NH.sub.2, R.sup.8 is R.sup.9, R.sup.10, R.sup.11, R.sup.12, R.sup.13, R.sup.14, R.sup.9 is phenyl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane, R.sup.10 is heteroaryl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane, R.sup.11 is cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloakenyl or heterocycloakynyl, each of which is unfused or fused with benzene, heteroarene, R.sup.12 is alkyl, alkenyl or alkynyl each of which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, SH, SMe, C(O)NH.sub.2, C(O)NHOH, CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)H, C(O)OH, C(O)OC.sub.2H.sub.5, OH, OCH.sub.3, OC.sub.2H.sub.5, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, CN, N.sub.3, NO.sub.2, F, Cl, Br, and I, R.sup.13 is phenyl which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, SH, SMe, C(O)NH.sub.2, C(O)NHOH, CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)H, C(O)OH, C(O)OC.sub.2H.sub.5, OH, OCH.sub.3, OC.sub.2H.sub.5, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, CN, N.sub.3, NO.sub.2, F, Cl, Br, and I, R.sup.14 is heteroaryl, which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, SH, SMe, C(O)NH.sub.2, C(O)NHOH, CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)H, C(O)OH, C(O)OC.sub.2H.sub.5, OH, OCH.sub.3, OC.sub.2H.sub.5, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, CN, N.sub.3, NO.sub.2, F, Cl, Br, and I, R.sup.6 is phenyl which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of R.sup.15, OH, OR.sup.15, SH, SR.sup.15, S(O)R.sup.15, SO.sub.2R.sup.15, C(O)R.sup.15, C(O)OR.sup.15, OC(O)R.sup.15, NHR.sup.15, N(R.sup.15).sub.2, C(O)NHR.sup.15, C(O)N(R.sup.15).sub.2, NHC(O)R.sup.15, NR.sup.15C(O)R.sup.15, NHC(O)OR.sup.15, NR.sup.15C(O)OR.sup.15, NHC(O)NH.sub.2, NHC(O)NHR.sup.15, NHC(O)N(R.sup.15).sub.2, NR.sup.15C(O)NHR.sup.15, NR.sup.15C(O)N(R.sup.15).sub.2, SO.sub.2NHR.sup.15, SO.sub.2N(R.sup.15).sub.2, NR.sup.15SO.sub.2R.sup.15, NHSO.sub.2NHR.sup.15, NHSO.sub.2N(R.sup.15).sub.2, NR.sup.15SO.sub.2NHR.sup.15, NR.sup.15SO.sub.2N(R.sup.15).sub.2, C(O)NHNOH, C(O)NHNOR.sup.15, C(O)NHSO.sub.2R.sup.15, C(NH)NH.sub.2, C(NH)NHR.sup.15, C(NH)N(R.sup.15).sub.2, NHSO.sub.2NHR.sup.15, NHSO.sub.2N(CH.sub.3)R.sup.15, N(CH.sub.3)SO.sub.2N(CH.sub.3)R.sup.15, F, Cl, Br, I, CN, NO.sub.2, N.sub.3, C(O)H, CHNOH, CH(NOCH.sub.3), CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)OH, and C(O)NH.sub.2, R.sup.15 is R.sup.16, R.sup.17, R.sup.18, R.sup.19, R.sup.20, R.sup.21, R.sup.16 is phenyl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane, R.sup.17 is heteroaryl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane, R.sup.18 is cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloakenyl or heterocycloakynyl, each of which is unfused or fused with benzene, heteroarene, R.sup.19 is alkyl, alkenyl or alkynyl each of which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, SH, SMe, C(O)NH.sub.2, C(O)NHOH, CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)H, C(O)OH, C(O)OC.sub.2H.sub.5, OH, OCH.sub.3, OC.sub.2H.sub.5, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, CN, N.sub.3, NO.sub.2, F, Cl, Br, and I, R.sup.20 is phenyl which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, SH, SMe, C(O)NH.sub.2, C(O)NHOH, CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)H, C(O)OH, C(O)OC.sub.2H.sub.5, OH, OCH.sub.3, OC.sub.2H.sub.5, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, CN, N.sub.3, NO.sub.2, F, Cl, Br, and I, R.sup.21 is heteroaryl, which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, SH, SMe, C(O)NH.sub.2, C(O)NHOH, CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)H, C(O)OH, C(O)OC.sub.2H.sub.5, OH, OCH.sub.3, OC.sub.2H.sub.5, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, CN, N.sub.3, NO.sub.2, F, Cl, Br, and I, R.sup.7 is heteroaryl, which is unsubstituted or substituted by one or more identical or different groups selected from R.sup.22, OH, OR.sup.22, SH, SR.sup.22, S(O)R.sup.22, SO.sub.2R.sup.22, C(O)R.sup.22, C(O)OR.sup.22, OC(O)R.sup.22, NHR.sup.22, N(R.sup.22).sub.2, C(O)NHR.sup.22, C(O)N(R.sup.22).sub.2, NHC(O)R.sup.22, NR.sup.22C(O)R.sup.22, NHC(O)OR.sup.22, NR.sup.22C(O)OR.sup.22, NHC(O)NH.sub.2, NHC(O)NHR.sup.22, NHC(O)N(R.sup.22).sub.2, NR.sup.22C(O)NHR.sup.22, NR.sup.22C(O)N(R.sup.22).sub.2, SO.sub.2NHR.sup.22, SO.sub.2N(R.sup.22).sub.2, NR.sup.22SO.sub.2R.sup.22, NHSO.sub.2NHR.sup.22, NHSO.sub.2N(R.sup.22).sub.2, NR.sup.22SO.sub.2NHR.sup.22, NR.sup.22SO.sub.2N(R.sup.22).sub.2, C(O)NHNOH, C(O)NHNOR.sup.22, C(O)NHSO.sub.2R.sup.22, C(NH)NH.sub.2, C(NH)NHR.sup.22, C(NH)N(R.sup.22).sub.2, NHSO.sub.2NHR.sup.22, NHSO.sub.2N(CH.sub.3)R.sup.22, N(CH.sub.3)SO.sub.2N(CH.sub.3)R.sup.22, F, Cl, Br, I, CN, NO.sub.2, N.sub.3, C(O)H, CHNOH, CH(NOCH.sub.3), CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)OH, C(O)NH.sub.2, R.sup.22 is R.sup.23, R.sup.24, R.sup.25, R.sup.26, R.sup.27, R.sup.28, R.sup.23 is phenyl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane, R.sup.24 is heteroaryl, which is unfused or fused with benzene, heteroarene, cycloalkane or heterocycloalkane, R.sup.25 is cycloalkyl, cycloalkenyl, cycloalkynyl, heterocycloalkyl, heterocycloakenyl or heterocycloakynyl, each of which is unfused or fused with benzene, heteroarene, R.sup.26 is alkyl, alkenyl or alkynyl each of which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, SH, SMe, C(O)NH.sub.2, C(O)NHOH, CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)H, C(O)OH, C(O)OC.sub.2H.sub.5, OH, OCH.sub.3, OC.sub.2H.sub.5, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, CN, N.sub.3, NO.sub.2, F, Cl, Br, and I, R.sup.27 is phenyl which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, SH, SMe, C(O)NH.sub.2, C(O)NHOH, CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)H, C(O)OH, C(O)OC.sub.2H.sub.5, OH, OCH.sub.3, OC.sub.2H.sub.5, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, CN, N.sub.3, NO.sub.2, F, Cl, Br, and I, R.sup.28 is heteroaryl, which is unsubstituted or substituted by one or more identical or different groups selected from the group consisting of NH.sub.2, NHCH.sub.3, N(CH.sub.3).sub.2, SH, SMe, C(O)NH.sub.2, C(O)NHOH, CF.sub.3, CF.sub.2CF.sub.3, OCF.sub.3, OCF.sub.2CF.sub.3, C(O)H, C(O)OH, C(O)OC.sub.2H.sub.5, OH, OCH.sub.3, OC.sub.2H.sub.5, CH.sub.3, C.sub.2H.sub.5, CH(CH.sub.3).sub.2, CN, N.sub.3, NO.sub.2, F, Cl, Br, and I, and/or pharmaceutically acceptable salts of the sulfonamides of general formula (I) thereof.

2. The fluorinated benzenesulfonamides according to claim 1, selected from the group consisting of: 2-(isopropylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-(benzylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-[(2-phenylethyl)amino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-[(1-phenylethyl)amino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-morpholin-4-yl-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-(cyclohexylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-(cycloheptylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-(cyclooctylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-(cyclododecylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-[(2,6-dimethoxybenzyl)amino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-[(3,4-dimethoxybenzyl)amino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-(2,3-dihydro-1H-inden-2-ylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-[(1S)-1,2,3,4-tetrahydronapthalen-1-ylamino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-{[(1S,2R)-2-hydroxy-1,2-diphenylethyl]amino}-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2-(cyclooctylamino)-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide; 2-(cyclododecylamino)-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide; 2-[(2,6-dimethoxybenzyl)amino]-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide; 2-[(3,4-dimethoxybenzyl)amino]-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide; 2-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide; 2-[(1S)-1,2,3,4-tetrahydronapthalen-1-ylamino)-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide; 2-{[(1S,2R)-2-hydroxy-1,2-diphenylethyl]amino}-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide; 2-(cyclooctylamino)-3,5,6-trifluorobenzenesulfonamide; 2-(cyclododecylamino)-3,5,6-trifluorobenzenesulfonamide; 3-(methylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-(tert-butylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-(benzylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-[(2-phenylethyl)amino]-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-morpholin-4-yl-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-(cyclooctylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-(cyclododecylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-[(2,6-dimethoxybenzyl)amino]-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-[(3,4-dimethoxybenzyl)amino]-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-(1-adamantylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-(2,3-dihydro-1H-inden-2-ylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-[(1S)-1,2,3,4-tetrahydronapthalen-1-ylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-{[(1S,2R)-2-hydroxy-1,2-diphenylethyl]amino}-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-{[(1R,2S)-2-hydroxy-1,2-diphenylethyl]amino}-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 3-(benzylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide; 3-(cyclooctylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide; 3-(cyclododecylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide; 3-[(2,6-dimethoxybenzyl)amino]-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide; 3-[(3,4-dimethoxybenzyl)amino]-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide; 3-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide; 3-[(1S)-1,2,3,4-tetrahydronapthalen-1-ylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide; 3-{[(1S,2R)-2-hydroxy-1,2-diphenylethyl]amino}-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide; 3,5-bis(cyclooctylamino)-2,6-difluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; and 3,5-bis[(3,4-dimethoxybenzyl)amino]-2,6-difluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide.

3. A composition for use in control of conditions where inhibition of carbonic anhydrase is necessary, said composition comprising an effective amount of a fluorinated benzenesulfonamide according to claim 1 as part of a pharmaceutical formulation, and wherein the conditions are selected from the group consisting of intraocular hypertension, glaucoma, altitude sickness, headaches, migraine, neurological disorders, obesity and cancer, and signs and/or symptoms thereof.

4. A composition for use in control of conditions where inhibition of carbonic anhydrase is necessary, said composition comprising an effective amount of a fluorinated benzenesulfonamide according to claim 2 as part of a pharmaceutical formulation, and wherein the conditions are selected from the group consisting of intraocular hypertension, glaucoma, altitude sickness, headaches, migraine, neurological disorders, obesity and cancer, and signs and/or symptoms thereof.

5. Fluorinated benzenesulfonamides selected from the group consisting of: 2,3,5,6-tetrafluoro-4-hydrazinobenzenesulfonamide; 4-(2-benzylidenehydrazino)-2,3,5,6-tetrafluorobenzenesulfonamide; 2,3,5,6-tetrafluoro-4[(2-hydroxyethyl)thio]benzenesulfonamide; 2,3,5,6-tetrafluoro-4[(2-hydroxyethyl)sulfonyl]benzenesulfonamide; 2-{[4-(aminosulfonyl)-2,3,5,6-tetrafluorophenyl]sulfonyl}ethyl acetate; 2,3,5,6-tetrafluoro-4-(propylthio)benzenesulfonamide; {[4-(aminosulfonyl)-2,3,5,6-tetrafluorophenyl]thio}acetic acid; 3-{[4-(aminosulfonyl)-2,3,5,6-tetrafluorophenyl]thio}propanoic acid; 6-{[4-(aminosulfonyl)-2,3,5,6-tetrafluorophenyl]amino}hexanoic acid; 2,3,5,6-tetrafluoro-4-(phenylthio)benzenesulfonamide; 2,3,5,6-tetrafluoro-4-(phenylsulfonyl)benzenesulfonamide; 2,3,5,6-tetrafluoro-4-phenoxybenzenesulfonamide; 4-(benzylthio)-2,3,5,6-tetrafluorobenzenesulfonamide; 4-(benzylamino)-2,3,5,6-tetrafluorobenzenesulfonamide; 2,3,5,6-tetrafluoro-4-{[2-(4-hydroxyphenyl)ethyl]amino}benzenesulfonamide; 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)thio]benzenesulfonamide; 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide; 2,3,5,6-tetrafluoro-4-morpholin-4-ylbenzenesulfonamide; 2,3,5,6-tetrafluoro-4-[(mesitylmethyl)thio]benzenesulfonamide; 4-[(4,6-dimethylpyrimidin-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide; 4-(1,3-benzothiazol-2-ylthio)-2,3,5,6-tetrafluorobenzenesulfonamide; 4-(1-adamantylamino)-2,3,5,6-tetrafluorobenzenesulfonamide; 3-{[4-(aminosulfonyl)-2,3,5,6-tetrafluorophenyl]thio}-[1,2,3]thiadiazolo[3,4-a]benzimidazole; and 4-[(4,5-diphenyl-1H-imidazol-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide; and pharmaceutically acceptable salts thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION

Abbreviations Used in the Text

(1) AZM—acetazolamide,

(2) CA—carbonic anhydrase,

(3) DMSO—dimethyl sulfoxide,

(4) Et.sub.3N—triethylamine,

(5) EZA—ethoxzolamide,

(6) HRMS—high-resolution mass spectrometry,

(7) ITC—isothermal titration calorimetry,

(8) K.sub.d—dissociation constant,

(9) NMR—nuclear magnetic resonance,

(10) Ph—phenyl,

(11) TSA—fluorescent thermal shift assay.

(12) New compounds of the invention are obtained according to general synthesis schemes A-J.

(13) Scheme A.

(14) Synthesis of 4-substituted-2,3,5,6-tetrafluorobenzenesulfonamides (compounds 2a-x). Sulfonamides 2a, c, f-j, l-p, r-x were obtained from compound 1 by using appropriate nucleophile in ethanol, methanol or DMSO in the presence of Et.sub.3N or K.sub.2CO.sub.3 (excess of nucleophile was used in several cases instead of mentioned bases). The compounds 2d, e were prepared by oxidation of 2c with CH.sub.3COOH\H.sub.2O.sub.2. Oxidation of the compounds 2j, p with CrO.sub.3 gave 2k, q. The reaction of 2a with benzaldehyde leaded to formation of 2b.

(15) ##STR00003##

(16) Scheme B.

(17) Synthesis of 2-substituted-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamides (compounds 3a-o). Sulfonamides 3a-o were obtained from compound 2p by using appropriate nucleophile in DMSO in the presence of Et.sub.3N.

(18) ##STR00004## ##STR00005##

(19) Scheme C.

(20) Synthesis of 2-substituted-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamides (compounds 4a-g). Sulfonamides 4a-g were obtained from compound 2c by using appropriate nucleophile in DMSO in the presence of Et.sub.3N.

(21) ##STR00006##

(22) Scheme D.

(23) Synthesis of 2-(cyclooctylamino)-3,5,6-trifluoro-4-(propylthio)benzenesulfonamide (compound 5). The compound 5 was obtained from compound 2f by using cyclooctylamine in DMSO in the presence of Et.sub.3N.

(24) ##STR00007##

(25) Scheme E.

(26) Synthesis of 2-(cyclooctylamino)-3,5,6-trifluoro-4-{[2-(4-hydroxyphenyl)ethyl]amino}benzensulfonamide (compound 6). The compound 6 was obtained from compound 2o by using cyclooctylamine in DMSO in the presence of Et.sub.3N.

(27) ##STR00008##

(28) Scheme F.

(29) Synthesis of 2-substituted-3,5,6-trifluorobenzensulfonamides (compounds 8a-f). Sulfonamides 8a-f were obtained from compound 7 by using appropriate nucleophile in DMSO in the presence of Et.sub.3N.

(30) ##STR00009##

(31) Scheme G.

(32) Synthesis of 3-substituted-2,5,6-tri fluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamides (compounds 9a-o). Sulfonamides 9d, f-o were obtained from compound 2q by using appropriate nucleophile in DMSO in presence of Et.sub.3N. The compound 9a was synthesized using excess of methylamine in MeOH. The compound 9c was synthesized in MeOH in presence of Et.sub.3N. Fluorinated derivatives 9b, 9e were obtained by using 2 eq of nucleophile in DMSO.

(33) ##STR00010## ##STR00011##

(34) Scheme H.

(35) Synthesis of 3-substituted-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamides (compounds 10a-h). Sulfonamides 10c-h were obtained from compound 2d by using 2 eq of appropriate nucleophile in DMSO. The compounds 10a, b were synthesized in MeOH.

(36) ##STR00012## ##STR00013##

(37) Scheme I.

(38) Synthesis of 3,5-bis(cyclooctylamino)-2,6-difluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (compound 11). The compound 11 was obtained from compound 2q by using 2 eq of cyclooctylamine in DMSO in the presence of Et.sub.3N.

(39) ##STR00014##

(40) Scheme J.

(41) Synthesis of 3,5-bis[(3,4-dimetoxybenzyl)amino-2,6-difluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (compound 12). The compound 12 was obtained from compound 2d by using 4 eq of 3,4-dimethoxybenzylamine in DMSO.

(42) ##STR00015##

Embodiments of the Invention

(43) Represented below are specific examples of invention compounds synthesis. These examples are presented only for illustrative purpose of the invention; they do not limit the scope of the invention.

Example 1. Preparation of 2,3,5,6-tetrafluoro-4-hydrazinobenzenesulfonamide (Compound 2a)

(44) The mixture of pentafluorobenzenesulfonamide (compound 1) (0.32 g, 1.295 mmol), NH.sub.2NH.sub.2×H.sub.2O (0.126 mL, 2.59 mmol), and EtOH (10 mL) was stirred at ambient temperature for 24 h. EtOH was evaporated in vacuum and the resultant precipitate was filtered, washed with H.sub.2O. Recrystallization was accomplished from H.sub.2O. Yield: 0.2 g, 60%, decomp. at 160-161° C.

(45) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 4.68 (2H, s, NH.sub.2), 7.75 (1H, s, NH), 7.98 (2H, s, SO.sub.2NH.sub.2).

(46) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 108.6 (C1, t, J(.sup.19F—.sup.13C)=14 Hz), 135 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 136 (C3, C5, d, J(.sup.19F—.sup.13C)=240 Hz), 144.1 (C2, C6, d, J(.sup.19F—.sup.13C)=240 Hz).

(47) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −143.05 (2F, d, J=15.8 Hz), −160.15 (2F, d, J=17.2 Hz).

(48) HRMS calcd. for C.sub.6H.sub.5F.sub.4N.sub.3O.sub.2S [(M+H).sup.+]: 335.9782. found: 335.9780.

Example 2. Preparation of 4-(2-benzylidenehydrazino)-2,3,5,6-tetrafluorobenzenesulfonamide (Compound 2b)

(49) The mixture of 2,3,5,6-tetrafluoro-4-hydrazinobenzenesulfonamide (compound 2a) (0.13 g, 0.5 mmol), benzaldehyde (0.051 mL, 0.5 mmol), and MeOH (10 mL) was stirred at ambient temperature for 4 h. MeOH was evaporated in vacuum. Recrystallization was accomplished from iPrOH. Yield: 0.14 g, 82%, decomp. at 272-273° C.

(50) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 7.35-7.55 (3H, m, Ph), 7.6-7.75 (2H, m, Ph), 8.12 (1H, s, NH), 8.25 (2H, s, SO.sub.2NH.sub.2), 10.96 (1H, s, CH).

(51) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 111.7 (C1, t, J(.sup.19F—.sup.13C)=14 Hz), 127.1 (Ph), 128.5 (C4, t, J(.sup.19F—.sup.13C)=13 Hz), 129.5 (Ph), 130.1 (Ph), 135.1 (Ph), 136.3 (C3, C5, d, J(.sup.19F—.sup.13C)=244 Hz), 144.7 (CH), 144.5 (C2, C6, d, J(.sup.19F—.sup.13C)=251 Hz).

(52) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −141.6 (2F, d, J=16.4 Hz), −156.6 (2F, d, J=18 Hz).

(53) HRMS calcd. for C.sub.13H.sub.9F.sub.4N.sub.3O.sub.2S [(M+H).sup.+]: 348.0424. found: 348.0433.

Example 3. Preparation of 2,3,5,6-tetrafluoro-4[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (Compound 2d)

(54) The mixture of 2,3,5,6-tetrafluoro-4[(2-hydroxyethyl)thio]benzenesulfonamide (compound 2c) (0.1 g, 0.33 mmol), CH.sub.3COOH (2 mL), H.sub.2O (1 mL) was heated at 70° C. for 22 h. H.sub.2O.sub.2 was added by portions (0.2 mL) every 4 h (overall amount 1 mL). The progress of reaction was monitored by TLC. The solvent was then removed in vacuum and crude product was purified by crystallization from H.sub.2O. Yield: 0.067 g, 61%, mp 139-140° C.

(55) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.75 (2H, t, J=5.4 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.86 (2H, t, J=5.4 Hz, SO.sub.2CH.sub.2CH.sub.2), 5.01 (1H, br s, OH), 8.65 (2H, s, SO.sub.2NH.sub.2).

(56) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 55.9 (SO.sub.2CH.sub.2CH.sub.2), 60.2 (SO.sub.2CH.sub.2CH.sub.2), 123.4 (C1 or C4, t, J(.sup.19F—.sup.13C)=15 Hz), 128 (C1 or C4, t, J(.sup.19F—.sup.13C)=16 Hz), 143.5 (C3, C5 or C2, C6, dd, .sup.1J(.sup.19F—.sup.13C)=254 Hz, .sup.2J(.sup.19F—.sup.13C)=18 Hz), 145 (C3, C5 or C2, C6, dd, .sup.1J(.sup.19F—.sup.13C)=248 Hz, .sup.2J(.sup.19F—.sup.13C) 15 Hz).

(57) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −136.7 (2F, dd, .sup.1J=26 Hz, .sup.2J=12 Hz), −137.6 (2F, dd, .sup.1J=26 Hz, .sup.2J=12 Hz).

(58) HRMS calcd. for C.sub.8H.sub.7F.sub.4NO.sub.5S.sub.2 [(M−H).sup.−]: 335.9629. found: 335.9635.

Example 4. Preparation of 2-{[4-(aminosulfonyl)-2,3,5,6-tetrafluorophenyl]sulfonyl}ethyl acetate (Compound 2e)

(59) The mixture of 2,3,5,6-tetrafluoro-4[(2-hydroxyethyl)thio]benzenesulfonamide (compound 2c) (0.1 g, 0.33 mmol), CH.sub.3COOH (2 mL) was heated at 70° C. for 24 h. H.sub.2O.sub.2 was added by portions (0.1 mL) every 8 h (overall amount 0.3 mL). The progress of reaction was monitored by TLC. The solvent was then removed in vacuum and crude product was purified by two times crystallization from H.sub.2O. Yield: 0.04 g, 36%, mp 154° C.

(60) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.85 (3H, s, CH.sub.3), 4.04 (2H, t, J=5.4 Hz, SO.sub.2CH.sub.2CH.sub.2), 4.43 (2H, t, J=5.4 Hz, SO.sub.2CH.sub.2CH.sub.2), 8.7 (2H, s, SO.sub.2NH.sub.2).

(61) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 20.8 (CH.sub.3), 56.6 (SO.sub.2CH.sub.2CH.sub.2), 58 (SO.sub.2CH.sub.2CH.sub.2), 122 (C1 or C4, t, J(.sup.19F—.sup.13C)=14 Hz), 128.6 (C1 or C4, t, J(.sup.19F—.sup.13C)=16 Hz), 143.7 (C3, C5 or C2, C6, d, J(.sup.19F—.sup.13C)=255 Hz), 145 (C3, C5 or C2, C6, d, J(.sup.19F—.sup.13C)=248 Hz), 170.2 (C═O).

(62) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −136.2 (2F, dd, .sup.1J=26 Hz, .sup.2J=12 Hz), −137.1 (2F, dd, .sup.1J=26 Hz, .sup.2J=12 Hz).

(63) HRMS calcd. for C.sub.10H.sub.9F.sub.4NO.sub.6S.sub.2 [(M−H).sup.−]: 377.9735. found: 377.9737.

Example 5. Preparation of 2,3,5,6-tetrafluoro-4[(2-hydroxyethyl)thio]benzenesulfonamide (Compound 2c), 2,3,5,6-tetrafluoro-4-(propylthio)benzenesulfonamide (Compound 2f), {[4-(aminosulfonyl)-2,3,5,6-tetrafluorophenyl]thio}acetic acid (Compound 2 g), 3-{[4-(aminosulfonyl)-2,3,5,6-tetrafluorophenyl]thio}propanoic acid (Compound 2 h), 6-{[4-(aminosulfonyl)-2,3,5,6-tetrafluorophenyl]amino}hexanoic acid (Compound 2i), 4-(benzylthio)-2,3,5,6-tetrafluorobenzenesulfonamide (Compound 2m), 4-(benzylamino)-2,3,5,6-tetrafluorobenzenesulfonamide (Compound 2n), 2,3,5,6-tetrafluoro-4-{[2-(4-hydroxyphenyl)ethyl]amino}benzenesulfonamide (Compound 2o), 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 2p), 2,3,5,6-tetrafluoro-4-[(mesitylmethyl)thio]benzenesulfonamide (Compound 2s), 3-{[4-(aminosulfonyl)-2,3,5,6-tetrafluorophenyl]thio}-[1,2,3]thiadiazolo[3,4-a]benzimidazole (Compound 2w)

(64) The mixture of pentafluorobenzenesulfonamide (compound 1) (0.25 g, 1 mmol), MeOH (10 mL), Et.sub.3N (0.141 mL, 1.01 mmol) and appropriate nucleophile (1.1 mmol) was refluxed. The compounds 2c, h, i, n, p, s were obtained after 8 h, the compound 2f was obtained after 10 h, the compounds 2g and 2o were obtained after 15 h, the compound 2m was obtained after 4 h, the compound 2w was obtained after 1 h. MeOH was evaporated in vacuum and the resultant precipitate was filtered, washed with H.sub.2O (except 2 g, h, i).

(65) The compound 2c. Recrystallization was accomplished from H.sub.2O. Yield: 0.22 g, 71%, mp 111-112° C.

(66) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.16 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.6 (2H, k, J=6 Hz, SCH.sub.2CH.sub.2), 4.97 (1H, t, J=3.6 Hz, OH), 8.43 (2H, s, SO.sub.2NH.sub.2).

(67) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 37.3 (SCH.sub.2CH.sub.2), 61.4 (SCH.sub.2CH.sub.2), 119.95 (C1, t, J(.sup.19F-.sup.13C)=14 Hz), 122.85 (C4, t, J(.sup.19F—.sup.13C)=14.9 Hz), 143.2 (C2, C6, ddd, .sup.1J(.sup.19F—.sup.13C)=254 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 147 (C3, C5, ddd, .sup.1J(.sup.19F—.sup.13C)=228 Hz, .sup.2J(.sup.19F—.sup.13C)=14 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz).

(68) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −133.54 (2F, dd, .sup.1J=26.8 Hz, .sup.2J=13.8 Hz), −139.97 (2F, dd, .sup.1J=26.2 Hz, .sup.2J=12.7 Hz).

(69) HRMS calcd. for C.sub.8H.sub.7F.sub.4NO.sub.3S.sub.2 [(M−H).sup.−]: 303.9731. found: 303.9729.

(70) The compound 2f. Recrystallization was accomplished from EtOH:H.sub.2O (2:1). Yield: 0.25 g, 81%, mp 120° C.

(71) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 0.96 (3H, t, J=7.2 Hz, CH.sub.3), 1.55 (2H, sex, J=7.2 Hz, CH.sub.2), 3.04 (2H, t, J=7.2 Hz, CH.sub.2), 8.41 (2H, s, SO.sub.2NH.sub.2).

(72) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 13.3 (CH.sub.3), 23.5 (CH.sub.2), 36.4 (CH.sub.2), 119.2 (C1, t, J(.sup.19F-.sup.13C)=20 Hz), 123.1 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 143.2 (C2, C6, dd, .sup.1J(.sup.19F—.sup.13C)=254 Hz, .sup.2J(.sup.19F-.sup.13C)=17 Hz), 147.2 (C3, C5, dd, .sup.1J(.sup.19F—.sup.13C)=244 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz).

(73) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −133.9 (2F, dd, .sup.1J=25 Hz, .sup.2J=11 Hz), −139.6 (2F, dd, .sup.1J=25 Hz, .sup.2J=14 Hz).

(74) HRMS calcd. for C.sub.9H.sub.9F.sub.4NO.sub.2S.sub.2 [(M−H).sup.−]: 301.9938. found: 301.9940.

(75) The compound 2 g. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with ethyl acetate. Yield: 0.12 g, 38%, mp 158-159° C.

(76) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.9 (2H, s, CH.sub.2), 8.44 (2H, s, SO.sub.2NH.sub.2), 12.8 (1H, br s, COOH).

(77) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 36 (CH.sub.2), 118.8 (C1, t, J(.sup.19F—.sup.13C)=20 Hz), 123.3 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 143.1 (C2, C6, dd, .sup.1J(.sup.19F—.sup.13C)=254 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz), 147 (C3, C5, d, J(.sup.19F—.sup.13C)=249 Hz), 170.3 (COOH).

(78) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −133.6 (2F, dd, .sup.1J=25 Hz, .sup.2J=10 Hz), −139.8 (2F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz).

(79) HRMS calcd. for C.sub.8H.sub.5F.sub.4NO.sub.4S.sub.2 [(M−H).sup.−]: 317.9523. found: 317.9525.

(80) The compound 2 h. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with ethyl acetate. Yield: 0.2 g, 59%, mp 168-169° C.

(81) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.59 (2H, t, J=6.9 Hz, CH.sub.2), 3.21 (2H, t, J=6.6 Hz, CH.sub.2), 8.42 (2H, s, SO.sub.2NH.sub.2), 12.4 (1H, br s, COOH).

(82) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 30.1 (CH.sub.2), 35.4 (CH.sub.2), 118.8 (C1, t, J(.sup.19F—.sup.13C)=20 Hz), 123.4 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 143.2 (C2, C6, dd, .sup.1J(.sup.19F—.sup.13C)=254 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz), 147.3 (C3, C5, dd, .sup.1J(.sup.19F—.sup.13C)=241 Hz, .sup.2J(.sup.19F—.sup.13C)=19 Hz), 173.1 (COOH).

(83) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −133.3 (2F, dd, .sup.1J=25 Hz, .sup.2J=10 Hz), −139.6 (2F, dd, .sup.1J=25 Hz, .sup.2J=10 Hz).

(84) HRMS calcd. for C.sub.9H.sub.7F.sub.4NO.sub.4S.sub.2 [(M−H).sup.−]: 331.968. found: 331.9683.

(85) The compound 2i. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with ethyl acetate. Yield: 0.15 g, 42%, mp 142-144° C.

(86) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.2-1.6 (8H, m, (CH.sub.2).sub.4), 2.22 (2H, t, J=7.2 Hz, CH.sub.2), 6.7 (1H, s, NH), 7.93 (2H, s, SO.sub.2NH.sub.2), 12.01 (1H, s, COOH).

(87) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 24.9 (CH.sub.2), 26.3 (CH.sub.2), 30.7 (CH.sub.2), 34.3 (CH.sub.2), 44.7 (CH.sub.2), 108.2 (C1, t, J(.sup.19F—.sup.13C)=15 Hz), 132 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 136.4 (C2, C6, d, J(.sup.19F—.sup.13C)=238 Hz), 144.7 (C3, C5, d, J(.sup.19F—.sup.13C)=247 Hz), 175.1 (COOH).

(88) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −142.7 (2F, d, J=16.6 Hz), −161.69 (2F, d, J=18.3 Hz).

(89) HRMS calcd. for C.sub.12H.sub.14F.sub.4N.sub.2O.sub.4S [(M−H).sup.−]: 357.0538. found: 357.0542.

(90) The compound 2m. Recrystallization was accomplished from iPrOH. Yield: 0.23 g, 64%, mp 184° C.

(91) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 4.3 (2H, s, CH.sub.2), 7.1-7.5 (5H, m, ArH), 8.44 (2H, s, SO.sub.2NH.sub.2).

(92) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 38.6 (CH.sub.2), 118.5 (C1, t, J(.sup.19F—.sup.13C)=21 Hz), 123.6 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 128.4 (Ar), 129.3 (Ar), 129.5 (Ar), 137.4 (Ar), 143.1 (C2, C6, dd, .sup.1J(.sup.19F-.sup.13C)=254 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz), 147.3 (C3, C5, dd, .sup.1J(.sup.19F—.sup.13C)=248 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz).

(93) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −132.8 (2F, dd, .sup.1J=27 Hz, .sup.2J=11 Hz), −139.8 (2F, dd, .sup.1J=26 Hz, .sup.2J=10 Hz).

(94) HRMS calcd. for C.sub.13H.sub.9F.sub.4NO.sub.2S.sub.2 [(M−H).sup.−]: 349.9938. found: 349.9940.

(95) The compound 2n. Recrystallization was accomplished from H.sub.2O:EtOH (1:1). Yield: 0.21 g, 62%, mp 132-133° C.

(96) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 4.56 (2H, d, J=6.3 Hz, CH.sub.2), 7.2-7.6 (6H, m, NH, ArH), 7.98 (2H, s, SO.sub.2NH.sub.2).

(97) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 47.9 (CH.sub.2), 109 (C1, t, J(.sup.19F—.sup.13C)=17 Hz), 127.2 (Ar), 127.7 (Ar), 129 (Ar), 131.8 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 136.7 (C2, C6, d, J(.sup.19F—.sup.13C)=240 Hz), 140.5 (Ar), 144.3 (C3, C5, d, J(.sup.19F—.sup.13C)=241 Hz).

(98) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −142.51 (2F, d, J=18.3 Hz), −160.38 (2F, d, J=18.3 Hz).

(99) HRMS calcd. for C.sub.13H.sub.10F.sub.4N.sub.2O.sub.2S [(M+H).sup.+]: 335.0472. found: 335.0472.

(100) The compound 2o. Recrystallization was accomplished from EtOH:H.sub.2O (1:2). Yield: 0.25 g, 68%, decomp. at 100° C.

(101) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.74 (2H, t, J=7.8 Hz, CH.sub.2), 3.45-3.6 (2H, m, CH.sub.2), 6.7 (2H, d, J=8.4 Hz, ArH), 7.01 (2H, d, J=8.4 Hz, ArH), 7.96 (2H, s, SO.sub.2NH.sub.2), 9.23 (1H, s, NH).

(102) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 36.5 (CH.sub.2), 46.8 (CH.sub.2), 108.4 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 115.9 (Ar), 129.4 (Ar), 130.3 (Ar), 131.9 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 136.5 (C2, C6, d, J(.sup.19F—.sup.13C)=240 Hz), 144.4 (C3, C5, d, J(.sup.19F—.sup.13C)=240 Hz), 156.5 (Ar).

(103) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −142.6 (2F, d, J=19 Hz), −161.4 (2F, d, J=18 Hz).

(104) HRMS calcd. for C.sub.14H.sub.12F.sub.4N.sub.2O.sub.3S [(M−H).sup.−]: 363.0432. found: 363.0435.

(105) The compound 2p. Recrystallization was accomplished from EtOH:H.sub.2O (2:1). Yield: 0.24 g, 71%, mp 121° C.

(106) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.91 (2H, t, J=7.2 Hz, SCH.sub.2CH.sub.2), 3.37 (2H, t, J=7.2 Hz, SCH.sub.2CH.sub.2), 7.1-7.4 (5H, m, ArH), 8.41 (2H, s, SO.sub.2NH.sub.2).

(107) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 35.4 (SCH.sub.2CH.sub.2), 36.6 (SCH.sub.2CH.sub.2), 119 (C1, t, J(.sup.19F-.sup.13C)=20 Hz), 122.9 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 127.2 (Ar), 128.9 (Ar), 129.3 (Ar), 139.7 (Ar), 143.2 (C2, C6, dd, .sup.1J(.sup.19F—.sup.13C)=257 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz), 147 (C3, C5, dd, .sup.1J(.sup.19F—.sup.13C)=249 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz).

(108) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −133.45 (2F, dd, .sup.1J=26.5 Hz, .sup.2J=13.5 Hz), −139.8 (2F, dd, .sup.1J=25.6 Hz, .sup.2J=10.7 Hz).

(109) HRMS calcd. for C.sub.14H.sub.11F.sub.4NO.sub.2S.sub.2 [(M−H).sup.−]: 364.0095. found: 364.0100.

(110) The compound 2s. Recrystallization was accomplished from EtOH. Yield: 0.29 g, 73%, mp 213-214° C.

(111) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.23 (3H, s, CH.sub.3), 2.3 (6H, s, CH.sub.3), 4.31 (2H, s, CH.sub.2), 6.89 (2H, s, ArH), 8.47 (2H, s, SO.sub.2NH.sub.2).

(112) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 19.6 (CH.sub.3), 21.3 (CH.sub.3), 34.3 (CH.sub.2), 119.2 (C1, t, J(.sup.19F-.sup.13C)=21 Hz), 123.6 (C4, t, J(.sup.19F—.sup.13C)=18 Hz), 129.4 (Ar), 129.7 (Ar), 137.8 (Ar), 137.9 (Ar), 143.3 (C2, C6, d, J(.sup.19F—.sup.13C)=253 Hz), 147.4 (C3, C5, d, J(.sup.19F—.sup.13C)=243 Hz).

(113) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −133.1 (2F, dd, .sup.1J=25 Hz, .sup.2J=10 Hz), −139.5 (2F, dd, .sup.1J=25 Hz, .sup.2J=11 Hz).

(114) HRMS calcd. for C.sub.16H.sub.15F.sub.4NO.sub.2S.sub.2 [(M−H).sup.−]: 392.0408. found: 392.0412.

(115) The compound 2w. The obtained compound was washed with MeOH. Yield: 0.13 g, 30%, decomp. at 233-234° C.

(116) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 7.33 (1H, t, J=7.8 Hz, ArH), 7.57 (1H, t, J=8.4 Hz, ArH), 7.81 (1H, d, J=8.7 Hz, ArH), 8.2 (1H, d, J=8.1 Hz, ArH), 8.55 (2H, s, SO.sub.2NH.sub.2).

(117) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 118.4 (Ar), 120.2 (C1, t, J(.sup.19F—.sup.13C)=15 Hz), 125.9 (Ar), 126 (Ar), 127.7 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 130 (Ar), 133.2 (Ar), 133.4 (Ar), 148 (C2, C6, d, J(.sup.19F-.sup.13C)=254 Hz), 152 (C3, C5, d, J(.sup.19F—.sup.13C)=236 Hz), 158.7 (Ar), 158.8 (Ar).

(118) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −127.24 (2F, dd, .sup.1J=25.9 Hz, .sup.2J=11.3 Hz), −134 (2F, dd, .sup.1J=25.9 Hz, .sup.2J=10.7 Hz).

(119) HRMS calcd. for C.sub.14H.sub.6F.sub.4N.sub.4O.sub.2S.sub.3 [(M+H).sup.+]: 434.9662. found: 434.9667.

Example 6. Preparation of 2,3,5,6-tetrafluoro-4-(phenylthio)benzenesulfonamide (Compound 2j)

(120) The mixture of pentafluorobenzenesulfonamide (compound 1) (0.28 g, 1.13 mmol), MeOH (10 mL), Et.sub.3N (0.158 mL, 1.13 mmol) and HSPh (0.116 mL, 1.13 mmol) was stirred at ambient temperature for 2 h. MeOH was evaporated in vacuum and the resultant precipitate was filtered, washed with H.sub.2O. Recrystallization was accomplished from EtOH:H.sub.2O (2:1). Yield: 0.28 g, 74%, mp 139° C.

(121) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 7.2-7.8 (5H, m, ArH), 8.47 (2H, s, SO.sub.2NH.sub.2).

(122) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 117.7 (C1, t, J(.sup.19F—.sup.13C)=19.6 Hz), 124.5 (C4, t, J(.sup.19F-.sup.13C)=16.3 Hz), 128.7 (Ar), 130.3 (Ar), 130.4 (Ar), 132.4 (Ar), 143.5 (C2, C6, ddd, .sup.1J(.sup.19F—.sup.13C)=255 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 147.2 (C3, C5, ddd, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz).

(123) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −132.59 (2F, dd, .sup.1J=24.5 Hz, .sup.2J=11.6 Hz), −138.75 (2F, dd, .sup.1J=24.5 Hz, .sup.2J=10.4 Hz).

(124) HRMS calcd. for C.sub.12H.sub.7F.sub.4NO.sub.2S.sub.2 [(M−H).sup.−]: 335.9782. found: 335.9780.

Example 7. Preparation of 2,3,5,6-tetrafluoro-4-(phenylsulfonyl)benzenesulfonamide (Compound 2k)

(125) The mixture of 2,3,5,6-tetrafluoro-4-(phenylthio)benzenesulfonamide (compound 2j) (0.2 g, 0.59 mmol), CrO.sub.3 (0.18 g, 1.8 mmol), CH.sub.3COOH (10 mL), H.sub.2O (0.5 mL) was heated at 70° C. for 2 h. The solvent was then removed in vacuum and the resultant precipitate was filtered, washed with H.sub.2O. Recrystallization was accomplished from EtOH. Yield: 0.17 g, 77%, mp 266-267° C.

(126) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 7.77 (2H, t, J=7.8 Hz, ArH), 7.87 (1H, t, J=7.5 Hz, ArH), 8.09 (2H, d, J=7.8 Hz, ArH), 8.59 (2H, s, SO.sub.2NH.sub.2).

(127) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 123 (C1, C4, t, J(.sup.19F—.sup.13C)=13 Hz), 128.4 (Ar), 130.7 (Ar), 136.2 (Ar), 140.4 (Ar), 143.8 (C2, C6 or C3, C5, dd, .sup.1J(.sup.19F—.sup.13C)=258 Hz, .sup.2J(.sup.19F-.sup.13C)=18 Hz), 144.4 (C2, C6 or C3, C5, dd, .sup.1J(.sup.19F—.sup.13C)=258 Hz, .sup.2J(.sup.19F—.sup.13C)=18 Hz).

(128) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −136.6 (4F, s).

(129) HRMS calcd. for C.sub.12H.sub.7F.sub.4NO.sub.4S.sub.2 [(M−H).sup.−]: 367.968. found: 367.9684.

Example 8. Preparation of 2,3,5,6-tetrafluoro-4-phenoxybenzenesulfonamide (Compound 2l)

(130) The mixture of pentafluorobenzenesulfonamide (compound 1) (0.2 g, 0.81 mmol), sodium phenoxide trihydrate (0.145 g, 0.85 mmol) and DMSO (1 mL) was stirred at ambient temperature for 4 h. The mixture was then diluted with H.sub.2O (20 mL) and the resultant precipitate was filtered, washed with H.sub.2O. Recrystallization was accomplished from EtOH:H.sub.2O (1:2). Yield: 0.07 g, 27%, mp 164-165° C.

(131) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 7.0-7.6 (5H, m, ArH), 8.44 (2H, s, SO.sub.2NH.sub.2).

(132) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 116.4 (Ar), 120.4 (C1, t, J(.sup.19F—.sup.13C)=14 Hz), 125 (Ar), 130.9 (Ar), 136.3 (C4, t, J(.sup.19F—.sup.13C)=14 Hz), 141.9 (C3, C5, d, J(.sup.19F—.sup.13C)=250 Hz), 144.4 (C2, C6, d, J(.sup.19F—.sup.13C)=256 Hz), 157 (Ar).

(133) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −139.6 (2F, d, J=16 Hz), −154 (2F, d, J=16 Hz).

(134) HRMS calcd. for C.sub.12H.sub.7F.sub.4NO.sub.3S [(M−H).sup.−]: 320.001. found: 320.0008.

Example 9. Preparation of 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 2q)

(135) The mixture of 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (2p) (0.1 g, 0.27 mmol), CrO.sub.3 (0.082 g, 0.82 mmol), CH.sub.3COOH (10 mL), H.sub.2O (0.2 mL) was heated at 60° C. for 4 h. The resultant precipitate was filtered, washed with H.sub.2O. Yield: 0.07 g, 64%, mp 248-249° C.

(136) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.12 (2H, t, J=7.2 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.97 (2H, t, J=7.8 Hz, SO.sub.2CH.sub.2CH.sub.2), 7.1-7.4 (5H, m, ArH), 8.66 (2H, s, SO.sub.2NH.sub.2).

(137) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 28.6 (SO.sub.2CH.sub.2CH.sub.2), 58 (SO.sub.2CH.sub.2CH.sub.2), 121.5 (C1 or C4, t, J(.sup.19F—.sup.13C)=15 Hz), 127.5 (Ar), 128.2 (C1 or C4, t, J(.sup.19F—.sup.13C)=16 Hz), 128.9 (Ar), 129.2 (Ar), 137.4 (Ar), 143.5 (C2, C6 or C3, C5, dd, .sup.1J(.sup.19F—.sup.13C)=258 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz), 144.8 (C2, C6 or C3, C5, dd, .sup.1J(.sup.19F—.sup.13C)=255 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz).

(138) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −136 (2F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −137.1 (2F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz).

(139) HRMS calcd. for C.sub.14H.sub.11F.sub.4NO.sub.4S.sub.2 [(M−H).sup.−]: 395.9993. found: 395.9996.

Example 10. Preparation of 2,3,5,6-tetrafluoro-4-morpholin-4-ylbenzenesulfonamide (Compound 2r)

(140) The mixture of pentafluorobenzenesulfonamide (compound 1) (0.2 g, 0.809 mmol), MeOH (10 mL), morpholine (0.141 mL, 1.62 mmol) was refluxed for 8 h. MeOH was evaporated in vacuum and the resultant precipitate was filtered, washed with H.sub.2O. Recrystallization was accomplished from EtOH:H.sub.2O (1:1). Yield: 0.13 g, 52%, mp 233-234° C.

(141) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.32 (4H, br s, 2CH.sub.2), 3.7 (4H, br s, 2CH.sub.2), 8.2 (2H, s, SO.sub.2NH.sub.2).

(142) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 51.2 (N(CH.sub.2).sub.2, t, J(.sup.19F—.sup.13C)=3.6 Hz), 67.2 (O(CH.sub.2).sub.2), 115.4 (C1, t, J(.sup.19F—.sup.13C)=19 Hz), 133.3 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 144.7 (C3, C5, d, J(.sup.19F—.sup.13C)=256 Hz), 146.3 (C2, C6, d, J(.sup.19F—.sup.13C)=244 Hz).

(143) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −141.6 (2F, d, J=15.8 Hz), −151.2 (2F, d, J=16.6 Hz).

(144) HRMS calcd. for C.sub.10H.sub.10F.sub.4N.sub.2O.sub.3S [(M+H).sup.+]: 315.0421. found: 315.0426.

Example 11. Preparation of 4-[(4,6-dimethylpyrimidin-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide (2t), 4-(1,3-benzothiazol-2-ylthio)-2,3,5,6-tetrafluorobenzenesulfonamide (2u), 4-[(4,5-diphenyl-1H-imidazol-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide (2x)

(145) The mixture of pentafluorobenzenesulfonamide (compound 1) (0.1 g, 0.404 mmol), K.sub.2CO.sub.3 (0.056 g, 0.406 mmol), DMSO (2 mL) and appropriate nucleophile (0.404 mmol) was stirred at ambient temperature for 5 h. The mixture was then diluted with H.sub.2O (20 mL) and extracted with EtAc (2×10 mL). The combined organic phase was dried over Na.sub.2SO.sub.4 and evaporated in vacuum.

(146) The compound 2t. Recrystallization was accomplished from EtOH:H.sub.2O (2:1). Yield: 0.12 g, 80%, mp 131-132° C.

(147) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.34 (6H, s, 2CH.sub.3), 7.15 (1H, s, ArH), 8.58 (2H, s, SO.sub.2NH.sub.2).

(148) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 24 (CH.sub.3), 114.1 (C1, t, J(.sup.19F—.sup.13C)=20 Hz), 118.5 (Ar), 125.5 (C4, t, J(.sup.19F—.sup.13C)=14 Hz), 143.3 (C2, C6, d, J(.sup.19F—.sup.13C)=255 Hz), 147.7 (C3, C5, d, J(.sup.19F-.sup.13C)=248 Hz), 166.3 (Ar), 169 (Ar).

(149) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −130.65 (2F, dd, .sup.1J=25.4 Hz, .sup.2J=10.7 Hz), −139.25 (2F, dd, .sup.1J=26.2 Hz, .sup.2J=11 Hz).

(150) HRMS calcd. for C.sub.12H.sub.9F.sub.4N.sub.3O.sub.2S.sub.2 [(M+H).sup.+]: 368.0145. found: 368.0142.

(151) The compound 2u. Recrystallization was accomplished from EtOH:H.sub.2O (2:1). Yield: 0.11 g, 69%, mp 171° C.

(152) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 7.44 (1H, t, J=8.1 Hz, ArH), 7.51 (1H, t, J=8.1 Hz, ArH), 7.9 (1H, d, J=7.5 Hz, ArH), 8.06 (1H, d, J=8.4 Hz, ArH), 8.65 (2H, s, SO.sub.2NH.sub.2).

(153) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 113.8 (C1, t, J(.sup.19F—.sup.13C)=20 Hz), 122.7 (Ar), 122.9 (Ar), 126.2 (Ar), 126.5 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 127.5 (Ar), 136 (Ar), 143.5 (C2, C6, dd, .sup.1J(.sup.19F—.sup.13C)=254 Hz, .sup.2J(.sup.19F—.sup.13C)=12 Hz), 147.6 (C3, C5, dd, .sup.1J(.sup.19F—.sup.13C)=250 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz), 153.1 (Ar), 162.4 (Ar).

(154) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −130.52 (2F, dd, .sup.1J=24.8 Hz, .sup.2J=11.6 Hz), −137.87 (2F, dd, .sup.1J=24.8 Hz, .sup.2J=11.6 Hz).

(155) HRMS calcd. for C.sub.13H.sub.6F.sub.4N.sub.2O.sub.2S.sub.3 [(M−H).sup.−]: 392.9455. found: 392.9457.

(156) The compound 2x. Recrystallization was accomplished from EtOH:H.sub.2O (2:1). Yield: 0.12 g, 63%, mp 221-122° C.

(157) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 7.2-7.5 (10H, m, ArH), 8.51 (2H, s, SO.sub.2NH.sub.2), 13.2 (1H, br s, NH).

(158) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 116 (C1, t, J(.sup.19F—.sup.13C)=15 Hz), 124.1 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 128.3 (br s, Ar), 129.3 (br s, Ar), 133.9 (Ar), 143.3 (C2, C6, d, J(.sup.19F—.sup.13C)=253 Hz), 146.7 (C3, C5, d, J(.sup.19F—.sup.13C)=250 Hz).

(159) .sup.13C NMR (75 MHz, DMSO-D.sub.6, CF.sub.3COOH): 115.1 (C1, t, J(.sup.19F—.sup.13C)=15 Hz), 125 (C4, t, J(.sup.19F—.sup.13C)=16 Hz), 128.6 (Ar), 129.3 (Ar), 129.5 (Ar), 130.2 (Ar), 133.4 (Ar), 134.2 (Ar), 143.5 (C2, C6, d, J(.sup.19F—.sup.13C)=255 Hz), 146.9 (C3, C5, d, J(.sup.19F—.sup.13C)=255 Hz).

(160) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −133.53 (2F, dd, J=24.8 Hz, J=10.2 Hz), −139.13 (2F, dd, J=24.8 Hz, J=10.2 Hz).

(161) HRMS calcd. for C.sub.21H.sub.13F.sub.4N.sub.3O.sub.2S.sub.2 [(M+H).sup.+]: 480.0458. found: 480.0449.

Example 12. Preparation of 4-(1-adamantylamino)-2,3,5,6-tetrafluorobenzenesulfonamide (Compound 2v)

(162) The mixture of pentafluorobenzenesulfonamide (compound 1) (0.2 g, 0.81 mmol), Et.sub.3N (0.226 mL, 1.62 mmol), adamantanamine hydrochloride (0.15 g, 0.81 mmol) and DMSO (2 mL) was stirred at ambient temperature for 48 h. The mixture was then diluted with H.sub.2O (20 mL) and extracted with EtAc (2×10 mL). The combined organic phase was dried over Na.sub.2SO.sub.4 and evaporated in vacuum. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:4), R.sub.f=0.63. Yield: 0.04 g, 12%, mp 122-123° C.

(163) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.6-1.8 (6H, m, adamantane), 1.8-2 (6H, m, adamantane), 2.1-2.25 (3H, m, adamantane), 4.05 (1H, s, NH), 5.59 (2H, s, SO.sub.2NH.sub.2).

(164) .sup.13C NMR (75 MHz, CDCl.sub.3): 30.1 (adamantane), 36.1 (adamantane), 43.6 (adamantane), 54.8 (adamantane), 110.2 (C1), 130.4 (C4, t, J(.sup.19F—.sup.13C)=14 Hz), 138 (C2, C6, d, J(.sup.19F—.sup.13C)=248 Hz), 144.5 (C3, C5, d, J(.sup.19F—.sup.13C)=251 Hz).

(165) .sup.19F NMR (282 MHz, CDCl.sub.3): −141.53 (2F, d, J=16 Hz), −152.4 (2F, d, J=17.5 Hz).

(166) HRMS calcd. for C.sub.16H.sub.18F.sub.4N.sub.2O.sub.2S [(M−H).sup.−]: 377.0952. found: 377.0952.

Example 13. Preparation of 2-(isopropylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3a), 2-(benzylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3b), 2-[(2-phenylethyl)amino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3c), 2-[(1-phenylethyl)amino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (compound 3d), 2-morpholin-4-yl-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (compound 3e), 2-(cyclohexylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3f), 2-(cycloheptylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3 g), 2-(cyclooctylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3 h), 2-(cyclododecylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3i) 2-[(2,6-dimethoxybenzyl)amino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3j), 2-[(3,4-dimethoxybenzyl)amino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3k), 2-(2,3-dihydro-1H-inden-2-ylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 31), 2-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3m), 2-[(1S)-1,2,3,4-tetrahydronapthalen-1-ylamino)-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (Compound 3n), 2-{[(1S,2R)-2-hydroxy-1,2-diphenylethyl]amino}-3,5,6-trifluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (compound 3o)

(167) The mixture of 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)thio]benzenesulfonamide (compound 2p) (0.2 g, 0.55 mmol), Et.sub.3N (0.08 mL, 0.57 mmol), DMSO (1 mL) and appropriate nucleophile (0.57 mmol) was stirred at 60° C. for 16 h, compounds 3n, o were obtained after 40 h, compound 3e was obtained after stirring at 70° C. for 26 h. The mixture was then diluted with H.sub.2O (20 mL) and extracted with EtAc (3×10 mL). The combined organic phase was dried over MgSO.sub.4 and evaporated in vacuum.

(168) The compound 3a. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.51. Yield: 0.12 g, 55%, mp 47-48° C.

(169) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.23 (6H, dd, .sup.1J=6.3 Hz, .sup.2J=1.2 Hz, 2CH.sub.3), 2.94 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.28 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.84-3.95 (1H, m, CH), 5.52 (2H, br s, SO.sub.2NH.sub.2), 7.2-7.4 (5H, m, ArH).

(170) .sup.13C NMR (75 MHz, CDCl.sub.3): 24 (2CH.sub.3), 35.4 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=3.7 Hz), 36.8 (SCH.sub.2CH.sub.2), 48.4 (CH, d, J(.sup.19F—.sup.13C)=11 Hz), 117.4 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 119.9 (C4, t, J(.sup.19F—.sup.13C)=21 Hz), 127 (Ar), 128.8 (Ar), 132.6 (C2, d, J(.sup.19F—.sup.13C)=16 Hz), 139.4 (Ar), 142.2 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=247 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 148.6 (C3, d, J(.sup.19F—.sup.13C)=243 Hz).

(171) .sup.19F NMR (282 MHz, CDCl.sub.3): −125.1 (C3-F, d, J=11 Hz), −143.4 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −148.5 (C6-F, d, J=26 Hz).

(172) HRMS calcd. for C.sub.17H.sub.19F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 405.0913. found: 405.0918.

(173) The compound 3b. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:14), Rf=0.45. Yield: 0.15 g, 60%, mp 94-95° C.

(174) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.74 (2H, t, J=7.4 Hz, SCH.sub.2CH.sub.2), 3.19 (2H, t, J=7.5 Hz, SCH.sub.2CH.sub.2), 4.51 (2H, dd, .sup.1J=6.3 Hz, .sup.2J=4.2 Hz, NHCH.sub.2), 6.81 (1H, td, .sup.1J=6.4 Hz, .sup.2J=1.8 Hz, NH), 7.1-7.4 (10H, m, ArH), 8.2 (2H, s, SO.sub.2NH.sub.2).

(175) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 35.3 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=3.2 Hz), 36.3 (SCH.sub.2CH.sub.2), 50.5 (NHCH.sub.2, d, J(.sup.19F—.sup.13C)=12 Hz), 118 (C4, t, J(.sup.19F—.sup.13C)=19 Hz), 119.2 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=4.5 Hz), 127.1 (Ar), 127.9 (Ar), 128.1 (Ar), 129 (Ar), 129.2 (Ar), 129.22 (Ar), 132.9 (C2, d, J(.sup.19F—.sup.13C)=14 Hz), 139.8 (Ar), 140.1 (Ar), 141.8 (C5 or C6, d, J(.sup.19F—.sup.13C)=234 Hz), 144.8 (C5 or C6, d, J(.sup.19F—.sup.13C)=261 Hz), 148.1 (C3, d, J(.sup.19F—.sup.13C)=242 Hz).

(176) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −121.2 (C3-F, d, J=9 Hz), −138.1 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −145.4 (C6-F, d, J=27 Hz).

(177) HRMS calcd. for C.sub.21H.sub.19F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 453.0913. found: 453.0917.

(178) The compound 3c. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (10%):CHCl.sub.3, Rf=0.53. Yield: 0.24 g, 92%, 90-91° C.

(179) .sup.1H NMR (300 MHz, CDCl.sub.3): 2.9-3.0 (4H, m, SCH.sub.2CH.sub.2, NHCH.sub.2CH.sub.2), 3.29 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.6-3.75 (2H, m, NHCH.sub.2), 5.21 (2H, s, SO.sub.2NH.sub.2), 7.2-7.4 (10H, m, ArH).

(180) .sup.13C NMR (75 MHz, CDCl.sub.3): 35.4 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=4 Hz), 36.8 (SCH.sub.2CH.sub.2), 37.1 (NHCH.sub.2CH.sub.2), 48.2 (NHCH.sub.2, d, J(.sup.19F—.sup.13C)=11.5 Hz), 116.3 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 120 (C4, t, J(.sup.19F—.sup.13C)=22 Hz), 126.9 (Ar), 127 (Ar), 128.8 (Ar), 128.9 (Ar), 129.2 (Ar), 133.1 (C2, d, J(.sup.19F—.sup.13C)=14 Hz), 139 (Ar), 139.4 (Ar), 141.9 (C5 or C6, ddd, .sup.1J(.sup.19F-.sup.13C)=242 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=253 Hz, .sup.2J(.sup.19F—.sup.13C)=11 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.2 (C3, d, J(.sup.19F—.sup.13C)=242 Hz).

(181) .sup.19F NMR (282 MHz, CDCl.sub.3): −126.6 (C3-F, d, J=11 Hz), −143.6 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −149.1 (C6-F, d, J=28 Hz).

(182) HRMS calcd. for C.sub.22H.sub.21F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 467.1069. found: 467.1077.

(183) The compound 3d. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.75. Yield: 0.15 g, 58%.

(184) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.59 (3H, dd, .sup.1J=7 Hz, .sup.2J=1 Hz, CH.sub.3), 2.78 (2H, td, .sup.1J=7.5 Hz, .sup.2J=3 Hz, SCH.sub.2CH.sub.2), 3.13 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 4.85-4.95 (1H, m, CH), 5.33 (2H, s, SO.sub.2NH.sub.2), 7.1-7.4 (10H, m, ArH).

(185) .sup.13C NMR (75 MHz, CDCl.sub.3): 24.6 (CH.sub.3), 35.5 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=3.5 Hz), 36.7 (SCH.sub.2CH.sub.2), 56.4 (NHCH, d, J(.sup.19F—.sup.13C)=12 Hz), 117.5 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F-.sup.13C)=5 Hz), 119.8 (C4, t, J(.sup.19F—.sup.13C)=19.5 Hz), 126.3 (Ar), 126.9 (Ar), 127.7 (Ar), 128.8 (Ar), 128.8 (Ar), 128.9 (Ar), 132.3 (C2, d, J(.sup.19F—.sup.13C)=13 Hz), 139.4 (Ar), 142.4 (C5 or C6, ddd, .sup.1J(.sup.19F-.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=15 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 144.9 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=248 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.8 (C3, d, J(.sup.19F—.sup.13C)=244 Hz).

(186) .sup.19F NMR (282 MHz, CDCl.sub.3): −122.5 (C3-F, d, J=11 Hz), −143.2 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −147.4 (C6-F, d, J=26 Hz).

(187) HRMS calcd. for C.sub.22H.sub.21F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 467.1069. found: 467.1069.

(188) The compound 3e. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:3), Rf=0.38. Yield: 0.1 g, 42%, mp 149-150° C.

(189) .sup.1H NMR (300 MHz, CDCl.sub.3): 2.9-3.05 (4H, m, SCH.sub.2CH.sub.2, morpholine), 3.33 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.48 (2H, t, J=11 Hz, morpholine), 3.73 (2H, t, J=11 Hz, morpholine), 4.0 (2H, d, J=11 Hz, morpholine), 6.12 (2H, s, SO.sub.2NH.sub.2), 7.15-7.35 (5H, m, ArH).

(190) .sup.13C NMR (75 MHz, CDCl.sub.3): 35.3 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=4 Hz), 36.9 (SCH.sub.2CH.sub.2), 51.3 (morpholine, d, J(.sup.19F—.sup.13C)=6 Hz), 67.7 (morpholine), 120.3 (C4, t, J(.sup.19F—.sup.13C)=21 Hz), 127.1 (Ar), 128.8 (Ar), 128.9 (Ar), 129.5 (C2, d, J(.sup.19F—.sup.13C)=7 Hz), 131.7 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=16 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 139.1 (Ar), 143.9 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=260 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 149.6 (C5 or C6, ddd, .sup.2J(.sup.19F—.sup.13C)=250 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz, .sup.3J(.sup.19F-.sup.13C)=6 Hz), 157.8 (C3, d, J(.sup.19F—.sup.13C)=251 Hz).

(191) .sup.19F NMR (282 MHz, CDCl.sub.3): −118.8 (C3-F, d, J=13 Hz), −131.5 (C6-F, d, J=25 Hz), −143 (C5-F, d, .sup.1J=24 Hz, .sup.2J=13 Hz).

(192) HRMS calcd. for C.sub.18H.sub.19F.sub.3N.sub.2O.sub.3S.sub.2 [(M+H).sup.+]: 433.0862. found: 433.0863.

(193) The compound 3f. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:9), Rf=0.63. Yield: 0.12 g, 50%, mp 62-63° C.

(194) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.2-1.5 (5H, m, cyclohexane), 1.6-1.7 (1H, m, cyclohexane), 1.7-1.85 (2H, m, cyclohexane), 1.9-2.05 (2H, m, cyclohexane), 2.93 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.27 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.6-3.7 (1H, m, CH of cyclohexane), 5.57 (2H, s, SO.sub.2NH.sub.2), 6.16 (1H, br s, NH), 7.2-7.4 (5H, m, ArH).

(195) .sup.13C NMR (75 MHz, CDCl.sub.3): 25 (cyclohexane), 25.8 (cyclohexane), 34.4 (cyclohexane), 35.4 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=4 Hz), 36.8 (SCH.sub.2CH.sub.2), 55.3 (CH of cyclohexane, d, J(.sup.19F—.sup.13C)=11 Hz), 117.2 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 119.6 (C4, t, J(.sup.19F—.sup.13C)=22 Hz), 127 (Ar), 128.8 (Ar), 132.6 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 139.4 (Ar), 142 (C5 or C6, ddd, .sup.1J(.sup.19F-.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145 (C5 or C6, ddd, .sup.2J(.sup.19F—.sup.13C)=248 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.5 (C3, d, J(.sup.19F—.sup.13C)=243 Hz).

(196) .sup.19F NMR (282 MHz, CDCl.sub.3): −125.1 (C3-F, d, J=10 Hz), −143.5 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −149 (C6-F, d, J=27 Hz).

(197) HRMS calcd. for C.sub.20H.sub.23F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 445.1226. found: 445.1235.

(198) The compound 3 g. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.63. Yield: 0.12 g, 48%.

(199) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.4-1.8 (10H, m, cycloheptane), 1.9-2.1 (2H, m, cycloheptane), 2.94 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.27 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.7-3.8 (1H, m, CH of cycloheptane), 5.57 (2H, s, SO.sub.2NH.sub.2), 6 (1H, br s, NH), 7.1-7.4 (5H, m, ArH).

(200) .sup.13C NMR (75 MHz, CDCl.sub.3): 24.1 (cycloheptane), 28.3 (cycloheptane), 35.4 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=4 Hz), 36.1 (cycloheptane), 36.8 (SCH.sub.2CH.sub.2), 57.5 (CH of cycloheptane, d, J(.sup.19F-.sup.13C)=10 Hz), 117.2 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 119.7 (C4, t, J(.sup.19F—.sup.13C)=19 Hz), 127 (Ar), 128.8 (Ar), 132.5 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 139.5 (Ar), 142 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C) 240 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=250 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.5 (C3, d, J(.sup.19F—.sup.13C)=243 Hz).

(201) .sup.19F NMR (282 MHz, CDCl.sub.3): −125.1 (C3-F, d, J=11 Hz), −143.4 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=12 Hz), −148.9 (C6-F, d, J=25 Hz).

(202) HRMS calcd. for C.sub.21H.sub.25F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 459.1382. found: 459.1388.

(203) The compound 3 h. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:6), Rf=0.8. Yield: 0.14 g, 54%.

(204) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.4-1.8 (12H, m, cyclooctane), 1.85-2 (2H, m, cyclooctane), 2.94 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.27 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.75-3.9 (1H, m, CH of cyclooctane), 5.45 (2H, s, SO.sub.2NH.sub.2), 7.1-7.4 (5H, m, ArH).

(205) .sup.13C NMR (75 MHz, CDCl.sub.3): 23.7 (cyclooctane), 25.8 (cyclooctane), 27.5 (cyclooctane), 33.1 (cyclooctane), 35.4 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=4 Hz), 36.8 (SCH.sub.2CH.sub.2), 56.3 (CH of cyclooctane, d, J(.sup.19F—.sup.13C)=10 Hz), 117 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=6 Hz), 119.8 (C4, t, J(.sup.19F—.sup.13C)=18 Hz), 127 (Ar), 128.8 (Ar), 132.6 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 139.5 (Ar), 141.8 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145.1 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=245 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.5 (C3, d, J(.sup.19F-.sup.13C)=243 Hz).

(206) .sup.19F NMR (282 MHz, CDCl.sub.3): −124.9 (C3-F, d, J=11 Hz), −143.4 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −149.2 (C6-F, d, J=25 Hz).

(207) HRMS calcd. for C.sub.22H.sub.27F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 473.1539. found: 473.1548.

(208) The compound 3i. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.65. Yield: 0.12 g, 41%, mp 98-99° C.

(209) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.3-1.8 (22H, m, cyclododecane), 2.94 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.27 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.84 (1H, br s, CH of cyclododecane), 5.4 (2H, s, SO.sub.2NH.sub.2), 7.1-7.4 (5H, m, ArH).

(210) .sup.13C NMR (75 MHz, CDCl.sub.3): 21.3 (cyclododecane), 23.4 (cyclododecane), 23.5 (cyclododecane), 24.3 (cyclododecane), 24.6 (cyclododecane), 31 (cyclododecane), 35.4 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=3.7 Hz), 36.8 (SCH.sub.2CH.sub.2), 53.6 (CH of cyclododecane, d, J(.sup.19F-.sup.13C)=11 Hz), 116.7 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=6 Hz), 119.8 (C4, t, J(.sup.19F—.sup.13C)=18 Hz), 127 (Ar), 128.8 (Ar), 133.1 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 139.4 (Ar), 141.7 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=237 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145.1 (C5 or C6, ddd, .sup.1J(.sup.19F-.sup.13C)=244.5 Hz, .sup.2J(.sup.19F—.sup.13C)=12 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.4 (C3, d, J(.sup.19F—.sup.13C)=242.6 Hz).

(211) .sup.19F NMR (282 MHz, CDCl.sub.3): −120.1 (C3-F, d, J=11 Hz), −138.6 (C5-F, dd, .sup.1J=23 Hz, .sup.2J=12 Hz), −144.7 (C6-F, d, J=26 Hz).

(212) HRMS calcd. for C.sub.26H.sub.35F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 529.2165. found: 529.2164.

(213) The compound 3j. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.53. Yield: 0.2 g, 71%, mp 118-119° C.

(214) .sup.1H NMR (300 MHz, CDCl.sub.3): 2.96 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.3 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.79 (6H, s, 2CH.sub.3), 4.53 (2H, d, J=1.5 Hz, NHCH.sub.2), 5.25 (2H, s, SO.sub.2NH.sub.2), 6.55 (2H, d, J=8.4 Hz, ArH), 7.2-7.4 (6H, m, ArH).

(215) .sup.13C NMR (75 MHz, CDCl.sub.3): 35.5 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=4 Hz), 36.8 (SCH.sub.2CH.sub.2), 40.3 (NHCH.sub.2, d, J(.sup.19F—.sup.13C)=11 Hz), 56 (2CH.sub.3), 104 (Ar), 115.3 (Ar), 119.1 (C4, t, J(.sup.19F—.sup.13C)=19 Hz), 119.6 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=11 Hz, .sup.2J(.sup.19F—.sup.13C)=4 Hz), 127 (Ar), 128.85 (Ar), 128.87 (Ar), 129.6 (Ar), 133.6 (C2, dd, .sup.1J(.sup.19F—.sup.13C)=15 Hz, .sup.2J(.sup.19F—.sup.13C)=3.3 Hz), 139.5 (Ar), 143.3 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=242 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 144.4 (C5 or C6, ddd, .sup.1J(.sup.19F-.sup.13C)=251 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 150.5 (C3, d, J(.sup.19F—.sup.13C)=245 Hz), 158.8 (Ar).

(216) .sup.19F NMR (282 MHz, CDCl.sub.3): −122.4 (C3-F, d, J=12 Hz), −144.2 (C5-F, dd, .sup.1J=24 Hz, .sup.2J=12 Hz), −146.3 (C6-F, d, J=25 Hz).

(217) HRMS calcd. for C.sub.23H.sub.23F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.+]: 513.1124. found: 513.1122.

(218) The compound 3k. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.43. Yield: 0.13 g, 46%, mp 104-105° C.

(219) .sup.1H NMR (300 MHz, CDCl.sub.3): 2.87 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.22 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.81 (3H, s, CH.sub.3), 3.88 (3H, s, CH.sub.3), 4.35 (2H, d, J=3.3 Hz, NHCH.sub.2), 5.41 (2H, s, SO.sub.2NH.sub.2), 6.76 (1H, d, J=8.1 Hz, ArH), 6.83-6.92 (2H, m, ArH), 7.14-7.36 (5H, m, ArH).

(220) .sup.13C NMR (75 MHz, CDCl.sub.3): 35.4 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=3.5 Hz), 36.8 (SCH.sub.2CH.sub.2), 51 (NHCH.sub.2, d, J(.sup.19F—.sup.13C)=12 Hz), 56.06 (CH.sub.3), 56.13 (CH.sub.3), 111.2 (Ar), 117.6 (C1, dd, .sup.1J(.sup.19F-.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 119.8 (C4, t, J(.sup.19F—.sup.13C)=21 Hz), 120.4 (Ar), 127 (Ar), 128.8 (Ar), 131.6 (Ar), 132.8 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 139.4 (Ar), 142.4 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 144.8 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=250 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.6 (Ar), 148.9 (C3, d, J(.sup.19F—.sup.13C)=243 Hz), 149.3 (Ar).

(221) .sup.19F NMR (282 MHz, CDCl.sub.3): −123.9 (C3-F, d, J=13 Hz), −143.5 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −147.7 (C6-F, d, J=26 Hz).

(222) HRMS calcd. for C.sub.23H.sub.23F.sub.3N.sub.2O.sub.4S.sub.2 [(M−H).sup.−]: 511.0979. found: 511.0982.

(223) The compound 3l. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (10%):CHCl.sub.3, Rf=0.55. Yield: 0.19 g, 73%, mp 73-74° C.

(224) .sup.1H NMR (300 MHz, CDCl.sub.3): 2.85-3.05 (4H, m, SCH.sub.2CH.sub.2, CH.sub.2 of indane), 3.25-3.4 (4H, m, SCH.sub.2CH.sub.2, CH.sub.2 of indane), 4.58-4.7 (1H, m, NHCH), 5.12 (2H, s, SO.sub.2NH.sub.2), 7.2-7.4 (9H, m, ArH).

(225) .sup.13C NMR (75 MHz, CDCl.sub.3): 35.4 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=4 Hz), 36.9 (SCH.sub.2CH.sub.2), 41.2 (CH.sub.2 of indane), 57.8 (NHCH, d, J(.sup.19F—.sup.13C)=11 Hz), 117.2 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5.5 Hz), 120.1 (C4, t, J(.sup.19F—.sup.13C)=22 Hz), 125.2 (Ar), 127 (Ar), 127.2 (Ar), 128.8 (Ar), 132.2 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 139.4 (Ar), 141.1 (Ar), 142.2 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=239 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=251 Hz, .sup.2J(.sup.19F—.sup.13C)=12 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.2 (C3, d, J(.sup.19F—.sup.13C)=242 Hz).

(226) .sup.19F NMR (282 MHz, CDCl.sub.3): −126 (C3-F, d, J=12 Hz), −143.3 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −148.3 (C6-F, d, J=25 Hz).

(227) HRMS calcd. for C.sub.23H.sub.21F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 479.1069. found: 479.1077.

(228) The compound 3m. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.53. Yield: 0.08 g, 31%, mp 101-102° C.

(229) .sup.1H NMR (300 MHz, CDCl.sub.3): 2.05 (1H, sex, J=6 Hz, indane), 2.56 (1H, sex, J=7 Hz, indane), 2.85-2.97 (1H, m, indane, signal overlaps with signal of SCH.sub.2CH.sub.2), 2.99 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.07-3.19 (1H, m, indane), 3.33 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 5.18 (3H, br s, SO.sub.2NH.sub.2, NHCH), 6.34 (1H, br s, NH), 7.18-7.4 (9H, m, ArH).

(230) .sup.13C NMR (75 MHz, CDCl.sub.3): 30.3 (indane), 35 (indane), 35.5 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=3.8 Hz), 36.9 (SCH.sub.2CH.sub.2), 62.3 (NHCH, d, J(.sup.19F—.sup.13C)=11 Hz), 117.6 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 120.1 (C4, t, J(.sup.19F—.sup.13C)=22 Hz), 124.3 (Ar), 125.3 (Ar), 126.9 (Ar), 127 (Ar), 128.4 (Ar), 128.8 (Ar), 132.9 (C2, dd, .sup.1J(.sup.19F—.sup.13C)=15 Hz, .sup.2J(.sup.19F—.sup.13C)=3 Hz), 139.4 (Ar), 142.5 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=15 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 143.7 (Ar), 144.3 (Ar), 145 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=248 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 148.8 (C3, d, J(.sup.19F—.sup.13C)=242 Hz).

(231) .sup.19F NMR (282 MHz, CDCl.sub.3): −124.1 (C3-F, d, J=12 Hz), −143.1 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=12 Hz), −147.9 (C6-F, d, J=25 Hz).

(232) HRMS calcd. for C.sub.23H.sub.21F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 479.1069. found: 479.1063.

(233) The compound 3n. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.79. Yield: 0.14 g, 52%, mp 123-124° C.

(234) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.8-2.1 (4H, m, tetrahydronapthalene), 2.7-2.95 (2H, m, tetrahydronapthalene), 2.99 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 3.33 (2H, t, J=8 Hz, SCH.sub.2CH.sub.2), 4.83 (1H, br s, NHCH), 5.1 (2H, s, SO.sub.2NH.sub.2), 6.26 (1H, br s, NH), 7.1-7.4 (9H, m, ArH).

(235) .sup.13C NMR (75 MHz, CDCl.sub.3): 19 (tetrahydronapthalene), 29.3 (tetrahydronapthalene), 30.3 (tetrahydronapthalene), 35.5 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=4 Hz), 36.9 (SCH.sub.2CH.sub.2), 54.7 (NHCH, d, J(.sup.19F—.sup.13C)=11 Hz), 118.2 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 120 (C4, t, J(.sup.19F—.sup.13C)=21 Hz), 126.2 (Ar), 127 (Ar), 127.7 (Ar), 128.9 (Ar), 129.1 (Ar), 129.7 (Ar), 132.6 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 137.57 (Ar), 137.6 (Ar), 139.4 (Ar), 142.7 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=249 Hz, .sup.2J(.sup.19F—.sup.13C)=12 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 149.3 (C3, d, J(.sup.19F—.sup.13C)=243 Hz).

(236) .sup.19F NMR (282 MHz, CDCl.sub.3): −123.1 (C3-F, d, J=11 Hz), −142.9 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −147.4 (C6-F, d, J=26 Hz).

(237) HRMS calcd. for C.sub.24H.sub.23F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 493.1226. found: 493.1222.

(238) The compound 3o. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (10%):CHCl.sub.3, Rf=0.37. Yield: 0.11 g, 35%.

(239) .sup.1H NMR (300 MHz, CDCl.sub.3): 2.73 (2H, t, J=7.2 Hz, SCH.sub.2CH.sub.2), 3.08 (2H, td, .sup.1J=7.7 Hz, .sup.2J=3.3 Hz, SCH.sub.2CH.sub.2), 5.01 (1H, dd, .sup.1J=5.4 Hz, .sup.2J=1.8 Hz, CH), 5.06 (1H, d, J=5.1 Hz, CH), 5.58 (2H, s, SO.sub.2NH.sub.2), 7.05-7.32 (15H, m, ArH).

(240) .sup.13C NMR (75 MHz, CDCl.sub.3): 35.5 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=3.4 Hz), 36.6 (SCH.sub.2CH.sub.2), 66.1 (NHCH, d, J(.sup.19F—.sup.13C)=11 Hz), 77.3 (CHOH, signal overlaps with CDCl.sub.3 signal), 117.7 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 119.8 (C4, t, J(.sup.19F—.sup.13C)=21 Hz), 126.8 (Ar), 126.9 (Ar), 128.2 (Ar), 128.3 (Ar), 128.5 (Ar), 128.7 (Ar), 128.8 (Ar), 131.6 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 138.1 (Ar), 139.3 (Ar), 140.4 (Ar), 142.5 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 144.8 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=248 Hz, .sup.2J(.sup.19F-.sup.13C)=12 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.6 (C3, d, J(.sup.19F—.sup.13C)=243 Hz).

(241) .sup.19F NMR (282 MHz, CDCl.sub.3): −122.6 (C3-F, d, J=12 Hz), −143.2 (C5-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −147.1 (C6-F, d, J=26 Hz).

(242) HRMS calcd. for C.sub.28H.sub.25F.sub.3N.sub.2O.sub.3S.sub.2 [(M+H).sup.+]: 559.1331. found: 559.1331.

Example 14. Preparation of 2-(cyclooctylamino)-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide (Compound 4a), 2-(cyclododecylamino)-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide (Compound 4b), 2-[(2,6-dimethoxybenzyl)amino]-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide (Compound 4c), 2-[(3,4-dimethoxybenzyl)amino]-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide (Compound 4d), 2-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide (Compound 4e), 2-[(1S)-1,2,3,4-tetrahydronapthalen-1-yl amino)-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide (Compound 4f), 2-{[(1S,2R)-2-hydroxy-1,2-diphenylethyl]amino}-3,5,6-trifluoro-4-[(2-hydroxyethyl)thio]benzenesulfonamide (Compound 4 g)

(243) The mixture of 2,3,5,6-tetrafluoro-4[(2-hydroxyethyl)thio]benzenesulfonamide (compound 2c) (0.2 g, 0.66 mmol), Et.sub.3N (0.095 mL, 0.68 mmol), DMSO (1 mL) and appropriate nucleophile (0.68 mmol) was stirred at 60° C. for 16 h. The mixture was then diluted with H.sub.2O (20 mL) and extracted with EtAc (3×10 mL). The combined organic phase was dried over MgSO.sub.4 and evaporated in vacuum.

(244) The compound 4a. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.59. Yield: 0.15 g, 56%, mp 68-69° C.

(245) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.4-1.75 (12H, m, cyclooctane), 1.8-1.95 (2H, m, cyclooctane), 2.54 (1H, br s, OH), 3.14 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.74 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.75-3.85 (1H, m, CH of cyclooctane, signal overlaps with signal of SCH.sub.2CH.sub.2), 5.77 (2H, s, SO.sub.2NH.sub.2), 6.16 (1H, br s, NH).

(246) .sup.13C NMR (75 MHz, CDCl.sub.3): 23.7 (cyclooctane), 25.8 (cyclooctane), 27.5 (cyclooctane), 33 (cyclooctane), 37.5 (SCH.sub.2CH.sub.2, br t), 56.4 (CH of cyclooctane, d, J(.sup.19F—.sup.13C)=11 Hz), 61.2 (SCH.sub.2CH.sub.2), 117.9 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 118.3 (C4, t, J(.sup.19F-.sup.13C)=21 Hz), 132.7 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 142.1 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F-.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145.1 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=247 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 149.1 (C3, d, J(.sup.19F—.sup.13C)=243 Hz).

(247) .sup.19F NMR (282 MHz, CDCl.sub.3): −124.5 (C3-F, d, J=11 Hz), −143 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −149 (C6-F, d, J=26 Hz).

(248) HRMS calcd. for C.sub.16H.sub.23F.sub.3N.sub.2O.sub.3S.sub.2 [(M+H).sup.+]: 413.1175. found: 413.1175.

(249) The compound 4b. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.65. Yield: 0.17 g, 55%, mp 113-114° C.

(250) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.3-1.7 (22H, m, cyclododecane), 2.4 (1H, br s, OH), 3.16 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.75 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.78-3.86 (1H, m, CH cyclododecane, signal overlaps with signal of SCH.sub.2CH.sub.2), 5.59 (2H, s, SO.sub.2NH.sub.2), 6.2 (1H, br s, NH).

(251) .sup.13C NMR (75 MHz, CDCl.sub.3): 21.3 (cyclododecane), 23.3 (cyclododecane), 23.4 (cyclododecane), 24.3 (cyclododecane), 24.6 (cyclododecane), 30.1 (cyclododecane), 37.6 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=3 Hz), 53.6 (CH of cyclododecane, d, J(.sup.19F—.sup.13C)=11 Hz), 61.1 (SCH.sub.2CH.sub.2), 117.5 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 118.4 (C4, t, J(.sup.19F-.sup.13C)=20 Hz), 133.3 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 141.9 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=239 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145.1 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=248 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F-.sup.13C)=4 Hz), 148.9 (C3, d, J(.sup.19F—.sup.13C)=243 Hz).

(252) .sup.19F NMR (282 MHz, CDCl.sub.3): −124.5 (C3-F, d, J=11 Hz), −142.9 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −149.4 (C6-F, d, J=24 Hz).

(253) HRMS calcd. for C.sub.20H.sub.31F.sub.3N.sub.2O.sub.3S.sub.2 [(M+H).sup.+]: 469.1801. found: 469.1804.

(254) The compound 4c. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.54. Yield: 0.1 g, 34%.

(255) .sup.1H NMR (300 MHz, CDCl.sub.3): 3.15 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.72 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.79 (6H, s, 2CH.sub.3), 4.51 (2H, s, CH.sub.2), 5.4 (2H, br s, SO.sub.2NH.sub.2), 6.55 (2H, d, J=8.4 Hz, ArH), 7.22 (1H, t, J=8.4 Hz, ArH).

(256) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.09 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.57 (2H, t, J=6.6 Hz, SCH.sub.2CH.sub.2), 3.62 (1H, s, OH), 3.75 (6H, s, 2CH.sub.3), 4.44 (2H, br s, CH.sub.2), 6.5 (1H, br s, NH), 6.65 (2H, d, J=8.4 Hz, ArH), 7.24 (1H, t, J=8.4 Hz, ArH), 7.94 (2H, s, SO.sub.2NH.sub.2).

(257) .sup.13C NMR (75 MHz, CDCl.sub.3): 37.4 (SCH.sub.2CH.sub.2, br t), 40.3 (NHCH.sub.2, d, J(.sup.19F—.sup.13C)=11 Hz), 56 (CH.sub.3), 61.2 (SCH.sub.2CH.sub.2), 104 (Ar), 115 (Ar), 117.9 (C4, t, J(.sup.19F—.sup.13C)=19 Hz), 120.3 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=11 Hz, .sup.2J(.sup.19F—.sup.13C)=4 Hz), 129.6 (Ar), 133.4 (C2, d, J(.sup.19F—.sup.13C)=16 Hz), 143.7 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=15 Hz), 144.4 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=248 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz), 150.9 (C3, d, J(.sup.19F—.sup.13C)=244 Hz), 158.8 (Ar).

(258) .sup.19F NMR (282 MHz, CDCl.sub.3): −121.9 (C3-F, d, J=12 Hz), −143.7 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −145.9 (C6-F, d, J=25 Hz).

(259) HRMS calcd. for C.sub.17H.sub.19F.sub.3N.sub.2O.sub.5S.sub.2 [(M+H).sup.+]: 453.076. found: 453.0752.

(260) The compound 4d. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.45. Yield: 0.27 g, 91%, mp 73-74° C.

(261) .sup.1H NMR (300 MHz, CDCl.sub.3): 3.08 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.63 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.84 (3H, s, CH.sub.3), 3.86 (3H, s, CH.sub.3), 4.41 (2H, d, J=3.3 Hz, CH.sub.2), 5.67 (2H, s, SO.sub.2NH.sub.2), 6.75-6.87 (3H, m, ArH).

(262) .sup.13C NMR (75 MHz, CDCl.sub.3): 37.4 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=3 Hz), 51 (NHCH.sub.2, d, J(.sup.19F-.sup.13C)=12 Hz), 56.11 (CH.sub.3), 56.18 (CH.sub.3), 61.1 (SCH.sub.2CH.sub.2), 111.3 (Ar), 118.3 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=11 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz signal overlaps with signal of C4), 118.5 (C4, t, J(.sup.19F—.sup.13C)=21 Hz, signal overlaps with signal of C1), 120.4 (Ar), 131.5 (Ar), 132.9 (C2, d, J(.sup.19F—.sup.13C)=16 Hz), 142.6 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=242 Hz, .sup.2J(.sup.19F—.sup.13C)=15 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 144.8 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=249 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 148.6 (Ar), 149.2 (Ar), 149.3 (C3, d, J(.sup.19F—.sup.13C)=243 Hz).

(263) .sup.19F NMR (282 MHz, CDCl.sub.3): −123.6 (C3-F, d, J=12 Hz), −143.1 (C5-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −147.6 (C6-F, d, J=26 Hz).

(264) HRMS calcd. for C.sub.17H.sub.19F.sub.3N.sub.2O.sub.5S.sub.2[(M−H).sup.−]: 451.0615. found: 451.0621.

(265) The compound 4e. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.71. Yield: 0.13 g, 48%.

(266) .sup.1H NMR (300 MHz, CDCl.sub.3): 2.02 (1H, sex, J=7.2 Hz, indane), 2.54 (1H, sex, J=5.4 Hz, indane), 2.88 (1H, pet, J=8 Hz, indane), 3.04-3.16 (1H, m, indane), 3.19 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.77 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 5.12-5.2 (1H, m, NHCH), 5.35 (2H, s, SO.sub.2NH.sub.2), 7.15-7.35 (4H, m, ArH).

(267) .sup.13C NMR (75 MHz, CDCl.sub.3): 30.3 (indane), 35 (indane), 37.6 (SCH.sub.2CH.sub.2, t, J(.sup.19F—.sup.13C)=2.5 Hz), 61.3 (SCH.sub.2CH.sub.2), 62.2 (NHCH, d, J(.sup.19F—.sup.13C)=10 Hz), 118.3 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 118.8 (C4, t, J(.sup.19F—.sup.13C)=21 Hz), 124.2 (Ar), 125.3 (Ar), 126.9 (Ar), 128.4 (Ar), 133 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 142.7 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=242 Hz, .sup.2J(.sup.19F-.sup.13C)=15 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 143.7 (Ar), 144.2 (Ar), 145.1 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=251 Hz, .sup.2J(.sup.19F—.sup.13C)=12 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 149.2 (C3, d, J(.sup.19F—.sup.13C)=242 Hz).

(268) .sup.19F NMR (282 MHz, CDCl.sub.3): −123.8 (C3-F, d, J=12 Hz), −142.7 (C5-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −147.7 (C6-F, d, J=25 Hz).

(269) HRMS calcd. for C.sub.17H.sub.17F.sub.3N.sub.2O.sub.3S.sub.2 [(M+H).sup.+]: 419.0705. found: 419.0714.

(270) The compound 4f. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.66. Yield: 0.1 g, 36%, mp 94-95° C.

(271) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.8-2.05 (4H, m, tetrahydronapthalene), 2.4 (1H, br s, OH), 2.7-3 (2H, m, tetrahydronapthalene), 3.19 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.78 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 4.76-4.86 (1H, m, NHCH), 5.3 (2H, br s, SO.sub.2NH.sub.2), 6.28 (1H, d, J=9 Hz, NH), 7.1-7.3 (4H, m, ArH).

(272) .sup.13C NMR (75 MHz, CDCl.sub.3): 18.9 (tetrahydronapthalene), 29.2 (tetrahydronapthalene), 30.3 (tetrahydronapthalene), 37.6 (SCH.sub.2CH.sub.2, br t, J(.sup.19F—.sup.13C)=3 Hz), 54.7 (NHCH, d, J(.sup.19F—.sup.13C)=11 Hz), 61.3 (SCH.sub.2CH.sub.2), 118.7 (C4, t, J(.sup.19F—.sup.13C)=22 Hz, signal overlaps with signal of C1), 118.9 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=4 Hz, signal overlaps with signal of C4), 126.1 (Ar), 127.7 (Ar), 129.1 (Ar), 129.7 (Ar), 132.7 (C2, d, J(.sup.19F—.sup.13C)=14 Hz), 137.48 (Ar), 137.54 (Ar), 142.9 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F—.sup.13C)=15 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145.1 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=250 Hz, .sup.2J(.sup.19F—.sup.13C)=12 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 149.7 (C3, d, J(.sup.19F-.sup.13C)=243 Hz).

(273) .sup.19F NMR (282 MHz, CDCl.sub.3): −122.7 (C3-F, d, J=11 Hz), −142.5 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −147.3 (C6-F, d, J=26 Hz).

(274) HRMS calcd. for C.sub.18H.sub.19F.sub.3N.sub.2O.sub.3S.sub.2 [(M−H).sup.−]: 431.0716. found: 431.0719.

(275) The compound 4 g. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.43. Yield: 0.13 g, 39%.

(276) .sup.1H NMR (300 MHz, CDCl.sub.3): 2.2 (1H, br s, OH), 2.88 (2H, t, J=6 Hz, SCH.sub.2CH.sub.2), 3.1 (1H, br s, OH), 3.35-3.45 (2H, m, SCH.sub.2CH.sub.2), 4.97 (1H, br t, J=6 Hz, CH), 5.05 (1H, d, J=5 Hz, CH), 5.97 (2H, br s, SO.sub.2NH.sub.2), 7-7.3 (10H, m, ArH).

(277) .sup.13C NMR (75 MHz, CDCl.sub.3): 37.1 (SCH.sub.2CH.sub.2, br t, J(.sup.19F—.sup.13C)=2 Hz), 60.9 (SCH.sub.2CH.sub.2), 66.1 (NHCH, d, J(.sup.19F—.sup.13C)=12 Hz), 77 (CHOH, signal overlaps with CDCl.sub.3 signal), 118.4 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=11 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz, signal overlaps with C4 signal), 118.3 (C4, t, J(.sup.19F-.sup.13C)=20 Hz, signal overlaps with C1 signal), 126.8 (Ar), 128 (Ar), 128.2 (Ar), 128.3 (Ar), 128.4 (Ar), 128.5 (Ar), 131.7 (C2, d, J(.sup.19F—.sup.13C)=15 Hz), 138.1 (Ar), 140.4 (Ar), 142.7 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=241 Hz, .sup.2J(.sup.19F—.sup.13C)=15 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 144.9 (C5 or C6, ddd, .sup.1J(.sup.19F-.sup.13C)=251 Hz, .sup.2J(.sup.19F—.sup.13C)=12 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.8 (C3, d, J(.sup.19F—.sup.13C)=243 Hz).

(278) .sup.19F NMR (282 MHz, CDCl.sub.3): −122.2 (C3-F, d, J=11 Hz), −142.9 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=12 Hz), −147.3 (C6-F, d, J=26 Hz).

(279) HRMS calcd. for C.sub.22H.sub.21F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.+]: 499.0968. found: 499.0967.

Example 15. Preparation of 2-(cyclooctylamino)-3,5,6-trifluoro-4-(propylthio)benzenesulfonamide (Compound 5)

(280) The mixture of 2,3,5,6-tetrafluoro-4-(propylthio)benzenesulfonamide (20 (0.2 g, 0.66 mmol), Et.sub.3N (0.095 mL, 0.68 mmol), DMSO (1 mL) and cyclooctylamine (0.1 mL, 0.72 mmol) was stirred at 60° C. for 12 h. The mixture was then diluted with H.sub.2O (20 mL) and extracted with EtAc (3×10 mL). The combined organic phase was dried over MgSO.sub.4 and evaporated in vacuum.

(281) The compound 5. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.64. Yield: 0.16 g, 59%.

(282) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.03 (3H, t, J=7.2 Hz, CH.sub.3), 1.4-1.75 (14H, m, CH.sub.2CH.sub.3, cyclooctane), 1.8-1.95 (2H, m, cyclooctane), 2.98 (2H, t, J=7.2 Hz, SCH.sub.2), 3.7-3.85 (1H, m, CH of cyclooctane), 5.62 (3H, br s, NH, SO.sub.2NH.sub.2).

(283) .sup.13C NMR (75 MHz, CDCl.sub.3): 13.3 (CH.sub.3), 23.5 (cyclooctane), 23.7 (cyclooctane), 25.8 (cyclooctane), 27.5 (cyclooctane), 33 (CH.sub.2), 36.3 (SCH.sub.2, t, J(.sup.19F—.sup.13C)=3.6 Hz), 56.5 (CH of cyclooctane, d, J(.sup.19F—.sup.13C)=11 Hz), 117.3 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C) 6 Hz), 120 (C4, t, J(.sup.19F—.sup.13C)=21 Hz), 132.4 (C2, d, J(.sup.19F—.sup.13C)=13 Hz), 142.2 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=239 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=249 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.9 (C3, d, J(.sup.19F—.sup.13C)=243 Hz).

(284) .sup.19F NMR (282 MHz, CDCl.sub.3): −124.8 (C3-F, d, J=11 Hz), −143.5 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −149 (C6-F, d, J=26 Hz).

(285) HRMS calcd. for C.sub.17H.sub.25F.sub.3N.sub.2O.sub.2S.sub.2 [(M+H).sup.+]: 411.1382. found: 411.1388.

Example 16. Preparation of 2-(cyclooctylamino)-3,5,6-trifluoro-4-{[2-(4-hydroxyphenyl)ethyl]amino}benzenesulfonamide (Compound 6)

(286) The mixture of 2,3,5,6-tetrafluoro-4{-[2-(4-hydroxyphenyl)ethyl]amino}benzenesulfonamide (2o) (0.2 g, 0.55 mmol), Et.sub.3N (0.085 mL, 0.61 mmol), DMSO (1 mL) and cyclooctylamine (0.085 mL, 0.61 mmol) was stirred at 70° C. for 28 h. The mixture was then diluted with H.sub.2O (20 mL) and extracted with EtAc (3×10 mL). The combined organic phase was dried over MgSO.sub.4 and evaporated in vacuum.

(287) The compound 6. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:3), Rf=0.6. Yield: 0.13 g, 50%.

(288) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.4-2 (14H, m, cyclooctane), 2.82 (2H, t, J=7 Hz, NHCH.sub.2CH.sub.2), 3.6-3.75 (3H, m, CH of cyclooctane, NHCH.sub.2CH.sub.2), 5.59 (2H, s, SO.sub.2NH.sub.2), 6.1 (2H, br s, 2NH), 6.79 (2H, d, J=8.4 Hz, ArH), 7.04 (2H, d, J=8.4 Hz, ArH).

(289) .sup.13C NMR (75 MHz, CDCl.sub.3): 23.8 (cyclooctane), 25.8 (cyclooctane), 27.5 (cyclooctane), 32.7 (cyclooctane), 36.6 (NHCH.sub.2CH.sub.2), 46.9 (NHCH.sub.2CH.sub.2), 56.4 (CH of cyclooctane, d, J(.sup.19F-.sup.13C)=10 Hz), 106.3 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 115.8 (C4, signal overlaps with Ar signal), 115.83 (Ar), 130.2 (Ar), 130.28 (Ar), 132 (C2, d, J(.sup.19F—.sup.13C)=13 Hz, signal overlaps with C5 or C6 signal), 133.8 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=239 Hz, .sup.2J(.sup.19F—.sup.13C)=18 Hz, .sup.3J(.sup.19F—.sup.13C)=6 Hz), 138.5 (C3, d, J(.sup.19F—.sup.13C)=233 Hz), 146.5 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=243 Hz, .sup.2J(.sup.19F—.sup.13C)=14 Hz, .sup.3J(.sup.19F—.sup.13C)=3 Hz), 154.8 (Ar).

(290) .sup.19F NMR (282 MHz, CDCl.sub.3): −144.8 (C5-F, dd, .sup.1J=23 Hz, .sup.2J=9 Hz), −154.1 (C3-F, s), −171.4 (C6-F, d, J=23 Hz).

(291) HRMS calcd. for C.sub.22H.sub.28F.sub.3N.sub.3O.sub.3S [(M+H).sup.+]: 472.1876. found: 472.1877.

Example 17. Preparation of 2-(cyclooctylamino)-3,5,6-trifluorobenzenesulfonamide (Compound 8a), 2-(cyclododecylamino)-3,5,6-trifluorobenzenesulfonamide (Compound 8b), 2-[(2,6-dimethoxybenzyl)amino]-3,5,6-trifluorobenzenesulfonamide (Compound 8c), 2-[(3,4-dimethoxybenzyl)amino]-3,5,6-trifluorobenzenesulfonamide (Compound 8d), 2-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-3,5,6-trifluorobenzenesulfonamide (Compound 8e), 2-[(1S)-1,2,3,4-tetrahydronapthalen-1-ylamino)-3,5,6-trifluorobenzenesulfonamide (Compound 8f)

(292) The mixture of 2,3,5,6-tetrafluorobenzenesulfonamide (7) (0.2 g, 0.87 mmol), Et.sub.3N (0.124 mL, 0.89 mmol), DMSO (1 mL) and appropriate nucleophile (0.93 mmol) was stirred at 60° C. for 8 h, compound 8d was obtained after 16 h, compound 8f was obtained after stirring at 70° C. for 16 h. The mixture was then diluted with H.sub.2O (20 mL) and extracted with EtAc (3×10 mL). The combined organic phase was dried over MgSO.sub.4 and evaporated in vacuum.

(293) The compound 8a. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:20), Rf=0.32. Yield: 0.15 g, 52%, mp 117-118° C.

(294) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.4-1.9 (14H, m, cyclooctane), 3.72 (1H, br s, CH of cyclooctane), 6.35 (1H, br s, NH), 7.65-7.8 (1H, m, ArH), 8.1 (2H, s, SO.sub.2NH.sub.2).

(295) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 23.6 (cyclooctane), 25.7 (cyclooctane), 27.6 (cyclooctane), 32.8 (cyclooctane), 55.7 (CH of cyclooctane, d, J(.sup.19F—.sup.13C)=10 Hz), 110.2 (C4, t, J(.sup.19F—.sup.13C)=25 Hz), 120.6 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 132.9 (C2, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=3 Hz), 141.1 (C5 or C6, t, .sup.1J(.sup.19F—.sup.13C)=240 Hz, .sup.2J(.sup.19F- .sup.13C)=14 Hz), 145 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=248 Hz, .sup.2J(.sup.19F—.sup.13C)=14 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 148.3 (C3, dd, .sup.1J(.sup.19F—.sup.13C)=236 Hz, .sup.2J(.sup.19F—.sup.13C)=6 Hz).

(296) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −120.6 (C3-F, t, J=13 Hz), −133.35: −133.56 (C5-F or C6-F, m), −145.2 (C5-F or C6-F, dd, .sup.1J=25 Hz, .sup.2J=11 Hz).

(297) HRMS calcd. for C.sub.14H.sub.19F.sub.3N.sub.2O.sub.2S [(M+H).sup.+]: 337.1192. found: 337.1195.

(298) The compound 8b. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:20), Rf=0.49. Yield: 0.1 g, 29%, mp 113-114° C.

(299) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.2-1.7 (22H, m, cyclododecane), 3.71 (1H, br s, CH of cyclododecane), 6.22 (1H, d=7.8 Hz, NH), 7.64-7.78 (1H, m, ArH), 8.09 (2H, s, SO.sub.2NH.sub.2).

(300) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 21.4 (cyclododecane), 23.4 (cyclododecane), 23.6 (cyclododecane), 24.1 (cyclododecane), 24.4 (cyclododecane), 31.1 (cyclododecane), 52.8 (CH of cyclododecane, d, J(.sup.19F—.sup.13C)=11 Hz), 110.2 (C4, t, J(.sup.19F—.sup.13C)=25 Hz), 120.6 (C1, dd, .sup.1J(.sup.19F—.sup.13C) 12 Hz, .sup.2J(.sup.19F—.sup.13C) 5 Hz), 133.4 (C2, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=2 Hz), 141.1 (C5 or C6, t, .sup.1J(.sup.19F—.sup.13C)=238 Hz, .sup.2J(.sup.19F—.sup.13C)=13 Hz), 145 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=249 Hz, .sup.2J(.sup.19F—.sup.13C)=14 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.1 (C3, dd, .sup.1J(.sup.19F—.sup.13C)=245 Hz, .sup.2J(.sup.19F- .sup.13C)=9 Hz).

(301) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −125.4 (C3-F, t, J=13 Hz), −138: −138.3 (C5-F or C6-F, m), −150.1 (C5-F or C6-F, dd, .sup.1J=25 Hz, .sup.2J=11 Hz).

(302) HRMS calcd. for C.sub.18H.sub.27F.sub.3N.sub.2O.sub.2S [(M+H).sup.+]: 393.1818. found: 393.1816.

(303) The compound 8c. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.4. Yield: 0.16 g, 48%, mp 137-138° C.

(304) .sup.1H NMR (300 MHz, D.sub.3OD): 3.79 (6H, s, 2CH.sub.3), 4.51 (2H, d, J=1.5 Hz, CH.sub.2), 4.91 (2H, s, SO.sub.2NH.sub.2), 6.61 (2H, d, J=8.4 Hz, ArH), 7.22 (1H, t, J=8.1 Hz, ArH), 7.29-7.41 (1H, m, ArH).

(305) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.75 (6H, s, 2CH.sub.3), 4.44 (2H, d, J=2.1 Hz, CH.sub.2), 6.65 (2H, d, J=8.4 Hz, ArH), 7.25 (1H, t, J=8.4 Hz, ArH), 7.68-7.8 (1H, m, ArH), 7.92 (2H, s, SO.sub.2NH.sub.2).

(306) .sup.1H NMR (300 MHz, CDCl.sub.3): 3.81 (6H, s, 2CH.sub.3), 4.56 (2H, br s, CH.sub.2), 4.92 (2H, br s, SO.sub.2NH.sub.2), 6.05 (1H, br s, NH), 6.57 (2H, d, J=8.4 Hz, ArH), 7.06-7.17 (1H, m, ArH), 7.24 (1H, t, J=8.4 Hz, ArH).

(307) .sup.13C NMR (75 MHz, D.sub.3OD): 39.3 (CH.sub.2, d, J(.sup.19F—.sup.13C)=12 Hz), 55 (CH.sub.3), 103.6 (Ar), 108.7 (C4, t, J(.sup.19F—.sup.13C)=25 Hz), 115.1 (Ar), 121.4 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=4 Hz), 129.2 (Ar), 134.3 (C2, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=3 Hz), 142.2 (C5 or C6, d, J(.sup.19F—.sup.13C)=241 Hz), 144.6 (C5 or C6, d, J(.sup.19F—.sup.13C)=248 Hz), 149.9 (C3, d, J(.sup.19F—.sup.13C)=249 Hz), 158.8 (Ar).

(308) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −124.1 (C3-F, t, J=13 Hz), −141.5: −141.7 (C5-F or C6-F, m), −150.3 (C5-F or C6-F, dd, .sup.1J=25 Hz, .sup.2J=10 Hz).

(309) HRMS calcd. for C.sub.15H.sub.15F.sub.3N.sub.2O.sub.4S [(M−H).sup.−]: 375.0632. found: 375.0634.

(310) The compound 8d. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (10%):CHCl.sub.3, Rf=0.29. Recrystallization was accomplished from EtOH:H.sub.2O (2:1) after chromatography. Yield: 0.1 g, 33%, mp 115-116° C.

(311) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.73 (3H, s, CH.sub.3), 3.75 (3H, s, CH.sub.3), 4.4 (2H, dd, J=6 Hz, J=3.6 Hz, CH.sub.2), 6.7 (1H, td, J=6 Hz, J=2 Hz, NH), 6.82-6.98 (3H, m, ArH), 7.65-7.78 (1H, m, ArH), 8.14 (2H, s, SO.sub.2NH.sub.2).

(312) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 50.3 (CH.sub.2, d, J(.sup.19F—.sup.13C)=12 Hz), 55.96 (CH.sub.3), 56.06 (CH.sub.3), 110.9 (C4, t, J(.sup.19F—.sup.13C)=24 Hz), 111.9 (Ar), 112.2 (Ar), 120.3 (Ar), 120.4 (C1, signal overlaps with Ar signal), 132.3 (Ar), 133.5 (C2, d, J(.sup.19F—.sup.13C)=13 Hz), 141.2 (C5 or C6, t, .sup.1J(.sup.19F—.sup.13C)=238 Hz, .sup.2J(.sup.19F—.sup.13C)=12 Hz), 144.8 (C5 or C6, d, J(.sup.19F—.sup.13C)=252 Hz), 148.2 (C3, d J(.sup.19F—.sup.13C)=240 Hz), 148.6 (Ar), 149.2 (Ar).

(313) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −124.9 (C3-F, t, J=13 Hz), −138.6: −138.8 (C5-F or C6-F, m), −149.6 (C5-F or C6-F, dd, .sup.1J=25 Hz, .sup.2J=10 Hz).

(314) HRMS calcd. for C.sub.15H.sub.15F.sub.3N.sub.2O.sub.4S [(M−H).sup.−]: 375.0632. found: 375.0631.

(315) The compound 8e. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:10), Rf=0.38. Yield: 0.09 g, 30%, mp 103-104° C.

(316) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.79-1.95 (1H, m, indane), 2.38-2.5 (1H, m, indane), 2.82 (1H, pet, J=8 Hz, indane), 2.91-3.06 (1H, m, indane), 5.1-5.2 (1H, m, NHCH), 6.59 (1H, dd, .sup.1J=8.6 Hz, .sup.2J=2 Hz, NH), 7.2-7.4 (4H, m, ArH), 7.75-7.9 (1H, m ArH), 8.13 (2H, s, SO.sub.2NH.sub.2).

(317) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 30.2 (indane), 35.2 (indane), 61.6 (CH of indane, d, J(.sup.19F—.sup.13C)=11 Hz), 110.5 (C4, t, J(.sup.19F—.sup.13C)=25 Hz), 120.5 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F-.sup.13C)=5 Hz), 124.7 (Ar), 125.5 (Ar), 127.3 (Ar), 128.6 (Ar), 133.2 (C2, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=3 Hz), 141.4 (C5 or C6, t, .sup.1J(.sup.19F—.sup.13C)=238 Hz, .sup.2J(.sup.19F—.sup.13C)=14 Hz), 143.6 (Ar), 144.7 (Ar), 144.9 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=233 Hz, .sup.2J(.sup.19F—.sup.13C)=14 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz), 148.2 (C3, d, J(.sup.19F—.sup.13C)=226 Hz).

(318) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −120 (C3-F, t, J=13 Hz), −133.35: −133.55 (C5-F or C6-F, m), −144.7 (C5-F or C6-F, dd, .sup.1J=25 Hz, .sup.2J=11 Hz).

(319) HRMS calcd. for C.sub.15H.sub.13F.sub.3N.sub.2O.sub.2S [(M−H).sup.−]: 341.0577. found: 341.0580.

(320) The compound 8f. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (10%):CHCl.sub.3, Rf=0.64. Yield: 0.1 g, 32%, mp 124-125° C.

(321) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.6-2 (4H, m, tetrahydronapthalene), 2.6-2.9 (2H, m, tetrahydronapthalene), 4.81 (1H, br s, NHCH), 6.53 (1H, d, J=8.7 Hz, NH), 7.1-7.25 (3H, m, ArH), 7.41 (1H, d, J=7.5 Hz, ArH), 7.73-7.85 (1H, m, ArH), 8.12 (2H, s, SO.sub.2NH.sub.2).

(322) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 19.3 (tetrahydronapthalene), 29.3 (tetrahydronapthalene), 30.2 (tetrahydronapthalene), 53.8 (CH of tetrahydronapthalene, d, J(.sup.19F—.sup.13C)=12 Hz), 110.4 (C4, t, J(.sup.19F—.sup.13C)=25 Hz), 121 (C1, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F-.sup.13C)=5 Hz), 126.6 (Ar), 127.9 (Ar), 129.6 (Ar), 129.7 (Ar), 132.7 (C2, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=2 Hz), 137.6 (Ar), 137.9 (Ar), 141.5 (C5 or C6, t, .sup.1J(.sup.19F—.sup.13C)=239 Hz, .sup.2J(.sup.19F-.sup.13C)=13 Hz), 145 (C5 or C6, d, J(.sup.19F—.sup.13C)=247 Hz), 148.4 (C3, d, J(.sup.19F—.sup.13C)=239 Hz).

(323) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −123.8 (C3-F, t, J=13 Hz), −137.9: −138.14 (C5-F or C6-F, m), −149.2 (C5-F or C6-F, dd, .sup.1J=25 Hz, .sup.2J=10 Hz).

(324) HRMS calcd. for C.sub.16H.sub.15F.sub.3N.sub.2O.sub.2S [(M−H).sup.−]: 355.0734. found: 355.0733.

Example 18. Preparation of 3-(methylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9a)

(325) The mixture of 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (compound 2q) (0.2 g, 0.5 mmol), MeOH (10 mL) and methylamine (2M in methanol) (0.75 mL, 1.5 mmol) was refluxed for 7 h. MeOH was evaporated in vacuum and the resultant precipitate was filtered, washed with H.sub.2O. Recrystallization was accomplished from EtOH:H.sub.2O (2:1). Yield: 0.12 g, 57%, mp 152-153° C.

(326) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.01 (3H, dd, .sup.1J=7.5 Hz, .sup.2J=5 Hz, CH.sub.3), 3.08 (2H, t, J=7.5 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.89 (2H, t, J=7 Hz, SO.sub.2CH.sub.2CH.sub.2), 6.6 (1H, br s, NH), 7.1-7.3 (5H, m, ArH), 8.31 (2H, s, SO.sub.2NH.sub.2).

(327) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 28.6 (SO.sub.2CH.sub.2CH.sub.2), 34.1 (CH.sub.3, d, J(.sup.19F—.sup.13C)=13 Hz), 57.5 (SO.sub.2CH.sub.2CH.sub.2), 114.4 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 127.5 (Ar), 128 (C1, t, J(.sup.19F—.sup.13C)=18 Hz), 129 (Ar), 129.1 (Ar), 137.4 (C3, d, J(.sup.19F—.sup.13C)=12 Hz), 137.5 (Ar), 136.7 (C5 or C6, d, J(.sup.19F—.sup.13C)=244 Hz), 144.4 (C2, d, J(.sup.19F—.sup.13C)=251 Hz), 146.1 (C5 or C6, d, J(.sup.19F—.sup.13C)=240 Hz).

(328) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −127.5 (C2-F, s), −135.9 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −152.6 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=7 Hz).

(329) HRMS calcd. for C.sub.15H.sub.15F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.+]: 409.0498. found: 409.0505.

Example 19. Preparation of 3-(benzylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9c)

(330) The mixture of 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (compound 2q) (0.3 g, 0.75 mmol), Et.sub.3N (0.109 mL, 0.78 mmol), MeOH (10 mL) and benzylamine (0.085 mL, 0.78 mmol) was refluxed for 18 h. MeOH was evaporated in vacuum and the resultant precipitate was filtered, washed with H.sub.2O. Recrystallization was accomplished from EtOH. Yield: 0.21 g, 57%, mp 59-61° C.

(331) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.0 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.82 (2H, t, J=7 Hz, SO.sub.2CH.sub.2CH.sub.2), 4.54 (2H, dd, J=5.9 Hz, J=4 Hz, NHCH.sub.2), 7.01 (1H, t, J=6 Hz, NH), 7.1-7.5 (10H, m, ArH), 8.4 (2H, br s, SO.sub.2NH.sub.2).

(332) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 28.5 (SO.sub.2CH.sub.2CH.sub.2), 50.5 (NHCH.sub.2, d, J(.sup.19F—.sup.13C)=13 Hz), 57.7 (SO.sub.2CH.sub.2CH.sub.2), 115.6 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 127.5 (Ar), 128.2 (Ar), 128.4 (Ar), 129 (Ar), 129.1 (Ar), 129.3 (Ar), 136 (C3, d, J(.sup.19F—.sup.13C)=14 Hz), 137.5 (Ar), 139.7 (Ar), 139.4 (C5 or C6, d, J(.sup.19F—.sup.13C)=244 Hz), 144.9 (C2, d, J(.sup.19F—.sup.13C)=253 Hz), 146 (C5 or C6, d, J(.sup.19F—.sup.13C)=253 Hz).

(333) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −124.7 (C2-F, s), −134.9 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −150.4 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=7 Hz).

(334) HRMS calcd. for C.sub.21H.sub.19F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.+]: 485.0811. found: 485.0814.

Example 20. Preparation of 3-(tert-butylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9b), 3-morpholin-4-yl-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9e)

(335) The mixture of 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (compound 2q) (0.2 g, 0.5 mmol), DMSO (1 mL) and appropriate nucleophile (1.02 mmol) was stirred at ambient temperature for 4 days. The mixture was then diluted with H.sub.2O (20 mL) and the resultant precipitate was filtered, washed with H.sub.2O.

(336) The compound 9b. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:4), Rf=0.62. Yield: 0.04 g, 18%, mp 127° C.

(337) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.38 (9H, d, J=2 Hz, 3CH.sub.3), 3.14 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.65 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 5.74 (2H, s, SO.sub.2NH.sub.2), 6.63 (1H, s, NH), 7.1-7.4 (5H, m, ArH).

(338) .sup.13C NMR (75 MHz, CDCl.sub.3): 28.8 (SO.sub.2CH.sub.2C1-12), 30.9 (CH.sub.3, d, J=7 Hz), 55.7 (SO.sub.2CH.sub.2CH.sub.2), 58.8 (NHC, d, J(.sup.19F—.sup.13C)=4 Hz), 118.5 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F- .sup.13C)=6 Hz), 126.3 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 127.6 (Ar), 128.5 (Ar), 129.2 (Ar), 135.8 (C3, dd, .sup.1J(.sup.19F—.sup.13C) 18 Hz, .sup.2J(.sup.19F—.sup.13C)=3 Hz), 136.6 (Ar), 138.3 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=252 Hz, .sup.2J(.sup.19F—.sup.13C)=18 Hz, .sup.3J(.sup.19F—.sup.13C)=5 Hz), 145.8 (C2, d, J(.sup.19F—.sup.13C)=254 Hz), 146.1 (C5 or C6, ddd, .sup.1J(.sup.19F—.sup.13C)=253 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz, .sup.3J(.sup.19F—.sup.13C)=4 Hz).

(339) .sup.19F NMR (282 MHz, CDCl.sub.3): −122.2 (C2-F, s), −137.6 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −152.9 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=6 Hz).

(340) HRMS calcd. for C.sub.18H.sub.21F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.4]: 451.0968. found: 451.0969.

(341) The compound 9e. Recrystallization was accomplished from EtOH. Yield: 0.11 g, 46%, mp 198-199° C.

(342) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.9 (2H, d, J=11 Hz, morpholine), 3.12 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.21 (2H, t, J=11 Hz, morpholine), 3.57 (2H, t, J=11 Hz, morpholine), 3.79 (2H, d, J=11 Hz, morpholine), 4.06 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 7.2-7.4 (5H, m, ArH), 8.48 (2H, s, SO.sub.2NH.sub.2).

(343) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 33.3 (SO.sub.2CH.sub.2CH.sub.2), 56.6 (morpholine, d, J(.sup.19F—.sup.13C)=4 Hz), 62.3 (SO.sub.2CH.sub.2CH.sub.2), 71.8 (morpholine), 132.2 (Ar), 133.8 (Ar), 134.1 (Ar), 136.1 (C1, t, J(.sup.19F—.sup.13C)=6 Hz), 139.7 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=16 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 142.9 (Ar), 150.7 (C5, C6, dd, .sup.1J(.sup.19F—.sup.13C)=261 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz), 159.3 (C2, d, J(.sup.19F—.sup.13C)=259 Hz).

(344) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −119.1 (C2-F, d, J=14 Hz), −132.4 (C5-F, d, J=25 Hz), −136.7 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=14 Hz).

(345) HRMS calcd. for C.sub.18H.sub.19F.sub.3N.sub.2O.sub.5S.sub.2 [(M+H).sup.+]: 465.076. found: 465.0765.

Example 21. Preparation of 3-[(2-phenylethy)amino]-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9d), 3-(cyclooctylamino)-2,5,6-trifluoro-4[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 91), 3-(cyclododecylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9 g), 3-[(2,6-dimethoxybenzyl)amino]-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9 h), 3-[(3,4-dimethoxybenzyl)amino]-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9i), 3-(2,3-dihydro-1H-inden-2-ylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9k), 3-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9l), 3-[(1S)-1,2,3,4-tetrahydronapthalen-1-ylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9m)

(346) The mixture of 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (compound 2q) (0.2 g, 0.5 mmol), Et.sub.3N (0.071 mL, 0.51 mmol), DMSO (1 mL) and appropriate nucleophile (0.51 mmol) was stirred at ambient temperature for 24 h. The mixture was then diluted with H.sub.2O (20 mL) and extracted with EtAc (3×10 mL). The combined organic phase was dried over MgSO.sub.4 and evaporated in vacuum.

(347) The compound 9d. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:6), Rf=0.48. Yield: 0.18 g, 72%, mp 141-142° C.

(348) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.88 (2H, t, J=7 Hz, NHCH.sub.2CH.sub.2), 2.98 (2H, t, J=7 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.6 (2H, br t, NHCH.sub.2CH.sub.2), 3.77 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 6.68 (1H, br s, NH), 7.1-7.4 (10H, m, ArH), 8.33 (2H, s, SO.sub.2NH.sub.2).

(349) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 28.6 (SO.sub.2CH.sub.2CH.sub.2), 36.8 (NHCH.sub.2CH.sub.2), 48.3 (NHCH.sub.2CH.sub.2, d, J(.sup.19F—.sup.13C)=13 Hz), 57.5 (SO.sub.2CH.sub.2CH.sub.2), 114.6 (C4, d, J(.sup.19F—.sup.13C)=12 Hz), 127.1 (Ar), 127.5 (Ar), 128.1 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 128.9 (Ar), 129 (Ar), 129.2 (Ar), 129.5 (Ar), 136.1 (C3, d, J(.sup.19F—.sup.13C)=13 Hz), 137.5 (Ar), 139.3 (Ar), 137 (C5 or C6, d, J(.sup.19F—.sup.13C)=244 Hz), 144.3 (C2, d, J(.sup.19F—.sup.13C)=250 Hz), 145.7 (C5 or C6, d, J(.sup.19F—.sup.13C)=233 Hz).

(350) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −127 (C2-F, s), −135.3 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −152 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=7 Hz).

(351) HRMS calcd. for C.sub.22H.sub.21F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.+]: 499.0968. found: 499.0971.

(352) The compound 9f. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:9), Rf=0.5. Yield: 0.22 g, 88%, mp 90-92° C.

(353) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.4-2 (14H, m, cyclooctane), 3.14 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.64 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.85-3.95 (1H, m, cyclooctane), 5.68 (2H, s, SO.sub.2NH.sub.2), 6.91 (1H, d, J=8.7 Hz, NH), 7.1-7.4 (5H, m, ArH).

(354) .sup.13C NMR (75 MHz, CDCl.sub.3): 23.5 (cyclooctane), 25.7 (cyclooctane), 27.5 (cyclooctane), 28.7 (SO.sub.2CH.sub.2CH.sub.2), 33.2 (cyclooctane), 56.3 (CH of cyclooctane, d, J(.sup.19F—.sup.13C)=11 Hz), 58.8 (SO.sub.2CH.sub.2CH.sub.2, d, J(.sup.19F—.sup.13C)=4 Hz), 114.7 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=7 Hz), 126.4 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 127.6 (Ar), 128.5 (Ar), 129.1 (Ar), 136 (C3, d, J(.sup.19F—.sup.13C)=13 Hz), 136.5 (Ar), 136.7 (C5 or C6, d, J(.sup.19F—.sup.13C)=251 Hz), 145.8 (C2, d, J(.sup.19F—.sup.13C)=252 Hz), 146.2 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=252 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz).

(355) .sup.19F NMR (282 MHz, CDCl.sub.3): −131 (C2-F, s), −138.2 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −156.9 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=7 Hz).

(356) HRMS calcd. for C.sub.22H.sub.27F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.+]: 505.1437. found: 505.1439.

(357) The compound 9 g. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:10), Rf=0.37. Yield: 0.13 g, 46%, mp 130-131° C.

(358) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.2-1.7 (22H, m, cyclododecane), 3.07 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.8 (1H, br s, CH of cyclododecane), 3.88 (2H, t, J=7 Hz, SO.sub.2CH.sub.2CH.sub.2), 6.55 (1H, d, J=8 Hz, NH), 7.1-7.3 (5H, m, ArH), 8.36 (2H, s, SO.sub.2NH.sub.2).

(359) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 21.2 (cyclododecane), 23.3 (cyclododecane), 23.4 (cyclododecane), 24.5 (cyclododecane), 24.7 (cyclododecane), 28.5 (SO.sub.2CH.sub.2CH.sub.2), 30.8 (cyclododecane), 53.5 (CH of cyclododecane, d, J(.sup.19F—.sup.13C)=12 Hz), 58 (SO.sub.2CH.sub.2CH.sub.2), 115.4 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=4 Hz), 127.5 (Ar), 128.2 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 129 (Ar), 135.8 (C3, d, J(.sup.19F—.sup.13C)=16 Hz), 137.6 (Ar), 137.5 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=J 246 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz), 144.7 (C2, d, J(.sup.19F—.sup.13C)=250 Hz), 146.2 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=249 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz).

(360) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −125.4 (C2-F, s), −134.5 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −151 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=6 Hz).

(361) HRMS calcd. for C.sub.26H.sub.35F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.+]: 561.2063. found: 561.2071.

(362) The compound 9 h. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:5), Rf=0.47. Yield: 0.13 g, 48%, mp 133-137° C.

(363) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.76 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.47 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.74 (6H, s, 2CH.sub.3), 4.52 (2H, d, J=5.4 Hz, NHCH.sub.2), 6.62 (2H, d, J=8.4 Hz, ArH) 6.69 (1H, br t, NH), 7.05-7.3 (6H, m, ArH), 8.4 (2H, s, SO.sub.2NH.sub.2).

(364) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 28.2 (SO.sub.2CH.sub.2CH.sub.2), 39.4 (NHCH.sub.2, d, J(.sup.19F—.sup.13C)=13 Hz, signal overlaps with signal of DMSO), 56.4 (CH.sub.3), 57.6 (SO.sub.2CH.sub.2CH.sub.2), 104.7 (Ar), 114.7 (Ar), 116.5 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 127.4 (Ar), 127.9 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 129 (Ar), 129.1 (Ar), 130.4 (Ar), 136.9 (C3, d, J(.sup.19F—.sup.13C)=13 Hz), 137.5 (Ar), 138.1 (C5 or C6, d .sup.1J(.sup.19F—.sup.13C)=251 Hz), 145.5 (C5 or C6, d, J(.sup.19F—.sup.13C)=253 Hz), 146.1 (C2, d, J(.sup.19F—.sup.13C)=254 Hz), 158.7 (Ar).

(365) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −121.8 (C2-F, dd, .sup.1J=11 Hz, .sup.2J=5 Hz), −135.5 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −149.6 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=5 Hz).

(366) HRMS calcd. for C.sub.23H.sub.23F.sub.3N.sub.2O.sub.6S.sub.2 [(M−H).sup.−]: 543.0877. found: 543.0881.

(367) The compound 9i. Recrystallization was accomplished from EtOH. Yield: 0.18 g, 67%, mp 167-168° C.

(368) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.95 (2H, t, J=7.8 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.69 (3H, s, CH.sub.3), 3.73 (3H, s, CH.sub.3), 3.8 (2H, t, J=7.8 Hz, SO.sub.2CH.sub.2CH.sub.2), 4.45 (2H, t, J=4.7 Hz, NHCH.sub.2), 6.8-7 (4H, m, ArH, NH), 7.1-7.3 (5H, m, ArH), 8.38 (2H, s, SO.sub.2NH.sub.2).

(369) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 28.5 (SO.sub.2CH.sub.2CH.sub.2), 50.3 (NHCH.sub.2, d, J(.sup.19F—.sup.13C)=12.5 Hz), 56.02 (CH.sub.3), 56.08 (CH.sub.3), 57.7 (SO.sub.2CH.sub.2CH.sub.2), 112.31 (Ar), 112.34 (Ar), 115.8 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 120.8 (Ar), 127.5 (Ar), 128.1 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 128.97 (Ar), 129.03 (Ar), 131.9 (Ar), 136 (C3, d, J(.sup.19F—.sup.13C)=14 Hz), 137.5 (Ar), 137.7 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=249 Hz, .sup.2J(.sup.19F—.sup.13C)=18 Hz), 145.1 (C2, d, J(.sup.19F—.sup.13C)=256 Hz), 146 (C5 or C6, d, J(.sup.19F—.sup.13C)=250 Hz), 148.9 (Ar), 149.4 (Ar).

(370) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −123.7 (C2-F, s), −134.8 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −150.4 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=6 Hz).

(371) HRMS calcd. for C.sub.23H.sub.23F.sub.3N.sub.2O.sub.6S.sub.2 [(M−H).sup.−]: 543.0877. found: 543.0875.

(372) The compound 9k. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:4), Rf=0.6. Recrystallization was accomplished from EtOH after chromatography. Yield: 0.12 g, 45%, mp 155° C.

(373) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.8-3 (4H, m, SO.sub.2CH.sub.2CH.sub.2 and CH.sub.2 of indane), 3.26 (1H, d, J=6.3 Hz, indane), 3.31 (1H, d, J=6.3 Hz, indane), 3.67 (2H, t, J=8 Hz, SO.sub.2CH.sub.2CH.sub.2), 4.45-4.55 (1H, m, CH of indane), 6.87 (1H, d, J=8 Hz, NH), 7.1-7.3 (10H, m, ArH), 8.38 (2H, s, SO.sub.2NH.sub.2).

(374) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 28.4 (SO.sub.2CH.sub.2CH.sub.2), 41.1 (CH.sub.2 of indane, signal overlaps with signal of DMSO-D.sub.6), 57.58 (SO.sub.2CH.sub.2CH.sub.2), 57.7 (CH of indane, d, J(.sup.19F—.sup.13C)=11 Hz), 115.3 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 125.4 (Ar), 127.38 (Ar), 127.45 (Ar), 128.2 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 129 (Ar), 129.1 (Ar), 135.4 (C3, d, J(.sup.19F—.sup.13C)=14 Hz), 137.5 (Ar), 137.6 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=247 Hz, .sup.2J(.sup.19F—.sup.13C)=17 Hz), 141.1 (Ar), 144.4 (C2, d, J(.sup.19F—.sup.13C)=252 Hz), 146.2 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=250 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz).

(375) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −126.1 (C2-F, s), −134.7 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −150.8 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=7 Hz).

(376) HRMS calcd. for C.sub.23H.sub.21F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.+]: 511.0968. found: 511.0972.

(377) The compound 9l. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (5%):CHCl.sub.3, Rf=0.38. Yield: 0.17 g, 66%, mp 90° C.

(378) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 2.0 (1H, sex, J=6 Hz, indane), 2.5 (1H, sex, indane, signal overlaps with signal of DMSO-D.sub.6), 2.8-3.2 (4H, m, CH.sub.2 of indane, SO.sub.2CH.sub.2CH.sub.2), 3.7-3.9 (2H, m, SO.sub.2CH.sub.2CH.sub.2), 5.18 (1H, br s, indane), 6.89 (1H, d, J=8 Hz, NH), 7.1-7.4 (9H, m, ArH), 8.43 (2H, s, SO.sub.2NH.sub.2).

(379) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 28.3 (SO.sub.2CH.sub.2CH.sub.2), 30.2 (indane), 35.3 (indane), 57.8 (SO.sub.2CH.sub.2CH.sub.2), 61.7 (CH of indane, d, J(.sup.19F—.sup.13C)=11.4 Hz), 115.6 (C4, dd, .sup.1J(.sup.19F-.sup.13C)=14 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 124.6 (Ar), 125.7 (Ar), 127.4 (Ar), 127.5 (Ar), 128.2 (C1, t, J(.sup.19F-.sup.13C)=16 Hz), 128.9 (Ar), 129 (Ar), 129.1 (Ar), 135.7 (C3, d, J(.sup.19F—.sup.13C)=15 Hz), 137.5 (Ar), 137.8 (C5 or C6, d, J(.sup.19F—.sup.13C)=246 Hz), 143.7 (Ar), 144.2 (Ar), 144.8 (C2, d, J(.sup.19F—.sup.13C)=252 Hz), 146.1 (C5 or C6, d, J(.sup.19F—.sup.13C)=251 Hz).

(380) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −124.2 (C2-F, s), −134.5 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −150.2 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=6 Hz).

(381) HRMS calcd. for C.sub.23H.sub.21F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.+]: 511.0968. found: 511.0964.

(382) The compound 9m. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:10), Rf=0.37. Yield: 0.13 g, 50%, mp 116-119° C.

(383) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.7-2.1 (4H, m, tetrahydronapthalene), 2.6-2.9 (2H, m, tetrahydronapthalene), 2.94 (2H, t, J=7.8 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.74 (2H, t, J=7.7 Hz, SO.sub.2CH.sub.2CH.sub.2), 4.8-4.9 (1H, m, CH of tetrahydronapthalene), 6.82 (1H, d, J=9 Hz, NH), 7.1-7.4 (9H, m, ArH), 8.41 (2H, s, SO.sub.2NH.sub.2).

(384) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 19.1 (tetrahydronapthalene), 28.3 (SO.sub.2CH.sub.2CH.sub.2), 29.1 (tetrahydronapthalene), 30.5 (tetrahydronapthalene), 54.1 (CH of tetrahydronapthalene, d, J(.sup.19F—.sup.13C)=12 Hz), 58 (SO.sub.2CH.sub.2CH.sub.2), 116.1 (C4, dd, .sup.1J(.sup.19F—.sup.13C) 13 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 126.8 (Ar), 127.5 (Ar), 128.2 (Ar), 128.2 (C1, t, J(.sup.19F—.sup.13C)=18 Hz, signal overlaps with signal of Ar), 129.03 (Ar), 129.08 (Ar), 129.5 (Ar), 129.9 (Ar), 135.3 (C3, d, J(.sup.19F—.sup.13C)=11 Hz), 137.41 (Ar), 137.48 (Ar), 137.57 (Ar), 138 (C5 or C6, d, J(.sup.19F—.sup.13C)=238 Hz), 145.1 (C2, d, J(.sup.19F-.sup.13C)=254 Hz), 146.1 (C5 or C6, d, J(.sup.19F—.sup.13C)=254 Hz).

(385) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −123.5 (C2-F, s), −134.3 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −149.9 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=5 Hz).

(386) HRMS calcd. for C.sub.24H.sub.23F.sub.3N.sub.2O.sub.4S.sub.2 [(M−H).sup.−]: 523.0979. found: 523.0983.

Example 22. Preparation of 3-(1-adamantylamino)-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9j), 3-{[(1S,2R)-2-hydroxy-1,2-diphenylethyl]amino}-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9n), 3-{[(1R,2S)-2-hydroxy-1,2-diphenylethyl]amino}-2,5,6-trifluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 9o)

(387) The mixture of 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (compound 2q) (0.2 g, 0.5 mmol), Et.sub.3N (0.071 mL, 0.51 mmol), DMSO (1 mL) and appropriate nucleophile (0.52 mmol) was stirred at ambient temperature for 3 days, compound 9j was obtained after stirring for 5 days. The mixture was then diluted with H.sub.2O (20 mL).

(388) The compound 9j. The resultant precipitate was filtered, washed with H.sub.2O. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:4), Rf=0.75. Yield: 0.02 g, 8%, mp 155-156° C.

(389) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.69 (6H, br s, adamantane), 1.91 (6H, br s, adamantane), 2.15 (3H, br s, adamantane), 3.16 (2H, t, J=6 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.67 (2H, t, J=7 Hz, SO.sub.2CH.sub.2CH.sub.2), 5.53 (2H, s, SO.sub.2NH.sub.2), 6.41 (1H, s, NH), 7.1-7.4 (5H, m, ArH).

(390) .sup.13C NMR (75 MHz, CDCl.sub.3): 28.7 (SO.sub.2CH.sub.2CH.sub.2), 30.2 (adamantane), 36.2 (adamantane), 43.4 (adamantane), 43.5 (adamantane), 56.6 (SO.sub.2CH.sub.2CH.sub.2), 58.9 (adamantane, d, J(.sup.19F—.sup.13C)=4 Hz), 119.6 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=6 Hz), 126 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 127.6 (Ar), 128.5 (Ar), 129.2 (Ar), 135.3 (C3, dd, .sup.1J(.sup.19F—.sup.13C) 18 Hz, .sup.2J(.sup.19F—.sup.13C)=3 Hz), 137 (Ar), 139 (C5 or C6, d, J(.sup.19F—.sup.13C)=252 Hz), 146 (C5 or C6, d, J(.sup.19F—.sup.13C)=254 Hz), 146.4 (C2, d, J(.sup.19F—.sup.13C)=253 Hz).

(391) .sup.19F NMR (282 MHz, CDCl.sub.3): −120.3 (C2-F, s), −137.6 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −152 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=6 Hz).

(392) HRMS calcd. for C.sub.24H.sub.27F.sub.3N.sub.2O.sub.4S.sub.2 [(M+H).sup.+]: 529.1437. found: 529.1440.

(393) The compound 9n. The mixture was then extracted with EtAc (3×10 mL). The combined organic phase was dried over MgSO.sub.4 and evaporated in vacuum. Recrystallization was accomplished from EtOH:H.sub.2O=2:1. Yield: 0.12 g, 40%, mp 175-176° C.

(394) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.06 (2H, t, J=7.2 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.75-3.95 (2H, m, SO.sub.2CH.sub.2CH.sub.2), 4.9-5 (1H, m, CH), 5.1 (1H, d, J=4.5 Hz, CH), 6 (1H, br s, OH), 7.1-7.3 (15H, m, ArH), 7.87 (1H, d, J=9 Hz, NH), 8.3 (2H, s, SO.sub.2NH.sub.2).

(395) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 28.5 (SO.sub.2CH.sub.2CH.sub.2), 58 (SO.sub.2CH.sub.2CH.sub.2), 65.4 (CH, d, J(.sup.19F—.sup.13C)=12.8 Hz), 75.6 (CH), 115.3 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=6 Hz), 127.2 (Ar), 127.4 (Ar), 127.8 (Ar), 127.9 (Ar), 128.2 (Ar), 128.3 (Ar), 128.93 (Ar), 128.99 (Ar), 129.04 (Ar), 135.2 (C3, d, J(.sup.19F—.sup.13C)=12 Hz), 137.2 (C5 or C6, d, J(.sup.19F—.sup.13C)=250 Hz), 137.5 (Ar), 139.7 (Ar), 142.9 (Ar), 144.5 (C2, d, J(.sup.19F—.sup.13C)=254 Hz), 146 (C5 or C6, d, J(.sup.19F-.sup.13C)=249 Hz).

(396) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −123.3 (C2-F, s), −134.7 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −150.8 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=7 Hz).

(397) HRMS calcd. for C.sub.28H.sub.25F.sub.3N.sub.2O.sub.5S.sub.2 [(M+H).sup.+]: 591.123. found: 591.1220.

(398) The compound 9o. The resultant precipitate was filtered, washed with H.sub.2O. Recrystallization was accomplished from EtOH:H.sub.2O=2:1. Yield: 0.12 g, 40%, mp 176-177° C.

(399) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.06 (2H, t, J=7.2 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.75-3.95 (2H, m, SO.sub.2CH.sub.2CH.sub.2), 4.9-5 (1H, m, CH), 5.1 (1H, t, J=4.2 Hz, CH), 6 (1H, d, J=4.2 Hz, OH), 7.1-7.3 (15H, m, ArH), 7.87 (1H, d, J=8 Hz, NH), 8.25 (2H, s, SO.sub.2NH.sub.2).

(400) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 28.5 (SO.sub.2CH.sub.2CH.sub.2), 58 (SO.sub.2CH.sub.2CH.sub.2), 65.4 (CH, d, J(.sup.19F—.sup.13C)=12.8 Hz), 75.6 (CH), 115.3 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=6 Hz), 127.2 (Ar), 127.4 (Ar), 127.8 (Ar), 127.9 (Ar), 128.2 (Ar), 128.3 (Ar), 128.93 (Ar), 128.99 (Ar), 129.04 (Ar), 135.2 (C3, d, J(.sup.19F—.sup.13C)=12 Hz), 137.2 (C5 or C6, d, J(.sup.19F—.sup.13C)=250 Hz), 137.5 (Ar), 139.7 (Ar), 142.9 (Ar), 144.5 (C2, d, J(.sup.19F—.sup.13C)=254 Hz), 146 (C5 or C6, d, J(.sup.19F-.sup.13C)=249 Hz).

(401) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −123.3 (C2-F, s), −134.7 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −150.8 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=7 Hz).

(402) HRMS calcd. for C.sub.28H.sub.25F.sub.3N.sub.2O.sub.5S.sub.2 [(M+H).sup.+]: 591.123. found: 591.1221.

Example 23. Preparation of 3-(benzylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (Compound 10a)

(403) The mixture of 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (compound 2d) (0.25 g, 0.74 mmol), MeOH (10 mL) and benzylamine (0.17 mL, 1.56 mmol) was stirred at ambient temperature for 24 h. MeOH was evaporated in vacuum and the resultant precipitate was filtered, washed with H.sub.2O. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:2), Rf=0.19. Yield: 0.11 g, 35%, mp 127° C.

(404) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.65 (2H, t, J=5.4 Hz, SO.sub.2CH.sub.2CH.sub.2), 2.83 (2H, k, J=5.4 Hz, SO.sub.2CH.sub.2CH.sub.2), 4.45-4.55 (2H, m, NHCH.sub.2), 5.03 (1H, t, J=5.1 Hz, OH), 6.96 (1H, br t, NH), 7.3-7.5 (5H, m, ArH), 8.36 (2H, s, SO.sub.2NH.sub.2).

(405) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 50.7 (NHCH.sub.2, d, J(.sup.19F—.sup.13C)=13 Hz), 55.8 (SO.sub.2CH.sub.2CH.sub.2), 60.1 (SO.sub.2CH.sub.2CH.sub.2), 117.6 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 127.9 (C1 signal overlaps with signal of Ar), 128.1 (Ar), 128.3 (Ar), 129.3 (Ar), 136.1 (C3, d, J(.sup.19F—.sup.13C)=13 Hz), 137.8 (C5 or C6, d, J(.sup.19F—.sup.13C)=246 Hz), 139.6 (Ar), 144.9 (C2, d, J(.sup.19F—.sup.13C)=252 Hz), 146.2 (C5 or C6, d, J(.sup.19F—.sup.13C)=252 Hz).

(406) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −125.1 (C2-F, s), −135.3 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=13 Hz), −150.7 (C5-F, dd, .sup.1J=26 Hz, .sup.2J=7 Hz).

(407) HRMS calcd. for C.sub.15H.sub.15F.sub.3N.sub.2O.sub.5S.sub.2 [(M+H).sup.+]: 425.0447. found: 425.0439.

Example 24. Preparation of 3-(cyclooctylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (Compound 10b)

(408) The mixture of 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (compound 2d) (0.38 g, 1.1 mmol), MeOH (10 mL) and cyclooctylamine (0.332 mL, 2.4 mmol) was refluxed for 6 h. MeOH was evaporated in vacuum and the resultant oil was washed with H.sub.2O. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.38. Yield: 0.2 g, 40%.

(409) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.4-2 (14H, m, cyclooctane), 3.59 (2H, t, J=6 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.8-3.9 (1H, m, CH of cyclooctane), 4.11 (2H, t, J=6 Hz, SO.sub.2CH.sub.2CH.sub.2), 6.08 (2H, s, SO.sub.2NH.sub.2), 6.74 (1H, br s, NH).

(410) .sup.13C NMR (75 MHz, CDCl.sub.3): 23.5 (cyclooctane), 25.7 (cyclooctane), 27.4 (cyclooctane), 33.1 (cyclooctane), 56.3 (cyclooctane), 56.5 (SO.sub.2CH.sub.2CH.sub.2), 59.8 (cyclooctane), 60.8 (SO.sub.2CH.sub.2CH.sub.2), 115.8 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=6 Hz), 126.5 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 135.7 (C3, d, J(.sup.19F—.sup.13C)=13 Hz), 137 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=246 Hz, .sup.2J(.sup.19F-.sup.13C)=14 Hz), 144.7 (C2, d, J(.sup.19F—.sup.13C)=253 Hz), 146.4 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=253 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz).

(411) .sup.19F NMR (282 MHz, CDCl.sub.3): −125.9 (C2-F, s), −134 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −152.1 (C5-F, dd, .sup.1J=24 Hz, .sup.2J=4 Hz).

(412) HRMS calcd. for C.sub.16H.sub.23F.sub.3N.sub.2O.sub.5S.sub.2 [(M+H).sup.+]: 445.1073. found: 445.1077.

Example 25. Preparation of 3-(cyclododecylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (Compound 10c), 3-[(2,6-dimethoxybenzyl)amino]-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (Compound 10d), 3-[(3,4-dimethoxybenzyl)amino]-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (Compound 10e), 3-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (Compound 10f), 3-[(1S)-1,2,3,4-tetrahydronapthalen-1-ylamino)-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (Compound 10 g), 3-{[(1S,2R)-2-hydroxy-1,2-diphenylethyl]amino}-2,5,6-trifluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (Compound 10 h)

(413) The mixture of 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (compound 2d) (0.2 g, 0.59 mmol), DMSO (1 mL) and appropriate nucleophile (1.2 mmol) was stirred at ambient temperature for 24 h. The mixture was then diluted with H.sub.2O (20 mL) and extracted with EtAc (3×10 mL). The combined organic phase was dried over MgSO.sub.4 and evaporated in vacuum.

(414) The compound 10c. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.5. Yield: 0.26 g, 88%, mp 143-144° C.

(415) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.2-1.7 (22H, m, cyclododecane), 3.68 (2H, t, J=5 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.8 (1H, br s, CH of cyclododecane, signal overlaps with signal of SO.sub.2CH.sub.2CH.sub.2), 3.83 (2H, t, J=5 Hz, SO.sub.2CH.sub.2CH.sub.2), 5.01 (1H, t, J=5 Hz, OH), 6.55 (1H, d, J=9 Hz, NH), 8.36 (2H, s, SO.sub.2NH.sub.2).

(416) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 21.3 (cyclododecane), 23.4 (cyclododecane), 23.5 (cyclododecane), 24.4 (cyclododecane), 24.6 (cyclododecane), 30.8 (cyclododecane), 53.4 (CH of cyclododecane, d, J(.sup.19F—.sup.13C)=12 Hz), 55.8 (SO.sub.2CH.sub.2CH.sub.2), 60.3 (SO.sub.2CH.sub.2CH.sub.2), 117.4 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=6 Hz), 127.9 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 135.7 (C3, d, J(.sup.19F—.sup.13C)=13 Hz), 137.4 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=246 Hz, .sup.2J(.sup.19F—.sup.13C)=19 Hz), 144.7 (C2, d, J(.sup.19F—.sup.13C)=253 Hz), 146.3 (C5 or C6, d, J(.sup.19F—.sup.13C)=247 Hz).

(417) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −125.4 (C2-F, s), −134.8 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −151.4 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=6 Hz).

(418) HRMS calcd. for C.sub.20H.sub.31F.sub.3N.sub.2O.sub.5S.sub.2 [(M+H).sup.+]: 501.1699. found: 501.1701.

(419) The compound 10d. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (60%):CHCl.sub.3, Rf=0.45. Yield: 0.15 g, 52%, mp 164-165° C.

(420) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.35 (2H, t, J=6 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.63 (2H, br t, SO.sub.2CH.sub.2CH.sub.2), 3.75 (6H, s, 2CH.sub.3), 4.48 (2H, d, J=5.4 Hz, NHCH.sub.2), 4.93 (1H, br s, OH), 6.58 (1H, br t, NH), 6.66 (2H, d, J=8.4 Hz, ArH), 7.26 (1H, t, J=8.4 Hz, ArH), 8.42 (2H, s, SO.sub.2NH.sub.2).

(421) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 39.5 (NHCH.sub.2), 55.4 (SO.sub.2CH.sub.2CH.sub.2), 56.3 (2CH.sub.3), 59.9 (SO.sub.2CH.sub.2CH.sub.2), 104.7 (Ar), 114.6 (Ar), 118.2 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=12 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 127.7 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 130.3 (Ar), 136.8 (C3, d, J(.sup.19F—.sup.13C)=11 Hz), 137.9 (C5 or C6, d, .sup.1J(.sup.19F—.sup.13C)=228 Hz), 146 (C2, d, J(.sup.19F—.sup.13C)=253 Hz), 144.8 (C5 or C6, d, J(.sup.19F—.sup.13C)=242 Hz), 158.7 (Ar).

(422) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −122.1 (C2-F, s), −135.9 (C6-F, dd, .sup.1J=26 Hz, .sup.2J=13 Hz), −150.1 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=6 Hz).

(423) HRMS calcd. for C.sub.17H.sub.19F.sub.3N.sub.2O.sub.7S.sub.2 [(M−H).sup.−]: 483.0513. found: 483.0517.

(424) The compound 10e. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (2:1), Rf=0.38. Recrystallization was accomplished from EtOH after chromatography. Yield: 0.1 g, 29%, mp 164-165° C.

(425) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.65 (2H, t, J=6 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.746 (3H, s, CH.sub.3), 3.755 (3H, s, CH.sub.3), 3.82 (2H, br t, SO.sub.2CH.sub.2CH.sub.2), 4.43 (2H, br s, NHCH.sub.2), 6.8-7 (3H, m, ArH), 6.99 (1H, s, NH), 8.38 (2H, s, SO.sub.2NH.sub.2).

(426) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 50.6 (NHCH.sub.2, d, J(.sup.19F—.sup.13C)=12 Hz), 55.8 (CH.sub.3), 56 (CH.sub.3), 56.1 (SO.sub.2CH.sub.2CH.sub.2), 60.1 (SO.sub.2CH.sub.2CH.sub.2), 112.2 (Ar), 112.3 (Ar), 117.7 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 120.7 (Ar), 127.8 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 131.8 (Ar), 136 (C3, d, J(.sup.19F—.sup.13C)=16 Hz), 137.8 (C5 or C6, d, J(.sup.19F—.sup.13C)=252 Hz), 145.1 (C2, d, J(.sup.19F—.sup.13C)=253 Hz), 146.1 (C5 or C6, dd, .sup.1J(.sup.19F—.sup.13C)=253 Hz, .sup.2J(.sup.19F—.sup.13C)=16 Hz), 148.9 (Ar), 149.5 (Ar).

(427) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −124.4 (C2-F, s), −135.2 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −150.7 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=6 Hz).

(428) HRMS calcd. for C.sub.17H.sub.19F.sub.3N.sub.2O.sub.7S.sub.2 [(M−H).sup.−]: 483.0513. found: 483.0515.

(429) The compound 10f. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.38. Yield: 0.16 g, 60%, mp 131-132° C.

(430) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.95 (1H, sex, J=7 Hz, indane), 2.51 (1H, sex, indane, signal overlaps with signal of DMSO-D.sub.6), 2.8-3.1 (2H, m, indane), 3.55-3.7 (2H, m, SO.sub.2CH.sub.2CH.sub.2), 3.7-3.85 (2H, m, SO.sub.2CH.sub.2CH.sub.2), 5.02 (1H, t, J=5 Hz, OH), 5.1-5.25 (1H, m, CH of indane), 6.88 (1H, d, J=6 Hz, NH), 7.2-7.5 (4H, m, ArH), 8.43 (2H, s, SO.sub.2NH.sub.2).

(431) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 30.2 (indane), 35.2 (indane), 55.8 (SO.sub.2CH.sub.2CH.sub.2), 60.2 (SO.sub.2CH.sub.2CH.sub.2), 61.9 (CH of indane, d, J(.sup.19F—.sup.13C)=12 Hz), 117.6 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 124.7 (Ar), 125.6 (Ar), 127.4 (Ar), 128 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 128.9 (Ar), 135.6 (C3, d, J(.sup.19F—.sup.13C)=12 Hz), 137.8 (C5 or C6, d, J(.sup.19F—.sup.13C)=253 Hz), 144.4 (Ar), 144.5 (Ar), 144.8 (C2, d, J(.sup.19F—.sup.13C)=251 Hz), 146.3 (C5 or C6, d, J(.sup.19F—.sup.13C)=258 Hz).

(432) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −124.6 (C2-F, s), −134.8 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −150.7 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=6 Hz).

(433) HRMS calcd. for C.sub.17H.sub.17F.sub.3N.sub.2O.sub.5S.sub.2 [(M−H).sup.−]: 449.0458. found: 449.0461.

(434) The compound 10 g. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (1:1), Rf=0.41. Yield: 0.14 g, 51%, mp 103-105° C.

(435) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 1.7-2.1 (4H, m, tetrahydronapthalene), 2.6-2.9 (2H, m, tetrahydronapthalene), 3.61 (2H, t, J=5.4 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.76 (2H, br t, SO.sub.2CH.sub.2CH.sub.2), 4.8-4.9 (1H, m, CH of tetrahydronapthalene), 5.01 (1H, br s, OH), 6.82 (1H, d, J=9 Hz, NH), 7.1-7.3 (3H, m, ArH), 7.4 (1H, d, J=7.7 Hz, ArH), 8.42 (2H, s, SO.sub.2NH.sub.2).

(436) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 19.3 (tetrahydronapthalene), 29.2 (tetrahydronapthalene), 30.6 (tetrahydronapthalene), 54.3 (CH of tetrahydronapthalene, d, J(.sup.19F—.sup.13C)=12 Hz), 55.7 (SO.sub.2CH.sub.2CH.sub.2), 60.3 (SO.sub.2CH.sub.2CH.sub.2), 117.9 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=5 Hz), 126.8 (Ar), 128 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 128.2 (Ar), 129.5 (Ar), 129.8 (Ar), 135.1 (C3, d, J(.sup.19F—.sup.13C)=15 Hz), 137.48 (Ar), 137.56 (Ar), 137.9 (C5 or C6, d, J(.sup.19F—.sup.13C)=245 Hz), 145.1 (C2, d, J(.sup.19F—.sup.13C)=255 Hz), 146.2 (C5 or C6, d, J(.sup.19F—.sup.13C)=254 Hz).

(437) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −123.9 (C2-F, s), −134.5 (C6-F, dd, .sup.1J=27 Hz, .sup.2J=12 Hz), −150.5 (C5-F, dd, .sup.1J=27 Hz, .sup.2J=6 Hz).

(438) HRMS calcd. for C.sub.18H.sub.19F.sub.3N.sub.2O.sub.5S.sub.2 [(M+H).sup.+]: 465.076. found: 465.0760.

(439) The compound 10 h. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc:CHCl.sub.3 (2:1), Rf=0.53. Yield: 0.12 g, 39%.

(440) .sup.1H NMR (300 MHz, CD.sub.3OD): 3.62 (2H, k, J=5.4 Hz, SO.sub.2CH.sub.2CH.sub.2), 4.04 (2H, k, J=5.4 Hz, SO.sub.2CH.sub.2CH.sub.2), 4.88 (SO.sub.2NH.sub.2, NH, OH signals overlap with signal of H.sub.2O), 5.07 (1H, dd, .sup.1J=5.1 Hz, .sup.2J=2.1 Hz, CH), 5.14 (1H, d, J=4.8 Hz, CH), 7.1-7.3 (10H, m, ArH).

(441) .sup.13C NMR (75 MHz, CD.sub.3OD): 55.5 (SO.sub.2CH.sub.2CH.sub.2), 59.8 (SO.sub.2CH.sub.2CH.sub.2), 65.7 (CH, d, J(.sup.19F-.sup.13C)=12.5 Hz), 76.3 (CH), 116.8 (C4, dd, .sup.1J(.sup.19F—.sup.13C)=13 Hz, .sup.2J(.sup.19F—.sup.13C)=5.4 Hz), 126.8 (Ar), 127.33 (Ar), 127.38 (Ar), 127.7 (Ar), 128.8 (Ar), 128.5 (Ar), 135 (C3, d, J(.sup.19F—.sup.13C)=14 Hz), 137.7 (C5 or C6, d, J(.sup.19F—.sup.13C)=250 Hz), 139.1 (Ar), 141.7 (Ar), 144.8 (C2, d, J(.sup.19F—.sup.13C)=257 Hz), 146.1 (C5 or C6, d, J(.sup.19F—.sup.13C)=247 Hz).

(442) .sup.19F NMR (282 MHz, CD.sub.3OD): −123.9 (C2-F, s), −136.4 (C6-F, dd, .sup.1J=25 Hz, .sup.2J=12 Hz), −152.3 (C5-F, dd, .sup.1J=24 Hz, .sup.2J=6 Hz).

(443) HRMS calcd. for C.sub.22H.sub.21F.sub.3N.sub.2O.sub.6S.sub.2 [(M+H).sup.+]: 531.0866. found: 531.0865.

Example 26. Preparation of 3,5-bis(cyclooctylamino)-2,6-difluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (Compound 11)

(444) The mixture of 2,3,5,6-tetrafluoro-4-[(2-phenylethyl)sulfonyl]benzenesulfonamide (compound 2q) (0.2 g, 0.5 mmol), Et.sub.3N (0.142 mL, 1.02 mmol), DMSO (1 mL) cyclooctylamine (0.142 mL, 1.02 mmol) was stirred at 60° C. for 32 h. The mixture was then diluted with H.sub.2O (20 mL) and extracted with EtAc (3×10 mL). The combined organic phase was dried over MgSO.sub.4 and evaporated in vacuum. The product was purified by chromatography on a column of silica gel (0.04-0.063 mm) with EtAc (10%):CHCl.sub.3, Rf=0.72. Yield: 0.15 g, 48%.

(445) .sup.1H NMR (300 MHz, CDCl.sub.3): 1.4-2 (28H, m, cyclooctane), 3.05-3.15 (2H, m, SO.sub.2CH.sub.2CH.sub.2), 3.5-3.6 (2H, m, SO.sub.2CH.sub.2CH.sub.2), 3.88 (2H, br s, 2×CH of cyclooctane), 5.58 (2H, s, SO.sub.2NH.sub.2), 6.43 (2H, br s, 2NH), 7.1-7.4 (5H, m, ArH).

(446) .sup.13C NMR (75 MHz, CDCl.sub.3): 23.8 (cyclooctane), 25.8 (cyclooctane), 27.4 (cyclooctane), 28.5 (SO.sub.2CH.sub.2CH.sub.2), 33.5 (cyclooctane), 55.9 (SO.sub.2CH.sub.2CH.sub.2), 56.2 (CH of cyclooctane, t, J=6 Hz), 111.1 (C4, t, J(.sup.19F—.sup.13C)=5 Hz), 126.3 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 127.4 (Ar), 128.6 (Ar), 129.2 (Ar), 135.3 (C3, dd, .sup.1J(.sup.19F—.sup.13C)=10 Hz, .sup.2J(.sup.19F—.sup.13C)=6 Hz), 137.3 (Ar), 139.4 (C2, dd, .sup.1J(.sup.19F—.sup.13C)=244 Hz, .sup.2J(.sup.19F—.sup.13C)=4.5 Hz).

(447) .sup.19F NMR (282 MHz, CDCl.sub.3): −144.1 (2F, s).

(448) HRMS calcd. for C.sub.30H.sub.43F.sub.2N.sub.3O.sub.4S.sub.2 [(M+H).sup.+]: 612.2736. found: 612.2729.

Example 27. Preparation of 3,5-bis[(3,4-dimethoxybenzyl)amino]-2,6-difluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (Compound 12)

(449) The mixture of 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide (compound 2d) (0.2 g, 0.59 mmol), DMSO (1 mL) and 3,4-dimethoxybenzylamine (0.359 mL, 2.38 mmol) was stirred at ambient temperature for 5 days. The mixture was then diluted with H.sub.2O (20 mL), the resultant precipitate was filtered, washed with H.sub.2O. Recrystallization was accomplished from EtOH. Yield: 0.2 g, 53%, mp 99-102° C.

(450) .sup.1H NMR (300 MHz, DMSO-D.sub.6): 3.4 (SO.sub.2CH.sub.2CH.sub.2, signal overlaps with signal of H.sub.2O), 3.65 (2H, k, J=6 Hz, SO.sub.2CH.sub.2CH.sub.2), 3.75 (12H, s, 4CH.sub.3), 4.4 (4H, d, J=5 Hz, 2NHCH.sub.2), 5.04 (1H, t, J=5.4 Hz, OH), 6.38 (2H, t, J=5.7 Hz, 2NH), 6.85-7.05 (6H, m, ArH), 8.15 (2H, s, SO.sub.2NH.sub.2).

(451) .sup.13C NMR (75 MHz, DMSO-D.sub.6): 51.2 (NHCH.sub.2, t, J(.sup.19F—.sup.13C)=6 Hz), 55.5 (SO.sub.2CH.sub.2CH.sub.2), 56.07 (CH.sub.3), 56.18 (CH.sub.3), 58.3 (SO.sub.2CH.sub.2CH.sub.2), 112.4 (Ar), 115.5 (C4, t, J(.sup.19F—.sup.13C)=3 Hz), 120.8 (Ar), 127.9 (C1, t, J(.sup.19F—.sup.13C)=16 Hz), 132.3 (Ar), 135.7 (C3, dd, .sup.1J(.sup.19F—.sup.13C)=10 Hz, .sup.2J(.sup.19F-.sup.13C)=6 Hz), 141.7 (C2, dd, .sup.1J(.sup.19F—.sup.13C)=247 Hz, .sup.2J(.sup.19F—.sup.13C)=4 Hz), 148.8 (Ar), 149.4 (Ar).

(452) .sup.19F NMR (282 MHz, DMSO-D.sub.6): −133.47 (2F, s).

(453) HRMS calcd. for C.sub.26H.sub.31F.sub.2N.sub.3O.sub.9S.sub.2 [(M+H).sup.+]: 632.1543. found: 632.1548.

(454) Compound Binding and Inhibition Measurements

(455) Inhibition of carbonic anhydrases is measured by determining the reduction in the velocity of catalysis. Carbonic anhydrases catalyse the reversible reaction:
CO.sub.2+H.sub.2OHCO.sub.3.sup.−+H.sup.+

(456) The inhibition of this reaction may be determined by measuring carbon dioxide consumption, bicarbonate appearance and the changes of pH (Krebs, J. F. and Fierke, C. A. (1993), J. Biol. Chem. 268, 948). All sulfonamides bind to the active center of carbonic anhydrases and diminish this reaction. Inhibition is equivalent to binding. (Chakravarty, S. and. Kannan, K. K. (1994), J. Mol. Biol. 243, 298; Lindskog, S. (1997), Pharmacol. Ther. 74, 1; Baird, T. T. J. et al. (1997), Biochemistry, 36, 2669). However, their binding and inhibitory efficiency varies greatly. Furthermore, the specificity of various sulfonamides varies greatly (Alterio, V. et al. (2012), Chem. Rev. 112, 4421). Sulfonamide binding to carbonic anhydrases is measured by a number of methods (Krishnamurthy, V. M. et al. (2008), Chem. Rev. 108, 946). Most often used methods are isothermal titration calorimetry, surface plasmon resonance, and ultracentrifugation. (Myszka, D. G. et al. (2003), J. Biomol. Tech. 14, 247). Specificity is determined by measuring binding constants with various isozymes and also by measuring intrinsic binding constants (Matulis, D. and Todd, M. J. (2004), Biocalorimetry 2).

Example 28. Determination of the Observed Binding Constants by the Fluorescent Thermal Shift Assay (TSA)

(457) Inhibitor binding to carbonic anhydrases was measured by the fluorescent thermal shift assay, which measures the binding constant of a ligand by determining the increase in the melting temperature of the protein in the presence of a ligand. TSA experiments were performed as previously described ({hacek over (C)}apkauskaitė, E. et al. (2012), Eur. J. Med. Chem. 51, 259). TSA data were fit and analyzed as previously described (Kazlauskas, E. et al. (2012), PLoS ONE, 7, e36899).

(458) FIG. 1 shows representative binding data obtained by TSA (isozyme CA XIII). The dissociation constants for several selected characteristic compounds are listed in Table 1. A widely used CA inhibitors acetazolamide (AZM) and ethoxzolamide (EZA) were used as controls in these experiments. The data in the Table show that the number of fluorine atom substitutions and the nature of the substituent on the benzene ring significantly influences the binding affinity against CA I, CA II, CA VII, CA XII and CA XIII isoforms. The 4-substituted-2,3,5,6-tetrafluorobenzenesulfonamides (compounds 2a-x) bind CAI, II, VII and XIII isozymes with low nanomolar and subnanomolar affinity, exhibiting especially strong binding of CA I (K.sub.d is in the range of 0.01-14 nM). The weakest binding is with CA XII (K.sub.d is in the range of 20-769 nM). Further substitution at position 2 (compounds 3a-o, 4a-g, 5, 6) significantly lowers affinity for all CA isozymes, especially for CAI (the binding is in the micromolar range). Compounds 4a-g (Table lists 4e) demonstrate high selectivity for hCA XIII with respect to the other isoforms, CA I, II, VII and XII. Compounds 8a-f (Table lists 8a) do not have substituent at position 4 and fluorine atom at position 2 is substituted by a bulky group. They bind stronger to CAI then the same compounds having substituent at position 4 (compounds 4a-f). Compounds 9a-o having substitution at position 3 are good inhibitors of CA XIII. It seems that binding to CA XIII does not strongly depend on the size of substituent at this position because K.sub.d varies only in the narrow nanomolar range (from 1.3 nM for 9a to 8.3 nM for 9 h). Compounds 10a-h act as nanomolar inhibitors of CA II, CA VII, CA XII, and CA XIII.

(459) TSA data of a selected representative compound binding to CA XIII (FIG. 1). Panels on the top show thermal shift assay raw data of 2c and 9c binding to CA XIII. Panel on the bottom show the dependence of the protein melting temperatures T.sub.m on ligand concentrations. The curves in this panel show the simulated curves according to literature model.

(460) TABLE-US-00001 TABLE 1 Dissociation constants of selected compound binding to five human recombinant CA isoforms as determined by TSA (37° C., pH 7.0). Com- Dissociation constants K.sub.d (nM) to CA isoforms pound CA I CA II CA VII CA XII CA XIII 1 2 3 4 5 6  2a 8.3  91.0 465    769 140     2c 0.11  6.7 45.5  222 8.3  2d 0.20 17.0 7.1 250 29.0   2g 0.20 11.0 5.0   50.0 6.7  2h 0.40 20.0 10.0    91.0 20.0   2i 0.10 67.0 147    200 14.3   2j 0.13  4.0 11.8    20.0 1.5  2l 0.10  2.5 1.0   50.0 1.0  2m 0.25  1.25  1.25    6.67  0.40  2t 2.5  10.0 10.0  290 2.5  2u 1.1   1.1  0.22 200  0.25  2w 0.40  6.7 13.0  110 2.5  2x 14.0   6.7 1.7 670 2.0  3a 3 300      500   130    2 900   67.0   3d 1 700      3 300     4 000     5 000   40.0   3f 25 000      250   170    500 500     3l 5 000      3 300     4 000     1 700   100     4e 8 300      2 780     1 100     1 250   33.3   8a 167    200   167    833 100     9a 67.0   5.9 8.3 290 1.3  9c 56.0   6.7 5.0   40.0 2.5  9d 500    17.0 4.0   33.0 6.7  9h 58.8  22.2 667    167 8.3  9i 213    22.2 6.7 250 3.3  9j 500    50.0 5.0   17.0 5.6  9n 1 700      33.0 10.0  250 5.6  9o 770    91.0 40.0  400 6.7 10a 200    83.0 130      25.0 14.0  10d 200    16.7 40.0    66.7 25.0  10e 83.3  25.0 14.3    66.7 4.3 EZA 14     0.71  0.71  36 13.0  AZM 1400     17.0 17.0  133 50.0 

Example 29. Determination of the Binding Constants by Isothermal Titration Calorimetry (ITC)

(461) The heat evolved upon inhibitor binding to carbonic anhydrase isozymes was measured by isothermal titration calorimetry. ITC measurements were performed as previously described ({hacek over (C)}apkauskaitė, E. et al. (2012), Eur. J. Med. Chem. 51, 259).

(462) FIGS. 2, 3 show representative binding data obtained by ITC (isozymes CA I and CA XIII). The binding of 2d to CA I is the case of very tight binding where ITC curve is too steep to be fitted precisely. Therefore TSA data is more reliable to determine tight binding than ITC. The observed dissociation constants for compounds 2t and 10a listed in Table 2 shows the negligible differences between observed K.sub.d's measured by two methods (see TSA data in Table 1). Due to laborious nature of ITC measurements, only two compounds were tested by ITC and demonstrated that there is good agreement between TSA and ITC data.

(463) FIG. 2 shows ITC data of 2d binding to CA I. FIG. 3 shows ITC data of 2c binding to CA XIII.

(464) TABLE-US-00002 TABLE 2 Dissociation constants of selected compound binding to five human recombinant CA isoforms as determined by ITC (37° C., pH 7.0). Dissociation constants K.sub.d (nM) to CA isoforms Compound CA I CA II CA VII CA XII CA XIII  2t 5.2 9.4 88.5 149 4.7 10a 130 139 405 12.2 45.2 EZA 25.0 0.38 8.8 23.0 12.0 AZM 780 17.7 83.3 79.2 64.4

Example 30. Determination of the Compound Inhibition Constants Ki by CO2 Hydration Assay

(465) In addition to the binding measurements by TSA and ITC, inhibition constants were also determined by conventional hydration inhibition assay for several selected characteristic compounds and confirmed that there is good general agreement between TSA, ITC, and inhibition data.

(466) The carbon dioxide hydration activity of recombinant human CAII was measured using Applied Photophysics SX.18MV-R stopped-flow spectrometer. Reaction velocities were measured by recording absorbance of bromothymol blue (40 μM). The reaction buffer contained 10 mM NaCl, 10 mM Hepes, pH 7.4. Saturated CO.sub.2 solutions were made by bubbling gas in milli-Q water at 25° C. CAII was incubated with inhibitors for 15 min at a room temperature to form enzyme-inhibitor complex. CAII concentration was 20 nM and final DMSO concentration was less than 0.04%. IC50 value was determined by fitting the sigmoidal curve on the data points and then K.sub.i was calculated using Cheng-Prusoff equation. The determined K.sub.i values for 2c, 4e, and AZM were 3.5, 500, and 10.6 nM, respectively (FIGS. 4 and 5). These values are systematically lower than the ones determined by TSA, but essentially within the standard deviation and the random error of both methods.

(467) FIG. 4 shows CO.sub.2 hydration catalyzed by CA II and inhibition by 2c. FIG. 5 shows inhibition curves of CA II with 2c, AZM and 4e.

(468) Newly synthesized sulfonamides of general formula (I)

(469) ##STR00016##

(470) exhibit significant affinity and selectivity, often better than the existing compounds, promising to help in solving the issue of non-specific binding of clinically used inhibitors.