Compounds and compositions for the inhibition of NAMPT

Abstract

The present invention relates to compounds and compositions for the inhibition of NAMPT, their synthesis, applications and antidotes. An embodiment of the invention is the provision of a compound of Formula IIIA. ##STR00001##

Claims

1. A compound of Formula IIIA: ##STR00774## or a pharmaceutically acceptable salt thereof, wherein: R.sup.a is present 4 times, and each R.sup.a is independently selected from the group consisting of hydrogen, amino, oxo, halo, alkoxy, alkyl, haloalkyl, —N(alkyl).sub.2, —NH(CO)O-alkyl, 1H-pyrazole, 1H-imidazole, and —C(O)NH.sub.2; the pyridine to which R.sup.a is attached can comprise a N-oxide formed with its N atom member; R.sup.1 is —NR.sup.3R.sup.4; R.sup.3 is H, alkyl or —S(O).sub.2alkyl; R.sup.4 is hydroxyalkyl, —S(O).sub.2alkyl, —(CH.sub.2).sub.qcycloalkyl, —(CH.sub.2).sub.qheterocycloalkyl, or phenyl; wherein each of said cycloalkyl, phenyl, or heterocycloalkyl of R.sup.4 is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents which can be the same or different and are independently selected from the group consisting of: cyano, hydroxyl, hydroxyalkyl, hydroxyalkoxy, alkoxy, alkylalkoxy, haloalkoxy, arylalkenyl-, aryloxy, benzyloxy, oxo, —(CH.sub.2).sub.q—NR.sup.bR.sup.c, —(CH.sub.2).sub.q—CONR.sup.bR.sup.c, —S(O).sub.2-alkyl, —S(O).sub.2NH-alkyl, —S(O).sub.2-heterocycloalkyl, —S(O).sub.2—CF.sub.3, —C(O)alkyl, —C(O)aryl, —C(O)alkylenylaryl, —C(O)O-alkyl, —(CH.sub.2).sub.qcycloalkyl, cycloalkylalkoxy-, arylalkyl-, —(CH.sub.2).sub.qheteroaryl, and —(CH.sub.2).sub.qheterocycloalkyl; wherein each of said cycloalkyl, heterocycloalkyl, or aryl may be substituted by one or more halo, nitro, haloalkyl, haloalkoxy, oxo, cyano, alkyl, haloalkyl, or alkoxy; R.sup.b and R.sup.c are independently selected from the group consisting of H, alkyl, hydroxyalkyl, alkoxy, aryl, alkoxyalkyl, —S(O).sub.2alkyl and cycloalkyl; or R.sup.b and R.sup.c can form a 5 or 6 membered heterocycloalkyl group together with the nitrogen atom to which they are attached, wherein said heterocycloalkyl group may contain one or more additional heteroatom(s) selected from the group consisting of N, S and O; and q is 0 or 1.

2. The compound of claim 1, wherein R.sup.3 is H or —S(O).sub.2alkyl.

3. The compound of claim 1, wherein R.sup.4 is hydroxyalkyl, —S(O).sub.2alkyl, —(CH.sub.2).sub.qcycloalkyl, or —(CH.sub.2).sub.qheterocycloalkyl.

4. The compound of claim 1, wherein R.sup.3 is H and R.sup.4 is substituted phenyl.

5. A pharmaceutical composition, comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

6. A compound selected from: 3-(4-{[2-methyl-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; N-[2-(pyridin-3-yl)ethyl]-4-{[3-(trifluoromethoxy)benzene]sulfonyl}benzamide; 1-[(6-aminopyridin-3-yl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea; 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H-pyrazol-1-yl)pyridin-3-yl]methyl}urea; 3-(4-{[2-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 4-(benzenesulfonyl)-N-{imidazo[1,2-a]pyridin-7-ylmethyl}benzamide; 4-(benzenesulfonyl)-N-(pyridin-3-ylmethyl)benzamide; 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H-imidazol-1-yl)pyridin-3-yl]methyl}urea; 3-{[({4-[(4-chlorobenzene)sulfinyl]phenyl}carbamoyl)amino]methyl}pyridin-1-ium-1-olate; N,N-dimethyl-4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[2-methoxy-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-(benzenesulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 1-[4-(benzenesulfonyl)phenyl]-3-(1H-pyrazol-3-ylmethyl)urea; N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethoxy)benzene]sulfonyl}benzamide; 1-{[4-(benzenesulfonyl)phenyl]methyl}-3-(quinolin-6-yl)urea; 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(dimethylamino)pyridin-3-yl]methyl}urea; 1-[6-(benzenesulfonyl)pyridin-3-yl]-3-(pyridin-3-ylmethyl)urea; 1-[(3-aminophenyl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea; 3-{4-[(4-chlorobenzene)sulfinyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(2H-1,3-benzodioxole-5-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 4-[(2-chlorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide; 4-[(3-chlorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide; 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(2-methoxyethoxy)pyridin-3-yl]methyl}urea; 1-{4-[(2-phenoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-[4-(benzenesulfonyl)phenyl]-3-{5H,6H,7H,8H-imidazo[1,2-a]pyridin-6-ylmethyl}urea; 3-{4-[(2-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(benzenesulfonyl)phenyl]-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea; 3-(4-{[3-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-(benzenesulfonyl)phenyl]-1-(quinolin-6-yl)urea; 1-{4-[(4-fluorobenzene)sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea; N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethyl)benzene]sulfonyl}benzamide; 4-[(3,5-difluorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide; 3-{4-[(4-methanesulfonylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-[(3-methoxybenzene)sulfonyl]benzamide; 1-(4-{8-oxatricyclo[7.4.0.0.sup.2,7]trideca-1(9),2(7),3,5,10,12-hexaene-6-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; N-(1,3-benzothiazol-6-ylmethyl)-4-[(3-chlorobenzene)sulfonyl]benzamide; 1-[4-(benzenesulfonyl)phenyl]-3-{thieno[2,3-c]pyridin-2-ylmethyl}urea; 1-(4-benzoylphenyl)-3-(pyridin-3-ylmethyl)urea; 3-[4-(benzenesulfonyl)phenyl]-1-(pyridin-3-yl)urea; 4-(benzenesulfonyl)-N-(pyridin-3-yl)benzamide; 4-(benzenesulfonyl)-N-(pyridin-4-yl)benzamide; 3-{4-[4-(3-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(phenylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chloro-4-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{8-methyl-2,8-diazaspiro[5.5]undecane-2-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{4-[4-(trifluoromethyl)phenyl]piperazine-1-sulfonyl}phenyl)urea; 3-{4-[(3,4-difluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-methyl-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyridine-2-carboxamide; 3-{4-[(4-chloro-2-methyl phenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(3-methoxyphenyl)pentan-3-yl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-methoxy-3-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-chloro-3-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(morpholin-4-yl)-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; (2S)—N,N-dimethyl-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidine-2-carboxamide; methyl 4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazine-1-carboxylate; 3-{4-[(2-methoxyethyl)(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[4-(2H-1,3-benzodioxol-5-yl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-(propan-2-yl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[(2-methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-fluoro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(cycloheptylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 1-{4-[4-(pyrazin-2-yl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(5-methylpyridin-3-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2-methoxyphenyl (piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[(1R,2R,3R,5S)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl]sulfamoyl}phenyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{4-[6-(trifluoromethyl)pyridin-2-yl]piperazine-1-sulfonyl}phenyl)urea; 3-{4-[4-(2-methylphenyl (piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(6-ethylpyridin-2-yl(sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-cyclopropyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl}urea; 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrimidin-5-ylmethyl)urea; 3-(4-{[2-(3-methoxyphenyl)ethyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; N-[(3R)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino(benzene)sulfonyl]pyrrolidin-3-yl]acetamide; 1-{4-[(4-phenylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2,4-difluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(dimethylsulfamoyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methoxy-6-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methanesulfonylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-chloro-2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-methyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide; 3-{4-[(4-chloro-2-methoxy-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(1,5-dimethyl-1H-pyrazol-3-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(2-methoxyethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,4-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{methyl[(1S)-1-phenylethyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{8-azaspiro[4.5]decane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[(5-chloro-2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,4-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,5-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{8-oxa-3-azabicyclo[3.2.1]octane-3-sulfonyl}benzamide; 1-{4-[(5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-(4-{4-[2-(morpholin-4-yl)-2-oxoethyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-{4-[(3-benzoylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(6-methoxypyridin-3-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chloro-4-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-ethyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[4-(2-methoxyethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-(6-methoxynaphthalene-2-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[4-(trifluoromethyl)phenyl]sulfamoyl}phenyl)urea; 3-{4-[cyclohexyl(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-(4-chlorophenoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-ethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-[4-({4-[(pyrrolidin-1-yl)carbonyl]benzene}sulfonyl)phenyl]urea; 3-(4-{[3-(2-hydroxyethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chloro-2,6-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,5-dimethylphenyl (piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-bromophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methylpyridin-4-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-fluoro-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[(3,4-difluorophenyl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea; 4-(piperidine-1-sulfonyl)phenyl N-(pyridin-3-ylmethyl)carbamate; 3-{4-[(4-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[2-(3,4-dichlorophenyl)acetyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-({2-[(2S)-2-hydroxypropoxy]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 1-[4-(1H-indole-7-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 1-{4-[(1-phenylcyclopentyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-{4-[(3-phenylbenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-{4-[(pyridin-2-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; (3S)—N,N-diethyl-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-3-carboxamide; 1-(4-{[(1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3-chlorophenyl)-4-cyanopiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-(4-methanesulfonylpiperazine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-ethoxy-2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-propylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-cyano-4-(4-methoxyphenyl (piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[(4-chlorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-[3-(piperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3-fluorophenoxy)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(pyridin-3-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-(4-{[2-chloro-5-(trifluoromethoxy)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 2-methyl-N-{3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]phenyl}propanamide; 1-[4-(cyclohexylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-[4-(piperidine-1-sulfonyl)phenyl]-1-[1-(pyridin-3-yl)ethyl]urea; 1-[(4-{[(pyridin-3-ylmethyl (carbamoyl]amino}benzene(sulfonyl]piperidine-4-carboxamide; 3-{4-[(2-tert-butylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[(4-methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-chloro-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-fluoro-3-(trifluoromethyl)phenyl]sulfamoyl}(phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{3-[(2-oxopyrrolidin-1-yl)methyl]piperidine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-(4-{[2-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-{4-[(2,4,6-trimethylphenyl)sulfamoyl]phenyl}urea; 3-[4-(piperidine-1-sulfonyl)phenyl]-1-[2-(pyridin-3-yl)ethyl]urea; 1-[4-(4-cyclohexylpiperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2-chloro-4-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-fluoro-2-methoxyphenyl(sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-(methylsulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,5-dichlorophenyl (sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea; N-(propan-2-yl)-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide; N,N-diethyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide; 1-(4-{[4-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3,5-dichloropyridin-4-yl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(cyclobutylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{4-[4-(trifluoromethyl)pyridin-2-yl]piperazine-1-sulfonyl}phenyl)urea; 1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-[4-(4-benzyl-1,4-diazepane-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; N-[(3 S)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidin-3-yl]acetamide; N,N-dimethyl-2-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; 1-{4-[(2H-1,3-benzodioxol-5-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2-chloro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,4-difluorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-(2-methylpropyl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[3-(difluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-methoxy-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2-ethoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-ethyl-4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[3-(propan-2-yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-{4-[(3-phenylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-(4-{[(3-fluorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-ethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methoxypyridin-3-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3 S)-3-methyl-4-(4-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[4-(piperidin-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-[4-(butylsulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-methylpyridin-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,4-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(3-cyanophenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[methanesulfonyl(piperidin-4-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[(4-fluorophenyl)carbonyl]piperidine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3S)-4-(4-methoxyphenyl)-3-methylpiperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[methyl(oxolan-3-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-(difluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-methyl-4-(propan-2-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{4-[3-(morpholin-4-yl)propyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(propane-1-sulfonamido)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2,3-dihydro-1,4-benzodioxin-6-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(5-chloro-2-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-chloro-4-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-{4-[4-(2H-1,3-benzodioxol-5-ylmethyl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; N-methyl-N-phenyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide; 1-(4-{4-[(furan-2-yl)carbonyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(5-chloro-2-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,6-dimethylphenyl (piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-chloro-N,N-diethyl-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-[2-fluoro-4-(piperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; N,N-dimethyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 1-(pyridin-3-ylmethyl)-3-[4-({[3-(trifluoromethyl)phenyl]methyl}sulfamoyl)phenyl]urea; pyridin-3-ylmethyl N-[4-(piperidine-1-sulfonyl)phenyl]carbamate; 1-(4-{[3-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(2-hydroxyethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-benzyl-1-[4-(piperidine-1-sulfonyl)phenyl]urea; 3-{4-[(2-hydroxyethyl)(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[4-(trifluoromethane)sulfonylphenyl]sulfamoyl}phenyl)urea; 3-{4-[(3-ethanesulfonamidobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-chloro-3-methoxyphenyl (piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methylpropyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-(2-hydroxyethyl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-{4-[(3-chloro-2-methyl phenyl (sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[(4-chlorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[methyl(2-methylpropyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{methyl[(1R)-1-phenylethyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2-chlorophenyl (piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-({2-[(1S)-1-hydroxyethyl]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,5-difluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-{[2-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-tert-butylphenyl (sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{methyl[2-(4-methylphenyl)ethyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,6-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N,N-dimethyl-2-{4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]phenyl}acetamide; 1-(4-{4-[2-oxo-2-(piperidin-1-yl)ethyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(3,5-dimethyl-1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(methoxymethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{[2-(morpholin-4-ylmethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; N-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]-4-(1,2,3,4-tetrahydroisoquinoline-2-sulfonyl)benzamide; methyl 4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzoate; 3-(4-{[2-(propan-2-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(propan-2-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-{4-[(3,4,5-trifluorophenyl(sulfamoyl]phenyl}urea; N,N-diethyl-4-fluoro-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 1-(4-{[4-(piperidine-1-sulfonyl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2,4-dichlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(ethyl sulfamoyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,2-dimethylpropyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(dibenzylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; (2S)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidine-2-carboxamide; 3-{4-[benzyl(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3-chloropyridin-2-yl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(propan-2-yloxy)phenyl]sulfamoyl (phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methanesulfonamidobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N,N-diethyl-3-fluoro-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[4-(methoxymethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; N,N-dimethyl-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-4-carboxamide; 3-{4-[(propan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-({3-[(morpholin-4-yl)carbonyl]benzene}sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-(4-{[(4-fluorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-ethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[benzyl(propan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-({[4-(dimethylamino)phenyl]methyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[benzyl(ethyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-acetylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(4-{[(2R)-oxolan-2-yl]carbonyl}piperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 2-methyl-N-{l-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidin-4-yl}propanamide; 1-(pyridin-3-ylmethyl)-3-(4-{[4-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea; 3-(pyridin-3-ylmethyl)-1-(4-{[4-(pyrrolidin-1-yl)phenyl]sulfamoyl}phenyl)urea; 3-(4-{[(3-chiorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(ethanesulfonyl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-(4-hydroxypiperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-(4-{[3-(hydroxymethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-acetylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-ethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 4-fluoro-N-(propan-2-yl)-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-{4-[4-(3-chlorophenyl)-4-hydroxypiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3 S)-3-methyl-4-(3-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,3-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,3-dichlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(4-benzylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 1-(4-{[(4-phenylphenyl)methyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-{4-[(5,6,7,8-tetrahydronaphthalen-1-yl)sulfamoyl]phenyl}urea; 3-{4-[(4-fluoro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(4-ethynyl phenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2-chloro-4,6-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2R)-2-benzylpiperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrazin-2-ylmethyl)urea; 1-{4-[(3,4-dihydro-2H-1,5-benzodioxepin-7-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(diethylamino)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-fluorophenyl)(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-(4-{3-oxa-8-azabicyclo[3.2.1]octane-8-sulfonyl}phenyl)urea; 3-{4-[(3-fluoro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-(4-methanesulfonylpiperidine-1-sulfonyl)phenyl]-1-(pyri di n-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-{4-[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-sulfonyl]phenyl}urea; 3-(4-{4-[(morpholin-4-yl)carbonyl]piperidine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[3-(2-chloro-4-fluorophenoxy)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[4-chloro-3-(trifluoromethyl)phenyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[bis(4-fluorophenyl)methyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{[3-(benzyloxy)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-(4-{[3-(pyrrolidin-1-yl)phenyl]sulfamoyl}phenyl)urea; 3-{4-[4-(3,4-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[3-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea; 3-{4-[(2-ethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methanesulfonylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-(propan-2-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-chloro-2-methyl phenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[(2-fluorophenyl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea; 1-{4-[(4-phenoxyphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-{4-[4-(azepan-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 1-(4-{[4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-{4-[(cyclohexylmethyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(4-ethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-bromophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,4-dichlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[4-(2-oxo-2,3-dihydro-1H-indol-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-[(6-isocyanopyridin-3-yl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea; 3-(4-{[2-(3-chlorophenyl)ethyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{[3-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-{4-[3-(pyrrolidin-1-yl)pyrrolidine-1-sulfonyl]phenyl}urea; 1-[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[3-(trifluoromethyl)phenyl]sulfamoyl}phenyl)urea; 3-{4-[methyl(2-phenylethyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[(4-fluorophenyl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea; 3-[4-(tert-butylsulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 1-[4-(4-phenylpiperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(5-methylpyrimidin-2-yl (piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea l-(pyridin-3-ylmethyl)-3-(4-{[2-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea; 3-{4-[(2-acetylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-bromo-3-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-{2-oxa-8-azaspiro[4.5]decane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-{4-[4-(2-phenylacetyl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-{4-[4-(3-phenylprop-2-en-1-yl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-{4-[(3-sulfamoylbenzene)sulfonyl]phenyl}urea; N-methyl-2-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; 3-(4-{[4-(propan-2-yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-hydroxyethyl)(propan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(adamantan-1-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-{4-[(2R)-2-(morpholin-4-ylmethyl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3,5-dichlorophenyl (piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-fluoro-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-{3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene(sulfonyl]phenyl}acetamide; N-methyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; 3-{4-[4-(4-chlorophenyl)-4-cyanopiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-methyl-3-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-[4-(4-phenylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-fluoro-N,N-dimethyl-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; N-[2-(pyridin-3-yl)ethyl]-4-{[3-(trifluoromethoxy)phenyl]sulfamoyl}benzamide; 3-{4-[cyclohexyl(ethyl)sulfamoyl]phenyl}-1-(pyridin-3-yl in ethyl)urea; 3-{4-[4-(3,4-dichlorophenyl (piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-fluoro-3-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-fluoro-5-(trifluoromethyl(phenyl]sulfamoyl}phenyl)-]-(pyridin-3-ylmethyl)urea; 3-[4-(4-{[4-(propan-2-yl)phenyl]methyl}piperazine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{4-[3-(trifluoromethyl)phenyl]piperazine-1-sulfonyl}phenyl)urea; 1-[4-(cyclopropylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N-[2-(pyridin-3-yl)ethyl]benzamide; 3-{4-[(3-aminophenyl((methanesulfonyl(sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2,3-dihydro-1H-inden-5-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-(4-{[3-chloro-4-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[1-(3-methoxyphenyl)-4-methylcyclohexyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-chloronaphthalen-1-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-acetyl-2-methoxybenzene(sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-chloro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(1R)-3-oxo-3H-spiro[2-benzofuran-1,3-pyrrolidine]-1-ylsulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2,4-dimethoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1-(pyridin-3-yl)urea; N-{1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidin-4-yl}acetamide; 3-{4-[(3-fluoro-4-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-{4-[(2-oxopyrrolidin-1-yl)methyl]piperidine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-{4-[(1-phenylcyclohexyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 1-(4-{4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-{4-[(4-sulfamoylphenyl)sulfamoyl]phenyl}urea; 3-(4-{4-[(4-tert-butylphenyl)methyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-(4-{[2-(1H-pyrrol-1-yl)phenyl]sulfamoyl}phenyl)urea; 3-(4-{4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; N,N-diethyl-2-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; 1-{4-[(piperidin-1-yl)carbonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; N-ethyl-N-[(3 S)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidin-3-yl]acetamide; 3-(pyridin-3-ylmethyl)-1-{4-[4-(pyrimidin-2-yl)piperazine-1-sulfonyl]phenyl}urea; 3-(pyridin-3-ylmethyl)-1-(4-{[(1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan-3-yl]sulfamoyl}phenyl)urea; 3-{4-[(4-fluoro-3-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-phenylpropan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{4-[(1R)-1-(4-chlorophenyl)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[(3-fluorophenyl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea; 3-{4-[4-cyano-4-(4-methylphenyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(3-phenoxyphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2,5-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-methoxy-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(dipropylamino)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[(4-fluorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-{4-[(3S)-3-[(pyrrolidin-1-yl)carbonyl]piperidine-1-sulfonyl]phenyl}urea; 3-{4-[(3-bromophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(2-phenoxyphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-(4-{4-[l-(4-chlorophenyl)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; N,N-dimethyl-4-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; 1-{4-[(4-phenylbenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3,5-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-[4-(4-acetyl-1,4-diazepane-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; N-cyclopentyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 1-(4-{[4-(morpholin-4-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-[4-({3-[(1S)-1-hydroxyethyl]phenyl}sulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,5-difluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3,5-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[ethyl(phenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{[2-(trifluoromethyl)phenyl]sulfamoyl}phenyl)urea; 3-(4-{[3-(5-methyl-1,3,4-oxadiazol-2-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-[4-({4-[(1S)-1-hydroxyethyl]phenyl}sulfatnoyl)phenyl]-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 4-[(3-chlorophenyl)sulfamoyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide; 3-{4-[(4-tert-butyl-2-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(cyclopentylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea; 3-(4-{4-[2-(diethylamino)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-chlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(3-fluorophenyl)ethyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[methyl({[3-(trifluoromethyl)phenyl]methyl})sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-{[3-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-(4-{[(2-chlorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-acetylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3,4-dimethoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N,N-dimethyl-3-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide; (2R)-1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidine-2-carboxamide; 3-(4-{[(3-methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[2-(difluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(pyridin-3-ylmethyl)-3-(4-{4-[5-(trifluoromethyl)pyridin-2-yl]piperazine-1-sulfonyl}phenyl)urea; 3-{4-[(4-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-fluoro-2-methylphenyl(sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(4-cyanophenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chloro-4-methyl phenyl (sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(3-chloro-5-methoxybenzene(sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-(4-((2-methoxyethyl)(methyl)amino)piperidin-1-ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2,4-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(pyridin-3-ylmethyl)-1-(4-{[2-(pyrrolidin-1-yl)phenyl]sulfamoyl}phenyl)urea; 3-{4-[(3-methoxy-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(4-nitrophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(2-chloro-4-fluorophenoxy(piperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-(4-{[4-chloro-2-(trifluoromethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[(4-chloro-3-methyl phenyl (sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2,3-dichlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-(4-{8-oxa-3-azabicyclo[3.2.1]octane-3-sulfonyl}phenyl)urea; 2-fluoro-N-(propan-2-yl)-5-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide; 3-(4-{[2-(2-hydroxyethoxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 3-{4-[4-(3-chlorophenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2S)-2-ethylpiperidine-1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-(4-{[4-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 1-{4-[(4-cyanobenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3,4-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(2-iodophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[2-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethoxy)phenyl]sulfamoyl}benzamide; and 4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide, or a pharmaceutically acceptable salt thereof.

7. A pharmaceutical composition, comprising a compound of claim 6, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

8. The compound of claim 1, wherein R.sup.3 is H.

9. The compound of claim 3, wherein R.sup.3 is H.

Description

DESCRIPTION OF THE PREFERRED EMBODIMENTS

(1) An aspect of the present invention concerns compounds disclosed herein.

(2) An aspect of the present invention concerns compounds which are or can be inhibitors of the formation of nicotinamide phosphoribosyltransferase.

(3) An aspect of the present invention concerns the use of an inhibitor of the formation of nicotinamide phosphoribosyltransferase for the preparation of a medicament used in the treatment, prevention, inhibition or elimination of tumors.

(4) An aspect of the present invention concerns the use of an inhibitor of the formation of nicotinamide phosphoribosyltransferase for the preparation of a medicament used in the treatment, prevention, inhibition or elimination of cancer.

(5) An aspect of the present invention concerns the use of an inhibitor of the formation of nicotinamide phosphoribosyltransferase for the preparation of a medicament used in the treatment, prevention, inhibition or elimination of cancer, where the cancer is selected from leukemia, lymphoma, ovarian cancer, breast cancer, uterine cancer, colon cancer, cervical cancer, lung cancer, prostate cancer, skin cancer, CNS cancer, bladder cancer, pancreatic cancer and Hodgkin's disease.

(6) The present invention also describes one or more methods of synthesizing the compounds of the present invention.

(7) The invention also describes one or more uses of the compounds of the present invention.

(8) The invention also describes one or more uses of the compounds of the present invention with an adjunctive agent such as use with TNF, GCSF, or other chemotherapeutic agents The invention also describes one or more uses of the pharmaceutical compositions of the present invention.

(9) An aspect of the present invention concerns the use as an inhibitor of the formation of nicotinamide phosphoribosyltransferase for the preparation of a medicament used in the treatment of inflammatory diseases.

(10) An aspect of the present invention concerns the use as an inhibitor of the formation of nicotinamide phosphoribosyltransferase for the preparation of a medicament used in the treatment of inflammatory diseases, such as Irritable Bowel Syndrome or Inflammatory Bowel Disease.

(11) An aspect of the present invention concerns the use as an inhibitor of the formation of nicotinamide phosphoribosyltransferase for the preparation of a medicament used in the treatment of disease of the bone such as osteoporosis.

(12) An aspect of the present invention concerns the use as an inhibitor of the formation of nicotinamide phosphoribosyltransferase for the preparation of a medicament used in the treatment of disease of the cardiovascular system, such as atherosclerosis.

(13) An aspect of the present invention concerns the use as an inhibitor of the formation of nicotinamide phosphoribosyltransferase for the preparation of a medicament used in the treatment of disease or a condition caused by an elevated level of NAMPT.

(14) Such disease or condition is one or more selected from the group consisting of cancer, ovarian cancer, breast cancer, uterine cancer, colon cancer, cervical cancer, lung cancer, prostate cancer, skin cancer, bladder cancer, pancreatic cancer, leukemia, lymphoma, Hodgkin's disease, viral infections, Human Immunodeficiency Virus, hepatitis virus, herpes virus, herpes simplex, inflammatory disorders, irritable bowel syndrome, inflammatory bowel disease, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, osteoarthritis, osteoporosis, dermatitis, atoptic dermatitis, psoriasis, systemic lupus erythematosis, multiple sclerosis, psoriatic arthritis, ankylosing spodylitis, graft-versus-host disease, Alzheimer's disease, cerebrovascular accident, atherosclerosis, diabetes, glomerulonephiritis, metabolic syndrome, non-small cell lung cancer, small cell lung cancer, multiple myeloma, leukemias, lymphomas, squamous cell cancers, kidney cancer, uretral and bladder cancers, cancers of head and neck, cancers of the brain and central nervous system (CNS).

(15) The compounds of the invention can be useful in the therapy of proliferative diseases such as cancer, autoimmune diseases, viral diseases, fungal diseases, neurological/neurodegenerative disorders, arthritis, inflammation, anti-proliferative (e.g., ocular retinopathy), neuronal, alopecia and cardiovascular disease.

(16) More specifically, the compounds can be useful in the treatment of a variety of cancers, including (but not limited to) the following: carcinoma, including that of the bladder, breast, colon, kidney, liver, lung, including small cell lung cancer, non-small cell lung cancer, head and neck, esophagus, gall bladder, ovary, pancreas, stomach, cervix, thyroid, prostate, and skin, including squamous cell carcinoma; hematopoietic tumors of lymphoid lineage, including leukemia, acute lymphocytic leukemia, acute lymphoblastic leukemia, B-cell lymphoma, T-cell lymphoma, Hodgkins lymphoma, non-Hodgkins lymphoma, hairy cell lymphoma, mantle cell lymphoma, myeloma, and Burkett® lymphoma; hematopoietic tumors of myeloid lineage, including acute and chronic myelogenous leukemias, myelodysplastic syndrome and promyelocytic leukemia;

(17) tumors of mesenchymal origin, including fibrosarcoma and rhabdomyosarcoma; tumors of the central and peripheral nervous system, including astrocytoma, neuroblastoma, glioma and schwannomas; and other tumors, including melanoma, seminoma, teratocarcinoma, osteosarcoma, xenoderoma pigmentosum, keratoctanthoma, thyroid follicular cancer and Kaposi sarcoma.

(18) The compounds of the invention may induce or inhibit apoptosis.

(19) The compounds of the invention may also be useful in the chemoprevention of cancer. Chemoprevention is defined as inhibiting the development of invasive cancer by either blocking the initiating mutagenic event or by blocking the progression of pre-malignant cells that have already suffered an insult or inhibiting tumor relapse.

(20) A further aspect of the invention is a method of inhibiting a NAMPT pathway in an animal, said method comprising administering to said animal a pharmaceutically acceptable amount of a compound of the invention to an animal in need thereof.

(21) A further aspect of the invention is a pharmaceutical formulation comprising a compound of the invention.

(22) Another embodiment of the invention comprises a pharmaceutical formulation of the invention, wherein the pharmaceutical formulation, upon administration to a human, results in a decrease in tumor burden.

(23) Still another embodiment of the invention is a pharmaceutical formulation, further comprising one or more of an antineoplastic agent, a chemotherapeutic agent, or an adjunctive chemotherapeutic agent.

(24) The pharmaceutical formulations of the invention may further comprise a therapeutic effective amount of an adjunctive chemotherapeutic agent.

(25) The adjunctive chemotherapeutic agent may be an agent, which modifies blood cell growth and maturation. Non-limiting examples of adjunctive chemotherapeutic agent are filgrastim, pegfilgrastim and erythropoietin.

(26) The invention is also directed to a method of treating or preventing a disorder associated with excessive rate of growth of cells in a mammal comprising administering to the mammal an effective amount of the pharmaceutical formulation of the invention. Non-limiting examples of disorder include cancer or metastasis from malignant tumors.

(27) Another aspect of the invention is a method of inhibiting tumor cell growth and rate of division in a mammal with cancer, or other disorder associated with abnormally dividing cells comprising administering to the mammal an effective amount of the pharmaceutical formulation of this invention.

(28) Another embodiment of the invention is a method of treating bone pain due to excessive growth of a tumor or metastasis to bone in a mammal in need thereof comprising administering to the mammal an effective amount of the pharmaceutical formulation of this invention.

(29) Still another embodiment of the invention is a method for administering a NAMPT-inhibitor-containing compound to a mammal in need thereof comprising administering to the mammal the pharmaceutical formulation of the invention. In one embodiment, the mammal is a human.

(30) A further embodiment of the invention is a method of preparing a pharmaceutical formulation comprising mixing at least one pharmaceutically acceptable compound of the present invention, and, optionally, one or more pharmaceutically acceptable excipients or additives.

(31) The invention is also directed to methods of synthesizing compounds of the present invention.

Compounds of the Invention

(32) The invention is directed to pharmaceutical compositions comprising one or more compounds as described herein and pharmaceutically acceptable salts, sovates, esters, prodrugs or isomers thereof. The invention further relates to molecules which are useful in inhibiting the enzyme nicotinamide phosphoribosyltransferase (NAMPT) and pharmaceutically acceptable salts, solvates, esters, prodrugs or isomers thereof.

(33) An aspect of the invention is the provision of compounds, compositions, kits, and antidotes for the NAMPT pathway in mammals having a compound of Formula I

(34) ##STR00039##
wherein Ar.sup.1 is aryl, heteroaryl or heterocycloalkyl, wherein the heteroatom of each of said heteroaryl and heterocycloalkyl numbers 1, 2 or 3, and is independently selected from N, S or O, further wherein each of said aryl, heteroaryl and heterocycloalkyl may independently be either substituted or fused with aryl, heteroaryl or heterocycloalkyl, still further wherein any of said aryl, heteroaryl and heterocycloalkyl is either unsubstituted or optionally independently substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CH.sub.zF.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, alkenyl, alkynyl, alkoxy-, -aryloxy-, (alkoxyalkyl)oxy-, (alkoxyalkyl)amino-, —N(R.sup.3)—C(O)-alkyl, —N(R.sup.3)—C(O)-aryl, —N(R.sup.3)—C(O)—O-alkyl, —N(R.sup.3)—C(O)—O-aryl, -cycloalkyl, -heterocycloalkyl, -aryl, —C(O)-aryl, —S(O)-aryl, and heteroaryl, with the proviso that no two adjacent ring heteroatoms are both S or both O; X is a straight or branched C.sub.1-C.sub.6 alkyl; L is selected from NHC(O)NH, OC(O)NH, NHC(O)O, OCH.sub.2C(O)NH, C(O)NH, NHC(S)NH, OC(S)NH, NHC(S)O, OCH.sub.2C(S)NH, or C(S)NH; A is aryl, heteroaryl, heterocycloalkyl or C.sub.3 to C.sub.8 cycloalkyl, with each of said aryl, heteroaryl, heterocycloalkyl and cycloalkyl being either unsubstituted or optionally independently substituted with 1, 2, 3 or 4 substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CH.sub.zF.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, alkenyl, alkynyl, alkoxy-, -aryloxy-, (alkoxyalkyl)oxy-, (alkoxyalkyl)amino-, —N(R.sup.3)—C(O)-alkyl, —N(R.sup.3)—C(O)-aryl, —N(R.sup.3)—C(O)—O-alkyl, —N(R.sup.3)—C(O)—O-aryl, -cycloalkyl, -heterocycloalkyl, -aryl, —C(O)-aryl, —S(O)-aryl, and heteroaryl; Q is C(O), S(O), S(O).sub.2; R.sup.3 is H, alkyl or arylalkyl-; z is 0, 1 or 2; and either: (i) (a) R.sup.1 is selected from H, a straight or branched C.sub.1 to C.sub.7 alkyl, straight or branched C.sub.1 to C.sub.7 alkoxy, straight or branched C.sub.1 to C.sub.4 hydroxyalkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl, arylalkyl-, heteroarylalkyl-, heterocycloalkylalkyl-, cycloalkylalkyl-, hydroxyalkyl-, alkoxyalkyl-, heterospirocycloalkyl and heterospiroheterocycloalkyl, wherein the heteroatoms of said heteroaryl and heterocycloalkyl in the moieties above are independently selected from one or more N, O and S, with the proviso that no two adjacent ring heteroatoms are both S or both O, further wherein R.sup.1 can be either unsubstituted or optionally independently (i) either substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CH.sub.zF.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, alkenyl, alkynyl, hydroxyalkyl-, (hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-, (heteroaryloxy)alkyl-, —NO.sub.2, (alkoxyalkyl)amino-, -alkylamino, dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy, heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl, —N(R.sup.3)—C(O)-alkyl, —N(R.sup.3)—C(O)-aryl, —S(O.sub.2)alkyl, —S(O.sub.2)CF.sub.3, -cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl, -aryl, and heteroaryl, or (ii) fused with a cycloalkyl, -heterocycloalkyl, -aryl, or heteroaryl; and (b) R.sup.2 is selected from H, a straight or branched C.sub.1 to C.sub.7 alkyl, straight or branched C.sub.1 to C.sub.7 alkoxy, straight or branched C.sub.1 to C.sub.4 hydroxyalkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl, arylalkyl-, heteroarylalkyl-, heterocycloalkylalkyl-, cycloalkylalkyl-, hydroxyalkyl-, alkoxyalkyl-, heterospirocycloalkyl and heterospiroheterocycloalkyl, wherein the heteroatoms of said heteroaryl and heterocycloalkyl in the moieties above are independently selected from one or more N, O and S, with the proviso that no two adjacent ring heteroatoms are both S or both O, further wherein R.sup.2 can be either unsubstituted or optionally independently (i) either substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CH.sub.zF.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, alkenyl, alkynyl, hydroxyalkyl-, (hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-, (heteroaryloxy)alkyl-, —NO.sub.2, (alkoxyalkyl)amino-, -alkylamino, dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy, heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl, —N(R.sup.3)—C(O)-alkyl, —N(R.sup.3)—C(O)-aryl, —S(O.sub.2)alkyl, —S(O.sub.2)CF.sub.3, -cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl, -aryl, and heteroaryl, or (ii) fused with a cycloalkyl, -heterocycloalkyl, -aryl, or heteroaryl; or (ii) R.sup.1 and R.sup.2 are joined together to form, along with the N they are shown attached to in the formula, a C.sub.3-C.sub.8 heterocycloalkyl, a C.sub.3-C.sub.8 heterocycloalkenyl, a fused bicyclic heterocycloalkyl, a fused tricyclic heterocycloalkyl, spiroheterocycloalkyl or a heterospiroheterocycloalkyl, wherein each of said heterocycloalkyl, heterocycloalkenyl, spiroheterocycloalkyl and heterospiroheterocycloalkyl can optionally contain one or more heteroatoms in addition to the N atom they are shown attached to in the formula, said heteroatoms being selected from N, S and O, with the proviso that no two adjacent ring heteroatoms are both S or both O, further wherein each of said heterocycloalkyl, fused bicyclic heterocycloalkyl, fused tricyclic heterocycloalkyl, heterocycloalkenyl, spiroheterocycloalkyl and heterospiroheterocycloalkyl can be either unsubstituted or optionally independently substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CH.sub.zF.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, alkenyl, alkynyl, hydroxyalkyl-, (hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-, (heteroaryloxy)alkyl-, —NO.sub.2, (alkoxyalkyl)amino-, -alkylamino, dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy, heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl, —N(R.sup.3)—C(O)-alkyl, —N(R.sup.3)—C(O)-aryl, —S(O.sub.2)alkyl, —S(O.sub.2)CF.sub.3, -cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl, -aryl, and heteroaryl;
and pharmaceutically acceptable salts, solvates, esters and isomers thereof, with the proviso that the compound of Formula I is not l-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea, 3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea or 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

(35) Another aspect of this invention is the provision of compounds, compositions, kits, and antidotes for the NAMPT pathway in mammals having a compound of the Formula I, where X, L, Q, Ar.sup.1 and A are as defined in Formula I and R.sup.1 is selected from H, a straight or branched Ci to C7 alkyl, straight or branched C.sub.1 to C.sub.7 alkoxy, straight or branched C.sub.1 to C.sub.4 hydroxyalkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl, arylalkyl-, heteroarylalkyl-, heterocycloalkylalkyl-, cycloalkylalkyl-, hydroxyalkyl-, alkoxyalkyl-, spiroheterocycloalkyl and heterospiroheterocycloalkyl, wherein the heteroatoms of said heteroaryl and heterocycloalkyl in the moieties above are independently selected from one or more N, O and S, with the proviso that no two adjacent ring heteroatoms are both S or both O, further wherein R.sup.1 can be either unsubstituted or optionally independently (i) either substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CH.sub.zF.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, alkenyl, alkynyl, hydroxyalkyl-, (hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-, (heteroaryloxy)alkyl-, —NO.sub.2, (alkoxyalkyl)amino-, -alkylamino, dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy, heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl, —N(R.sup.3)—C(O)-alkyl, —N(R.sup.3)—C(O)-aryl, —S(O.sub.2)alkyl, —S(O.sub.2)CF.sub.3, -cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl, -aryl, and heteroaryl, or (ii) fused with a cycloalkyl, -heterocycloalkyl, -aryl, or heteroaryl; and

(36) R.sup.2 is selected from H, a straight or branched C.sub.1 to C.sub.7 alkyl, straight or branched C.sub.1 to C.sub.7 alkoxy, straight or branched C.sub.1 to C.sub.4 hydroxyalkyl, aryl, heteroaryl, heterocycloalkyl, cycloalkyl, arylalkyl-, heteroarylalkyl-, heterocycloalkylalkyl-, cycloalkylalkyl-, hydroxyalkyl-, alkoxyalkyl-, heterospirocycloalkyl and heterospiroheterocycloalkyl, wherein the heteroatoms of said heteroaryl and heterocycloalkyl in the moieties above are independently selected from one or more N, O and S, with the proviso that no two adjacent ring heteroatoms are both S or both O, further wherein R.sup.2 can be either unsubstituted or optionally independently (i) either substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CH.sub.zF.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, alkenyl, alkynyl, hydroxyalkyl-, (hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-, (heteroaryloxy)alkyl-, —NO.sub.2, (alkoxyalkyl)amino-, -alkylamino, dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy, heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl, —N(R.sup.3)—C(O)-alkyl, —N(R.sup.3)—C(O)-aryl, —S(O.sub.2)alkyl, —S(O.sub.2)CF.sub.3, -cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl, -aryl, and heteroaryl, or (ii) fused with a cycloalkyl, -heterocycloalkyl, -aryl, or heteroaryl;

(37) with the proviso that the compound of Formula I is not l-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea, 3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea or 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

(38) Another aspect of this invention is the provision of compounds, compositions, kits, and antidotes for the NAMPT pathway in mammals having a compound of the Formula I, where X, L, Q, Ar.sup.1 and A are as defined in Formula I and R.sup.1 and R.sup.2 are joined together to form, along with the N they are shown attached to in the formula, a C.sub.3-C.sub.8 heterocycloalkyl, a C.sub.3-C.sub.8 heterocycloalkenyl, a fused bicyclic heterocycloalkyl, a fused tricyclic heterocycloalkyl, spiroheterocyclaolkyl or a heterospiroheterocycloalkyl, wherein each of said heterocycloalkyl, heterocycloalkenyl, spiroheterocyclaolkyl and heterospiroheterocycloalkyl can optionally contain one or more heteroatoms in addition to the N atom they are shown attached to in the formula, said heteroatoms being selected from N, S and O, with the proviso that no two adjacent ring heteroatoms are both S or both O, further wherein each of said heterocycloalkyl, fused bicyclic heterocycloalkyl, fused tricyclic heterocycloalkyl, heterocycloalkenyl, spiroheterocyclaolkyl and heterospiroheterocycloalkyl can be either unsubstituted or optionally independently substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CH.sub.zF.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, alkenyl, alkynyl, hydroxyalkyl-, (hydroxyalkyl)oxy, -alkoxy, carboxy, (alkoxyalkyl)-, (heteroaryloxy)alkyl-, —NO.sub.2, (alkoxyalkyl)amino-, -alkylamino, dialkylamino, (heterocycloalkyloxo)alkyl-, aryloxy, heterocycloalkyloxy-, aminocarbonyl-, —CHO, —C(O)alkyl, —N(R.sup.3)—C(O)-alkyl, —N(R.sup.3)—C(O)-aryl, —S(O.sub.2)alkyl, —S(O.sub.2)CF.sub.3, -cycloalkyl, alkylenedioxy (e.g, methylenedioxy), -heterocycloalkyl, -aryl, and heteroaryl;

(39) R.sup.3 is H, alkyl or arylalkyl with the proviso that the compound is not l-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea, 3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea or 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

(40) In one embodiment, the invention relates to compounds of Formula I and pharmaceutically acceptable salts, solvates, ester or isomers thereof.

(41) In the compounds of Formula I, the various moieties and substituents are independently selected.

(42) The following embodiments are directed to Formula I as applicable. Further, the moieties aryl, heteroaryl, heterocycloalkyl, cycloalkyl, spiroheterocycloalkyl and heterospiroheterocycloalkyl as well as their representative moieties in these embodiments can be independently unsubstituted or optionally substituted or optionally fused as described earlier. Any one or more of the embodiments relating to Formula I below can be combined with one or more other embodiments of Formula I.

(43) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1 is aryl, and z, X, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(44) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, and z, X, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(45) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1 is heterocycloalkyl, and z, X, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(46) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1 is aryl fused with an aryl, heteroaryl or heterocycloalkyl, and z, X, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(47) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1 is heteroaryl fused with an aryl, heteroaryl or heterocycloalkyl, and z, X, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(48) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1 is heterocycloalkyl fused with an aryl, heteroaryl or heterocycloalkyl, and z, X, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(49) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1 is aryl substituted as shown under Formula I, IA or IB, and z, X, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(50) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1 is heteroaryl substituted as shown under Formula I, IA or IB, and z, X, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(51) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1 is heterocycloalkyl substituted as shown under Formula I, IA or IB, and z, X, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(52) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, X is a straight chain alkyl, and Ar.sup.1, z, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(53) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, X is a branched chain alkyl, and Ar.sup.1, z, L, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(54) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, L is —N(H)—C(O)—N(H)—, and Ar.sup.1, z, X, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(55) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Q is —S(O.sub.2)—, and Ar.sup.1, z, X, A, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(56) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.3 is H, and Ar.sup.1, z, X, A, Q, R.sup.1, and R.sup.2 are as defined.

(57) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.3 is alkyl, and Ar.sup.1, z, X, A, Q, R.sup.1, and R.sup.2 are as defined.

(58) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.3 is arylalkyl, and Ar.sup.1, z, X, A, Q, R.sup.1, and R.sup.2 are as defined.

(59) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, z is 0, and Ar.sup.1, X, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(60) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, z is 1, and Ar.sup.1, X, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(61) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, z is 2, and Ar.sup.1, X, A, Q, R.sup.1, R.sup.2 and R.sup.3 are as defined.

(62) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, and Ar.sup.1, z, X, A, Q, R.sup.2 and R.sup.3 are as defined.

(63) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.2 is H, and Ar.sup.1, z, X, A, Q, R.sup.2 and R.sup.3 are as defined.

(64) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are H, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(65) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is alkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(66) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is aryl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(67) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is heteroaryl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(68) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is heterocycloalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(69) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is cycloalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(70) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is alkoxy, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(71) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is hydroxyalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(72) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is aryloxy, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(73) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is arylalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(74) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is heteroarylalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(75) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is cycloalkylalkyl-, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(76) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is heterocycloalkylalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(77) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is alkoxyalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(78) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is spiroheterocycloalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(79) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is spiroheterocycloalkylalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(80) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is alkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(81) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is aryl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(82) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is heteroaryl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(83) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is heterocycloalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(84) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is cycloalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(85) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is aryloxy with the aryl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(86) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is arylalkyl with the aryl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(87) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is heteroarylalkyl with the heteroaryl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(88) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is cycloalkylalkyl—with the cycloalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(89) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is heterocycloalkylalkyl with the heterocycloalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(90) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is spiroheterocycloalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(91) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is spiroheterocycloalkylalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(92) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is alkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(93) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is aryl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(94) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is heteroaryl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(95) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is heterocycloalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(96) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is cycloalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(97) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is aryloxy, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(98) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is arylalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(99) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is heteroarylalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(100) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is cycloalkylalkyl-, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(101) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is heterocycloalkylalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(102) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is spiroheterocycloalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(103) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is spiroheterocycloalkylalkyl, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(104) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is alkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(105) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is aryl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(106) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is heteroaryl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(107) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is heterocycloalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(108) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is cycloalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(109) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is aryloxy with the aryl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(110) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is arylalkyl with the aryl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(111) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is heteroarylalkyl with the heteroaryl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(112) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is cycloalkylalkyl-with the cycloalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(113) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is heterocycloalkylalkyl with the heterocycloalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(114) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is spiroheterocycloalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(115) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is alkyl, R.sup.2 is spiroheterocycloalkylalkyl substituted or fused as described earlier, and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(116) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is bicycloheptanyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(117) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is cyclopropyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(118) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is cyclobutyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(119) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is cyclopentyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(120) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is cyclopentylmethyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(121) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is benzyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(122) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is furanyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(123) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is furanylmethyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(124) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is phenyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(125) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is naphthalenyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(126) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is biphenylmethyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(127) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is biphenyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(128) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is tolyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(129) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is pyridinyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(130) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is unsubstituted, pyridinylmethyl (substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(131) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is phenylethyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(132) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is benzyl (unsubstituted, substituted or fused as described earlier), R.sup.2 is benzyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(133) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is quinolinyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(134) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is oxazolyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(135) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is indazolyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(136) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is dihydrobenzodioxepinyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(137) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is pyrazolyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(138) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is terrahydronaphthalenyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(139) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is isoquinolinyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(140) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 is H, R.sup.2 is oxolanyl (unsubstituted, substituted or fused as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(141) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a heterocycloalkyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(142) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a heterocycloalkenyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(143) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a fused bicyclic heterocycloalkyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(144) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a fused tricyclic heterocycloalkyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(145) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a spiroheterocycloalkyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(146) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a heterospiroheterocycloalkyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(147) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a piperidinyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(148) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a piperazinyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(149) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a morpholinyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(150) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, an azapenyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(151) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, an azetidinyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(152) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a oxaazabicyclooctanyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(153) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, an azabicycloheptanyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(154) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a dihydrobenzoxazinyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(155) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a dihydroindolyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(156) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a thiomorpholinyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(157) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, an azatricyclotridecapentaenyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(158) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, an azaspirodecanyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(159) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a terrahydronaphthyridinyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(160) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, an azabicyclooctanyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(161) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a diazepanyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(162) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a decahydroquinolyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(163) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a diazaspiroundecanyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(164) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, R.sup.1 and R.sup.2 are joined together to form, along with the N, a terahydroisoquinolinyl (unsubstituted or substituted as described earlier), and Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined.

(165) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined, and R.sup.1 and R.sup.2 are the same or different, wherein said R.sup.1 and R.sup.2 independently are unsubstituted or substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of —C(O)NH.sub.2, alkyl, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, halo, morpholinyl, alkoxyalkyl-, alkenyl, alkyl, CF.sub.3, OH, CN, phenyl, isocyano, —N(H)C(O)CH.sub.3, phenylethyl-, —C(O)CH.sub.3, phenoxy, —S(O.sub.2)CH.sub.3, —S(O.sub.2)CF.sub.3, pyrazinyl, —OCHF.sub.2, OCF.sub.3, OCH.sub.2F, —C═CH, —CH═CH.sub.2, methylenedioxy, ethylenedioxy, benzyloxy, piperidinyl, —C(O)O—CH.sub.3, phenoxy, oxopiperazinyl, oxopyrrolidinylmethyl-, NH2, NH(alkyl, —N(alkyl).sub.2, morpholinyloxoethyl-, oxopyrrolinylmethyl-, azapanyl, nitrophenyl-, cyclopropyl, hydroxymethyl-, (hydroxyalkyl)oxy-, isopropyl, ethyl, methyl and phenylpropenyl-.

(166) An embodiment of the invention is the provision of a compound of Formula I, where the various moieties are independently selected, Ar.sup.1, z, X, A, Q, and R.sup.3 are as defined, and R.sup.1 and R.sup.2 are joined together to form, along with the N, a C.sub.3-C.sub.8 heterocycloalkyl, a C.sub.3-C.sub.8 heterocycloalkenyl, a fused bicyclic heterocycloalkyl, a fused tricyclic heterocycloalkyl, spiroheterocycloalkyl or a heterospiroheterocycloalkyl, wherein each of said C.sub.3-C.sub.8 heterocycloalkyl, a C.sub.3-C.sub.8 heterocycloalkenyl, a fused bicyclic heterocycloalkyl, a fused tricyclic heterocycloalkyl, spiroheterocycloalkyl or a heterospiroheterocycloalkyl independently is unsubstituted or bears one or more substituents which can be the same or different and are independently selected from the group consisting of —C(O)NH.sub.2, alkyl, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, halo, morpholinyl, alkoxyalkyl-, alkenyl, alkyl, CF.sub.3, OH, CN, phenyl, isocyano, —N(H)C(O)CH.sub.3, phenylethyl-, —C(O)CH.sub.3, phenoxy, —S(O.sub.2)CH.sub.3, —S(O.sub.2)CF.sub.3, pyrazinyl, —OCHF.sub.2, OCF.sub.3, OCH.sub.2F, —CsCH, —CH═CH.sub.2, methylenedioxy, ethylenedioxy, benzyloxy, piperidinyl, —C(O)O—CH.sub.3, phenoxy, oxopiperazinyl, oxopyrrolidinylmethyl-, NH2, NH(alkyl, —N(alkyl).sub.2, morpholinyloxoethyl-, oxopyrrolinylmethyl-, azapanyl, nitrophenyl-, cyclopropyl, hydroxymethyl-, (hydroxyalkyl)oxy-, isopropyl, ethyl, methyl and phenylpropenyl-.

(167) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, R.sup.1 is H, R.sup.2 is aryl, and z, X, L, A, Q, and R.sup.3 are as defined.

(168) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, R.sup.1 is H, R.sup.2 is heteroaryl, and z, X, L, A, Q, and R.sup.3 are as defined.

(169) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, R.sup.1 is H, R.sup.2 is heterocycloalkyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(170) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, R.sup.1 is H, R.sup.2 is spiroheterocycloalkyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(171) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, R.sup.1 is H, R.sup.2 is heterospiroheterocycloalkyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(172) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is aryl, and z, X, L, A, Q, and R.sup.3 are as defined.

(173) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is heteroaryl, and z, X, L, A, Q, and R.sup.3 are as defined.

(174) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is heterocycloalkyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(175) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is spiroheterocycloalkyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(176) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is heterospiroheterocycloalkyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(177) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, R.sup.1 is H, R.sup.2 is aryl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(178) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, R.sup.1 is H, A is phenyl, R.sup.2 is heteroaryl, and z, X, L, Q, and R.sup.3 are as defined.

(179) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, R.sup.1 is H, A is phenyl, R.sup.2 is heterocycloalkyl, and z, X, L, Q, and R.sup.3 are as defined.

(180) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, R.sup.1 is H, A is phenyl, R.sup.2 is spiroheterocycloalkyl, and z, X, L, Q, and R.sup.3 are as defined.

(181) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, R.sup.1 is H, A is phenyl, R.sup.2 is heterospiroheterocycloalkyl, and z, X, L, Q, and R.sup.3 are as defined.

(182) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is aryl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(183) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is heteroaryl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(184) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is heterocycloalkyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(185) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is spiroheterocycloalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(186) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is heterospiroheterocycloalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(187) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is phenyl, R.sup.1 is H, R.sup.2 is aryl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(188) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is phenyl, R.sup.1 is H, A is phenyl, R.sup.2 is heteroaryl, and z, X, L, Q, and R.sup.3 are as defined.

(189) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is phenyl, R.sup.1 is H, A is phenyl, R.sup.2 is heterocycloalkyl, and z, X, L, Q, and R.sup.3 are as defined.

(190) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is phenyl, R.sup.1 is H, A is phenyl, R.sup.2 is spiroheterocycloalkyl, and z, X, L, Q, and R.sup.3 are as defined.

(191) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is phenyl, R.sup.1 is H, A is phenyl, R.sup.2 is heterospiroheterocycloalkyl, and z, X, L, Q, and R.sup.3 are as defined.

(192) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is aryl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(193) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is heteroaryl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(194) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is heterocycloalkyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(195) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is spiroheterocycloalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(196) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R.sup.1 is H, R.sup.2 is heterospiroheterocycloalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(197) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridyl, R.sup.1 is H, R.sup.2 is aryl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(198) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridyl, R.sup.1 is H, R.sup.2 is heteroaryl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(199) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridyl, R.sup.1 is H, R.sup.2 is heterocycloalkyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(200) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridyl, R.sup.1 is H, R.sup.2 is spiroheterocycloalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(201) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridyl, R.sup.1 is H, R.sup.2 is heterospiroheterocycloalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(202) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is piperidinyl, R.sup.1 is H, R.sup.2 is aryl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(203) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is piperidinyl, R.sup.1 is H, R.sup.2 is heteroaryl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(204) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is piperidinyl, R.sup.1 is H, R.sup.2 is heterocycloalkyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(205) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is piperidinyl, R.sup.1 is H, R.sup.2 is spiroheterocycloalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(206) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is piperidinyl, R.sup.1 is H, R.sup.2 is heterospiroheterocycloalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(207) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is piperidinyl, R.sup.1 is H, R.sup.2 is pyrrolyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(208) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is piperidinyl, R.sup.1 is H, R.sup.2 is pyrrolyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(209) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is piperidinyl, R.sup.1 is H, R.sup.2 is pyridinylmethyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(210) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is pyrrolyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(211) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is piperidinyl, R.sup.1 is H, R.sup.2 is pyrrolyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(212) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is pyridinylmethyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(213) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is alkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(214) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is hydroxyalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(215) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is phenylalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(216) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is cycloalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(217) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is oxolanyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(218) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is quinolinyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(219) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is oxazolyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(220) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is spiroheterocycloakyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(221) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is heterospiroheterocycloalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(222) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is tetrahydronaphthalenyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(223) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is dihydrobenzodioxepinyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(224) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is acyclic, where the various moieties are independently selected, Ar.sup.1 is pyridinyl, R.sup.1 is H, R.sup.2 is alkoxyalkyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(225) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is piperidinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(226) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is morpholinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(227) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is piperazinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(228) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azapenyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(229) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azetidinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(230) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is oxaazabicyclooctanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(231) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azabicycloheptanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(232) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is dihydrobenzoxazinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(233) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is dihydroindolyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(234) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is thiomorpholinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(235) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azatricyclotridecapentaenyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(236) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azaspirodecanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(237) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azaspiroundecanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(238) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is tetrahydronaphthyridinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(239) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azabicyclooctanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(240) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is diazepanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(241) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is decahydroquinolinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(242) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is diazaspiroundecanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(243) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is tetrahydroisoquinolinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(244) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is piperidinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(245) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is morpholinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(246) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is piperazinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(247) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azapenyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(248) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azetidinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(249) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is oxaazabicyclooctanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(250) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azabicycloheptanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(251) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is dihydrobenzoxazinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(252) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is dihydroindolyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(253) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is thiomorpholinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(254) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azatricyclotridecapentaenyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(255) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azaspirodecanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(256) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azaspiroundecanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(257) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is tetrahydronaphthyridinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(258) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azabicyclooctanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(259) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is diazepanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(260) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is decahydroquinolinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(261) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is diazaspiroundecanyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(262) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is tetrahydroisoquinolinyl, and z, X, L, A, Q, and R.sup.3 are as defined.

(263) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is piperidinyl, A is phenyl, and z, X, L, Q, and R.sup.3 are as defined.

(264) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is morpholinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(265) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is piperazinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(266) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azapenyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(267) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azetidinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(268) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is oxaazabicyclooctanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(269) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azabicycloheptanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(270) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is dihydrobenzoxazinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(271) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is dihydroindolyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(272) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is thiomorpholinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(273) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azatricyclotridecapentaenyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(274) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azaspirodecanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(275) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azaspiroundecanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(276) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic), where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is tetrahydronaphthyridinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(277) An embodiment of the invention is the prevision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is azabicyclooctanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(278) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is diazepanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(279) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is decahydroquinolinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(280) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is diazaspiroundecanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(281) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is aryl, NR.sup.1R.sup.2 is tetrahydroisoquinolinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(282) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is piperidinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(283) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is morpholinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(284) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is piperazinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(285) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azapenyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(286) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azetidinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(287) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is oxaazabicyclooctanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(288) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azabicycloheptanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(289) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is dihydrobenzoxazinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(290) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is dihydroindolyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(291) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is thiomorpholinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(292) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azatricyclotridecapentaenyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(293) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azaspirodecanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(294) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azaspiroundecanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(295) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is tetrahydronaphthyridinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(296) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is azabicyclooctanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(297) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is diazepanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(298) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is decahydroquinolinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(299) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is diazaspiroundecanyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(300) An embodiment of the invention is the provision of a compound of Formula I where NR.sup.1R.sup.2 is cyclic, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, NR.sup.1R.sup.2 is tetrahydroisoquinolinyl, A is phenyl and z, X, L, Q, and R.sup.3 are as defined.

(301) Another embodiment of this invention is the provision of compounds, compositions, kits, and antidotes for the NAMPT pathway in mammals having a compound of the Formula II:
Ar.sup.1—(CHR).sub.n-L-Ar.sup.2—X—R.sup.1   II
wherein Ar.sup.1 is aryl, heteroaryl or heterocycloalkyl, wherein the heteroatom of each of said heteroaryl and heterocycloalkyl numbers 1, 2 or 3, and is independently selected from N, S or O, further wherein each of said aryl, heteroaryl and heterocycloalkyl may independently be either substituted or fused with aryl, heteroaryl or heterocycloalkyl, still further wherein any of said aryl, heteroaryl and heterocycloalkyl is either unsubstituted or optionally independently substituted with one or more substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CH.sub.zF.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, alkenyl, alkynyl, alkoxy-, -aryloxy-, (alkoxyalkyl)oxy-, (alkoxyalkyl)amino-, —N(R.sup.3)—C(O)-alkyl, —N(R.sup.3)—C(O)-aryl, —N(R.sup.3)—C(O)—O-alkyl, —N(R.sup.3)—C(O)—O-aryl, -cycloalkyl, -heterocycloalkyl, -aryl, —C(O)-aryl, —S(O)-aryl, and heteroaryl, with the proviso that no two adjacent ring heteroatoms are both S or both O; R is H, a straight or branched C.sub.1-C.sub.6 alkyl, or arylalkyl; n is 0, 1, 2, 3 or 4; L is selected from NHC(O)NH, OC(O)NH, NHC(O)O, OCH.sub.2C(O)NH, C(O)NH, NHC(S)NH, OC(S)NH, NHC(S)O, OCH.sub.2C(S)NH, or C(S)NH, with the proviso that when L is C(O)NH, then n is 0; Ar.sup.2 is aryl, heteroaryl, heterocycloalkyl or C.sub.3 to C.sub.8 cycloalkyl, with each of said aryl, heteroaryl, heterocycloalkyl and cycloalkyl being either unsubstituted or optionally independently substituted with 1, 2, 3 or 4 substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, isocyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CH.sub.zH.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, alkenyl, alkynyl, alkoxy-, -aryloxy-, (alkoxyalkyl)oxy-, (alkoxyalkyl)amino-, —N(R.sup.3)—C(O)-alkyl, —N(R.sup.3)—C(O)-aryl, —N(R.sup.3)—C(O)—O-alkyl, —N(R.sup.3)—C(O)—O-aryl, -cycloalkyl, -heterocycloalkyl, -aryl, —C(O)-aryl, —S(O)-aryl, and heteroaryl; X is S, S(O), S(O).sub.2, O or C(O); R.sup.1 is cycloalkyl, —CH.sub.zF.sub.3-z, aryl, heterocycloalkyl, heteroaryl, alkyl, -alkenyl, -alkynyl, (aryl)alkyl-, (heteroaryl)alkyl- or (heterocycloalkyl)alkyl-, (i) wherein each of said cycloalkyl, aryl, heterocycloalkyl, heteroaryl and alkyl is either unsubstituted or optionally substituted with 1, 2, 3, 4 or 5 substituents which can be the same or different and are independently selected from the group consisting of deuterium, halo, cyano, amino, aminoalkyl-, (amino)alkoxy-, —CONH.sub.2, —C(O)NH(alkyl), —C(O)N(alkyl).sub.2, —C(O)NH(aryl), —C(O)N(aryl).sub.2, —CFI.sub.zF.sub.3-z, —OCH.sub.zF.sub.3-z, alkyl, -alkenyl, -alkynyl, alkoxy-, hydroxy, -alkylhydroxy, aryloxy- or (alkoxyalkyl)amino-, -cycloalkyl, -heterocycloalkyl, -aryl, —S(O).sub.2-alkyl, —S(O).sub.2-aryl, —S(O).sub.2—CF.sub.3, —C(O)N(alkyl).sub.2, —C(O)alkyl, —NH—C(O)-alkyl, —NH—C(O)-aryl, methylenedioxy, and heteroaryl, (ii) further wherein each of said cycloalkyl, aryl, heterocycloalkyl, and heteroaryl may additionally optionally be fused with independently selected aryl, heteroaryl, heterocycloalkyl or cyloalkyl; R.sup.3 is H, alkyl or arylalkyl-; z is 0, 1, or 2;
and pharmaceutically acceptable salts, solvates, esters, prodrugs and isomers thereof, with the proviso that the compound of Formula I is not 3-{l-[(4-methoxybenzene)sulfonyl]piperidin-4-yl}-1-(pyridin-3-ylmethyl)urea, or 1-(4-phenoxyphenyl)-3-(pyridin-3-ylmethyl)thiourea.

(302) In the compounds of Formula II, the various moieties are independently selected.

(303) The following embodiments are directed to Formula II as applicable. Further, the moieties aryl, heteroaryl, heterocycloalkyl, cycloalkyl, spiroheterocycloalkyl and heterospiroheterocycloalkyl as well as their representative moieties in these embodiments can be independently unsubstituted or optionally substituted or optionally fused as described earlier. Any one or more of the embodiments relating to Formula II below can be combined with one or more other embodiments of Formula II.

(304) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(305) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(306) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heterocycloalkyl, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(307) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl fused with an aryl, heteroaryl or heterocycloalkyl, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(308) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl fused with an aryl, heteroaryl or heterocycloalkyl, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(309) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heterocycloalkyl fused with an aryl, heteroaryl or heterocycloalkyl, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(310) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl substituted as shown under Formula II, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(311) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl substituted as shown under Formula II, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(312) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heterocycloalkyl substituted as shown under Formula II, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(313) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is H, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(314) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a straight chain alkyl, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(315) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a branched chain alkyl, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(316) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is H, n is 1, and z, X, L, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(317) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a straight chain alkyl, n is 1, and z, X, L, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(318) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a branched chain alkyl, n is 1, and z, X, L, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(319) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, and z, X, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(320) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, and z, X, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(321) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, and z, X, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(322) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(323) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(324) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(325) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(326) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(327) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(328) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(329) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(330) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(331) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(332) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(333) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is aryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(334) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(335) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(336) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, and z, X, L, n, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(337) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, and z, X, L, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(338) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, and z, X, L, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(339) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, and z, X, L, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(340) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(341) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(342) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(343) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is I, L is —N(H)—C(O)—N(H)—, X is —S(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(344) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(345) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(346) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(347) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(348) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(349) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(350) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(351) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, and z, Ar.sup.2, R.sup.1 and R.sup.3 are as defined.

(352) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, Ar.sup.2 is aryl, and z, X, L, n, R.sup.1 and R.sup.3 are as defined.

(353) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, Ar.sup.2 is aryl, and z, X, L, n, R.sup.1 and R.sup.3 are as defined.

(354) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, Ar.sup.2 is aryl, and z, X, L, n, R.sup.1 and R.sup.3 are as defined.

(355) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, Ar.sup.2 is aryl, and z, X, L, R.sup.1 and R.sup.3 are as defined.

(356) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, Ar.sup.2 is aryl, n is 1, and z, X, L, R.sup.1 and R.sup.3 are as defined.

(357) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, Ar.sup.2 is aryl, n is 1, and z, X, L, R.sup.1 and R.sup.3 are as defined.

(358) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(359) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(360) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(361) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(362) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(363) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(364) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(365) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(366) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(367) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(368) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(369) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, and z, R.sup.1 and R.sup.3 are as defined.

(370) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(371) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(372) An embodiment of the invention is the provision of a compound, of Formula II where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(373) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(374) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, Ar.sup.2 is aryl, n is 1, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(375) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, Ar.sup.2 is aryl, n is 1, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(376) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(377) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(378) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(379) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(380) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(381) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(382) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(383) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(384) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(385) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(386) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(387) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is cycloalkyl, and z, X, L, n, and R.sup.3 are as defined.

(388) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(389) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(390) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(391) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(392) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, Ar.sup.2 is aryl, n is 1, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(393) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, Ar.sup.2 is aryl, n is 1, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(394) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(395) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(396) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(397) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(398) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(399) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(400) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(401) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(402) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(403) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(404) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(405) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(406) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, Ar.sup.2 is heteroaryl, R.sup.1 is aryl, and z, X, L, n, and R.sup.3 are as defined.

(407) An embodiment of the invention is the provision of a compound, of Formula II where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(408) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(409) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(410) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, Ar.sup.2 is aryl, n is 1, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(411) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, Ar.sup.2 is aryl, n is 1, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(412) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(413) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(414) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(415) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(416) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(417) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(418) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(419) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(420) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(421) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(422) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(423) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is heteroaryl, and z, X, L, n, and R.sup.3 are as defined.

(424) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, Ar.sup.2 is heteroaryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(425) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(426) An embodiment of the invention is the provision of a compound of Formula II where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(427) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(428) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, Ar.sup.2 is aryl, n is 1, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(429) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, Ar.sup.2 is aryl, n is 1, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(430) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(431) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(432) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O.sub.2)—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(433) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(434) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(435) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —S(O)—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(436) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(437) An embodiment of the invention is the provision of a compound, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(438) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(FI)—C(O)—N(H)—, X is —C(O)—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(439) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is H, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(440) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a straight chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(441) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is heteroaryl, R is a branched chain alkyl, n is 1, L is —N(H)—C(O)—N(H)—, X is —O—, Ar.sup.2 is aryl, R.sup.1 is CF.sub.3, and z, X, L, n, and R.sup.3 are as defined.

(442) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, Ar.sup.1 is selected from the group consisting of pyridinyl, imidazopyridinyl, pyrazolyl, quinolinyl and thienopyridinyl. Each of these moieties may be unsubstituted or optionally independently substituted with one or more groups which can be the same or different and are independently selected from the group consisting of —NH.sub.2, —N(alkyl).sub.2, (alkoxyalkyl)oxy-, and pyrazolyl.

(443) An embodiment of the invention is the provision of a compound of Formula II, where the various moieties are independently selected, R.sup.1 is selected from the group consisting of cyclopentyl, CF.sub.3, phenyl, naphthalenyl, pyrimidinyl, oxazolyl, 8-oxatricyclotridecahexaenyl and thienyl. Each of these moieties may be unsubstituted or optionally independently substituted with one or more groups which can be the same or different and are independently selected from the group consisting of—C(O)NH.sub.2, —S(O.sub.2)CH.sub.3, F, C1, Br, methylenedioxy, CF.sub.3, OCF.sub.3, alkyl, alkoxy, pyrazolyl, C(O)CH.sub.3 and phenoxy.

(444) An especially preferred moiety for Ar.sup.1—(CHR).sub.n-L- in Formula II is the moiety:

(445) ##STR00040##

(446) Another aspect of this invention is the provision of compounds, compositions, kits, and antidotes for the NAMPT pathway in mammals derived from compounds of Formula I and Formula II and having the Formula III:

(447) ##STR00041##
wherein,

(448) Ar.sup.1 is 5 to 12 membered heteroaryl comprising 1, 2, 3 or 4 heteroatom(s) independently selected from N, S or O, wherein said heteroaryl is unsubstituted or substituted by one or more R.sup.a selected from the group consisting of —NH.sub.2, oxo, halo, haloalkyl, —NH(CO)O-alkyl, —C(O)NH.sub.2 and 3,4-dihydroxy-5-methyltetrahydrofurane; and wherein said heteroaryl can comprise one or more N-oxide(s) formed with a N atom member of said heteroaryl, with the proviso that no two adjacent ring heteroatoms are both S or both O;

(449) Ar.sup.2 is aryl or 5 or 6 membered heteroaryl comprising 1, 2, 3 or 4 heteroatom(s) independently selected from N, S or O;

(450) R is H, a straight or branched C.sub.1-C.sub.6 alkyl, or arylalkyl;

(451) R.sup.1 is —NR.sup.3R.sup.4 wherein R.sup.3 is H, alkyl or —S(O).sub.2alkyl and R.sup.4 is alkyl, hydroxyalkyl, —S(O).sub.2alkyl, —(CH.sub.2).sub.qcycloalkyl, —(CH.sub.2).sub.qheterocycloalkyl, aryl, arylalkyl-, —(CH.sub.2).sub.qheteroaryl; haloalkyl, cycloalkyl; aryl; heterocycloalkyl; or heteroaryl; wherein: each of said cycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents which can be the same or different and are independently selected from the group consisting of: deuterium, halo, cyano, alkyl, hydroxyl, hydroxyalkyl, hydroxyalkoxy, cyanoalkyl, haloalkyl, alkenyl, alkynyl, alkoxy, alkylalkoxy, haloalkoxy, arylalkenyl-, aryloxy, benzyloxy, oxo, —(CH.sub.2).sub.q—NR.sup.bR.sup.c, —(CH.sub.2).sub.q—CONR.sup.bR.sup.c, —S(O).sub.2-alkyl, —S(O).sub.2-aryl, —S(O).sub.2NH-alkyl, —S(O).sub.2N(alkyl).sub.2, —S(O).sub.2-heterocycloalkyl, —S(O).sub.2—CF.sub.3, —C(O)alkyl, —C(O)aryl, —C(O)alkylenylaryl, —C(O)O-alkyl, —NH—C(O)alkyl, —NH—C(O)aryl, methylenedioxy, —(CH.sub.2).sub.qcycloalkyl, cycloalkylalkoxy-, aryl, arylalkyl-, —(CH.sub.2).sub.qheteroaryl, and —(CH.sub.2).sub.qheterocycloalkyl, wherein each of said cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted by one or more halo, nitro, haloalkyl, haloalkoxy, oxo, cyano, alkyl, haloalkyl, or alkoxy and; each of said cycloalkyl, heterocycloalkyl, aryl, or heteroaryl may optionally additionally be fused with independently selected aryl, heteroaryl, heterocycloalkyl or cycloalkyl to from a bicyclic or tricyclic group that may be substituted by one or more halo, cyano, alkyl or alkoxy;

(452) R.sup.2 is O or absent,

(453) R.sup.b and R.sup.c are independently selected from the group consisting of H, alkyl, hydroxyalkyl, alkoxy, aryl, alkoxyalkyl, —S(O).sub.2alkyl and cycloalkyl or R.sup.b and R.sup.c can form a 5 or 6 membered heterocycloalkyl group together with the nitrogen atom to which they are attached, wherein said heterocycloalkyl group may contain one or more additional heteroatom(s) selected from N, S or O;

(454) n is 0, or 1;

(455) q is 0, 1 or 2;

(456) and pharmaceutically acceptable salts, solvates, esters and isomers thereof,

(457) with the proviso that the compound of Formula I is not 1-(pyridin-3-ylmethyl)-3-(4-sulfamoylphenyl)thiourea, 3-[4-(morpholine-4-sulfonyl)phenyl]-1-(pyridine-4-ylmethyl)thiourea or 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrdin-4-ylmethyl)thiourea.

(458) In an embodiment, this invention discloses compounds of Formula III and pharmaceutically acceptable salts, solvates, ester or isomers thereof.

(459) In the compounds of Formula III, the various moieties are independently selected.

(460) The following embodiments are directed to Formula III as applicable. Further, the moieties aryl, heteroaryl, heterocycloalkyl, cycloalkyl, spiroheterocycloalkyl and heterospiroheterocycloalkyl as well as their representative moieties in these embodiments can be independently unsubstituted or optionally substituted or optionally fused as described earlier. Any one or more of the embodiments related to Formula III below can be combined with one or morerother embodiments of Formula III.

(461) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and Ar.sup.2 is aryl.

(462) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and Ar.sup.2 is phenyl.

(463) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and Ar.sup.2 has the following formula:

(464) ##STR00042##

(465) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and Ar.sup.1 is pyridine.

(466) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and Ar.sup.1 has the following formula:

(467) ##STR00043##
where R.sup.a is selected from the group consisting of —NH.sub.2, oxo, halo, haloalkyl, —NH(CO)O-alkyl, —C(O)NH.sub.2 and 3,4-dihydroxy-5-methyltetrahydrofurane.

(468) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and Ar.sup.1 has the formula of:

(469) ##STR00044##

(470) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and n is 1.

(471) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and n is 1.

(472) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1 and Ar.sup.2 is aryl.

(473) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1 and Ar.sup.2 is phenyl.

(474) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and Ar.sup.2 is phenyl.

(475) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and Ar.sup.2 has the following formula:

(476) ##STR00045##
and Ar.sup.1 is pyridine.

(477) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R is H.

(478) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R is H.

(479) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, n is 1 and R is H.

(480) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R is H.

(481) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, n is 1, Ar.sup.2 is phenyl and R is H.

(482) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R is H.

(483) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is —NR.sup.3R.sup.4 wherein R.sup.3 is H, alkyl or —S(O).sub.2alkyl and R.sup.4 is alkyl, hydroxyalkyl, —S(O).sub.2alkyl, —(CH.sub.2).sub.qcycloalkyl, —(CH.sub.2).sub.qheterocycloalkyl, aryl, arylalkyl-, —(CH.sub.2).sub.qheteroaryl.

(484) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is —NR.sup.3R.sup.4 wherein R.sup.3 is H and R.sup.4 is aryl.

(485) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is —NR.sup.3R.sup.4 wherein R.sup.3 is H and R.sup.4 is aryl.

(486) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is —NR.sup.3R.sup.4 wherein R.sup.3 is H and R.sup.4 is aryl.

(487) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is —NR.sup.3R.sup.4 wherein R.sup.3 is H and R.sup.4 is aryl.

(488) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is —NR.sup.3R.sup.4 wherein R.sup.3 is H and R.sup.4 is aryl.

(489) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is —NR.sup.3R.sup.4 wherein R.sup.3 is H and R.sup.4 is aryl.

(490) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is haloalkyl.

(491) An embodiment of the invention is the provision of a compound of Formula IIII, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is haloalkyl.

(492) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is haloalkyl.

(493) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is haloalkyl.

(494) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is haloalkyl.

(495) An embodiment of the invention is the provision of a compound, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is haloalkyl.

(496) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is haloalkyl.

(497) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, nisi, Ar.sup.2 is phenyl and R.sup.1 is haloalkyl.

(498) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl.

(499) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl.

(500) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl.

(501) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl.

(502) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl.

(503) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl.

(504) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl, wherein the cycloalkyl is selected from the group consisting of cyclopropyl, cyclopentane, cycloheptyl, azaspiro[4.5]decane, bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan, adamantane, and (1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

(505) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl, wherein the cycloalkyl is selected from the group consisting of cyclopropyl, cyclopentane, cycloheptyl, azaspiro[4.5]decane, bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan, adamantane, and (1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

(506) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl, wherein the cycloalkyl is selected from the group consisting of cyclopropyl, cyclopentane, cycloheptyl, azaspiro[4.5]decane, bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan, adamantane, and (1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

(507) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl, wherein the cycloalkyl is selected from the group consisting of cyclopropyl, cyclopentane, cycloheptyl, azaspiro[4.5]decane, bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan, adamantane, and (1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

(508) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is unsubstituted or substituted C3-C12-cycloalkyl, wherein the cycloalkyl is selected from the group consisting of cyclopropyl, cyclopentane, cycloheptyl, azaspiro[4.5]decane, bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan, adamantane, and (1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

(509) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl, wherein the cycloalkyl is selected from the group consisting of cyclopropyl, cyclopentane, cycloheptyl, azaspiro[4.5]decane, bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan, adamantane, and (1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

(510) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl.

(511) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl.

(512) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl.

(513) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl.

(514) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl.

(515) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl.

(516) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl, wherein the aryl is selected from the group consisting of phenyl, naphatalene, tetrahydronaphthalene, and 1H-inden-5-yl.

(517) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is unsubstituted or substituted C5-C10-aryl, wherein the aryl is selected from the group consisting of phenyl, naphatalene, tetrahydronaphthalene, and 1H-inden-5-yl.

(518) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl, wherein the aryl is selected from the group consisting of phenyl, naphatalene, tetrahydronaphthalene, and 1H-inden-5-yl.

(519) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl, wherein the aryl is selected from the group consisting of phenyl, naphatalene, tetrahydronaphthalene, and 1H-inden-5-yl.

(520) An embodiment of the invention is the provision of a compound, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl, wherein the aryl is selected from the group consisting of phenyl, naphatalene, tetrahydronaphthalene, and 1H-inden-5-yl.

(521) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl, wherein the aryl is selected from the group consisting of phenyl, naphatalene, tetrahydronaphthalene, and 1H-inden-5-yl.

(522) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is unsubstituted or substituted heterocycloalkyl.

(523) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is unsubstituted or substituted heterocycloalkyl.

(524) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted heterocycloalkyl.

(525) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted heterocycloalkyl.

(526) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is aryl and R.sup.1 is unsubstituted or substituted heterocycloalkyl.

(527) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is unsubstituted or substituted heterocycloalkyl.

(528) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted heterocycloalkyl.

(529) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(530) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(531) An embodiment of the invention is the provision of a compound, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(532) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(533) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(534) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(535) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heterocycloalkyl is selected from the group consisting of azetidine, piperidine, pyrrolidine, piperazine, thiophorpholine, 2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane, 1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

(536) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heterocycloalkyl is selected from the group consisting of azetidine, piperidine, pyrrolidine, piperazine, thiophorpholine, 2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane, 1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

(537) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heterocycloalkyl is selected from the group consisting of azetidine, piperidine, pyrrolidine, piperazine, thiophorpholine, 2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane, 1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

(538) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heterocycloalkyl is selected from the group consisting of azetidine, piperidine, pyrrolidine, piperazine, thiophorpholine, 2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane, 1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

(539) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heterocycloalkyl is selected from the group consisting of azetidine, piperidine, pyrrolidine, piperazine, thiophorpholine, 2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane, 1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

(540) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heterocycloalkyl is selected from the group consisting of azetidine, piperidine, pyrrolidine, piperazine, thiophorpholine, 2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane, 1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

(541) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is unsubstituted or substituted heteroaryl.

(542) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is unsubstituted or substituted heteroaryl.

(543) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted heteroaryl.

(544) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted heteroaryl.

(545) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is aryl and R.sup.1 is unsubstituted or substituted heteroaryl.

(546) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, nisi, and R.sup.1 is unsubstituted or substituted heteroaryl.

(547) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted heteroaryl.

(548) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(549) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(550) An embodiment of the invention is the provision of a compound, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(551) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(552) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(553) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(554) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected and R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heteroaryl is selected from the group consisting of 1,3,4-oxadiazol, (1R)-3-oxo-3H-spiro[2-benzofuran-1,3-pyrrolidine, 3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol, 3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline, indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole, 8-oxatricyclo[7.4.0.0.sup.2,7]trideca-1(9),2(7),3,5,10,12-hexaene, 5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine, 3-azaspiro[5.5]undecane, azatricyclo[7.3.1.0.sup.5,13]trideca-1(13),5,7,9,11-pentaene, (4aR,8aS)-decahydroisoquinoline, and 5,6,7,8-tetrahydro-1,6-naphthyridine.

(555) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine and R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heteroaryl is selected from the group consisting of 1,3,4-oxadiazol, (1R)-3-oxo-3H-spiro[2-benzofuran-1,3-pyrrolidine, 3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol, 3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline, indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole, 8-oxatricyclo[7.4.0.0.sup.2,7]trideca-1(9),2(7),3,5,10,12-hexaene, 5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine, 3-azaspiro[5.5]undecane, azatricyclo[7.3.1.0.sup.5,13]trideca-1 (13),5,7,9,11-pentaene, (4aR,8aS)-decahydroisoquinoline, and 5,6,7,8-tetrahydro-1,6-naphthyridine.

(556) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heteroaryl is selected from the group consisting of 1,3,4-oxadiazol, (1R)-3-oxo-3H-spiro[2-benzofuran-1,3-pyrrolidine, 3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol, 3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline, indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole, 8-oxatricyclo[7.4.0.0.sup.2,7]trideca-1(9),2(7),3,5,10,12-hexaene, 5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine, 3-azaspiro[5.5]undecane, azatricyclo[7.3.1.0.sup.5,13]trideca-1(13),5,7,9,11-pentaene, (4aR,8aS)-decahydroisoquinoline, and 5,6,7,8-tetrahydro-1,6-naphthyridine.

(557) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heteroaryl is selected from the group consisting of 1,3,4-oxadiazol, (1R)-3-oxo-3H-spiro[2-benzofuran-1,3-pyrrolidine, 3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol, 3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline, indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole, 8-oxatricyclo[7.4.0.0.sup.2,7]trideca-1(9),2(7),3,5,10,12-hexaene, 5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine, 3-azaspiro[5.5]undecane, azatricyclo[7.3.1.0.sup.5,13]trideca-1(13),5,7,9,11-pentaene, (4aR,8aS)-decahydroisoquinoline, and 5,6,7,8-tetrahydro-1,6-naphthyridine.

(558) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, and R.sup.1 is unsubstituted or substituted unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heteroaryl is selected from the group consisting of 1,3,4-oxadiazol, (1R)-3-oxo-3H-spiro[2-benzofuran-1,3-pyrrolidine, 3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol, 3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline, indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole, 8-oxatricyclo[7.4.0.0.sup.2,7]trideca-1(9),2(7),3,5,10,12-hexaene, 5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine, 3-azaspiro[5.5]undecane, azatricyclo[7.3.1.0.sup.5,13]trideca-1(13),5,7,9,11-pentaene, (4aR,8aS)-decahydroisoquinoline, and 5,6,7,8-tetrahydro-1,6-naphthyridine.

(559) An embodiment of the invention is the provision of a compound of Formula III, where the various moieties are independently selected, Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and R.sup.1 is unsubstituted or substituted unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S, wherein the heteroaryl is selected from the group consisting of 1,3,4-oxadiazol, (1R)-3-oxo-3H-spiro[2-benzofuran-1,3-pyrrolidine, 3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol, 3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline, indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole, 8-oxatricyclo[7.4.0.0.sup.2,7]trideca-1 (9),2(7),3,5,10,12-hexaene, 5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine, 3-azaspiro[5.5]undecane, azatricyclo[7.3.1.0.sup.5,13]trideca-1(13),5,7,9,l 1-pentaene, (4aR,8aS)-decahydroisoquinoline, and 5,6,7,8-tetrahydro-1,6-naphthyridine.

(560) Another embodiment of the invention is the provision of a compound of Formula III where Ar.sup.1 is pyridine, n is 1, Ar.sup.2 is phenyl and the Formula becomes Formula III A:

(561) ##STR00046##

(562) wherein R.sup.1 and R.sup.a are as defined in Formula III with the proviso that the compounds are not N-[4-(phenylsulfonyl)phenyl]-NE(3-pyridinylmethyl)urea, N,N-diethyl-4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide, or 4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide.

(563) Another embodiment of the invention is compounds of Formula III where Ar.sup.2 is phenyl and Ar1 has the structure of

(564) ##STR00047##
and the formula becomes Formula IIIB

(565) ##STR00048##
wherein: R.sup.a is one of more and can be selected from the group consisting of amino, oxo, halo, halo(C.sub.1-C.sub.6)alkyl, —NH(CO)O—(C.sub.1-C.sub.6)alkyl and —C(O)NH.sub.2; and wherein said pyridine can comprise a N-oxide formed with its N atom member; R.sup.1 is —NR.sup.3R.sup.4 wherein R.sup.3 is H, C.sub.1-C.sub.6-alkyl or —S(O).sub.2(C.sub.1-C.sub.6)alkyl and R.sup.4 is (C.sub.1-C.sub.6)alkyl, hydroxy(C.sub.1-C.sub.6)alkyl, —S(O).sub.2(C.sub.1-C.sub.6)alkyl, —(CH.sub.2).sub.qcycloalkyl, —(CH.sub.2).sub.qheterocycloalkyl, aryl, aryl(C.sub.1-C.sub.6)alkyl-, —(CH.sub.2).sub.qheteroaryl;

(566) halo(C.sub.1-C.sub.6)alkyl,

(567) cycloalkyl;

(568) aryl;

(569) heterocycloalkyl; or

(570) heteroaryl

(571) wherein: each of said cycloalkyl, aryl, or heteroaryl is unsubstituted or substituted with 1, 2, 3, 4 or 5 substituents which can be the same or different and are independently selected from the group consisting of: halo, cyano, (C.sub.1-C.sub.6)alkyl, hydroxyl, hydroxy(C.sub.1-C.sub.6)alkyl, hydroxy(C.sub.1-C.sub.6)alkoxy, halo(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, (C.sub.1-C.sub.6)alkyl(C.sub.1-C.sub.6)alkoxy, halo(C.sub.1-C.sub.6)alkoxy, aryl(C.sub.2-C.sub.6)alkenyl-, aryloxy, benzyloxy, oxo, —(CH.sub.2).sub.q—NR.sup.bR.sup.c, —(CH.sub.2).sub.q—CONR.sup.bR.sup.c, —S(O).sub.2—(C.sub.1-C.sub.6)alkyl, —S(O).sub.2NH—(C.sub.1-C.sub.6)alkyl, —S(O).sub.2-heterocycloalkyl, —S(O).sub.2—CF.sub.3, —C(O)(C.sub.1-C.sub.6)alkyl, —C(O)aryl, —C(O) (C.sub.2-C.sub.6)alkylenylaryl, —C(O)O—(C.sub.1-C.sub.6)alkyl, —(CH.sub.2).sub.qcycloalkyl, cycloalkyl(C.sub.1-C.sub.6)alkoxy-, aryl, aryl(C.sub.1-C.sub.6)alkyl-, —(CH.sub.2).sub.qheteroaryl, and —(CH.sub.2).sub.qheterocycloalkyl, wherein each of said cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be substituted by one or more halo, nitro, halo(C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkoxy, oxo, cyano, (C.sub.1-C.sub.6)alkyl, halo(C.sub.1-C.sub.6)alkyl, or (C.sub.1-C.sub.6)alkoxy; R.sup.b and R.sup.c are independently selected from the group consisting of H, (C.sub.1-C.sub.6)alkyl, hydroxy(C.sub.1-C.sub.6)alkyl, (C.sub.1-C.sub.6)alkoxy, aryl, (C.sub.1-C.sub.6)alkoxy(C.sub.1-C.sub.6)alkyl, —S(O).sub.2(C.sub.1-C.sub.6)alkyl and (C.sub.3-C.sub.6)cycloalkyl or R.sup.b and R.sup.c can form a 5 or 6 membered heterocycloalkyl group together with the nitrogen atom to which they are attached, wherein said heterocycloalkyl group may contain one or more additional heteroatom(s) selected from N, S or O
q is 0 or 1; and
pharmaceutically acceptable salts thereof,
with the proviso that the compounds of Formula Ia are not: N-[4-(phenylsulfonyl)phenyl]-N-(3-pyridinylmethyl)urea, N,N-diethyl-4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide, or 4-[[[(3-pyridinylmethyl)amino]carbonyl]amino]benzenesulfonamide.

(572) An embodiment of the invention is compounds of Formula IIIB, wherein R.sup.1 is —NR.sup.3R.sup.4 wherein R.sup.3 is H, alkyl or —S(O).sub.2alkyl and R.sup.4 is alkyl, hydroxyalkyl, —S(O).sub.2alkyl, —(CH.sub.2).sub.qcycloalkyl, —(CH.sub.2).sub.qheterocycloalkyl, aryl, arylalkyl-, —(CH.sub.2).sub.qheteroaryl.

(573) Another embodiment of the invention is compounds of Formula IIIB, where R.sup.1 is NR.sup.3R.sup.4 wherein R.sup.3 is H and R.sup.4 is aryl.

(574) Another embodiment of the invention is compounds of Formula IIIB wherein R.sup.1 is haloalkyl.

(575) Another embodiment of the invention is compounds of Formula IIIB wherein R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl.

(576) Still another embodiment of the invention is compounds of Formula IIIB, wherein R.sup.1 is unsubstituted or substituted C.sub.3-C.sub.12-cycloalkyl and the cycloalkyl is selected from the group consisting of cyclopropyl, cyclopentane, cycloheptyl, azaspiro[4.5]decane, bicyclo[2.2.1]heptan, bicyclo[3.1.1]heptan, adamantane, and (1S,2S,3S,5R)-2,6,6-trimethylbicyclo[3.1.1]heptan.

(577) Yet another embodiment of the invention is compounds of Formula IIIB wherein R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl.

(578) A further embodiment of the invention is compounds of Formula III B wherein R.sup.1 is unsubstituted or substituted C.sub.6-C.sub.10-aryl and the aryl is selected from the group consisting of phenyl, naphatalene, tetrahydronaphthalene, and 1H-inden-5-yl.

(579) Another embodiment of the invention is compounds of Formula IIIB, wherein R.sup.1 is unsubstituted or substituted heterocycloalkyl.

(580) One embodiment of the invention is compounds of Formula III B, wherein R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(581) One embodiment of the invention is compounds of Formula IIIB, wherein R.sup.1 is unsubstituted or substituted 5 to 12 membered heterocycloalkyl comprising 1, 2 or 3 heteroatoms selected from N, O and S, and the heterocycloalkyl is selected from the group consisting of azetidine, piperidine, pyrrolidine, piperazine, thiophorpholine, 2,8-diazaspiro[5.5]undecane, 8-oxa-3-azabicyclo[3.2.1]octane, 1,4-diazepane, 2-oxa-8-azaspiro[4.5]decane, and decahydroquinoline.

(582) Another embodiment of the invention is compounds of Formula IIIB, wherein R.sup.1 is unsubstituted or substituted heteroaryl.

(583) Another embodiment of the invention is compounds of Formula IIIB, wherein R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S.

(584) Still another embodiment of the invention is compounds of Formula IIIB, wherein R.sup.1 is unsubstituted or substituted 5 to 12 heteroaryl comprising 1, 2 or 3 heteroatoms selected from N, O and S, and the heteroaryl is selected from the group consisting of 1,3,4-oxadiazol, (1R)-3-oxo-3H-spiro[2-benzofuran-1,3-pyrrolidine, 3,4-dihydro-2H-1,4-benzoxazine, oxo-2,3-dihydro-1H-indol, 3,4-dihydro-2H-1,5-benzodioxepin, 1,2,3,4-tetrahydroisoquinoline, indole, indazole, thiophene, pyrazol, pyridine, pyrimidine, 1,2-oxazole, 8-oxatricyclo[7.4.0.0.sup.2,7]trideca-1(9),2(7),3,5,10,12-hexaene, 5-oxo-5,6,7,8-tetrahydronaphthalen-1-yl, phenoxathiine, 3-azaspiro[5.5]undecane, azatricyclo[7.3.1.0.sup.5,13]trideca-1(13),5,7,9,11-pentaene, (4aR,8aS)-decahydroisoquinoline, and 5,6,7,8-tetrahydro-1,6-naphthyridine

(585) Illustrative compounds of the invention are:

(586) TABLE-US-00002 Structure Chemical Name 1-(pyridin-3-ylmethyl)-3-(4-{[2- (trifluoromethoxy)benzene]sulfonyl} phenyl)urea 0 3-{4-[(4-bromobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-(4-{[2-methyl-4-(1H-pyrazol-1- yl)benzene]sulfonyl}phenyl)-1-(pyridin- 3-ylmethyl)urea N-[2-(pyridin-3-yl)ethyl]-4-{[3- (trifluoromethoxy)benzene]sulfonyl} benzamide 3-{4-[(4-methoxy-2- methylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(2,4- dimethoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-[(6-aminopyridin-3-yl)methyl]-3-{4- [(4-fluorobenzene)sulfonyl]phenyl}urea 3-{4-[(3,5- dimethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-[(6-aminopyridin-3-yl)methyl]-3-[4- (benzenesulfonyl)phenyl]urea 3-{4-[(4-methylbenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H- pyrazol-1-yl)pyridin-3-yl]methyl}urea 0 3-(4-{[2-fluoro-4-(1H-pyrazol-1- yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea 4-(benzenesulfonyl)-N-{imidazo[1,2- a]pyridin-7-ylmethyl}benzamide 3-{4-[(2-bromobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 4-(benzenesulfonyl)-N-(pyridin-3- ylmethyl)benzamide 3-{4-[(2-ethoxybenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H- imidazol-1-yl)pyridin-3-yl]methyl}urea 3-{4-[(3,4- dimethoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{[({4-[(4- chlorobenzene)sulfinyl]phenyl}carbamoyl) amino]methyl}pyridin-1-ium-1-olate 1-(pyridin-3-ylmethyl)-3-(4-{[4- (trifluoromethyl)benzene]sulfonyl}phenyl) urea 3-{4-[(2,5- dimethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 0 1-(pyridin-3-ylmethyl)-3-(4-{[3- (trifluoromethoxy)benzene]sulfonyl} phenyl)urea N,N-dimethyl-4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene) sulfonyl]benzamide 3-(4-{[2-methoxy-4-(1H-pyrazol-1- yl)benzene]sulfonyl}phenyl)-1-(pyridin- 3-ylmethyl)urea 3-[4-(benzenesulfonyl)phenyl]-1-(pyridin- 3-ylmethyl)urea 1-[4-(benzenesulfonyl)phenyl]-3-(1H- pyrazol-3-ylmethyl)urea 3-{4-[(3-bromobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[3- (trifluoromethyl)benzene]sulfonyl} phenyl)urea N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4- {[3-(trifluoromethoxy)benzene]sulfonyl} benzamide 1-{[4-(benzenesulfonyl)phenyl]methyl}-3- (quinolin-6-yl)urea 3-{4-[(5-fluoro-2- methylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 0 3-[4-(benzenesulfonyl)phenyl]-1-{[6- (dimethylamino)pyridin-3-yl]methyl}urea 3-{4-[(4-chloro-2- methylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(2-fluoro-3- methoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(2,3-difluorobenzene)sulfonyl] phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(2-chloro-6-fluoro-3- methylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-[4-(pyrimidine-5- sulfonyl)phenyl]urea 3-{4-[(3,5-difluorobenzene)sulfonyl] phenyl}-1-(pyridin-3-ylmethyl)urea 1-[6-(benzenesulfonyl)pyridin-3-yl]-3- (pyridin-3-ylmethyl)urea 3-{4-[(2,4-dichlorobenzene)sulfonyl] phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(2,5-difluoro-4- methoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 0 1-[(3-aminophenyl)methyl]-3-[4- (benzenesulfonyl)phenyl]urea 3-{4-[(4-ethylbenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(4-chlorobenzene)sulfinyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(2-chlorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(4-chloro-2- fluorobenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-{4-[(4-chlorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(5-fluoro-2- methoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(2-methoxybenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(4-fluorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-[4-(2-methoxynaphthalene-1- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl) urea 00 3-{[({4-[(4- chlorobenzene)sulfonyl]phenyl}carbamoyl) amino]methyl}pyridin-1-ium-1-olate 01 3-{4-[(3-fluorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 02 1-[4-(2H-1,3-benzodioxole-5- sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 03 4-[(2-chlorobenzene)sulfonyl]-N- {imidazo[1,2-a]pyridin-6- ylmethyl}benzamide 04 4-[(3-chlorobenzene)sulfonyl]-N- {imidazo[1,2-a]pyridin-6- ylmethyl}benzamide 05 3-{4-[(3-chlorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 06 3-(4-{[2- (methoxymethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 07 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(2- methoxyethoxy)pyridin-3-yl]methyl}urea 08 3-{4-[(2,3-dichlorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 09 3-{4-[(4-fluoro-2- methylbenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 0 1-{4-[(2-phenoxybenzene)sulfonyl]phenyl}- 3-(pyridin-3-ylmethyl)urea 1-[4-(benzenesulfonyl)phenyl]-3- {5H,6H,7H,8H-imidazo[1,2-a]pyridin-6- ylmethyl}urea 3-(4-{[3-(propan-2- yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-{4-[(2-acetylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-[4-(benzenesulfonyl)phenyl]-3- {imidazo[1,2-a]pyridin-6-ylmethyl}urea 3-{4-[(2,3- dimethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-[4-(cyclopentanesulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 3-{4-[(2-fluoro-6- methoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-(4-{[3-fluoro-4-(1H-pyrazol-1- yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-[4-(benzenesulfonyl)phenyl]-1-(quinolin- 6-yl)urea 0 3-{4-[(2,5- dimethoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-[4- (trifluoromethane)sulfonylphenyl]urea 3-{4-[(2-fluoro-4- methoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-{4-[(4-fluorobenzene)sulfonyl]phenyl}-3- {imidazo[1,2-a]pyridin-6-ylmethyl}urea 3-[4-(3,5-dimethyl-1,2-oxazole-4- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 3-{4-[(4-chloro-3- fluorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4- {[3-(trifluoromethyl)benzene]sulfonyl} benzamide 3-(4-{[2-chloro-5- (trifluoromethyl)benzene]sulfonyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 3-{4-[(2-fluorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 4-[(3,5-difluorobenzene)sulfonyl]-N- {imidazo[1,2-a]pyridin-6- ylmethyl}benzamide 0 1-(pyridin-3-ylmethyl)-3-(4-{[2- (trifluoromethyl)benzene]sulfonyl} phenyl)urea 3-(4-{[4-chloro-3- (trifluoromethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(4- methanesulfonylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(2-fluoro-4- methylbenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-{4-[2-chloro-6-(propan-2-yl)pyridine-3- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(2-methoxy-5- methylbenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-[4-(pyridine-4- sulfonyl)phenyl]urea N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-[(3- methoxybenzene)sulfonyl]benzamide 3-{4-[(2-chloro-4- fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(2-ethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 0 3-{4-[(3-fluoro-4- methylbenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-{4-[(2,5-dichlorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-[4-(pyridine-3- sulfonyl)phenyl]urea 3-{4-[(3-methylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(2,4-difluorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(2,6- dimethoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-(4-{8-oxatricyclo[7.4.0.0.sup.2,7]trideca- 1(9),2(7),3,5,10,12-hexaene-6- sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-[4-(pyridine-2- sulfonyl)phenyl]urea N-(1,3-benzothiazol-6-ylmethyl)-4-[(3- chlorobenzene)sulfonyl]benzamide 3-{4-[(5-chloro-2- methoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 0 3-(4-{[2-methoxy-5-(propan-2- yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-(4-{[3-(propan-2- yloxy)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-{4-[(2,4,6- trimethylbenzene)sulfonyl]phenyl}urea 3-{4-[(3-fluoro-4- methoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(2-methylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-[4-(benzenesulfonyl)phenyl]-3-{thieno[2,3- c]pyridin-2-ylmethyl}urea 3-{4-[(2,4- dimethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(2,5-difluorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(2-fluoro-5- methylbenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[4- (trifluoromethoxy)benzene]sulfonyl] phenyl)urea 0 3-[4-(1-methyl-1H-pyrazole-4- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 3-[4-(5-methylthiophene-2-sulfonyl)phenyl]- 1-(pyridin-3-ylmethyl)urea 3-{4-[(3,4-difluorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 1-(4-benzoylphenyl)-3-(pyridin-3- ylmethyl)urea 3-[4-(benzenesulfonyl)phenyl]-1-(pyridin-3- yl)urea 3-{4-[(2,6- dimethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 4-(benzenesulfonyl)-N-(pyridin-3- yl)benzamide 4-(benzenesulfonyl)-N-(pyridin-4- yl)benzamide 3-[4-(2-methoxypyrimidine-5- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 3-{4-[4-(3-methoxyphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0 3-{4-[(4-methoxy-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 1-{4-(phenylsulfamoyl)phenyl]-3-(pyridin-3- ylmethyl)urea 3-{4-[(3-chloro-4- fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-(4-{8-methyl-2,8-diazaspiro[5.5]undecane- 2-sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{4-[4- (trifluoromethyl)phenyl]piperazine-1- sulfonyl}phenyl)urea 3-{4-[(3,4-difluorophenyl)sulfamoyl] phenyl}-1-(pyridin-3-ylmethyl)urea N-methyl-5-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene) sulfonyl]pyridine-2-carboxamide 3-{4-[(2R)-2-(methoxymethyl)pyrrolidine- 1-sulfonyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-(4-{[3-fluoro-5-(2,2,2- trifluoroethoxy)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(4-chloro-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 0 3-(4-{[3-(3-methoxyphenyl)pentan-3- yl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-{4-[(3-fluoro-4- propoxybenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-(4-{[4-fluoro-3- (trifluoromethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(4-methoxy-3- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-(4-{[4-chloro-3- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[6-(dimethylamino)pyridine-3- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-(4-{[2-(morpholin-4-yl)-5- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 1-[4-(3,5-dimethylpiperidine-1- sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea (2S)-N,N-dimethyl-1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] pyrrolidine-2-carboxamide methyl 4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperazine-1-carboxylate 0 3-{4-[(2- methoxyethyl)(methyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-{4-[4-(2H-1,3-benzodioxol-5-yl)piperazine- 1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 3-{4-[(2-methoxyphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea N-(propan-2-yl)-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 3-(4-{[(2- methoxyphenyl)methyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-[4-(1-methyl-1H-indole-2-sulfonyl)phenyl]- 1-(pyridin-3-ylmethyl)urea 3-{[4-(piperidine-1-sulfonyl)phenyl]methyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(2-fluoro-4- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(4-fluorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-[4-(cycloheptylsulfamoyl)phenyl]-3- (pyridin-3-ylmethyl)urea 00 1-{4-[4-(pyrazin-2-yl)piperazine-1- sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 01 3-{4-[(5-methylpyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 02 3-{4-[4-(2-methoxyphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 03 1-(pyridin-3-ylmethyl)-3-(4-{[(1R,2R,3R,5S)- 2,6,6-trimethylbicyclo[3.1.1]heptan-3- yl]sulfamoyl}phenyl)urea 04 1-(pyridin-3-ylmethyl)-3-(4-{4-[6- (trifluoromethyl)pyridin-2-yl]piperazine-1- sulfonyl}phenyl)urea 05 3-{4-[(3-ethoxy-4- fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- ylmethyl)urea 06 3-{4-[4-(2-methylphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 07 3-{4-[(6-ethylpyridin-2-yl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 08 3-{4-[3-(2-methoxyethyl)piperidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 09 3-[4-(1-methyl-1H-indazole-7- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0 3-{4-[(4-methoxybenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea N-cyclopropyl-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 3-{4-[(4-methoxy-3,5- dimethylbenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-(4-{[2-methyl-4- (trifluoromethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1- {4-[4-(morpholin-4-yl)piperidine-1- sulfonyl]phenyl}urea 3-[4-(piperidine-1-sulfonyl)phenyl]-1- (pyrimidin-5-ylmethyl)urea 3-(4-{[2-(3- methoxyphenyl)ethyl](methyl)sulfamoyl} phenyl)-1-(pyridin-3-ylmethyl)urea N-[(3R)-1-[(4-{[pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] pyrrolidin-3-yl]acetamide 1-{4-[(4-phenylphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[(2,4-difluorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 0 3-(4-{[3- (dimethylsulfamoyl)benzene]sulfonyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 3-{4-[(2-methoxy-6- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(3- methanesulfonylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(4-chloro-2- fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea N-methyl-2-{4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperazin-1-yl}acetamide 3-{4-[(4-chloro-2-methoxy-5- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-(4-{[3-chloro-5- (trifluoromethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(1,5-dimethyl-1H-pyrazol-3- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-(4-{[3-(2- methoxyethoxy)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[4-(2,4-dimethylphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0 3-(4-{methyl[(1S)-1- phenylethyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 1-(4-{8-azaspiro[4.5]decane-8- sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 3-{4-[(5-chloro-2- fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(2,4-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(2,5-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 1-[4-(piperidine-1-sulfonyl)phenyl]-3-(pyridin- 3-ylmethyl)urea 1-{4-[(3S)-3-cyanopiperidine-1- sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 3-{4-[(2S)-2-(methoxymethyl)pyrrolidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{8- oxa-3-azabicyclo[3.2.1]octane-3- sulfonyl}benzamide 1-{4-[(5-oxo-5,6,7,8-tetrahydronaphthalen-1- yl)sulfamoyl]phenyl}-3-(pyridin-3- ylmethyl)urea 0 1-(4-{4-[2-(morpholin-4-yl)-2- oxoethyl]piperazine-1-sulfonyl}phenyl)-3- (pyridin-3-ylmethyl)urea 1-{4-[(3-benzoylphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[(6-methoxypyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(3-chloro-4- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea N-ethyl-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 3-(4-{[4-(2- methoxyethoxy)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-[4-(6-methoxynaphthalene-2- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[4- (trifluoromethyl)phenyl]sulfamoyl}phenyl)urea 3-{4-[cyclohexyl(methyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(3-methoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 0 3-(4-{[4-(4- chlorophenoxy)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(2-ethylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-[4-({4-[(pyrrolidin-1- yl)carbonyl]benzene}sulfonyl)phenyl]urea 3-(4-{[3-(2- hydroxyethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(3-chloro-2,6- dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-{4-[4-(2,5-dimethylphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-[4-(3-methylpiperidine-1-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea 3-{4-[4-(4-bromophenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(3-methylpyridin-4- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(5-fluoro-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 0 1-[(3,4-difluorophenyl)methyl]-3-[4- (piperidine-1-sulfonyl)phenyl]urea 4-(piperidine-1-sulfonyl)phenyl N-(pyridin-3- ylmethyl)carbamate 3-{4-[(4-methoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-(4-{4-[2-(3,4- dichlorophenyl)acetyl]piperazine-1- sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea 3-[4-({2-[(2S)-2- hydroxypropoxy]phenyl}sulfamoyl)phenyl]-1- (pyridin-3-ylmethyl)urea 1-[4-(1H-indole-7-sulfonyl)phenyl]-3-(pyridin- 3-ylmethyl)urea 3-{4-[(3-chloro-5- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-(4-{[4- (ethoxymethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 1-{4-[(1- phenylcyclopentyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-{4-[3- (trifluoromethyl)piperidine-1- sulfonyl]phenyl}urea 0 1-{4-[(3-phenylbenzene)sulfonyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[(3,4-dichlorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 1-{4-[(pyridin-2-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea (3S)-N,N-diethyl-1-[(4-{(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperidine-3-carboxamide 3-(pyridin-3-ylmethyl)-1-[4-(quinoline-6- sulfonyl)phenyl]urea 1-(4-{[(1S,2S,4R)-bicyclo[2.2.1]heptan-2- yl]sulfamoyl}phenyl)-3-(pyridin-3- ylmethyl)urea 3-[(5-chloropyridin-3-yl)methyl]-1-[4- (piperidine-1-sulfonyl)phenyl]urea 3-{4-[4-(3-chlorophenyl)-4-cyanopiperidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-[4-(4-methanesulfonylpiperazine-1- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-[4-(1H-pyrrole-1- sulfonyl)phenyl]urea 0 3-{4-[(4-ethoxy-2- fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(4-propylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[4-cyano-4-(4-methoxyphenyl) piperidine-1-sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-(4-{[(4- chlorophenyl)methyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 1-[3-(piperidine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 3-{4-[4-(3-fluorophenoxy)piperidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 1-{4-[(pyridin-3-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-[4-(thiomorpholine- 4-sulfonyl)phenyl]urea 3-(4-{[2-chloro-5- (trifluoromethoxy)benzene]sulfonyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-[4-(pyrrolidine-1- sulfonyl)phenyl]urea 0 2-methyl-N-{3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene) sulfonyl]phenyl}propanamide 1-[4-(cyclohexylsulfamoyl)phenyl]-3- (pyridin-3-ylmethyl)urea 3-[4-(piperidine-1-sulfonyl)phenyl]-1-[1- (pyridin-3-yl)ethyl]urea 1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperidine-4-carboxamide 3-{4-[(2-tert-butylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-(4-{[(4- methoxyphenyl)methyl]sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 3-{4-[(2-chloro-5- methylphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-(4-{[4-fluoro-3- (trifluoromethyl)phenyl]sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 1-(4-{3-[(2-oxopyrrolidin-1- yl)methyl]piperidine-1-sulfonyl}phenyl)-3- (pyridin-3-ylmethyl)urea 1-(4-{[2-(morpholin-4- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- ylmethyl)urea 00 1-(pyridin-3-ylmethyl)-3-{4-[(2,4,6- trimethylphenyl)sulfamoyl]phenyl}urea 01 3-[4-(piperidine-1-sulfonyl)phenyl]-1-[2- (pyridin-3-yl)ethyl]urea 02 1-[4-(4-cyclohexylpiperazine-1- sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 03 3-{4-[(2-chloro-4- fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 04 3-{4-[(5-fluoro-2- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 05 3-[4-(methylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea 06 1-[4-(phenoxathiine-4-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 07 3-{4-[(3,5-dichlorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 08 1-{4-[(2R,6S)-2,6-dimethylmorpholine-4- sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6- ylmethyl}urea 09 N-(propan-2-yl)-2-{4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperazin-1-yl}acetamide 0 N,N-diethyl-2-{4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperazin-1-yl}acetamide 3-(pyridin-3-ylmethyl)-1-[4-(quinoline-8- sulfonyl)phenyl]urea 1-(4-{[4-(piperidin-1- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- ylmethyl)urea 3-{4-[4-(3,5-dichloropyridin-4-yl)piperazine- 1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl) urea 1-[4-(cyclobutylsulfamoyl)phenyl]-3-(pyridin- 3-ylmethyl)urea 3-[4-(4-methylpiperidine-1-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{4-[4- (trifluoromethyl)pyridin-2-yl]piperazine-1- sulfonyl]phenyl)urea 1-{4-[4-(morpholin-4-yl)piperidine-1- sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 1-[4-(4-benzyl-1,4-diazepane-1- sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea N-[(3S)-1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] pyrrolidin-3-yl]acetamide 0 3-(pyridin-3-ylmethyl)-1-[4-(quinoline-3- sulfonyl)phenyl]urea 3-(4-{[3-fluoro-5-(2- methylpropoxy)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea N,N-dimethyl-2-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene) sulfonamido]benzamide 1-{4-[(3-cyanobenzene)sulfonyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-[(5-fluoropyridin-3-yl)methyl]-1-[4- (piperidine-1-sulfonyl)phenyl]urea 1-{4-[(2H-1,3-benzodioxol-5- yl)sulfamoyl]phenyl}-3-(pyridin-3- ylmethyl)urea 1-[4-(isoquinoline-4-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 3-{4-[(2-chloro-4-methylphenyl) sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 1-(4-{3-azaspiro[5.5]undecane-3- sulfonyl}phenyl)-3-(pyridin-3-ylmethyl) urea 3-{4-[4-(2,4-difluorophenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0 3-[4-(diethylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea N-(2-methylpropyl)-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 3-(4-{[3- (difluoromethoxy)phenyl]sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 3-(4-{[2-methoxy-5- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[4-(2-ethoxyphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea N-ethyl-4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 3-[4-(6-methoxypyridine-3-sulfonyl)phenyl]- 1-(pyridin-3-ylmethyl)urea 3-(4-{[3-(propan-2- yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 1-{4-[(3-phenylphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-(4-{[(3- fluorophenyl)methyl](methyl)sulfamoyl} phenyl)-1-(pyridin-3-ylmethyl)urea 0 3-{4-[(3-propoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-{4-[4- (trifluoromethyl)piperidine-1- sulfonyl]phenyl}urea 3-{4-[(3-ethylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-(4-{[4-(propan-2- yloxy)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea 1-[4-(benzylsulfamoyl)phenyl]-3-(pyridin-3- ylmethyl)urea 3-{4-[(4-ethoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(2-methoxypyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 1-[4-(4,4-difluoropiperidine-1- sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 3-{4-[(3S)-3-methyl-4-(4- methylphenyl)piperazine-1-sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-[4-(1-methyl-1H-indazole-4- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0 1-{4-[4-(piperidin-1-yl)piperidine-1- sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 3-[4-(butylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea 3-{4-[(5-methylpyridin-2- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(3,4- dimethoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-{4-[(3-cyanophenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[(3-chlorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-[4-(dimethylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea 3-{4-[methanesulfonyl(piperidin-4- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-(4-{4-[(4-fluorophenyl)carbonyl] piperidine-1-sulfonyl}phenyl)-1-(pyridin- 3-ylmethyl)urea 3-{4-[(3S)-4-(4-methoxyphenyl)-3- methylpiperazine-1-sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 0 1-(pyridin-3-ylmethyl)-3-{4-[(3S)-3- (trifluoromethyl)piperidine-1- sulfonyl]phenyl}urea 3-{4-[methyl(oxolan-3-yl)sulfamoyl] phenyl}-1-(pyridin-3-ylmethyl)urea 1-[4-(2,3-dihydro-1-benzofuran-7- sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 3-{4-[4-(2-methoxyethyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 1-[4-(2,3-dihydro-1,4-benzodioxine-6- sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 3-(4-{[4- (difluoromethoxy)phenyl]sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 3-(4-{[3-methyl-4-(propan-2- yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-{4-[methyl({[5-(trifluoromethyl)pyridin-2- yl]methyl})sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 1-(4-{4-[3-(morpholin-4-yl)propyl]piperazine- 1-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 3-(4-{[3-(propane-1- sulfonamido)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 0 1-{4-[(2,3-dihydro-1,4-benzodioxin-6- yl)sulfamoyl]phenyl}-3-(pyridin-3- ylmethyl)urea 3-{4-[4-(5-chloro-2-methylphenyl)piperazine- 1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 1-{4-[(naphthalen-1-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-(4-{[3-chloro-4- (trifluoromethoxy)phenyl]sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 1-{4-[4-(2H-1,3-benzodioxol-5- ylmethyl)piperazine-1-sulfonyl]phenyl}-3- (pyridin-3-ylmethyl)urea N-methyl-N-phenyl-2-{4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperazin-1-yl}acetamide 1-(4-{4-[(furan-2-yl)carbonyl]piperazine-1- sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 3-{4-[4-(5-chloro-2- methoxyphenyl)piperazine-1-sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[4-(propan-2-yl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(5-fluoropyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 0 3-[4-(2-methyl-3-oxopiperazine-1- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 3-{4-[(3-ethoxybenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[4-(2,6-dimethylphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(2-chlorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-[4-(1H-indole-4-sulfonyl)phenyl]-3-(pyridin- 3-ylmethyl)urea 3-chloro-N,N-diethyl-5-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 3-[2-fluoro-4-(piperidine-1-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea N,N-dimethyl-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 1-(pyridin-3-ylmethyl)-3-[4-({[3- (trifluoromethyl)phenyl]methyl}sulfamoyl) phenyl]urea pyridin-3-ylmethyl N-[4-(piperidine-1- sulfonyl)phenyl]carbamate 0 1-(4-{[3-(piperidin-1- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- ylmethyl)urea 3-(4-{[2-(2- hydroxyethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-benzyl-1-[4-(piperidine-1- sulfonyl)phenyl]urea 3-{4-[(2- hydroxyethyl)(methyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[4- (trifluoromethane)sulfonylphenyl]sulfamoyl} phenyl)urea 3-{4-[(4-chlorobenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(3- ethanesulfonamidobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[4-(4-chloro-3- methoxyphenyl)piperazine-1-sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-[4-(1-methyl-1H-indazole-6- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 3-{4-[(2-methylpropyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 00 N-(2-hydroxyethyl)-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 01 3-{4-[(3-chloro-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 02 3-(4-{[3-fluoro-4- (trifluoromethoxy)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 03 3-{4-[(3-chloro-4- methoxybenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 04 3-(4-{[4-fluoro-3-(2,2,2- trifluoroethoxy)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 05 1-[4-(morpholine-4-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 06 3-(4-{[(4-chlorophenyl) methyl](methyl)sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 07 3-{4-[methyl(2-methylpropyl) sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 08 3-{4-[(4-chlorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 09 3-(4-{methyl[(1R)-1- phenylethyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 0 3-{4-[4-(2-chlorophenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-[4-({2-[(1S)-1- hydroxyethyl]phenyl}sulfamoyl)phenyl]-1- (pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-{4-[(quinolin-6- yl)sulfamoyl]phenyl}urea 3-{4-[(2,5-difluorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 1-(4-{[2-(piperidin-1- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- ylmethyl)urea 3-{4-[(3-tert-butylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-(4-{methyl[2-(4- methylphenyl)ethyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(2,6-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-{4-[(1,3,5-trimethyl- 1H-pyrazol-4-yl)sulfamoyl]phenyl}urea 1-(4-{3-azatricyclo[7.3.1.0.sup.5,13]trideca- 1(13),5,7,9,11-pentaene-3-sulfonyl}phenyl)-3- (pyridin-3-ylmethyl)urea 0 N,N-dimethyl-2-{4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene) sulfonamido]phenyl}acetamide 3-[(6-chloropyridin-3-yl)methyl]-1-[4- (piperidine-1-sulfonyl)phenyl]urea 3-(4-{[(5-methylfuran-2- yl)methyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 1-(4-{4-[2-oxo-2-(piperidin-1- yl)ethyl]piperazine-1-sulfonyl}phenyl)-3- (pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-[4-(3,3,5- trimethylazepane-1-sulfonyl)phenyl]urea 3-(4-{[3-(3,5-dimethyl-1H-pyrazol-1- yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-(4-{[3- (methoxymethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-[4-(1-propyl-1H-pyrazole-4- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 3-(4-{[3-fluoro-5- (trifluoromethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 1-(4-{[2-(morpholin-4- ylmethyl)benzene]sulfonyl}phenyl)-3-(pyridin- 3-ylmethyl)urea 0 N-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]-4- (1,2,3,4-tetrahydroisoquinoline-2- sulfonyl)benzamide methyl 4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzoate 3-(4-{[2-(propan-2- yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-(4-{[3-(propan-2- yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-(4-{[3-fluoro-4-(2,2,2- trifluoroethoxy)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-{4-[(3,4,5- trifluorophenyl)sulfamoyl]phenyl}urea 1-{4-[(pyridin-2-ylmethyl)sulfamoyl]phenyl}- 3-(pyridin-3-ylmethyl)urea N,N-diethyl-4-fluoro-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 1-(4-{[4-(piperidine-1- sulfonyl)phenyl]sulfamoyl}phenyl)-3-(pyridin- 3-ylmethyl)urea 3-{4-[(2,4-dichlorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 0 3-(4-{[3- (ethylsulfamoyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 1-[4-(4-cyanopiperidine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 3-{4-[(2,2-dimethylpropyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 1-[4-(dibenzylsulfamoyl)phenyl]-3-(pyridin-3- ylmethyl)urea (2S)-1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] pyrrolidine-2-carboxamide 1-(4-{3-oxa-8-azabicyclo[3.2.1]octane-8- sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 1-{4-[(1H-indazol-5-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea tert-butyl N-{5-[({[4-(piperidine-1- sulfonyl)phenyl]carbamoyl}amino)methyl] pyridin-2-yl}carbamate 3-{4-[benzyl(methyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[4-(3-chloropyridin-2-yl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0 3-(4-{[2-(propan-2- yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-{4-[(3- methanesulfonamidobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea N,N-diethyl-3-fluoro-5-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 3-(4-{[4- (methoxymethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea N,N-dimethyl-1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperidine-4-carboxamide 3-{4-[(propan-2-yl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-[4-({3-[(morpholin-4- yl)carbonyl]benzene}sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 3-(4-{[(4- fluorophenyl)methyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(4-ethoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[benzyl(propan-2-yl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 0 3-[4-({[4- (dimethylamino)phenyl]methyl}sulfamoyl) phenyl]-1-(pyridin-3-ylmethyl)urea 3-{4-[benzyl(ethyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(4-acetylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-[4-(4-{[(2R)-oxolan-2- yl]carbonyl}piperazine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 2-methyl-N-{1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperidin-4-yl}propanamide 1-(pyridin-3-ylmethyl)-3-(4-{[4- (trifluoromethoxy)phenyl]sulfamoyl} phenyl)urea 3-(pyridin-3-ylmethyl)-1-(4-{[4-(pyrrolidin-1- yl)phenyl]sulfamoyl}phenyl)urea 3-(4-{[(3- chlorophenyl)methyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-(4-{[3- (ethanesulfonyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-[4-(4-hydroxypiperidine-1-sulfonyl)phenyl]- 1-(pyridin-3-ylmethyl)urea 0 3-(4-{[3- (hydroxymethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(3-acetylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(3-ethoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 4-fluoro-N-(propan-2-yl)-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 3-{4-[4-(3-chlorophenyl)-4-hydroxypiperidine- 1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(3S)-3-methyl-4-(3- methylphenyl)piperazine-1-sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(4-chloro-3- methoxybenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-{4-[(2,3-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[4-(2,3-dichlorophenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 1-[4-(4-benzylpiperidine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 0 1-(4-{[(4- phenylphenyl)methyl]sulfamoyl}phenyl)-3- (pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-{4-[(5,6,7,8- tetrahydronaphthalen-1- yl)sulfamoyl]phenyl}urea rel-3-{4-[(2R,6S)-2,6-dimethylmorpholine-4- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 1-[4-(decahydroquinoline-1-sulfonyl)phenyl]- 3-(pyridin-3-ylmethyl)urea 3-{4-[(4-fluoro-2- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 1-{4-[(4-ethynylphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[(3-chloro-4- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(2-chloro-4,6- dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-(4-{[3-fluoro-4- (trifluoromethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 1-{4-[(2R)-2-benzylpiperidine-1- sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrazin- 2-ylmethyl)urea 3-{4-[(4-fluoro-3- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- ylmethyl)urea 1-{4-[(3,4-dihydro-2H-1,5-benzodioxepin-7- yl)sulfamoyl]phenyl}-3-(pyridin-3- ylmethyl)urea 3-{4-[4-(diethylamino)piperidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(4- fluorophenyl)(methyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-[4-(2-methylpyridine-3-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea 1-{4-[6-(morpholin-4-yl)pyridine-3- sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 3-{4-[(3-fluoro-5- methoxybenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-(4- {3-oxa-8-azabicyclo[3.2.1]octane-8- sulfonyl}phenyl)urea 3-{4-[(3-fluoro-4- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 00 3-{4-[(2-methylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 01 rel-3-{4-[(4aR,8aS)-decahydroisoquinoline-2- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 02 3-[4-(4-methanesulfonylpiperidine-1- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 03 3-(pyridin-3-ylmethyl)-1-{4-[(2S)-2- (pyrrolidin-1-ylmethyl)pyrrolidine-1- sulfonyl]phenyl}urea 04 3-{4-[(6-methylpyridin-2- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 05 3-(4-{4-[(morpholin-4-yl)carbonyl]piperidine- 1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea 06 3-{4-[3-(2-chloro-4-fluorophenoxy)piperidine- 1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 07 3-(4-{4-[4-chloro-3- (trifluoromethyl)phenyl]piperazine-1- sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea 08 3-(4-{[3-(2- methylpropoxy)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 09 3-(4-{4-[bis(4-fluorophenyl)methyl]piperazine- 1-sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea 0 3-[4-(1-methyl-1H-indazole-5- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 1-(4-{[3- (benzyloxy)phenyl]sulfamoyl}phenyl)-3- (pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-(4-{[3-(pyrrolidin-1- yl)phenyl]sulfamoyl}phenyl)urea 3-{4-[(4-ethoxy-3- fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(3,5-dichlorobenzene)sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[4-(3,4-dimethylphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[3- (trifluoromethoxy)phenyl]sulfamoyl} phenyl)urea 3-{4-[(2-ethoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(3- methanesulfonylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(3-methoxy-4- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- ylmethyl)urea 0 3-[4-(6-methylpyridine-3-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-[4-(5,6,7,8- tetrahydro-1,6-naphthyridine-6- sulfonyl)phenyl]urea 3-[4-(2,4-dimethoxypyrimidine-5- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 3-{4-[(5-methoxy-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-(4-{[4-(propan-2- yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-{4-[(5-chloro-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-[(2-fluorophenyl)methyl]-1-[4-(piperidine-1- sulfonyl)phenyl]urea 3-(4-{[2-(4-fluorophenoxy)pyridin-3- yl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 1-{4-[(4-phenoxyphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-{4-[(pyridin-4- ylmethyl)sulfamoyl]phenyl}urea 0 1-{4-[4-(azepan-1-yl)piperidine-1- sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 1-(4-{[4-(1H-pyrazol-1- yl)benzene]sulfonyl}phenyl)-3-(pyridin-3- ylmethyl)urea 1-{4-[(cyclohexylmethyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[(4-ethylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(4-bromophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-[(6-aminopyridin-3-yl)methyl]-1-[4- (piperidine-1-sulfonyl)phenyl]urea 3-{4-[(3,4-dichlorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(4-tert-butylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 1-{4-[4-(2-oxo-2,3-dihydro-1H-indol-1- yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3- ylmethyl)urea 0 1-[(6-isocyanopyridin-3-yl)methyl]-3-[4- (piperidine-1-sulfonyl)phenyl]urea 3-(4-{[2-(3- chlorophenyl)ethyl](methyl)sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 3-{4-[(4-fluoro-3- methoxybenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 1-(4-{[3-(1H-pyrazol-1- yl)benzene]sulfonyl}phenyl)-3-(pyridin-3- ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-{4-[3-(pyrrolidin-1- yl)pyrrolidine-1-sulfonyl]phenyl}urea 1-[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]- 3-(pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[3- (trifluoromethyl)phenyl]sulfamoyl}phenyl)urea 3-{4-[methyl(2- phenylethyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 1-[4-(3,4-dihydro-2H-1,4-benzoxazine-4- sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 3-{4-[(3S)-3-methylpiperidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0 1-[(4-fluorophenyl)methyl]-3-[4-(piperidine-1- sulfonyl)phenyl]urea 3-[4-(tert-butylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea 1-[4-(4-phenylpiperazine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 3-{4-[4-(5-methylpyrimidin-2-yl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-[4-(azepane-1-sulfonyl)phenyl]-1-(pyridin-3- ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[2- (trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea 3-(4-{[3-chloro-4- (trifluoromethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(2-acetylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(4-methylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[4-(4-bromo-3- methoxyphenyl)piperazine-1-sulfonyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 0 3-[4-(piperidine-1-sulfonyl)phenyl]-1-{[6- (trifluoromethyl)pyridin-3-yl]methyl}urea 3-[4-(5-fluoropyridine-3-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea 1-(4-{2-oxa-8-azaspiro[4.5]decane-8- sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 1-{4-[4-(2-phenylacetyl)piperazine-1- sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 1-{4-[4-(3-phenylprop-2-en-1-yl)piperazine-1- sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-{4-[(3- sulfamoylbenzene)sulfonyl]phenyl}urea N-methyl-2-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)s ulfonamido]benzamide 3-(4-{[4-(propan-2- yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-{4-[(2-hydroxyethyl)(propan-2- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 1-{4-[(adamantan-1-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 0 1-{4-[(2R)-2-(morpholin-4- ylmethyl)piperidine-1-sulfonyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[4-(3,5-dichlorophenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(2-fluoro-5- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea N-{3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] phenyl}acetamide N-methyl-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene) sulfonamido]benzamide 3-{4-[4-(4-chlorophenyl)-4-cyanopiperidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-(4-{[4-methyl-3- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 1-[4-(4-phenylpiperidine-1-sulfonyl)phenyl]-3- (pyridin-3-ylmethyl)urea 3-{4-[(3-acetylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[4-(methoxymethyl)piperidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0 3-fluoro-N,N-dimethyl-5-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide N-[2-(pyridin-3-yl)ethyl]-4-{[3- (trifluoromethoxy)phenyl]sulfamoyl}benzamide 3-{4-[cyclohexyl(ethyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[4-(3,4-dichlorophenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(4-fluoro-3- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-(4-{[2-fluoro-5- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-[4-(4-{[4-(propan-2- yl)phenyl]methyl}piperazine-1- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{4-[3- (trifluoromethyl)phenyl]piperazine-1- sulfonyl}phenyl)urea 1-[4-(cyclopropylsulfamoyl)phenyl]-3- (pyridin-3-ylmethyl)urea 4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N- [2-(pyridin-3-yl)ethyl]benzamide 0 3-{4-[(3- aminophenyl)(methanesulfonyl)sulfamoyl] phenyl}-1-(pyridin-3-ylmethyl)urea 1-{4-[(2,3-dihydro-1H-inden-5- yl)sulfamoyl]phenyl}-3-(pyridin-3- ylmethyl)urea 3-(4-{[3-chloro-4-(morpholin-4- yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-{4-[2-(dimethylamino)pyrimidine-5- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-(4-{4-[1-(3-methoxyphenyl)-4- methylcyclohexyl]piperazine-1- sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea 3-(4-{[(5-ethylpyridin-2- yl)methyl](methyl)sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(3-chloro-4- propoxybenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-{4-[(4-chloronaphthalen-1- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(5-acetyl-2- methoxybenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 3-{4-[(5-chloro-2- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 00 1-{4-[(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′- pyrrolidine]-1′-ylsulfonyl]phenyl}-3-(pyridin- 3-ylmethyl)urea 01 3-{4-[4-(2,4-dimethoxyphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 02 3-{[4-(piperidine-1-sulfonyl)phenyl]methyl}- 1-(pyridin-3-yl)urea 03 N-{1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] piperidin-4-yl}acetamide 04 3-(4-{[3- (methoxymethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 05 3-{4-[(3-fluoro-4- methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 06 1-{4-[(2-phenylphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 07 1-(4-{4-[(2-oxopyrrolidin-1- yl)methyl]piperidine-1-sulfonyl}phenyl)-3- (pyridin-3-ylmethyl)urea 08 3-(4-{[2-(piperidin-1-yl)-5- (trifluoromethyl)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 09 3-(4-{[2-methoxy-5- (trifluoromethyl)benzene]sulfonyl}phenyl)-1- (pyridin-3-ylmethyl)urea 0 1-[4-(2,6-dimethylpiperidine-1- sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 1-{4-[(1-phenylcyclohexyl)sulfamoyl]phenyl}- 3-(pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-{4-[6- (trifluoromethyl)pyridine-3- sulfonyl]phenyl}urea 3-{4-[(4-methylpyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[4-(2-methylpropyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 1-(4-{4-[2-oxo-2-(pyrrolidin-1- yl)ethyl]piperazine-1-sulfonyl}phenyl)-3- (pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-{4-[(4- sulfamoylphenyl)sulfamoyl]phenyl}urea 5-[({[4-(piperidine-1- sulfonyl)phenyl]carbamoyl}amino)methyl] pyridine-2-carboxamide 3-(4-{4-[(4-tert- butylphenyl)methyl]piperazine-1- sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea 3-[4-(azetidine-1-sulfonyl)phenyl]-1-(pyridin- 3-ylmethyl)urea 0 3-(pyridin-3-ylmethyl)-1-(4-{[2-(1H-pyrrol-1- yl)phenyl]sulfamoyl}phenyl)urea 3-(4-{4-[3-chloro-5-(trifluoromethyl)pyridin-2- yl]piperazine-1-sulfonyl]phenyl)-1-(pyridin-3- ylmethyl)urea N,N-diethyl-2-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene) sulfonamido]benzamide 1-{4-[(piperidin-1-yl)carbonyl]phenyl}-3- (pyridin-3-ylmethyl)urea N-ethyl-N-[(3S)-1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] pyrrolidin-3-yl]acetamide 3-(pyridin-3-ylmethyl)-1-{4-[4-(pyrimidin-2- yl)piperazine-1-sulfonyl]phenyl}urea 3-{4-[(3-ethylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[3-chloro-2-(morpholin-4-yl)pyridine-4- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-(4-{[(1S,2S,3S,5R)- 2,6,6-trimethylbicyclo[3.1.1]heptan-3- yl]sulfamoyl}phenyl)urea 3-{4-[(4-fluoro-3- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 0 3-{4-[(2-phenylpropan-2- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-(4-{4-[(1R)-1-(4- chlorophenyl)ethyl]piperazine-1- sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea 3-[4-(5-chloropyridine-3-sulfonyl)phenyl]-1- (pyridin-3-ylmethyl)urea 3-[(3-fluorophenyl)methyl]-1-[4-(piperidine-1- sulfonyl)phenyl]urea 3-{4-[4-cyano-4-(4-methylphenyl)piperidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 1-{4-[(3-phenoxyphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[(2,5- dimethoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(3-fluoro-5- methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(2-methoxy-5- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-{4-[(pyridin-3- ylmethyl)sulfamoyl]phenyl}urea 0 3-{4-[4-(dipropylamino)piperidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[(3-methylphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-(4-{[(4-fluorophenyl) methyl](methyl)sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-{4-[(3S)-3- [(pyrrolidin-1-yl)carbonyl]piperidine-1- sulfonyl]phenyl}urea 3-{4-[(3-bromophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-{4-[(2-phenoxyphenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-(4-{4-[1-(4-chlorophenyl)ethyl]piperazine-1- sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea N,N-dimethyl-4-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene) sulfonamido]benzamide 1-{4-[(4-phenylbenzene)sulfonyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[(3,5-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 0 3-{4-[4-(4-methylphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-[4-(4-acetyl-1,4-diazepane-1- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea N-cyclopentyl-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 3-[4-(3,3-difluoroazetidine-1-sulfonyl)phenyl]- 1-(pyridin-3-ylmethyl)urea 1-(4-{[4-(morpholin-4- yl)benzene]sulfonyl}phenyl)-3-(pyridin-3- ylmethyl)urea 3-[4-({3-[(1S)-1- hydroxyethyl]phenyl}sulfamoyl)phenyl]-1- (pyridin-3-ylmethyl)urea 3-{4-[(3,5-ditluorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(3,5- dimethoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[ethyl(phenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[2- (trifluoromethyl)phenyl]sulfamoyl}phenyl)urea 0 3-(4-{[3-(5-methyl-1,3,4-oxadiazol-2- yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea 3-[4-({4-[(1S)-1- hydroxyethyl]phenyl}sulfamoyl)phenyl]-1- (pyridin-3-ylmethyl)urea 3-{4-[(3-methoxy-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 4-[(3-chlorophenyl)sulfamoyl]-N- {imidazo[1,2-a]pyridin-6-ylmethyl}benzamide 3-{4-[(4-tert-butyl-2- chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 1-(4-{8-azabicyclo[3.2.1]octane-8- sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 1-[4-(cyclopentylsulfamoyl)phenyl]-3- (pyridin-3-ylmethyl)urea 3-(4-{4-[2-(diethylamino)ethyl]piperazine-1- sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea 3-{4-[4-(4-chlorophenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-(4-{[2-(3- fluorophenyl)ethyl](methyl)sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 0 3-{4-[methyl({[3- (trifluoromethyl)phenyl]methyl})sulfamoyl] phenyl}-1-(pyridin-3-ylmethyl)urea 1-(4-{[3-(morpholin-4- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- ylmethyl)urea 3-(4-{[(2- chlorophenyl)methyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 1-(4-{8-oxa-3-azabicyclo[3.2.1]octane-3- sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 3-{4-[4-(4-acetylphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 1-{4-[(1H-indazol-6-yl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[4-(3,4-dimethoxyphenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea N,N-dimethyl-3-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene) sulfonamido]benzamide 1-(4-{[3- (cyclopropylmethoxy)benzene]sulfonyl} phenyl)-3-(pyridin-3-ylmethyl)urea (2R)-1-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] pyrrolidine-2-carboxamide 0 3-(4-{[(3- methoxyphenyl)methyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 3-{4-[(2-methylpyridin-3- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-[4-(ethylsulfamoyl)phenyl]-1-(pyridin-3- ylmethyl)urea 3-{4-[(2-fluorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-(4-{[2- (difluoromethoxy)phenyl]sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 1-(4-{2-azabicyclo[2.2.1]heptane-2- sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 3-{4-[(3,5-dimethyl-1,2-oxazol-4- yl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{4-[5- (trifluoromethyl)pyridin-2-yl]piperazine-1- sulfonyl}phenyl)urea 3-[4-(2,3-dihydro-1H-indole-1- sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 3-{4-[(4-acetylbenzene)sulfonyl]phenyl}-1- (pyridin-3-ylmethyl)urea 0 3-{4-[(4-fluoro-2- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 1-{4-[(4-cyanophenyl)sulfamoyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[(3-chloro-4- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[(3-chloro-5- methoxybenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 1-(4-(4-((2- methoxyethyl)(methyl)amino)piperidin-1- ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea 3-{4-[(2,4- dimethoxyphenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-(4-{[2-(pyrrolidin-1- yl)phenyl]sulfamoyl}phenyl)urea 3-{4-[(3-methoxy-4- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 3-{4-[4-(4-nitrophenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 3-{4-[4-(2-chloro-4-fluorophenoxy)piperidine- 1-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 00 3-(4-{[4-chloro-2- (trifluoromethoxy)phenyl]sulfamoyl}phenyl)- 1-(pyridin-3-ylmethyl)urea 01 3-{4-[(4-chloro-3- methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- ylmethyl)urea 02 3-{4-[(2,3-dichlorophenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 03 3-(4-{[4-(propan-2- yl)benzenelsulfonyl}phenyl)-1-(pyridin-3- ylmethyl)urea 04 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-(4-{8- oxa-3-azabicyclo[3.2.1]octane-3- sulfonyl}phenyl)urea 05 2-fluoro-N-(propan-2-yl)-5-[(4-{[(pyridin-3- ylmethyl)carbamoyl]amino}benzene)sulfonyl] benzamide 06 3-(4-{[2-(2- hydroxyethoxy)phenyl]sulfamoyl}phenyl)-1- (pyridin-3-ylmethyl)urea 07 3-{4-[(2R,6S)-2,6-dimethylmorpholine-4- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 08 3-{4-[(4-fluoro-2- methoxybenzene)sulfonyl]phenyl}-1-(pyridin- 3-ylmethyl)urea 09 3-{4-[4-(3-chlorophenyl)piperazine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0 3-{4-[(2S)-2-ethylpiperidine-1- sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 1-(4-{[4-(morpholin-4- yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- ylmethyl)urea 1-{4-[(4-cyanobenzene)sulfonyl]phenyl}-3- (pyridin-3-ylmethyl)urea 3-{4-[(2-bromophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 3-{4-[(3,4-dimethylphenyl)sulfamoyl]phenyl}- 1-(pyridin-3-ylmethyl)urea 3-{4-[(2-iodophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea 1-{4-[2-(morpholin-4-yl)pyridine-3- sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 3-{4-[(3-fluorophenyl)sulfamoyl]phenyl}-1- (pyridin-3-ylmethyl)urea N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3- (trifluoromethoxy)phenyl]sulfamoyl}benzamide 1-[4-(piperazine-1-sulfonyl)phenyl]-3-(pyridin- 3-ylmethyl)urea 0 4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N- {imidazo[1,2-a]pyridin-6-ylmethyl}benzamide

(587) The following compounds are not compounds of the invention but are NAMPT inhibitors:

(588) ##STR00721##

(589) The disclosures in this application of all articles and references, including patents and patent applications are incorporated herein by reference.

EXAMPLES

(590) The invention is illustrated further by the following examples, which are not to be construed as limiting the invention in scope or spirit to the specific procedures described in them. Those having skill in the art will recognize that the starting materials may be varied and additional steps employed to produce compounds encompassed by the present inventions, as demonstrated by the following examples. In some cases, protection of certain reactive functionalities may be necessary to achieve some of the above transformations. In general, such need for protecting groups, as well as the conditions necessary to attach and remove such groups, will be apparent to those skilled in the art of organic synthesis. Unless otherwise specified, all reagents and solvents are of standard commercial grade and are used without further purification.

(591) The following are illustrative, but non-limiting, examples of certain embodiments of the present invention.

(592) Definitions used in the following Schemes and elsewhere herein are:

(593) CDCl.sub.3 deuterated chloroform δ chemical shift (ppm) DCM dichloromethane or methylene chloride DIEA N, N-diisopropylethylamine DMA N, N-dimethylacetamide DMAP N, N-dimethylpyridin-4-amine DMF dimethylformamide DMSO dimethylsulfoxide DMSO-d.sub.6 deuterated dimethylsulfoxide EDCI N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride EtOAc ethyl acetate EtOH ethanol GF/F glass microfiber filter .sup.1H NMR proton nuclear magnetic resonance HOAc acetic acid HATU 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate HOBT 1H-benzo[d][1,2,3]triazol-1-ol hydrate HPLC high pressure liquid chromatography MHz megahertz KOAc potassium acetate i-PrOH isopropanol LC-MS liquid chromatography/mass spectrometry (M+1) mass+1 m-CPBA w-chloroperbenzoic acid MeOH methanol N.sub.2 nitrogen NaHCO.sub.3 sodium bicarbonate MgSO.sub.4 magnesium sulfate SRB Sulforhodamine B colorimetric assay TEA triethylamine THE tetrahydrofuran TLC thin layer chromatography
Preparation of Compounds

(594) The compounds of the present invention can be prepared through numerous routes well-known to those skilled in the art of organic synthesis. By way of example, compounds of the present invention can be synthesized using the methods described below, together with synthetic methods known in the art of synthetic organic chemistry, or variations thereon as appreciated by those skilled in the art. Preferred methods include but are not limited to those methods described below.

(595) Compounds of the present invention urea-sulfonamide (IV) can be synthesized by following the steps outlined in Scheme 1.

(596) ##STR00722##

(597) Intermediate II can be obtained by treating I with phosgene, thiophosgene, carbonyldiimidazole, or other such activating group in an inert solvent such as dichloromethane, benzene, or toluene at temperatures ranging from −78° C. to 200° C. Intermediate V can be obtained by treating I with 4-nitrophenyl carbonochloridate in an inert solvent such as dichloromethane, benzene, or toluene at temperatures ranging from −78° C. to 200° C. The compound of present invention IV can be obtained by treating compound III with either II or V in an organic solvent at temperatures ranging from −78° C. to 200° C.

(598) Compounds of the present invention urea-sulfone (IV) can be synthesized by following the steps outlined in Scheme 2.

(599) ##STR00723##

(600) Intermediate II can be obtained by treating I with phosgene, thiophosgene, carbonyldiimidazole (or similar reagent) in an inert solvent such as dichloromethane, benzene, or toluene at temperatures ranging from −78° C. to 200° C. The compound of present invention IV can be obtained by treating intermediate II with III in an organic solvent at temperatures ranging from −78° C. to 200° C.

(601) The compound of present invention urea-sulfone IV can also be synthesized by following the steps outlined in Scheme 2A.

(602) ##STR00724##

(603) Intermediate VI can be obtained by treating III with V in an inert solvent such as dichloromethane and benzene at temperatures ranging from −78° C. to 200° C. Treatment of VI with agents such as NaBH.sub.4, NaI, or Na.sub.2S.sub.2O.sub.3 in a solvent such as water or THF at temperatures ranging from −78° C. to 200° C. gives intermediate VII. Compound IV can be obtained by treating VII and VIII with a suitable transition metal catalyst such as, but not limited to, Pd(PPh.sub.3).sub.4, palladium(II) acetate, or Cu(OAc).sub.2 in the presence of a base (eg: K.sub.2CO.sub.3, Cs.sub.2CO.sub.3, NRIR.sub.2R.sub.3, NaOR, KOR) in an inert solvent such as N, N-dialkylformamide, N, N-dialkylacetamide, or dichloromethane at temperatures ranging from −78° C. to 200° C.

(604) Those having skill in the art will recognize that the starting materials may be varied and additional steps may be employed to produce the compounds encompassed by the present inventions (as demonstrated by the following examples). Unless otherwise specified, all reagents and solvents are of standard commercial grade and are used without further purification.

(605) The disclosures in this application of all articles and references, including patents, are incorporated herein by reference.

(606) Preparation of Representative Urea-Sulfonamide and Urea SofoneAnalogues

(607) These examples illustrate the preparation of representative substituted urea-sulfonamide and urea-sulfone analogues.

Example 1

1-((5-fluoropyridin-3-yl)methyl)-3-(4-(piperidin-1-ylsulfonyl)phenyl)urea

(608) ##STR00725##

(609) Triphosgene (41 mg, 0.137 mmol) was dissolved in DCM (5 mL) and cooled to −10° C. under N.sub.2 atmosphere. To this cooled solution was added dropwise a mixture of 4-(piperidin-1-ylsulfonyl) aniline (100 mg, 0.416 mmol) and TEA (127 mg, 1.25 mmol) in DCM (5 mL). The mixture was stirred at −10° C. for 5 minutes and allowed to warn up to room temperature for 1 hour. A solution of 5-fluoropyridin-3-yl)methanamine (55 mg, 0.50 mmol) and TEA (127 mg, 1.25 mmol) in DCM (5 mL) was then added. The reaction mixture was stirred at room temperature for 16 hours. The mixture was diluted with DCM (25 mL), washed with brine (2×15 mL), dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The crude was purified by Biotage using 5% MeOH/DCM to afford the desired product as a white amorphous powder.

(610) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 9.23 (s, 1H), 8.36-8.48 (m, 2H), 7.50-7.68 (m, 5H), 6.95 (t, 1H), 4.36 (d, 2H), 2.75-2.90 (m, 4H), 1.48-1.75 (m, 4H), 1.38-1.42 (m, 2H) LC-MS: 393.04 (M+1).

Example 2

N-(naphthalen-1-yl)-4-(3-(pyridin-3-ylmethyl)ureido)benzenesulfonamide

(611) ##STR00726##

A: N-(naphthalen-1-yl)-4-nitrobenzenesulfonamide

(612) ##STR00727##

(613) To a cooled solution of naphthalen-1-amine (2000 mg, 13.97 mmol) in pyridine (45.0 mL) was added DMAP (171 mg, 1.4 mmol) and a solution of 4-nitrobenzene-1-sulfonyl chloride (3410 mg, 15.4 mmol) in pyridine (15.0 mL) at 0° C. The mixture was stirred at 0° C. for 15 min and heated to 80° C. for 16 h. After being cooled to room temperature, the mixture was acidified with 2M HCl, extracted with EtOAc (3×50 mL), washed several times with brine, dried over MgSO.sub.4 and concentrated in vacuo. The crude was purified by Combiflash using (5% EtOAc/hexanes) to afford the title compound.

(614) .sup.1H NMR (300 MHz, CD.sub.3OD): δ 7.21-7.38 (m, 6H), 7.68-7.85 (m, 4H), 8.15-8.20 (m, 2H).

(615) LC-MS: 329.14 (M+1).

B: 4-amino-N-(naphthalen-1-yl)benzenesulfonamide

(616) ##STR00728##

(617) A mixture of N-(naphthalen-1-yl)-4-nitrobenzenesulfonamide (3.9 g, 12 mmol) and tin (II) chloride dihydrate (13.5 g, 60 mmol) was refluxed in EtOAc (120 mL) for 2.5 h. After being cooled to room temperature, the mixture was treated with 2N NaOH (100 mL) and stirred for 1 h, then filtered through celite and washed with EtOAc. The combined filtrates were concentrated in vacuo. The crude was purified by Combiflash using (40% EtOAc/hexanes) to afford the title compound.

(618) .sup.1H NMR (300 MHz, CD.sub.3OD): δ 6.45-6.51 (m, 2H), 7.12-7.18 (m, 1H), 7.25-7.38 (m, 5H), 7.65 (d, 1H), 7.72-7.76 (m, 1H), 7.91-7.98 (m, 1H).

(619) LC-MS: 299.04 (M+1).

C: N-(naphthalen-1-yl)-4-(3-(pyridin-3-ylmethyl)ureido)benzenesulfonamide

(620) ##STR00729##

(621) A mixture of 4-amino-N-(naphthalen-1-yl)benzenesulfonamide (1000 mg, 3.35 mmol) and 4-nitrophenyl carbonochloridate (676 mg, 3.35 mmol) in DCM (35 mL) was stirred and cooled to 0° C. under N.sub.2 atmosphere, followed by addition of pyridine (1060 mg, 13.41 mmol). After being stirred for 10 minutes, pyridin-3-methanamine (1087 mg, 10.5 mmol) was added and the reaction mixture was stirred for 40 minutes at room temperature. The mixture was then diluted with DCM-MeOH (100 mL, 1:1), washed with water (5×40 mL), dried over MgSO.sub.4, and concentrated under vacuum. The residue was purified by flash chromatography using 10% MeOH/DCM to afford the title compound.

(622) .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ 4.21 (d, 2H), 6.82-6.88 (m, 1H), 7.10-7.16 (m, 1H), 7.32-7.55 (m, 8H), 7.58-7.68 (m, 2H), 7.85-7.89 (m, 1H), 8.05-8.10 (m, 1H), 8.40-8.46 (m, 1H), 8.52 (s, 1H), 9.08 (s, 1H), 10.08 (s, 1H).

(623) LC-MS: 433.25 (M+1).

Example 3

1-(4-(4,4-difluoropiperidin-1-ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

(624) ##STR00730##

A: 4-(3-(pyridin-3-ylmethyl)ureido)benzene-1-sulfonyl chloride

(625) ##STR00731##

(626) To an ice-cooled solution of 4-isocyanatobenzene-1-sulfonyl chloride (6 g, 27.6 mmol) in THF (250 mL) was added pyridin-3-ylmethanamine (2.79 mL, 27.6 mmol). The mixture was allowed to slowly warm to room temperature over 16 hours. The resulting precipitates were filtered off. The filtrate was concentrated to half volume and then treated with 200 mL of anhydrous ether. The resulting precipitates were filtered again, and the mother liquor was treated with 200 mL of anhydrous ether. The combined precipitates were collected as the title compound and used for next step without further purification.

(627) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 4.54 (s, 2H), 7.21 (br s, 1H), 7.33 (d, 2H), 7.47 (d, 2H), 8.08 (dd, 1H), 8.55 (dt, 1H), 8.50 (m, 2H), 9.24 (s, 1H).

B: 1-(4-(4,4-difluoropiperidin-1-ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

(628) ##STR00732##

(629) To an ice-cooled solution of 4,4-difluoropiperidine hydrochloride (2 g, 12.69 mmol) and triethylamine (4.72 mL, 33.8 mmol) in anhydrous dichloromethane (100 mL) was added 4-(3-(pyridin-3-ylmethyl)ureido)benzene-1-sulfonyl chloride (4.24 g, 8.46 mmol) in one portion. The mixture was stirred at 0° C. for 5 minutes and at room temperature for 16 hours. The mixture was diluted with methylene chloride and washed successively with saturated aqueous sodium bicarbonate, water, and saturated aqueous sodium chloride. The organic extract was dried over MgSO.sub.4, filtered and concentrated under vacuum. The crude was purified by Biotage using 10% MeOH/DCM to give the title compound.

(630) .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ 2.05 (m, 4H), 3.02 (t, 4H), 4.33 (d, 2H), 6.93 (t, 1H), 7.36 (dd, 1H), 7.64 (m, 4H), 7.71 (m, 1H), 8.46 (d, 1H), 8.53 (s, 1H), 9.24 (s, 1H);

(631) LC-MS: 410.40 (M+1)

(632) Anal. Calcd. for C.sub.18H.sub.20F.sub.2N.sub.4O.sub.3S: C, 52.67; H, 4.91; N, 13.65; F, 9.26; S, 7.81.

(633) Found: C, 52.44; H, 4.85; N, 13.49; F, 9.26; S, 7.53.

Example 4

1-(4-(4-morpholinopiperidin-1-ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

(634) ##STR00733##

A: 4-(l-(4-nitrophenylsulfonyl)piperidin-4-yl)morpholine

(635) ##STR00734##

(636) To an ice-cooled solution of 4-nitrobenzene-1-sulfonyl chloride (4 g, 18.05 mmol) in DCM (50 mL) was added a solution of 4-piperidin-4-yl)morpholine (3.69 g, 21.66 mmol) and TEA (3.77 mL, 27.1 mmol) in DCM (920 mL). The mixture was stirred at 0° C. for 15 minutes and at room temperature for 16 hours. The mixture was diluted with DCM, washed with 1M NaOH, brine, dried over Na.sub.2SO.sub.4 and concentrated in vacuo. The residue was treated with ether and the resulting precipitates were collected to give the title compound.

(637) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 8.32-8.39 (m, 2H), 7.89-7.97 (m, 2H), 3.84 (d, 2H), 3.60-3.71 (m, 4H), 2.15-2.50 (m, 6H), 2.09-2.19 (m, 1H), 1.85-1.92 (m, 2H), 1.50-1.70 (m, 2H)

(638) LC-MS: 356.06 (M+1).

B: 4-(4-morpholinopiperidin-1-ylsulfonyl)aniline

(639) ##STR00735##

(640) A mixture of 4-(1-(4-nitrophenylsulfonyl)piperidin-4-yl)morpholine (6.2 g, 17.44 mmol) and Raney Ni (1.02 g) in HOAc (50 mL) was hydrogenated for 16 h at 50 psi. The reaction mixture was filtered and the filtrate was concentrated. The residue was suspended in water (50 mL) and neutralized with saturated aqueous NaHCO.sub.3. The precipitate was collected and dried under reduced pressure to afford the title compound. .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ 7.21 (d, 2H), 6.61 (d, 2H), 6.03 (br s, 2H) 3.45-3.65 (m, 6H), 2.30-2.41 (m, 4H), 1.95-2.17 (m, 3H), 1.69-1.79 (m, 2H), 1.30-1.45 (m, 2H)

(641) LC-MS: 326.07 (M+1)

C: 1-(4-(4-morpholinopiperidin-1-ylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

(642) ##STR00736##

(643) The title compound was prepared following Example 1, substituting pyridin-3-ylmethanamine and 4-(4-morpholinopiperidin-1-ylsulfonyl)aniline for (5-fluoropyridin-3-yl)methanamine and 4-(piperidin-1-ylsulfonyl)aniline, respectively.

(644) .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ 9.17 (s, 1H), 8.51 (d, 1H), 8.44 (dd, 1H), 7.68 (dd, 1H), 7.52-7.69 (m, 4H), 7.30-7.38 (m, 1H), 6.89 (t, 1H), 4.32 (d, 2H), 3.45-3.59 (m, 6H), 2.30-2.41 (m, 4H), 2.00-2.17 (m, 3H), 1.69-1.79 (m, 2H), 1.30-1.44 (m, 2H)

(645) LC-MS: 460.21 (M+1).

Example 5

1-[(6-cyanopyridin-3-yl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea

(646) ##STR00737##

(647) Triphosgene (41 mg, 0.137 mmol) was dissolved in DCM (5 mL) and cooled to −10° C. under N.sub.2 atmosphere. To this cooled solution was added dropwise a mixture of 4-(piperidin-1-ylsulfonyl) aniline (100 mg, 0.416 mmol) and TEA (127 mg, 1.25 mmol) in DCM (5 mL). The mixture was stirred at −10° C. for 5 minutes and allowed to warm up to room temperature for 1 hour. A solution of 5-(aminomethyl)picolinonitrile HCl (85 mg, 0.50 mmol) and TEA (2.52 mmol) in DCM (5 mL) was then added. The reaction mixture was stirred at room temperature for 16 hours. The mixture was diluted with DCM (25 mL), washed with brine (2×15 mL), dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The crude was purified by Biotage using 5% MeOH/DCM to afford the desired product as a white amorphous powder (54 mg, 32.5% yield).

(648) .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ 8.63 (s, 1H), 7.79 (m, 2H), 7.60 (m, 2H), 7.48-7.54 (m, 3H), 6.10 (m, 1H), 4.50 (d, 2H), 2.93 (m, 4H), 1.61 (m, 4H), 1.41 (m, 2H)

(649) LC-MS: 400.01 (M+1).

Example 6

5-(Y3-(4-(piperidin-1-yl) phenyl) ureido) methyl) nicotinamide

(650) ##STR00738##

(651) To a solution of 1-((6-cyanopyridin-3-yl)methyl)-3-(4-(piperidin-1-ylsulfonyl)phenyl) urea (Example 5, 49 mg, 0.123 mmol) and potassium carbonate (33.9 mg, 0.245 mmol) in DMSO (5 mL) was added hydrogen peroxide (0.038 ml, 0.368 mmol). The mixture was stirred at room temperature for 16 hours, then was diluted with EtOAc and washed successively with 1M NaOH and brine. The extracts were dried over Na.sub.2SO.sub.4, filtered, concentrated in vacuo, and purified by Biotage using 10% MeOH/DCM to afford the title compound.

(652) .sup.1H NMR (300 MHz, DMSO-de): δ 9.00 (s, 1H), 8.42 (m, 2H), 7.62 (dd, 1H), 7.52-7.57 (m, 3H), 7.30-7.34 (m, 1H), 6.34 (t, 1H), 3.36-3.39 (m, 2H), 2.74-2.82 (m, 4H), 1.51 (m, 4H) 1.32 (m, 2H)

(653) LC-MS: 418.14 (M+1).

Example 7

tert-butyl N-{5-[({[4-(piperidine-1-sulfonyl)phenyl]carbamoyl}amino)methyl]pyridin-2-yl}carbamate

(654) ##STR00739##

(655) Triphosgene (122 mg, 0.412 mmol) was dissolved in DCM (5 mL) and cooled to −10° C. under N.sub.2 atmosphere. To this cooled solution was added dropwise a mixture of 4-(piperidin-1-ylsulfonyl) aniline (300 mg, 1.248 mmol) and TEA (2.52 mmol) in DCM (10 mL). The mixture was stirred at −10° C. for 5 minutes and allowed to warm up to room temperature for 1 hour. A solution tert-butyl 5-(aminomethyl)pyridin-2-ylcarbamate (293 mg, 1.311 mmol) and TEA (2.52 mmol) in DCM (5 mL) was then added. The reaction mixture was stirred at room temperature for 16 hours. The mixture was diluted with DCM (25 mL), washed with brine (2×15 mL), dried over MgSO.sub.4, filtered and concentrated under reduced pressure. The crude was purified by Biotage using 5% MeOH/DCM to afford the desired product as a white amorphous powder (200 mg, 32.7% yield).

(656) .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ 8.19 (s, 1H), 7.81 (m, 1H), 7.74 (s, 1H), 7.62 (m, 4H), 4.36 (s, 2H), 2.93 (t, 4H), 1.62 (m, 4H), 1.52 (s, 9H), 1.42 (m, 2H)

(657) LC-MS: 489.99 (M+1).

Example 8

1-((6-aminopyridin-3-yl) methyl-3-(4-(piperidine-1-ylsulfonyl) urea

(658) ##STR00740##

(659) A solution of tert-butyl 5-((3-(4-(piperidin-1-ylsulfonyl) phenyl)ureido)methyl)-pyridin-2-yl carbamate (Example 7, 87 mg, 0.178 mmol) in 20 ml of 1:1 TFA/DCM was stirred at room temperature for 16 hours. After removal of the solvent, the residue was purified by Biotage using 10% MeOH (2 M NH.sub.3)/DCM to afford the title compound.

(660) .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ 8.00 (s, 1H), 7.81 (m, 1H), 7.7.40-7.50 (m, 4H), 7.20-7.35 (dd, 1H), 6.38 (d, 1H). 5.77 (t, 1H), 4.18 (d, 2H), 2.85 (m, 4H), 1.53 (m, 4H), 1.32 (m, 2H)

(661) LC-MS: 390.02 (M+1).

Example 9

4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide

(662) ##STR00741##

A. N-(5-chloro-2-methoxyphenyl)-4-cyanobenzenesulfonamide

(663) ##STR00742##

(664) To a solution of 5-chloro-2-methoxyaniline (821 mg, 5.21 mmol, 1.05 eq) and DMAP (61 mg, 0.496 mmol, 0.1 eq) in pyridine (15 mL) cooled to 0° C. was added dropwise a solution of 4-cyanobenzene-1-sulfonyl chloride (1.0 g, 4.96 mmol, 1.0 eq) in pyridine (5 mL). The reaction was heated at 80° C. overnight then all volatiles were removed in vacuo. The resulting residue was dissolved in dichloromethane (20 mL), washed sequentially with 1N hydrochloric acid (20 mL), water (20 mL) and saturated sodium chloride (20 mL) then dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. The resulting residue was triturated twice with hexanes (10 mL) and once with diethyl ether (10 mL) and then dried under vacuum to afford N-(5-chloro-2-methoxyphenyl)-4-cyanobenzenesulfonamide (1.19 g, 74%) as a pale purple solid a portion of which was used without further purification in the subsequent step.

B. 4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)benzoic Acid

(665) ##STR00743##

(666) N-(5-chloro-2-methoxyphenyl)-4-cyanobenzenesulfonamide (0.387 mmol, 125 mg) was dissolved in 2-propanol (8.0 mL) and 1.8 M aqueous potassium hydroxide (6.5 mL, 11.6 mmol). The reaction was heated at 75° C. for 18 hours then cooled to ambient temperature and the 2-propanol removed on a rotary evaporator. The aqueous phase was extracted with ethyl acetate (5 mL) then the pH was adjusted to pH 2-3 with 2N hydrochloric acid and the aqueous phase was extracted thrice with ethyl acetate (10 mL). The combined organic phase was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford 4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)benzoic acid as a white solid (123 mg, 93%) which was used without further purification in the subsequent step.

C. 4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)-N-(imidazo[1,2-a]pyridin-6-ylmethyl)benzamide

(667) ##STR00744##

(668) To a solution of 4-(N-(5-chloro-2-methoxyphenyl)sulfamoyl)benzoic acid (116 mg, 0.340 mmol, 1 eq) in dry DMF (3 mL) was added imidazo[1,2-a]pyridin-7-ylmethanamine (50 mg, 0.340 mmol, 1 eq), followed by benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP, 194 mg, 0.374 mmol, 1.1 eq) and diisopropylethylamine (71 μL, 0.408 mmol, 1.2 eq). The resultant yellow solution stirred at ambient temperature for 4.5 hrs the all volatiles were removed under vacuum. The crude material was purified by flash column chromatography (eluting with 2-8% methanol/dichloromethane) to afford the title compound as a colorless oil which upon repeated trituration with Et.sub.2O gave a white solid (91 mg, 57%).

(669) LCMS MH.sup.+=471.1

(670) .sup.1H NMR (DMSO): δH 9.95 (s, 1H), 9.24 (t, 1H), 8.49 (s, 1H), 8.00 (2, 2H), 7.94 (s, 1H), 7.82 (d, 2H), 7.53 (m, 2H), 7.19 (m, 3H), 6.94 (d, 1H), 4.47 (d, 2H) and 3.48 (s, 3H).

Example 10

1-(4-(phenylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

(671) ##STR00745##

(672) A solution of triphosgene (84 mg, 0.283 mmol) in DCM (5.0 mL) was cooled to −10° C. under N.sub.2 atmosphere and was treated dropwise with a solution of 4-(phenylsulfonyl)aniline (200 mg, 0.857 mmol) and TEA (260 mg, 2.57 mmol) in DCM (5.0 mL). The mixture was stirred at −10° C. for 5 minutes, then at ambient temperature for 1 hour, whereupon this mixture was added to a solution of pyridin-3-ylmethanamine (97 mg, 0.90 mmol) and TEA (260 mg, 2.57 mmol) in DCM (5.0 mL). The mixture was stirred for 16 hours at ambient temperature, and then was diluted with DCM (25 mL), washed with brine (2×15 mL), and dried over MgSO.sub.4. After filtration, the filtrate was concentrated under vacuum and purified by Biotage using 5% MeOH/DCM to afford the title compound.

(673) .sup.1H NMR (300 MHz, DMSO-de): δ 4.29 (d, 2H), 6.90 (t, 1H), 7.26-7.35 (m, 1H), 7.54-7.70 (m, 6H), 7.65-7.80 (m, 2H), 7.81-7.90 (m, 2H), 8.40-8.45 (m, 1H), 8.49-8.55 (m, 1H), 9.21 (s, 1H). LC-MS: 368.15 (M+H).

Example 11

1-(pyridin-3-ylmethyl)-3-(4-(2-(trifluoromethoxy)phenylsulfonyl)phenyl)urea

(674) ##STR00746##

A: 4-(3-(pyridin-3-ylmethyl)ureido)benzene-1-sulfonyl chloride

(675) ##STR00747##

(676) 4-Isocyanatobenzene-1-sulfonyl chloride (6 g, 27.6 mmol) was taken up in THF (250 mL) and cooled to 0° C., whereupon pyridin-3-ylmethanamine (2.79 mL, 27.6 mmol) was added and the resulting mixture was allowed to warm slowly to ambient temperature over 16 hours. The mixture was filtered and the filtrate was concentrated to half its original volume and was treated with 200 mL of anhydrous Et.sub.2O. The precipitates were again filtered off and the filtrate was treated with 200 mL of anhydrous Et.sub.2O. The resulting precipitates were collected by vacuum filtration and used in the next step without further purification.

(677) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 4.54 (s, 2H), 7.21 (br s, 1H), 7.33 (d, 2H), 7.47 (d, 2H), 8.08 (dd, 1H), 8.55 (dt, 1H), 8.50 (m, 2H), 9.24 (s, 1H).

B: Ammonium 4-(3-(pyridin-3-ylmethyl)ureido)benzenesulfinate

(678) ##STR00748##

(679) 4-(3-(Pyridin-3-ylmethyl)ureido)benzene-1-sulfonyl chloride (3.99 g, 12.25 mmol) was added to a solution of sodium sulfite (6.18 g, 49.0 mmol) and sodium bicarbonate (6.17 g, 73.5 mmol) in water (175 mL), and the resulting mixture was stirred at 80° C. for 3 hours. The mixture was then concentrated to dryness under reduced pressure, and the resulting solids were triturated with hot DMF (100 mL) and the solids filtered off. The solvent was then removed under reduced pressure, and the resulting residue was triturated with hot DCM (100 mL) and the off-white crystalline solids were collected by vacuum filtration. The solids were purified by SCX ion-exchange column (eluting with 5:1 CH.sub.3CN/NH.sub.4OH) to afford the title compound.

(680) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 4.28 (d, 2H), 7.35 (m, 6H), 7.70 (dt, 1H), 8.42 (dd, 1H), 8.51 (d, 1H), 9.23 (br s, 1H). LC-MS: 292.01 (M+1)

C: 1-(pyridin-3-ylmethyl)-3-(4-(2-(trifluoromethoxy)phenylsulfonyl)phenyl)urea

(681) ##STR00749##

(682) A mixture of ammonium 4-(3-(pyridin-3-ylmethyl)ureido)benzenesulfinate (30.8 mg, 0.1 mmol), 2-(trifluoromethyl)phenylboronic acid (25.7 mg, 0.125 mmol), copper(II) acetate (22.7 mg, 0.125 mmol), and TEA (0.063 mL, 0.45 mmol) in DMSO (1.5 mL) was heated at 60° C. for 16 hours. The mixture was cooled to ambient temperature and was partitioned between EtOAc and brine. The organic layer was separated, dried (MgSO.sub.4), concentrated, and purified by PTLC (100% EtOAc) to afford the title compound.

(683) .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ 9.26 (s, 1H), 8.50 (d, 1H), 8.44-8.42 (m, 1H), 8.17-8.14 (m, 1H), 7.84-7.78 (m, 1H), 7.75-7.59 (m, 6H), 7.52-7.49 (m, 1H), 7.35-7.31 (m, 1H), 6.93 (t, 1H), 4.30 (d, 2H). LC-MS: 452.09 (M+1)

Example 12

1-(3-aminobenzyl)-3-(4-(phenylsulfonyl)phenyl)urea

(684) ##STR00750##

A: tert-butyl 3-((3-(4-(phenylsulfonyl)phenyl)ureido)methyl)phenylcarbamate

(685) ##STR00751##

(686) The title compound was prepared according to Example 1, substituting tert-butyl 3-(aminomethyl) phenylcarbamate for pyridin-3-ylmethanamine.

(687) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 7.82-7.89 (m, 2H), 7.70-7.76 (m, 2H), 7.42-7.58 (m, 4H), 7.38 (d, 2H), 7.29 (s, 1H), 7.10-7.16 (m, 2H), 6.62-6.89 (m, 1H), 6.65 (s, 1H), 5.52 (t, 1H), 4.22 (d, 2H), 1.47 (s, 9H) LC-MS: 482.08 (M+H).

B: 4-(3-(pyridin-3-ylmethyl)ureido)benzene-1-sulfonyl chloride

(688) ##STR00752##

(689) A solution of tert-butyl 3-((3-(4-(phenylsulfonyl)phenyl)ureido)methyl)phenyl-carbamate (390 mg, 0.810 mmol) and TFA (5 mL, 64.9 mmol) in DCM (10 mL) was stirred at ambient temperature for 16 hours. The mixture was concentrated and partitioned between DCM and saturated NaHCO.sub.3. The organic layer was washed with brine (2×15 mL), dried over Na.sub.2SO.sub.4, filtered, and concentrated. The residue was purified by Biotage using 10% MeOH/DCM to offer the title compound.

(690) .sup.1H NMR (300 MHz, DMSO-de): δ 9.21 (s, 1H), 8.49-8.55 (m, 2H), 8.40-8.45 (m, 2H), 7.81-7.90 (m, 5H), 6.90 (t, 1H), 6.69 (t, 1H), 6.40-6.50 (m, 3H), 5.41 (br, s, 2H), 4.14 (d, 2H) LC-MS: 382.28 (M+H).

Example 13

1-(4-(4-chlorophenylthio)phenyl)-3-(pyridin-3-ylmethyl)urea

(691) ##STR00753##

A: 4-(4-chlorophenylthio)aniline

(692) ##STR00754##

(693) A solution of (4-chlorophenyl)(4-nitrophenyl)sulfane (1.71 g, 6.44 mmol) in 2:1 MeOH/EtOAc (75 mL) was treated with platinum(IV) oxide (100 mg) and the resulting mixture was placed under an atmosphere of hydrogen (45 psi) for 16 hours. The mixture was filtered through GF/F paper, rinsed with MeOH, and concentrated under reduced pressure to afford the title compound as a yellow solid.

(694) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 7.32-7.27 (m, 2H), 7.19-7.14 (m, 2H), 7.05-7.01 (m, 2H), 6.70-6.65 (m, 2H), 3.83 (s, 2H).

B: 1-(4-(4-chlorophenylthio)phenyl)-3-(pyridin-3-ylmethyl)urea

(695) ##STR00755##

(696) The title compound was prepared according to Example 1, substituting 4-(4-chlorophenylthio)aniline for 4-(phenylsulfonyl)aniline.

(697) .sup.1H NMR (DMSO-d.sub.6): δ 8.90 (s, 1H), 8.51 (d, 1H), 8.45-8.43 (m, 1H), 7.71-7.67 (m, 1H), 7.51-7.46 (m, 2H), 7.37-7.31 (m, 5H), 7.11-7.06 (m, 2H), 6.81 (t, 1H), 4.30 (d, 2H).

C. 1-(4-(4-chlorophenylthio)phenyl)-3-(pyridin-3-ylmethyl)urea

(698) ##STR00756##

(699) A solution of 1-(4-(4-chlorophenylthio)phenyl)-3-(pyridin-3-ylmethyl)urea (50 mg, 0.135 mmol) in 10:1 DCM:MeOH (3.3 mL) was treated with m-CPBA (2.0 equiv), and the solution was stirred for 16 hours at ambient temperature. The mixture was then diluted with saturated NaHCO.sub.3 and DCM and the layers separated. The organic layer was dried over MgSO.sub.4 and purified by PTLC (6% MeOH/DCM) to afford the title compound.

(700) .sup.1H NMR (300 MHz, DMSO-d.sub.6): § 9.24 (s, 1H), 8.49 (s, 1H), 8.43-8.42 (m, 1H), 7.88 (d, 2H), 7.79 (d, 2H), 7.68-7.58 (m, 5H), 7.35-7.31 (m, 1H), 6.92 (t, 1H), 4.30 (d, 2H). LC-MS: 402.00 (M+1)

Example 14

1-((6-(dimethylamino)pyridin-3-yl)methyl)-3-(4-(phenylsulfonyl)phenyl)urea

(701) ##STR00757##

A: 6-(dimethylamino)nicotinonitrile

(702) ##STR00758##

(703) In a sealed tube, 6-chloronicotinonitrile (510 mg, 3.68 mmol) was taken up in DMF (4 mL) and dimethylamine (4.0 mL of a 2.0M THF solution) and DIEA (3.0 mL, 17.18 mmol) were added. The mixture was heated to 140° C. for 17 hours, and was then diluted with EtOAc and washed with brine (3×) and dried (MgSO.sub.4). After filtration and concentration, the residue was purified by Biotage SP1 (100% MeOH/DCM/NH.sub.3) to afford the title compound as a pale yellow solid.

(704) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 8.40 (d, 1H), 7.60-7.56 (m, 1H), 6.49-6.46 (m, 1H), 3.15 (s, 6H).

B: 5-(aminomethyl)-N,N-dimethylpyridin-2-amine

(705) ##STR00759##

(706) A solution of 6-(dimethylamino)nicotinonitrile (506 mg, 3.44 mmol) in 2:1 2N NH.sub.3 (75 mL) was treated with Raney Nickel and placed under a 40 psi atmosphere of hydrogen for 16 hours. The mixture was then carefully filtered through Celite (caution: to minimize danger of fire, do not allow solids to become dry), the filtrate concentrated to dryness, and purified by Biotage SP1 (DCM/MeOH/NH.sub.3). The concentrated fractions were then triturated with Et.sub.2O to afford the title compound as a white solid.

(707) .sup.1H NMR (300 MHz, DMSO-de): δ 7.97-7.94 (m, 1H), 7.48-7.37 (m, 1H), 6.57 (d, 1H), 3.95 (d, 2H), 3.55 (br s, 2H), 2.96 (s, 6H).

C: 1-((6-(dimethylamino)pyridin-3-yl)methyl)-3-(4-(phenylsulfonyl)phenyl)urea

(708) ##STR00760##

(709) The title compound was prepared according to Example 1, substituting 5-(aminomethyl)-N,N-dimethylpyridin-2-amine for pyridin-3-ylmethanamine.

(710) .sup.1H NMR (300 MHz, DMSO-d6): δ 9.05 (s, 1H), 7.99 (d, 1H), 7.90-7.86 (m, 2H), 7.77 (d, 2H), 7.65-7.55 (m, 5H), 7.44-7.41 (m, 1H), 6.66 (t, 1H), 6.57 (d, 1H), 4.10 (d, 2H), 2.96 (s, 6H). LC-MS: 411.06 (M+1)

Example 15

1-(4-(4-bromophenylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

(711) ##STR00761##

A: (4-bromophenyl)(4-nitrophenyl)sulfane

(712) ##STR00762##

(713) A solution of 4-bromobenzenethiol (4.97 g, 26.3 mmol) in DMF (50 mL) was cooled to 0° C. and treated with K.sub.2CO.sub.3 (4.3 g, 31.1 mmol). After addition was complete, the solution was warmed to ambient temperature over 15 minutes and then 1-fluoro-4-nitrobenzene (2.62 mL, 24.70 mmol) was added. The mixture was heated to 80° C. for 16 hours, and was then poured onto ice and diluted with EtOAc. The layers were separated and the organic layer was washed successively with saturated NaHCO.sub.3 and brine (2×). The organics were dried over MgSO.sub.4, filtered, and concentrated to afford the title compound as a yellow solid.

(714) .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ 8.18-8.13 (m, 2H), 7.87-7.84 (m, 2H), 7.53-7.41 (m, 2H), 7.31-7.27 (m, 2H).

B: 4-bromo-2-(4-nitrophenylsulfonyl)benzene

(715) ##STR00763##

(716) A solution of (4-bromophenyl)(4-nitrophenyl)sulfane (3.942 g, 12.71 mmol) in CHCl.sub.3 (40 ml) was cooled in an ice bath and treated with m-CPBA (2.2 equiv) portionwise. The mixture was allowed to warm slowly to ambient temperature over 16 hours, then the mixture was filtered through GF/F paper and the filtrate washed with IN NaOH and brine. The organics were dried over MgSO.sub.4, filtered, and concentrated to the crude solid. The solid can be triturated (if desired) with DCM and collected by vacuum filtration to afford the title compound.

(717) .sup.1H NMR (300 MHz, DMSO-de): δ 8.42-8.36 (m, 4H), 8.18-8.13 (m, 2H), 7.87-7.84 (m, 2H).

C: 4-(2-bromophenylsulfonyl)aniline

(718) ##STR00764##

(719) A mixture of 1-bromo-4-(4-nitrophenylsulfonyl)benzene (1.57 g, 4.59 mmol) and tin(II) chloride dihydrate (4.35 g, 22.94 mmol) was heated in EtOH (40 mL) for 2 hours at 70° C. The volatiles were removed under reduced pressure, and the residue was taken up in EtOAc (100 mL) and 2N NaOH (40 mL). The mixture was stirred vigorously for 1 hour, then filtered through Celite. The organic layer was separated, dried over MgSO.sub.4, and purified by Biotage SP1 to afford the title compound.

(720) .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ d 7.78-7.71 (m, 4H), 7.52 (d, 2H), 6.59 (d, 2H), 6.22 (s, 2H).

D: 1-(4-(4-bromophenylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

(721) ##STR00765##

(722) The title compound was prepared according to Example 1, substituting 4-(4-bromophenylsulfonyl)aniline for 4-(phenylsulfonyl)aniline.

(723) .sup.1H NMR (300 MHz, DMSO-de): δ 9.26 (s, 1H), 8.50 (d, 1H), 8.44-8.42 (m, 1H), 7.83-7.70 (m, 6H), 7.69-7.65 (m, 1H), 7.62-7.58 (m, 2H), 7.35-7.31 (m, 1H), 6.93 (t, 1H), 4.30 (d, 2H). LC-MS: 447.95 (M+1).

Example 16

1-[(6-aminopyridin-3-yl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea

(724) ##STR00766##

A: tert-butyl 5-((3-(4-(phenylsulfonyl)phenyl)ureido)methyl)pyridin-2-ylcarbamate

(725) ##STR00767##

(726) A solution of 4-phenylsulfonylaniline (1.5 g, 6.43 mmol) in EtOAc (10 mL) was added dropwise over 30 minutes to a solution of phosgene (6 ml, 20% in Toluene) in toluene (5 mL), and was then heated to reflux for 5 hours. The volatiles were removed under reduced pressure, and DCM (50 mL), tert-butyl 5-(aminomethyl) pyidin-2-yl carbamate (1.507 g, 6.75 mol), and DIEA (4 mL) were added to the residue. The mixture was stirred at ambient temperature for 16 hours, then was diluted with DCM and washed with saturated sodium bicarbonate. The organics were dried over MgSO.sub.4, concentrated, and purified by Biotage SP1 to afford the title compound.

(727) .sup.1H NMR (300 MHz, DMSO-d.sub.6): δ 9.69 (s, 1H), 9.15 (s, 1H), 8.14 (s, 1H), 7.87 (dd, 2H), 7.78 (m, 2H), 7.70-7.73 (m, 1H), 7.57-7.66 (m, 6H), 6.81 (t, 1H), 4.21 (d, 2H), 1.44 (s, 9H).

B: 1-[(6-aminopyridin-3-yl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea

(728) ##STR00768##

(729) The title compound was prepared according to Example 3B, substituting tert-butyl 5-((3-(4-(phenylsulfonyl)phenyl)ureido)methyl)pyridin-2-ylcarbamate for tert-butyl 3-((3-(4-(phenylsulfonyl)phenyl)ureido)methyl)phenyl-carbamate.

(730) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 9.03 (s, 1H), 7.86-7.89 (m, 2H), 7.78-7.81 (m, 3H), 7.58-7.77 (m, 5H), 7.27-7.31 (dd, 1H), 6.63 (t, 1H), 6.37 (d, 1H), 5.81 (s, 2H), 4.06 (d, 2H)

(731) LC-MS: 383.13 (M+1).

Example 17

1-(4-(phenylsulfonyl)phenyl)-3-(pyridin-3-ylmethyl)urea

(732) ##STR00769##

(733) A mixture of (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (37.8 mg, 0.065 mmol), Cs.sub.2CO.sub.3 (319 mg, 0.980 mmol), tri(dibenzylideneacetone)dipalladium(O) (29.9 mg, 0.033 mmol), sodium 4-methylbenzenesulfinate (140 mg, 0.784 mmol), l-(4-bromophenyl)-3-(pyridine-3-ylmethyl)urea (200 mg, 0.653 mg), and tertrabutylammonium iodide (290 mg, 0.784 mmol) in toluene (10 mL) was heated at 100° C. for 16 hours. The mixture was cooled to ambient temperature and DCM was added. The organic layer was washed successively with water and brine, dried over MgSO.sub.4, concentrated, and purified by Biotage SP1 to afford the title compound.

(734) .sup.1H NMR (300 MHz, CDCl.sub.3): δ 8.47 (s, 1H), 8.44 (d, 1H), 8.32 (s, 1H), 7.69-7.74 (m, 4H), 7.63 (d, 1H), 7.47-7.51 (dd, 2H), 7.26-7.46 (m, 3H), 6.12 (s, 1H), 4.38 (d, 2H), 2.37 (s, 3H) LC-MS: 382.15 (M+1).

Example 18

N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(phenylsulfonyl)benzamide

(735) ##STR00770##

A. 4-sulfonylbenzonitrile

(736) ##STR00771##

(737) 4-fluorobenzonitrile (46.5 mmol, 5.63 g) and sodium benzenesulfinate (51.1 mmol, 8.39 g) were dissolved in DMSO (35.8 mL). The reaction was heated at 130° C. for 48 hours then cooled to ambient temperature and poured onto ice. The precipitated solids were collected by suction filtration, washed with water and then dried under vacuum to afford 4-sulfonylbenzonitrile (11.2 g) a portion of which was used in the subsequent step without further purification.

B. 4-phenylsulfonylbenzoic Acid

(738) ##STR00772##

(739) 4-sulfonylbenzonitrile (4.11 mmol, 1.0 g) was dissolved in 2-propanol (88 mL) and 1.0 M aqueous potassium hydroxide (140 mL). The reaction was heated at 75° C. for 18 hours then cooled to ambient temperature and the 2-propanol removed on a rotary evaporator. The aqueous phase was extracted with ethyl acetate (70 mL) then the pH was adjusted to pH 2-3 with 6N hydrochloric acid and the aqueous phase was extracted thrice with ethyl acetate (100 mL). The combined organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to afford 4-phenylsulfonylbenzoic acid as a white solid (1.01 g) a portion of which was used without further purification in the subsequent step.

C. N-(imidazo[1,2-a]pyridin-6-ylmethyl)-4-(phenylsulfonyl)benzamide

(740) ##STR00773##

(741) Oxalyl chloride (66.7 μL, 0.763 mmol) was added dropwise to a solution of 4-phenylsulfonylbenzoic acid (100 mg, 0.381 mmol) in dichloromethane (3.81 mL) at 0° C. The reaction stirred for 2 hours then all volatiles were removed under vacuum. The crude 4-phenylsulfonylbenzoyl chloride was re-dissolved in dichloromethane (3.8 mL) then imidazo[1,2-a]pyridin-7-ylmethanamine hydrochloride (77 mg, 0.419 mmol) and triethylamine (117 μL, 0.839 mmol) were added successively. The reaction stirred for 1 hour at ambient temperature then saturated sodium bicarbonate (3.8 mL) was added. The organic phase was separated, washed with saturated sodium chloride (3 mL), dried over anhydrous magnesium sulfate and concentrated in vacuum. The resulting residue was purified by flash column chromatography (eluting with 5% methanol/dichlormethane) to afford the title compound as a white solid (73 mg, 49%).

(742) LCMS MH.sup.+=391.9

(743) .sup.1H NMR (MeOD): 5H 8.29 (s, 1H), 8.00 (s, 4H), 7.93 (d, 2H), 7.65-7.48 (m, 6H), 7.27 (dd, 1H) and 4.50 (s, 2H).

(744) Assays:

Assay Example 1

(745) Biochemical Inhibition Assay

(746) NAMPT Protein Purification

(747) Recombinant His-tagged NAMPT was produced in E. coli cells, purified over a Ni column, and further purified over a size-exclusion column by XTAL Biostructures.

(748) The NAMPT Enzymatic Reaction

(749) The NAMPT enzymatic reactions were carried out in Buffer A (50 mM Hepes pH 7.5, 50 mM NaCl, 5 mM MgCl.sub.2, and 1 mM THP) in 96-well V-bottom plates. The compound titrations were performed in a separate dilution plate by serially diluting the compounds in DMSO to make a 100× stock. Buffer A (89 μL) containing 33 nM of NAMPT protein was added to 1 μL of 100× compound plate containing controls (e.g. DMSO or blank). The compound and enzyme mix was incubated for 15 minutes at room temperature, then 10 μL of 10× substrate and co-factors in Buffer A were added to the test well to make a final concentration of 1 μM NAM, 100 μM 5-Phospho-D-ribose 1-diphosphate (PRPP), and 2.5 mM Adenosine 5′-triphosphate (ATP). The reaction was allowed to proceed for 30 minutes at room temperature, then was quenched with the addition of 11 μL of a solution of formic acid and L-Cystathionine to make a final concentration of 1% formic acid and 10 μM L-Cystathionine. Background and signal strength was determined by addition (or non-addition) of a serial dilution of NMN to a pre-quenched enzyme and cofactor mix.

(750) Quantification of NMN

(751) A mass spectrometry-based assay was used to measure the NAMPT reaction product (NMN) and the internal control (L-Cystathionine). NMN and L-Cystathionine were detected using the services of Biocius Lifesciences with the RapidFire system. In short, the NMN and L-Cystathionine are bound to a graphitic carbon cartridge in 0.1% formic acid, eluted in 30% acetonitrile buffer, and injected into a Sciex 4000 mass spectrometer. The components of the sample were ionized with electrospray ionization and the positive ions were detected. The Q1 (parent ion) and Q3 (fragment ion) masses of NMN were 334.2 and 123.2, respectively. The Q1 and Q3 for L-Cystathionine were 223.1 and 134.1, respectively. The fragments are quantified and the analyzed by the following method.

(752) % Inhibitions are Determined Using this Method.

(753) First the NMN signal is normalized to the L-Cystathionine signal by dividing the NMN signal by the L-Cystathionine signal for each well. The signal from the background wells are averaged and subtracted from the test plates. The compound treated cells re then assayed for % inhibition by using this formula.
% Inh=100−100*x/y
wherein x denotes the average signal of the compound treated wells and y denotes the average signal of the DMSO treated wells.
IC.sub.50s are Determined Using Excel and this Formula.
IC50=10{circumflex over ( )}(LOG 10(X)+(((50-% Inh at Cmpd Concentration 1)/(XX−YY)*(LOG 10(X)−LOG 10(Y))))
wherein X denotes the compound concentration 1, Y denotes the compound concentration 2, XX denotes the % inhibition at compound concentration 1 (X), and YY denotes the % inhibition at compound concentration 2 (Y).

(754) The NAMPT-inhibitor compounds of thi sinvetnion have IC50 values that are under 10 μM, preferably under 1 μM, more preferably under 0.1 μM, and most preferably under 0.01 μM. Results for representative compounds are provided in Table 3 below.

Assay Example 2

(755) In-Vitro Cell Proliferation Assay

(756) A2780 cells were seeded in 96-well plates at 1×10.sup.3 cells/well in 180 μL of culture medium (10% FBS, 1% Pen/Strep Amphotecricin B, RPMI-1640) with and without the addition of either (3-nicotinamide mononucleotide (NMN) or nicotinamide (NAM). After overnight incubation at 37° C. and 5% CO.sub.2, the compound titrations were performed in a separate dilution plate by serially diluting the compounds in DMSO to make a 1000× stock. The compounds were then further diluted to 10× final concentration in culture media, whereupon 20 μL of each dilution was added to the plated cells with controls (e.g. DMSO and blank) to make a final volume of 200 μL. The final DMSO concentration in each well was 0.1%. The plates were then incubated for 72 hours at 37° C. in a 5% CO.sub.2 incubator. The number of viable cells was then assessed using sulforhodamine B (SRB) assay. Cells were fixed at 4° C. for 1 hour with the addition of 50 μL 30% trichloroacetic acid (TCA) to make a final concentration of 6% TCA. The plates were washed four times with H.sub.2O and allowed to dry for at least 1 hour, whereupon 100 μL of a 4% SRB in 1% acetic acid solution was added to each well and incubated at room temperature for at least 30 minutes. The plates were then washed three times with 1% acetic acid, dried, and treated with 100 μL of 10 mM Tris-Base solution. The plates were then read in a microplate reader at an absorbance of 570 nm. Background was generated on a separate plate with media only.

(757) Method for Determining % Inhibition

(758) First, the signals from the background plate are averaged, then the background was subtracted from the test plates. The compound-treated cells were then assayed for % inhibition by using the following formula:
% Inh=100−100*x/y
wherein x denotes the average signal of the compound-treated cells and y denotes the average signal of the DMSO-treated cells.
Formula for Determining IC.sub.50 Values:
IC50=10{circumflex over ( )}(LOG 10(X)+(((50−% Inh at Cmpd Concentration 1)/(XX−YY)*(LOG 10(X)−LOG 10(Y))))

(759) wherein X denotes the compound concentration 1, Y denotes the compound concentration 2, XX denotes the % inhibition at compound concentration 1 (X), and YY denotes the % inhibition at compound concentration 2 (Y).

(760) Specificity of Cytotoxicity.

(761) Inhibition of NAMPT could be reversed by the addition of NAM or NMN. The specificity of the compounds were determined via cell viability assay in the presence of the compound and either NAM or NMN. Percent inhibitions were determined using the method given above.

(762) The NAMPT-inhibitor compounds of this invention have IC50 values that are preferably under 1 μM, more preferably under 0.1 μM, and most preferably under 0.01 μM. Most preferable compounds of this invention are compounds that have both the enzymatic IC50-value and the A2780 IC50-value under under 10 μM, preferably under 1 μM, more preferably under 0.1 μM, and most preferably under 0.01 μM.

(763) Results for representative compounds is provided in Table 3 below.

(764) TABLE-US-00003 TABLE 3 Biochem A2780 Compound IC50 uM IC50 uM (3S)-N,N-diethyl-1-[(4-{[(pyridin-3- 0.006 0.025 ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-3-carboxamide 1-(4-{[(1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl]sulfamoyl}phenyl)-3-(pyridin- 0.007 0.046 3-ylmethyl)urea 1-(4-{[2-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- 0.005 0.011 ylmethyl)urea 1-(4-{[2-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- 0.004 0.018 ylmethyl)urea 1-(4-{[3-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- 0.006 0.103 ylmethyl)urea 1-(4-{[4-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- 0.005 0.173 ylmethyl)urea 1-(4-{[4-(piperidin-1-yl)phenyl]sulfamoyl}phenyl)-3-(pyridin-3- 0.004 0.054 ylmethyl)urea 1-(4-{2-azabicyclo[2.2.1]heptane-2-sulfonyl}phenyl)- 0.01 0.236 3-(pyridin-3-ylmethyl)urea 1-(4-{2-oxa-8-azaspiro[4.5]decane-8-sulfonyl}phenyl)- 0.005 0.089 3-(pyridin-3-ylmethyl)urea 1-(4-{3-[(2-oxopyrrolidin-1-yl)methyl]piperidine-1-sulfonyl}phenyl)-3- 0.003 0.143 (pyridin-3-ylmethyl)urea 1-(4-{3-azaspiro[5.5]undecane-3-sulfonyl}phenyl)- 0.011 0.145 3-(pyridin-3-ylmethyl)urea 1-(4-{3-azatricyclo[7.3.1.0.sup.5,.sup.13]trideca-1(13),5,7,9,11- 0.002 0.026 pentaene-3-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 1-(4-{3-oxa-8-azabicyclo[3.2.1]octane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 0.012 0.287 1-(4-{4-[(2-oxopyrrolidin-1-yl)methyl]piperidine-1-sulfonyl}phenyl)-3- 0.002 0.078 (pyridin-3-ylmethyl)urea 1-(4-{4-[(furan-2-yl)carbonyl]piperazine-1-sulfonyl}phenyl)-3-(pyridin-3- 0.004 0.168 ylmethyl)urea 1-(4-{4-[2-(morpholin-4-yl)-2-oxoethyl]piperazine-1-sulfonyl}phenyl)-3- 0.004 0.135 (pyridin-3-ylmethyl)urea 1-(4-{4-[2-oxo-2-(piperidin-1-yl)ethyl]piperazine-1-sulfonyl}phenyl)-3- 0.009 0.021 (pyridin-3-ylmethyl)urea 1-(4-{4-[2-oxo-2-(pyrrolidin-1-yl)ethyl]piperazine-1-sulfonyl}phenyl)-3- 0.004 0.099 (pyridin-3-ylmethyl)urea 1-(4-{4-[3-(morpholin-4-yl)propyl]piperazine-1-sulfonyl}phenyl)-3- 0.003 0.024 (pyridin-3-ylmethyl)urea 1-(4-{8-azabicyclo[3.2.1]octane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 0.004 0.064 1-(4-{8-azaspiro[4.5]decane-8-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 0.004 0.343 1-(4-{8-oxa-3-azabicyclo[3.2.1]octane-3-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 0.007 0.029 1-(pyridin-3-ylmethyl)-3-(4-{[(1R,2R,3R,5S)-2,6,6- 0.08 0.091 trimethylbicyclo[3.1.1]heptan-3-yl]sulfamoyl}phenyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[2- 0.0012 0.007 (trifluoromethoxy)phenyl]sulfamoyl}phenyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[3- 0.006 (trifluoromethyl)phenyl]sulfamoyl}phenyl)urea 1-(pyridin-3-ylmethyl)-3-[4-(1H-pyrrole-1-sulfonyl)phenyl]urea 0.019 1.788 1-(pyridin-3-ylmethyl)-3-{4-[(3S)-3-(trifluoromethyl)piperidine-1- 0.003 0.029 sulfonyl]phenyl}urea 1-(pyridin-3-ylmethyl)-3-{4-[3-(trifluoromethyl)piperidine-1- 0.003 0.026 sulfonyl]phenyl}urea 1-[(3,4-difluorophenyl)methyl]-3-[4- 0.092 29 (piperidine-1-sulfonyl)phenyl]urea 1-[(4-{[(pyridin-3-ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-4-carboxamide 0.01 1.481 1-[(4-fluorophenyl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea 0.245 25 1-[(6-isocyanopyridin-3-yl)methyl]-3-[4-(piperidine-1-sulfonyl)phenyl]urea 1.734 >30 1-[3-(piperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea >30 >30 1-[4-(2,6-dimethylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.011 0.164 1-[4-(3,4-dihydro-2H-1,4-benzoxazine-4-sulfonyl)phenyl]-3-(pyridin-3- 0.01 0.459 ylmethyl)urea 1-[4-(3,5-dimethylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3- 0.006 0.014 ylmethyl)urea 1-[4-(4,4-difluoropiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.025 0.299 1-[4-(4-{[(2R)-oxolan-2-yl]carbonyl[piperazine-1-sulfonyl)phenyl]-3- 0.008 0.030 (pyridin-3-ylmethyl)urea 1-[4-(4-benzyl-1,4-diazepane-1-sulfonyl)phenyl]-3-(pyridin-3- 0.005 0.137 ylmethyl)urea 1-[4-(4-phenylpiperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.005 1-[4-(4-phenylpiperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.003 1-[4-(cycloheptylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.003 0.080 1-[4-(cyclohexylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.001 0.204 1-[4-(decahydroquinoline-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.011 0.014 1-[4-(dibenzylsulfamoyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.0008 0.0003 1-[4-(morpholine-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.023 1.35 1-[4-(piperidine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.011 0.167 1-{4-[(1-phenylcyclopentyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.029 0.180 1-{4-[(1R)-3-oxo-3H-spiro[2-benzofuran-1,3′-pyrrolidine]-1′- 0.005 0.041 ylsulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 1-{4-[(2-phenylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.003 0.047 1-{4-[(2R)-2-(morpholin-4-ylmethyl)piperidine-1-sulfonyl]phenyl}-3- 0.051 0.081 (pyridin-3-ylmethyl)urea 1-{4-[(2R)-2-benzylpiperidine-1-sulfonyl]phenyl}-3-(pyridin-3- 0.004 0.024 ylmethyl)urea 1-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-3- 0.008 0.025 {imidazo[1,2-a]pyridin-6-ylmethyl}urea 1-{4-[(cyclohexylmethyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.004 0.181 1-{4-[(naphthalen-1-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.001 0.019 1-{4-[4-(2-oxo-2,3-dihydro-1H-indol-1-yl)piperidine-1-sulfonyl]phenyl}-3- 0.003 0.058 (pyridin-3-ylmethyl)urea 1-{4-[4-(azepan-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3- 0.005 0.006 ylmethyl)urea 1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3- 0.009 0.013 ylmethyl)urea 1-{4-[4-(piperidin-1-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3- 0.007 0.013 ylmethyl)urea 2-methyl-N-{1-[(4-{[(pyridin-3- 0.005 0.123 ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidin-4-yl}propanamide 3-(4-{[(2-chlorophenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.003 0.201 ylmethyl)urea 3-(4-{[(2-methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.008 0.097 ylmethyl)urea 3-(4-{[(3-fluorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3- 0.002 0.156 ylmethyl)urea 3-(4-{[(4-chlorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3- 0.002 0.484 ylmethyl)urea 3-(4-{[(4-fluorophenyl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin-3- 0.003 ylmethyl)urea 3-(4-{[(4-methoxyphenyl)methyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.016 0.507 ylmethyl)urea 3-(4-{[(5-ethylpyridin-2-yl)methyl](methyl)sulfamoyl}phenyl)-1-(pyridin- 0.005 0.134 3-ylmethyl)urea 3-(4-{[2-(4-fluorophenoxy)pyridin-3-yl]sulfamoyl}phenyl)-1-(pyridin-3- 0.011 0.149 ylmethyl)urea 3-(4-{[2-(difluoromethoxy)phenyl]sulfamoyl} phenyl)-1-(pyridin-3- 0.0006 0.031 ylmethyl)urea 3-(4-{[2-(morpholin-4-yl)-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1- 0.008 0.007 (pyridin-3-ylmethyl)urea 3-(4-{[2-(piperidin-1-yl)-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1- 0.005 0.022 (pyridin-3-ylmethyl)urea 3-(4-{[2-(propan-2-yloxy)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.002 0.015 ylmethyl)urea 3-(4-{[2-methoxy-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin- 0.0001 0.002 3-ylmethyl)urea 3-(4-{[3-chloro-4-(morpholin-4-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.001 0.024 ylmethyl)urea 3-(4-{[3-methyl-4-(propan-2-yl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.002 0.108 ylmethyl)urea 3-(4-{[4-chloro-2-(trifluoromethoxy)phenyl]sulfamoyl[phenyl)-1-(pyridin- 0.006 0.113 3-ylmethyl)urea 3-(4-{[4-methyl-3-(trifluoromethyl)phenyl]sulfamoyl[phenyl)-1-(pyridin- 0.002 0.179 3-ylmethyl)urea 3-(4-{4-[(4-fluorophenyl)carbonyl]piperidine-1-sulfonyl}phenyl)-1- 0.010 0.206 (pyridin-3-ylmethyl)urea 3-(4-{4-[(morpholin-4-yl)carbonyl]piperidine-1-sulfonyl}phenyl)-1- 0.008 0.04 (pyridin-3-ylmethyl)urea 3-(4-{4-[1-(3-methoxyphenyl)-4-methylcyclohexyl]piperazine-1- 0.004 0.005 sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea 3-(4-{4-[2-(diethylamino)ethyl]piperazine-1-sulfonyl}phenyl)-1-(pyridin-3- 0.004 0.023 ylmethyl)urea 3-(4-{4-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperazine-1- 0.005 0.128 sulfonyl}phenyl)-1-(pyridin-3-ylmethyl)urea 3-(4-{4-[bis(4-fluorophenyl)methyl]piperazine-1-sulfonyl}phenyl)-1- 0.005 0.007 (pyridin-3-ylmethyl)urea 3-(4-{8-methyl-2,8-diazaspiro[5.5]undecane-2-sulfonyl}phenyl)-1- 0.001 0.001 (pyridin-3-ylmethyl)urea 3-(4-{methyl[(1S)-1-phenylethyl]sulfamoyl}phenyl)-1-(pyridin-3- 0.001 0.008 ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-(4-{[(1S,2S,3S,5R)-2,6,6- 0.012 0.096 trimethylbicyclo[3.1.1]heptan-3-yl]sulfamoyl}phenyl)urea 3-(pyridin-3-ylmethyl)-1-(4-{[2-(1H-pyrrol-1- 0.003 0.076 yl)phenyl]sulfamoyl}phenyl)urea 3-(pyridin-3-ylmethyl)-1-(4-{[2-(pyrrolidin-1- 0.013 0.011 yl)phenyl]sulfamoyl}phenyl)urea 3-(pyridin-3-ylmethyl)-1-[4-(5,6,7,8-tetrahydro-1,6-naphthyridine-6- 0.016 0.111 sulfonyl)phenyl]urea 3-(pyridin-3-ylmethyl)-1-[4-(pyrrolidine-1-sulfonyl)phenyl]urea 0.037 1.399 3-(pyridin-3-ylmethyl)-1-{4-[(3S)-3-[(pyrrolidin-1-yl)carbonyl]piperidine- 0.009 0.137 1-sulfonyl]phenyl}urea 3-(pyridin-3-ylmethyl)-1-{4-[(5,6,7,8-tetrahydronaphthalen-1- 0.0003 0.045 yl)sulfamoyl]phenyl}urea 3-[(2-fluorophenyl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea 0.016 >30 3-[(3-fluorophenyl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea 0.033 >30 3-[(5-chloropyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea 0.048 18 3-[(6-chloropyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea 0.008 >30 3-[2-fluoro-4-(piperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.023 1.005 3-[4-({[4-(dimethylamino)phenyl]methyl}sulfamoyl)phenyl]-1-(pyridin-3- 0.003 0.148 ylmethyl)urea 3-[4-({2-[(2S)-2-hydroxypropoxy]phenyl}sulfamoyl)phenyl]-1-(pyridin-3- 0.012 0.088 ylmethyl)urea 3-[4-({3-[(1S)-1-hydroxyethyl]phenyl}sulfamoyl)phenyl]-1-(pyridin-3- 0.007 0.164 ylmethyl)urea 3-[4-(2,3-dihydro-1H-indole-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.002 0.031 3-[4-(3,3-difluoroazetidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.059 7.859 3-[4-(3-methylpiperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.007 0.067 3-[4-(4-methylpiperidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.004 0.254 3-[4-(azepane-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.007 0.139 3-[4-(azetidine-1-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.041 1.622 3-[4-(diethylsulfamoyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.016 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrazin-2-ylmethyl)urea 0.273 >30 3-[4-(piperidine-1-sulfonyl)phenyl]-1-(pyrimidin-5-ylmethyl)urea 1.14 >30 3-[4-(piperidine-1-sulfonyl)phenyl]-1-[1-(pyridin-3-yl)ethyl]urea 22.089 >30 3-[4-(piperidine-1-sulfonyl)phenyl]-1-[2-(pyridin-3-yl)ethyl]urea 0.01 0.661 3-[4-(piperidine-1-sulfonyl)phenyl]-1-{[6-(trifluoromethyl)pyridin-3- 0.189 >30 yl]methyl]urea 3-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1-(pyridin-3-yl)urea 0.037 2.259 3-{[4-(piperidine-1-sulfonyl)phenyl]methyl}-1-(pyridin-3-ylmethyl)urea 0.017 0.547 3-{4-[(2,2-dimethylpropyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.017 0.159 3-{4-[(2,3-dichlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.002 0.030 3-{4-[(2,3-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0009 0.074 3-{4-[(2,4-dichlorophenyl)sulfamoyl]phenyl]-1-(pyridin-3-ylmethyl)urea 0.003 0.189 3-{4-[(2,4-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.003 0.109 3-{4-[(2,5-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0012 0.004 3-{4-[(2,5-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.006 0.116 3-{4-[(2-bromophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.002 0.024 3-{4-[(2-chloro-4-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0009 0.036 ylmethyl)urea 3-{4-[(2-chloro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.001 0.032 ylmethyl)urea 3-{4-[(2-chloro-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0003 0.009 ylmethyl)urea 3-{4-[(2-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.003 0.041 3-{4-[(2-ethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.003 0.032 3-{4-[(2-fluoro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.002 0.157 ylmethyl)urea 3-{4-[(2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.008 3-{4-[(2-iodophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0008 0.039 3-{4-[(2-methoxy-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.002 0.002 ylmethyl)urea 3-{4-[(2-methoxypyridin-3-yl)sulfamoyl]phenyl}-1-(pyridin-3- 0.007 0.114 ylmethyl)urea 3-{4-[(2-phenylpropan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.005 0.039 3-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-1-(pyridin-3- 0.01 0.009 ylmethyl)urea 3-{4-[(2S)-2-(methoxymethyl)pyrrolidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.002 0.060 ylmethyl)urea 3-{4-[(2S)-2-ethylpiperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.004 0.018 ylmethyl)urea 3-{4-[(3,4-dichlorophenyl)sulfamoyl]phenyl]-1-(pyridin-3-ylmethyl)urea 0.006 0.122 3-{4-[(3,4-dimethoxyphenyl)sulfamoyl]phenyl]-1-(pyridin-3-ylmethyl)urea 0.005 0.116 3-{4-[(3,4-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.003 0.093 3-{4-[(3,5-dimethoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.005 0.096 3-{4-[(3,5-dimethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.001 0.041 3-{4-[(3-aminophenyl)(methanesulfonyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.003 0.110 ylmethyl)urea 3-{4-[(3-bromophenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.003 3-{4-[(3-chloro-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0014 0.026 ylmethyl)urea 3-{4-[(3-chlorophenyl)sulfamoyl]phenyl]-1-(pyridin-3-ylmethyl)urea 0.001 3-{4-[(3-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.002 0.057 ylmethyl)urea 3-{4-[(3-methoxy-4-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.004 0.148 ylmethyl)urea 3-{4-[(3-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.010 3-{4-[(3S)-3-methyl-4-(3-methylphenyl)piperazine-1-sulfonyl]phenyl}-1- 0.003 0.034 (pyridin-3-ylmethyl)urea 3-{4-[(3S)-3-methyl-4-(4-methylphenyl)piperazine-1-sulfonyl]phenyl}-1- 0.004 0.095 (pyridin-3-ylmethyl)urea 3-{4-[(3S)-3-methylpiperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.003 0.105 ylmethyl)urea 3-{4-[(4-chloro-2-methoxy-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin- 0.001 0.006 3-ylmethyl)urea 3-{4-[(4-chloronaphthalen-1-yl)sulfamoyl]phenyl}-1-(pyridin-3- 0.005 0.053 ylmethyl)urea 3-{4-[(4-ethoxy-2-fluorophenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.004 0.157 ylmethyl)urea 3-{4-[(4-ethylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.007 3-{4-[(4-fluoro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.007 0.116 ylmethyl)urea 3-{4-[(4-tert-butyl-2-chlorophenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0014 0.097 ylmethyl)urea 3-{4-[(5-chloro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.0009 0.003 ylmethyl)urea 3-{4-[(5-chloro-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.001 0.035 ylmethyl)urea 3-{4-[(5-fluoro-2-methoxyphenyl)sulfamoyl]phenyl]-1-(pyridin-3- 0.0010 0.033 ylmethyl)urea 3-{4-[(5-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.002 0.079 ylmethyl)urea 3-{4-[3-(2-methoxyethyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.004 0.089 ylmethyl)urea 3-{4-[4-(2,5-dimethylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.005 0.101 ylmethyl)urea 3-{4-[4-(2-ethoxyphenyl)piperazine-1-sulfonyl]phenyl]-1-(pyridin-3- 0.002 0.006 ylmethyl)urea 3-{4-[4-(2-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.007 0.035 ylmethyl)urea 3-{4-[4-(2-methylphenyl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.006 0.106 ylmethyl)urea 3-{4-[4-(3,5-dichloropyridin-4-yl)piperazine-1-sulfonyl]phenyl}-1- 0.003 0.029 (pyridin-3-ylmethyl)urea 3-{4-[4-(3-chloropyridin-2-yl)piperazine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.001 0.018 ylmethyl)urea 3-{4-[4-(5-chloro-2-methoxyphenyl)piperazine-1-sulfonyl]phenyl}-1- 0.002 0.050 (pyridin-3-ylmethyl)urea 3-{4-[4-(5-chloro-2-methylphenyl)piperazine-1-sulfonyl]phenyl}-1- 0.002 0.162 (pyridin-3-ylmethyl)urea 3-{4-[4-(diethylamino)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.005 0.014 ylmethyl)urea 3-{4-[4-(dipropylamino)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.004 0.003 ylmethyl)urea 3-{4-[4-(methoxymethyl)piperidine-1-sulfonyl]phenyl}-1-(pyridin-3- 0.022 0.130 ylmethyl)urea 3-{4-[benzyl(ethyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0009 0.007 3-{4-[benzyl(methyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0011 0.107 3-{4-[benzyl(propan-2-yl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.002 0.026 3-{4-[cyclohexyl(ethyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.005 0.123 3-{4-[methyl({[3-(trifluoromethyl)phenyl]methyl})sulfamoyl]phenyl}-1- 0.007 (pyridin-3-ylmethyl)urea 3-{4-[methyl(2-methylpropyl)sulfamoyl]phenyl}-1-(pyridin-3- 0.007 ylmethyl)urea 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-(4-{8-oxa-3- 0.008 0.006 azabicyclo[3.2.1]octane-3-sulfonyl}phenyl)urea 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-{4-[4-(morpholin-4-yl)piperidine- 0.004 0.005 1-sulfonyl]phenyl}urea 3-benzyl-1-[4-(piperidine-1-sulfonyl)phenyl]urea 0.718 >30 5-[({[4-(piperidine-1-sulfonyl)phenyl]carbamoyl}amino)methyl]pyridine- >10 27.477 2-carboxamide N-(propan-2-yl)-2-{4-[(4-{[(pyridin-3- 0.003 0.037 ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide N,N-diethyl-2-[(4-{[(pyridin-3- 0.008 0.006 ylmethyl)carbamoyl]amino]benzene)sulfonamido]benzamide N,N-diethyl-2-{4-[(4-{[(pyridin-3- 0.005 0.045 ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide N,N-dimethyl-1-[(4-{[(pyridin-3- 0.009 0.164 ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperidine-4-carboxamide N,N-dimethyl-2-[(4-{[(pyridin-3- 0.016 0.055 ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide N-ethyl-N-[(3S)-1-[(4-{[(pyridin-3- 0.006 0.079 ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyrrolidin-3-yl]acetamide N-methyl-2-[(4-{[(pyridin-3- 0.001 0.011 ylmethyl)carbamoyl]amino}benzene)sulfonamido]benzamide N-methyl-N-phenyl-2-{4-[(4-{[(pyridin-3- 0.008 0.030 ylmethyl)carbamoyl]amino}benzene)sulfonyl]piperazin-1-yl}acetamide rel-3-{4-[(4aR,8aS)-decahydroisoquinoline-2-sulfonyl]phenyl}-1-(pyridin- 0.002 0.101 3-ylmethyl)urea tert-butylN-{5-[({[4-(piperidine-1- 3.135 9.782 sulfonyl)phenyl]carbamoyl}amino)methyl]pyridin-2-yl}carbamate 1-(4-{8-oxatricyclo[7.4.0.0.sup.2,.sup.7]trideca-1(9),2(7),3,5,10,12-hexaene-6- 0.002 0.003 sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea 1-(4-benzoylphenyl)-3-(pyridin-3-ylmethyl)urea 0.017 0.735 1-(pyridin-3-ylmethyl)-3-(4-{[2- 0.001 0.003 (trifluoromethoxy)benzene]sulfonyl}phenyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[2- 0.003 0.569 (trifluoromethyl)benzene]sulfonyl}phenyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[3- 0.001 0.083 (trifluoromethoxy)benzene]sulfonyl}phenyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[3- 0.004 0.247 (trifluoromethyl)benzene]sulfonyl}phenyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[4- 0.005 0.420 (trifluoromethoxy)benzene]sulfonyl}phenyl)urea 1-(pyridin-3-ylmethyl)-3-(4-{[4- 0.009 0.604 (trifluoromethyl)benzene]sulfonyl}phenyl)urea 1-(pyridin-3-ylmethyl)-3-[4-(trifluoromethane)sulfonylphenyl]urea 0.226 10.0 1-(pyridin-3-ylmethyl)-3-{4-[(2,4,6-trimethylbenzene)sulfonyl]phenyl}urea 0.011 >1 1-[(6-aminopyridin-3-yl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea 0.003 0.081 1-[(6-aminopyridin-3-yl)methyl]-3-{4-[(4- 0.002 0.043 fluorobenzene)sulfonyl]phenyl}urea 1-[4-(2H-1,3-benzodioxole-5-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.001 0.322 1-[4-(benzenesulfonyl)phenyl]-3-(1H-pyrazol-3-ylmethyl)urea >10 >20 1-[4-(benzenesulfonyl)phenyl]-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea 0.001 0.033 1-[4-(benzenesulfonyl)phenyl]-3-{thieno[2,3-c]pyridin-2-ylmethyl}urea 0.46 >30 1-[4-(cyclopentanesulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.043 1.86 1-[6-(benzenesulfonyl)pyridin-3-yl]-3-(pyridin-3-ylmethyl)urea 0.015 2.356 1-{[4-(benzenesulfonyl)phenyl]methyl}-3-(quinolin-6-yl)urea 2.258 >30 1-{4-[(2-phenoxybenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.002 0.008 1-{4-[(4-fluorobenzene)sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6- 0.003 0.029 ylmethyl[urea 3-(4-{[2-(methoxymethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.006 0.039 ylmethyl)urea 3-(4-{[2-chloro-5-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.005 0.339 ylmethyl)urea 3-(4-{[2-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.001 0.014 ylmethyl)urea 3-(4-{[2-methoxy-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1- 0.002 0.003 (pyridin-3-ylmethyl)urea 3-(4-{[2-methoxy-5-(propan-2-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.003 0.031 ylmethyl)urea 3-(4-{[2-methyl-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin- 0.002 0.021 3-ylmethyl)urea 3-(4-{[3-(propan-2-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.002 0.038 ylmethyl)urea 3-(4-{[3-(propan-2-yloxy)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.004 0.079 ylmethyl)urea 3-(4-{[3-fluoro-4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.000 0.054 ylmethyl)urea 3-(4-{[4-chloro-3-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.005 0.167 ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-[4-(pyridine-2-sulfonyl)phenyl]urea 0.869 3-(pyridin-3-ylmethyl)-1-[4-(pyridine-3-sulfonyl)phenyl]urea 0.005 0.595 3-(pyridin-3-ylmethyl)-1-[4-(pyridine-4-sulfonyl)phenyl]urea 0.011 0.488 3-(pyridin-3-ylmethyl)-1-[4-(pyrimidine-5-sulfonyl)phenyl]urea 0.020 0.871 3-[4-(1-methyl-1H-pyrazole-4-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.004 0.247 3-[4-(2-methoxynaphthalene-1-sulfonyl)phenyl]-1-(pyridin-3- 0.002 0.012 ylmethyl)urea 3-[4-(3,5-dimethyl-1,2-oxazole-4-sulfonyl)phenyl]-1-(pyridin-3- 0.020 0.850 ylmethyl)urea 3-[4-(5-methylthiophene-2-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.003 0.383 3-[4-(benzenesulfonyl)phenyl]-1-(pyridin-3-yl)urea >30 27.465 3-[4-(benzenesulfonyl)phenyl]-1-(quinolin-6-yl)urea 0.090 15.86 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H-imidazol-1-yl)pyridin-3- >10 yl]methyl}urea 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(1H-pyrazol-1-yl)pyridin-3- 3.791 >10 yl]methyl}urea 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(2-methoxyethoxy)pyridin-3- 2.121 >10 yl]methyl}urea 3-{[({4-[(4- 0.444 20.611 chlorobenzene)sulfinyl]phenyl}carbamoyl)amino]methyl}pyridin-1-ium-1- olate 3-{[({4-[(4- 0.728 >30 chlorobenzene)sulfonyl]phenyl}carbamoyl)amino]methyl}pyridin-1-ium-1- olate 3-{4-[(2,3-dichlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.001 0.446 3-{4-[(2,3-difluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.004 0.546 3-{4-[(2,3-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.005 0.298 3-{4-[(2,4-dichlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.004 0.827 3-{4-[(2,4-difluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.001 0.344 3-{4-[(2,4-dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.005 0.047 3-{4-[(2,4-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.018 0.967 3-{4-[(2,5-dichlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.006 0.652 3-{4-[(2,5-difluoro-4-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.004 0.105 ylmethyl)urea 3-{4-[(2,5-difluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.004 0.403 3-{4-[(2,5-dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.001 0.007 3-{4-[(2,5-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.014 0.473 3-{4-[(2,6-dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.007 0.026 3-{4-[(2,6-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.008 0.387 3-{4-[(2-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.002 0.326 3-{4-[(2-bromobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.006 0.250 3-{4-[(2-chloro-4-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.008 ylmethyl)urea 3-{4-[(2-chloro-6-fluoro-3-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.007 0.336 ylmethyl)urea 3-{4-[(2-chlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.005 0.475 3-{4-[(2-ethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.002 0.0004 3-{4-[(2-ethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.002 0.169 3-{4-[(2-fluoro-3-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.001 0.387 ylmethyl)urea 3-{4-[(2-fluoro-4-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.003 0.311 ylmethyl)urea 3-{4-[(2-fluoro-4-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.002 0.517 ylmethyl)urea 3-{4-[(2-fluoro-5-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.012 >1 ylmethyl)urea 3-{4-[(2-fluoro-6-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.002 0.010 ylmethyl)urea 3-{4-[(2-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.003 0.493 3-{4-[(2-methoxy-5-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.004 0.007 ylmethyl)urea 3-{4-[(2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.002 0.010 3-{4-[(2-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.002 0.450 3-{4-[(3,4-difluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.003 0.214 3-{4-[(3,4-dimethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.005 0.017 3-{4-[(3,5-difluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.003 0.284 3-{4-[(3,5-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.001 0.040 3-{4-[(3-bromobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.002 0.322 3-{4-[(3-chlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.003 0.518 3-{4-[(3-fluoro-4-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.002 0.173 ylmethyl)urea 3-{4-[(3-fluoro-4-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.001 0.206 ylmethyl)urea 3-{4-[(3-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.001 0.238 3-{4-[(3-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.002 0.157 3-{4-[(4-chloro-2-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.002 0.415 ylmethyl)urea 3-{4-[(4-chloro-2-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.006 0.755 ylmethyl)urea 3-{4-[(4-chloro-3-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.003 0.221 ylmethyl)urea 3-{4-[(4-chlorobenzene)sulfmyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.008 0.041 3-{4-[(4-ethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.003 0.533 3-{4-[(4-fluoro-2-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.005 0.287 ylmethyl)urea 3-{4-[(4-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.004 0.171 3-{4-[(4-methanesulfonylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.002 0.091 ylmethyl)urea 3-{4-[(4-methoxy-2-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.008 0.352 ylmethyl)urea 3-{4-[(5-chloro-2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.005 0.021 ylmethyl)urea 3-{4-[(5-fluoro-2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.002 0.004 ylmethyl)urea 3-{4-[(5-fluoro-2-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.004 0.489 ylmethyl)urea 3-{4-[2-chloro-6-(propan-2-yl)pyridine-3-sulfonyl]phenyl}-1-(pyridin-3- 0.003 0.006 ylmethyl)urea N,N-dimethyl-4-[(4-{[(pyridin-3- 0.005 0.053 ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide 1-(4-{[2-(morpholin-4-ylmethyl)benzene]sulfonyl}phenyl)-3-(pyridin-3- 0.0036 0.0079 ylmethyl)urea 1-(4-{[3-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3- 0.0022 0.0980 ylmethyl)urea 1-(4-{[3-(cyclopropylmethoxy)benzene]sulfonyl}phenyl)-3-(pyridin-3- 0.0086 0.1-1 ylmethyl)urea 1-(4-{[4-(1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3- 0.0055 0.0550 ylmethyl)urea 1-(4-{[4-(morpholin-4-yl)benzene]sulfonyl}phenyl)-3-(pyridin-3- 0.0018 0.0147 ylmethyl)urea 1-(pyridin-3-ylmethyl)-3-[4-(3,3,5-trimethylazepane-1- 0.0020 0.0092 sulfonyl)phenyl]urea 1-(pyridin-3-ylmethyl)-3-{4-[(3-sulfamoylbenzene)sulfonyl]phenyl}urea 0.0038 0.1-1 1-(pyridin-3-ylmethyl)-3-{4-[6-(trifluoromethyl)pyridine-3- 0.0279   1-10 sulfonyl]phenyl}urea 1-[4-({3-[(morpholin-4-yl)carbonyl]benzene}sulfonyl)phenyl]-3-(pyridin- 0.0050 0.1-1 3-ylmethyl)urea 1-[4-(1H-indole-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.0016 0.0134 1-[4-(1H-indole-7-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.0005 0.0034 1-[4-(2,3-dihydro-1,4-benzodioxine-6-sulfonyl)phenyl]-3-(pyridin-3- 0.0011 0.1-1 ylmethyl)urea 1-[4-(2,3-dihydro-1-benzofuran-7-sulfonyl)phenyl]-3-(pyridin-3- 0.0011 0.0105 ylmethyl)urea 1-[4-(2H-1,3-benzodioxole-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.0043 0.1-1 1-[4-(isoquinoline-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.0014 0.0083 1-[4-(phenoxathiine-4-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.0029 0.0018 1-{4-[(3-benzoylphenyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.0044   1-10 1-{4-[(3-cyanobenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.0080 0.1-1 1-{4-[(3-phenylbenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.0068 0.1-1 1-{4-[(4-cyanobenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.0076 0.1-1 1-{4-[(4-phenylbenzene)sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.0058 0.1-1 1-{4-[(pyridin-2-ylmethyl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea 0.0084   1-10 1-{4-[2-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3- 0.0160 0.1-1 ylmethyl)urea 1-{4-[4-(2-phenylacetyl)piperazine-1-sulfonyl]phenyl}-3-(pyridin-3- 0.0030 0.9323 ylmethyl)urea 1-{4-[6-(morpholin-4-yl)pyridine-3-sulfonyl]phenyl}-3-(pyridin-3- 0.0036 0.0304 ylmethyl)urea 2-fluoro-N-(propan-2-yl)-5-[(4-{[(pyridin-3- 0.0209 0.1-1 ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide 2-methyl-N-{3-[(4-{[(pyridin-3- 0.0012 0.0101 ylmethyl)carbamoyl]amino}benzene)sulfonyl]phenylJpropanamide 3-(4-{[2-chloro-5-(trifluoromethoxy)benzene]sulfonyl}phenyl)-1-(pyridin- 0.0063 0.1-1 3-ylmethyl)urea 3-(4-{[2-methoxy-5-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin- 0.0014 0.0033 3-ylmethyl)urea 3-(4-{[2-methyl-4-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.0118 0.1-1 ylmethyl)urea 3-(4-{[3-(2-methylpropoxy)benzene]sulfonyl]phenyl)-1-(pyridin-3- 0.0033 0.1-1 ylmethyl)urea 3-(4-{[3-(3,5-dimethyl-1H-pyrazol-1-yl)benzene]sulfonyl}phenyl)-1- 0.0016 0.0159 (pyridin-3-ylmethyl)urea 3-(4-{[3-(5-methyl-1,3,4-oxadiazol-2-yl)benzene]sulfonyl]phenyl)-1- 0.0073 0.1-1 (pyridin-3-ylmethyl)urea 3-(4-{[3-(dimethylsulfamoyl)benzene]sulfonyl]phenyl)-1-(pyridin-3- 0.0033 0.0793 ylmethyl)urea 3-(4-{[3-(ethanesulfonyl)benzene]sulfonyl]phenyl)-1-(pyridin-3- 0.0076 0.1-1 ylmethyl)urea 3-(4-{[3-(ethylsulfamoyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.0072 0.1-1 ylmethyl)urea 3-(4-{[3-(methoxymethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.0033 0.0933 ylmethyl)urea 3-(4-{[3-(propane-1-sulfonamido)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.0016 0.0860 ylmethyl)urea 3-(4-{[3-chloro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.0040 0.1-1 ylmethyl)urea 3-(4-{[3-chloro-5-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.0013 0.0255 ylmethyl)urea 3-(4-{[3-fluoro-4-(2,2,2-trifluoroethoxy)benzene]sulfonyl}phenyl)-1- 0.0022 0.1-1 (pyridin-3-ylmethyl)urea 3-(4-{[3-fluoro-4-(trifluoromethoxy)benzene]sulfonyl}phenyl)-1-(pyridin- 0.0055 0.1-1 3-ylmethyl)urea 3-(4-{[3-fluoro-4-(trifluoromethyl)benzene]sulfonyl}phenyl)-1-(pyridin-3- 0.0041 0.1-1 ylmethyl)urea 3-(4-{[3-fluoro-5-(2,2,2-trifluoroethoxy)benzene]sulfonyl]phenyl)-1- 0.0011 0.0297 (pyridin-3-ylmethyl)urea 3-(4-{[3-fluoro-5-(2-methylpropoxy)benzene]sulfonyl}phenyl)-1-(pyridin- 0.0040 0.0564 3-ylmethyl)urea 3-(4-{[3-fluoro-5-(trifluoromethyl)benzene]sulfonyl[phenyl)-1-(pyridin-3- 0.0007 0.0576 ylmethyl)urea 3-(4-{[4-(ethoxymethyl)benzene]sulfonyl[phenyl)-1-(pyridin-3- 0.0010 0.1-1 ylmethyl)urea 3-(4-{[4-(propan-2-yl)benzene]sulfonyl[phenyl)-1-(pyridin-3- 0.0030 0.1-1 ylmethyl)urea 3-(4-{[4-(propan-2-yloxy)benzene]sulfonyl[phenyl)-1-(pyridin-3- 0.0017 0.0291 ylmethyl)urea 3-(4-{[4-fluoro-3-(2,2,2-trifluoroethoxy)benzene]sulfonyl[phenyl)-1- 0.0021 0.0234 (pyridin-3-ylmethyl)urea 3-(4-{[4-fluoro-3-(trifluoromethyl)benzene]sulfonyl[phenyl)-1-(pyridin-3- 0.0015 0.0862 ylmethyl)urea 3-(4-{4-[2-(3,4-dichlorophenyl)acetyl]piperazine-1-sulfonyl[phenyl)-1- 0.0037   1-10 (pyridin-3-ylmethyl)urea 3-(pyridin-3-ylmethyl)-1-[4-({4-[(pyrrolidin-1- 0.0013 0.0076 yl)carbonyl]benzene}sulfonyl)phenyl]urea 3-(pyridin-3-ylmethyl)-1-[4-(quinoline-3-sulfonyl)phenyl]urea 0.0028 0.0280 3-(pyridin-3-ylmethyl)-1-[4-(quinoline-6-sulfonyl)phenyl]urea 0.0027 0.0441 3-(pyridin-3-ylmethyl)-1-[4-(quinoline-8-sulfonyl)phenyl]urea 0.0014 0.0022 3-[(4-{[(pyridin-3- 0.0080   1-10 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide 3-[4-(1-methyl-1H-indazole-4-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0010 0.0599 3-[4-(1-methyl-1H-indazole-5-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0018 0.0925 3-[4-(1-methyl-1H-indazole-6-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0025 0.0354 3-[4-(1-methyl-1H-indazole-7-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0144 0.1-1 3-[4-(1-methyl-1H-indole-2-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0030 0.0635 3-[4-(1-propyl-1H-pyrazole-4-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0063 0.0131 3-[4-(2,4-dimethoxypyrimidine-5-sulfonyl)phenyl]-1-(pyridin-3- 0.0067 0.0210 ylmethyl)urea 3-[4-(2-methoxypyrimidine-5-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0087 0.1-1 3-[4-(2-methylpyridine-3-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0072 0.1-1 3-[4-(4-{[4-(propan-2-yl)phenyl]methyl[piperazine-1-sulfonyl)phenyl]-1- 0.0358   1-10 (pyridin-3-ylmethyl)urea 3-[4-(5-chloropyridine-3-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0026 0.0982 3-[4-(5-fluoropyridine-3-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0087 0.1-1 3-[4-(6-methoxynaphthalene-2-sulfonyl)phenyl]-1-(pyridin-3- 0.0016 0.1-1 ylmethyl)urea 3-[4-(6-methoxypyridine-3-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0050 0.1-1 3-[4-(6-methylpyridine-3-sulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea 0.0049 0.1-1 3-{4-[(3,4-dichlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0029 0.1-1 3-{4-[(3,5-dichlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0019 0.1-1 3-{4-[(3-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0021 0.1-1 3-{4-[(3-chloro-4-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0013 0.0929 ylmethyl)urea 3-{4-[(3-chloro-4-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0009 0.1-1 ylmethyl)urea 3-{4-[(3-chloro-4-propoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0046 0.1-1 ylmethyl)urea 3-{4-[(3-chloro-5-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0013 0.0272 ylmethyl)urea 3-{4-[(3-chloro-5-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0018 0.0671 ylmethyl)urea 3-{4-[(3-ethanesulfonamidobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0011 0.0695 ylmethyl)urea 3-{4-[(3-ethoxy-4-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0039 0.0283 ylmethyl)urea 3-{4-[(3-ethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0017 0.0837 3-{4-[(3-ethylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0020 0.0708 3-{4-[(3-fluoro-4-propoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0013 0.0585 ylmethyl)urea 3-{4-[(3-fluoro-5-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0017 0.1-1 ylmethyl)urea 3-{4-[(3-fluoro-5-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0017 0.0993 ylmethyl)urea 3-{4-[(3-methanesulfonamidobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0013 0.0761 ylmethyl)urea 3-{4-[(3-methanesulfonylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0066 0.1-1 ylmethyl)urea 3-{4-[(3-methoxy-4-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0027 0.0179 ylmethyl)urea 3-{4-[(3-propoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0038 0.1-1 3-{4-[(4-acetylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0020 0.1-1 3-{4-[(4-acetylphenyl)sulfanoyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0144   1-10 3-{4-[(4-chloro-3-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0044 0.0632 ylmethyl)urea 3-{4-[(4-chlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0031 0.1-1 3-{4-[(4-ethoxy-3-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0012 0.0217 ylmethyl)urea 3-{4-[(4-ethoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0022 0.1-1 3-{4-[(4-fluoro-2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0020 0.0282 ylmethyl)urea 3-{4-[(4-fluoro-3-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0037 0.0446 ylmethyl)urea 3-{4-[(4-fluoro-3-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0037 0.1-1 ylmethyl)urea 3-{4-[(4-methoxy-3,5-dimethylbenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0021 0.0089 ylmethyl)urea 3-{4-[(4-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.0024 0.1-1 3-{4-[(5-acetyl-2-methoxybenzene)sulfonyl]phenyl}-1-(pyridin-3- 0.0013 0.0017 ylmethyl)urea 3-{4-[2-(dimethylamino)pyrimidine-5-sulfonyl]phenyl}-1-(pyridin-3- 0.0059 0.1-1 ylmethyl)urea 3-{4-[3-chloro-2-(morpholin-4-yl)pyridine-4-sulfonyl]phenyl}-1-(pyridin- 0.0040 0.0142 3-ylmethyl)urea 3-{4-[4-(3-chlorophenyl)-4-hydroxypiperidine-1-sulfonyl]phenyl}-1- 0.0052 0.9563 (pyridin-3-ylmethyl)urea 3-{4-[6-(dimethylamino)pyridine-3-sulfonyl]phenyl}-1-(pyridin-3- 0.0030 0.0749 ylmethyl)urea 3-chloro-N,N-diethyl-5-[(4-{[(pyridin-3- 0.0035 0.0017 ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide 3-fluoro-N,N-dimethyl-5-[(4-{[(pyridin-3- 0.0015 0.0133 ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide 4-fluoro-N-(propan-2-yl)-3-[(4-{[(pyridin-3- 0.0154 0.1-1 ylmethyl)carbamoyl]amino}benzene)sulfonyl]benzamide N-(2-hydroxyethyl)-3-[(4-{[(pyridin-3- 0.0078 0.1-1 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide N-(2-methylpropyl)-3-[(4-{[(pyridin-3- 0.0097 0.1-1 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide N-(propan-2-yl)-3-[(4-{[(pyridin-3- 0.0100 0.1-1 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide N,N-diethyl-3-fluoro-5-[(4-{[(pyridin-3- 0.0012 0.0015 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide N,N-diethyl-4-fluoro-3-[(4-{[(pyridin-3- 0.0024 0.0885 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide N,N-dimethyl-3-[(4-{[(pyridin-3- 0.0074 0.1-1 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide N-{3-[(4-{[(pyridin-3- 0.0015 0.0395 ylmethyl)carbamoyl]amino}benzene)sulfonyl]phenyl}acetamide N-cyclopentyl-3-[(4-{[(pyridin-3- 0.0096 0.1-1 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide N-cyclopropyl-3-[(4-{[(pyridin-3- 0.0064 0.1-1 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide N-ethyl-3-[(4-{[(pyridin-3- 0.0067 0.1-1 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide N-ethyl-4-[(4-{[(pyridin-3- 0.0013 0.0402 ylmethyl)carbamoyl]amino[benzene)sulfonyl]benzamide N-methyl-5-[(4-{[(pyridin-3- 0.0038 0.0838 ylmethyl)carbamoyl]amino}benzene)sulfonyl]pyridine-2-carboxamide rel-3-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-1-(pyridin- 0.0039 0.0135 3-ylmethyl)urea 4-[(3-chlorophenyl)sulfamoyl]-N-{imidazo[1,2-a]pyridin-6- 0.138 0.00712 ylmethyl}benzamide 4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N-[2-(pyridin-3- 4.72 0.0312 yl)ethyl]benzamide 4-[(5-chloro-2-methoxyphenyl)sulfamoyl]-N-{imidazo[1,2-a]pyridin-6- 0.00216 0.0023 ylmethyl}benzamide N-[2-(pyridin-3-yl)ethyl]-4-{[3- 20.5 1.55 (trifluoromethoxy)phenyl]sulfamoyl[benzamide N-[4-(pyridin-3-yl)-1,3-thiazol-2-yl]-4-(1,2,3,4-tetrahydroisoquinoline-2- 11.1 2.62 sulfonyl)benzamide N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3- 0.467 0.00858 (trifluoromethoxy)phenyl]sulfamoyl}benzamide N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{8-oxa-3- 0.109 0.0271 azabicyclo[3.2.1]octane-3-sulfonyl}benzamide 4-(benzenesulfonyl)-N-(pyridin-3-yl)benzamide 1.89 2.73 4-(benzenesulfonyl)-N-(pyridin-4-yl)benzamide 0.651 1.31 4-(benzenesulfonyl)-N-(pyridin-3-ylmethyl)benzamide 0.0805 0.216 N-[2-(pyridin-3-yl)ethyl]-4-{[3- 9.37 0.374 (trifluoromethoxy)benzene]sulfonyl}benzamide N-(1,3-benzothiazol-6-ylmethyl)-4-[(3-chlorobenzene)sulfonyl]benzamide 11.4 0.00971 N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethoxy)benzene]sulfonyl}benzamide 0.139 0.0018 N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-{[3-(trifluoromethyl)benzene]sulfonyl}benzamide 0.00703 0.00433 4-(benzenesulfonyl)-N-{imidazo[1,2-a]pyridin-7-ylmethyl}benzamide 0.0308 0.0259 N-{imidazo[1,2-a]pyridin-6-ylmethyl}-4-[(3- 0.0192 0.00354 methoxybenzene)sulfonyl]benzamide 4-[(3-chlorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6- 0.0121 0.00639 ylmethyl}benzamide 4-[(2-chlorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide 0.0195 0.00392 4-[(3,5-difluorobenzene)sulfonyl]-N-{imidazo[1,2-a]pyridin-6-ylmethyl}benzamide 0.0177 0.00571 3-[(5-fluoropyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea 0.024 0.752 3-[(6-aminopyridin-3-yl)methyl]-1-[4-(piperidine-1-sulfonyl)phenyl]urea 0.0085 0.0714 1-[(3-aminophenyl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea 0.011 2.54 3-[4-(benzenesulfonyl)phenyl]-1(pyridin-3-ylmethyl)urea 0.0035 0.16 3-[4-(benzenesulfonyl)phenyl]-1-{[6-(dimethylamino)pyridin-3- >30 27.6 yl]methyl]urea 3-{4-[(4-bromobenzene)sulfonyl]phenyl]-1-(pyridin-3-ylmethyl)urea 0.003 0.239 3-{4-[(4-chlorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.00452 0.241 3-{4-[(4-methylbenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea 0.00433 0.141 1-[4-(piperazine-1-sulfonyl)phenyl]-3-(pyridin-3-ylmethyl)urea 0.0486 >2
Xenograft Studies:

(765) C.B-17-Igh-1b-Prkdc.sup.scid mice (female) were injected s.c. with 5×10.sup.6 A2780 cells (NCI) in the left flank. 10-12 days later when tumors reached 100-200 mm3 in size, mice were randomized into treatment groups of 8 mice per group including vehicle control and reference standard groups. The compounds were formulated in 60:30:10 PEG-400:D5W: Ethanol and administered p.o., at the dose volume of 10 ml/kg BID for a duration of 5 or 10 days. The dose used for efficacy was selected from the MTD (Maximum Tolerated Dose) study. Mice were weighed and tumors measured using vernier calipers every alternate day. Tumor volume was calculated according to the formula (length×width.sup.2)/2. All animal work was approved by the Institutional Animal Care and Use Committee of Biological Resource Centre, Singapore.

(766) Results:

(767) The following compound produced tumor regression. 1-(4-{8-oxa-3-azabicyclo[3.2.1]octane-3-sulfonyl}phenyl)-3-(pyridin-3-ylmethyl)urea; and 1-(pyridin-3-ylmethyl)-3-(4-{[2-(trifluoromethoxy)benzene]sulfonyl}phenyl)urea.

(768) The following compound produced tumor stasis: 3_{4-[(4-chloro-2-methoxy-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(4-fluorobenzene)sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea; 3-[4-(benzenesulfonyl)phenyl]-1-(pyridin-3-ylmethyl)urea; and l-[(6-aminopyridin-3-yl)methyl]-3-[4-(benzenesulfonyl)phenyl]urea.

(769) The following compounds delayed tumor growth: 1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-(4-{[2-methoxy-5-(trifluoromethyl)phenyl]sulfamoyl}phenyl)-1-(pyridin-3-ylmethyl)urea; 1-(4-{[(1S,2S,4R)-bicyclo[2.2.1]heptan-2-yl]sulfamoyl}phenyl)-3-(pyridin-3-ylmethyl)urea; 3-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{imidazo[1,2-a]pyridin-6-ylmethyl}-1-{4-[4-(morpholin-4-yl)piperidine-1-sulfonyl]phenyl}urea; 1-{4-[(2R,6S)-2,6-dimethylmorpholine-4-sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea; 3-{4-[(2-chloro-5-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-{4-[(naphthalen-1-yl)sulfamoyl]phenyl}-3-(pyridin-3-ylmethyl)urea; 3-{4-[(3-methoxy-2-methylphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 3-{4-[(5-chloro-2-methoxyphenyl)sulfamoyl]phenyl}-1-(pyridin-3-ylmethyl)urea. 3-{4-[(4-fluorobenzene)sulfonyl]phenyl}-1-(pyridin-3-ylmethyl)urea; 1-[4-(benzenesulfonyl)phenyl]-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea; and 1-{4-[(4-fluorobenzene)sulfonyl]phenyl}-3-{imidazo[1,2-a]pyridin-6-ylmethyl}urea

(770) While the present invention has been described in conjunction with the specific embodiments set forth above, many alternatives, modifications and other variations thereof will be apparent to those of ordinary skill in the art. All such alternatives, modifications and variations are intended to fall within the spirit and scope of the present invention.