Substituted benzamides and their uses

Abstract

Provided herein are Substituted Benzamides, compositions, and method of their manufacture and use.

What is claimed is: 
     
         1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, hydrate, solvate, prodrug, enantiomer or stereoisomer thereof, 
         wherein:
 A is a nitrogen-containing heteroaryl ring chosen from pyridinyl, pyrazinyl, and imidazolyl, each of which is optionally substituted; 
 X is CH 2 CH 2 NR, CH 2 NR, or NR wherein each R is independently chosen from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, each of which, except for hydrogen, is optionally substituted; 
 R 1 , R 2 , R 3 , and R 4  are each independently chosen from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, each of which, except for hydrogen, is optionally substituted; 
 Y is chosen from O, S, NR; wherein each R is independently chosen from hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heterocycloalkyl, and heteroaryl, each of which, except for hydrogen, is optionally substituted; 
 B is an optionally substituted aryl ring; 
 
         provided that if A is 3-pyridinyl, X is CH 2 NH, R 1 , R 2 , and R 4  are each hydrogen, R 3  is methyl, and Y is O, then B is not phenyl or 4-methylphenyl. 
       
     
     
         2 . The compound of  claim 1 , wherein A is chosen from 2-pyrazinyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-imidazolyl, and 5-imidazolyl, each of which is optionally substituted. 
     
     
         3 . The compound of  claim 1 , wherein A is chosen from 2-pyrazinyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, (1-methyl)-2-imidazolyl, and (1-methyl)-5-imidazolyl. 
     
     
         4 . The compound of  claim 1 , wherein A is chosen from 2-pyridinyl, 3-pyridinyl, and 4-pyridinyl. 
     
     
         5 . The compound of  claim 1 , wherein A is 3-pyridinyl. 
     
     
         6 . The compound of  claim 1 , wherein R1 is chosen from hydrogen and optionally substituted alkyl. 
     
     
         7 . The compound of  claim 1 , wherein R1 is chosen from hydrogen and lower alkyl. 
     
     
         8 . The compound of  claim 1 , wherein R1 is hydrogen or methyl. 
     
     
         9 . The compound of  claim 1 , R1 is hydrogen. 
     
     
         10 . The compound of  claim 1 , wherein R2, R3 and R4 are each independently chosen from hydrogen and optionally substituted alkyl. 
     
     
         11 . The compound of  claim 1 , wherein R 2  is hydrogen. 
     
     
         12 . The compound of  claim 1 , wherein R 3  is chosen from hydrogen and lower alkyl. 
     
     
         13 . The compound of  claim 1 , wherein R 3  is hydrogen or methyl. 
     
     
         14 . The compound of  claim 1 , wherein R 4  is chosen from hydrogen and lower alkyl. 
     
     
         15 . The compound of  claim 1 , wherein R 4  is hydrogen. 
     
     
         16 . The compound of  claim 1 , wherein X is chosen from CH 2 CH 2 NR, CH 2 NR, or NR. 
     
     
         17 . The compound of  claim 1 , wherein R is chosen from hydrogen and lower alkyl. 
     
     
         18 . The compound of  claim 1 , wherein R is hydrogen. 
     
     
         19 . The compound of  claim 1 , wherein Y is chosen from O, S, or NR. 
     
     
         20 . The compound of  claim 1 , wherein R is chosen from hydrogen and lower alkyl. 
     
     
         21 . The compound of  claim 1 , wherein R is hydrogen. 
     
     
         22 . The compound of  claim 1 , wherein R is O. 
     
     
         23 . The compound of  claim 1 , wherein R is S. 
     
     
         24 . The compound of  claim 1 , wherein B is phenyl optionally substituted with one or more groups chosen from halo, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, hydroxyl, alkoxy, aryloxy, acyl, carboxy, alkoxycarbonyl, NO 2 , optionally substituted amino, and CN, wherein each of said alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, heterocycloalkyl, alkoxy, and aryloxy groups may be optionally independently substituted with one or more groups chosen from halo, alkyl, hydroxyl, alkoxy, carboxy, alkoxycarbonyl, heterocycloalkyl, and optionally substituted amino. 
     
     
         25 . The compound of  claim 1 , wherein B is phenyl optionally substituted with one or more groups chosen from optionally substituted amino, halo, and lower alkyl optionally substituted with optionally substituted amino, heterocycloalkyl, alkoxy, or hydroxyl. 
     
     
         26 . The compound of  claim 1 , wherein B is phenyl optionally substituted with one or more groups chosen from halo, optionally substituted amino and lower alkyl optionally substituted with optionally substituted amino or heterocycloalkyl. 
     
     
         27 . The compound of  claim 1 , wherein B is chosen from phenyl, 3-methylphenyl, 3-methoxyphenyl, 4-chlorophenyl, 4-tert-butylphenyl, 4-bromophenyl, 4-fluorophenyl, 4-methoxyphenyl, 4-(4-methylpiperazinyl)phenyl, 4-morpholinylphenyl, 3,5-dimethylphenyl, 2,4-dimethylphenyl, 3,4-dimethoxyphenyl. 
     
     
         28 . The compound of  claim 1  selected from the group consisting of:
 4-(5-Methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(3-pyridinyl)benzamide; 
 4-(5-Methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(4-pyridinyl)benzamide; 
 N-Methyl-4-(5-methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(3-pyridinyl)benzamide; 
 4-(5-Methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(2-pyridinylmethyl)benzamide; 
 4-(5-Methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(5-Methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(4-pyridinylmethyl)benzamide; 
 N-Methyl-4-(5-methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(5-Methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-[2-(3-pyridinyl)ethyl]benzamide; 
 4-(5-Methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(2-pyrazinylmethyl)benzamide; 
 N-[(1-Methyl-1H-imidazol-2-yl)methyl]-4-(5-methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)benzamide; 
 N-[(1-Methyl-1H-imidazol-5-yl)methyl]-4-(5-methyl-4-{[(4-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)benzamide; 
 4-{5-Methyl-4-[(phenylsulfonyl)methyl]-1,3-oxazol-2-yl}-N-(3-pyridinylmethyl)benzamide; 
 4-(4-{[(4-Chlorophenyl)sulfonyl]methyl}-5-methyl-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(4-{[(4-tert-Butylphenyl)sulfonyl]methyl}-5-methyl-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(4-{[(3,5-Dimethylphenyl)sulfonyl]methyl}-5-methyl-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(4-{[(4-Bromophenyl)sulfonyl]methyl}-5-methyl-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(5-Methyl-4-{[(3-methylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(4-{[(4-Methoxyphenyl)sulfonyl]methyl}-5-methyl-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(5-Methyl-4-{[(3-methoxyphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(4-{[(3,4-Dimethoxyphenyl)sulfonyl]methyl}-5-methyl-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(5-Methyl-4-{[(2,4-dimethylphenyl)sulfonyl]methyl}-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-(4-{[(4-Fluorophenyl)sulfonyl]methyl}-5-methyl-1,3-oxazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 4-[5-Methyl-4-({[4-(4-methyl-1-piperazinyl)phenyl]sulfonyl}methyl)-1,3-oxazol-2-yl]-N-(3-pyridinylmethyl)benzamide; 
 4-[5-Methyl-4-({[4-(4-morpholinyl)phenyl]sulfonyl}methyl)-1,3-oxazol-2-yl]-N-(3-pyridinylmethyl)benzamide; 
 4-(4-{[(4-Methylphenyl)sulfonyl]methyl}-1,3-thiazol-2-yl)-N-(3-pyridinylmethyl)benzamide; 
 or a pharmaceutically acceptable salt thereof.