Pyridinyl and pyrimidinyl sulfoxide and sulfone derivatives

Abstract

Disclosed are certain pyridinyl and pyrimidinyl sulfoxide and sulfone compounds, pharmaceutical compositions comprising such compounds and methods of treatment using such compounds.

What is claimed is: 
     
         1 . A compound of Formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         A is CH or N; 
         E is O or is absent; 
         R is (a) a bicyclic heteroaryl comprising one or more heteroatom ring members independently selected from N, S or O, wherein said bicyclic heteroaryl is unsubstituted or is substituted with one or more substituents selected from the group consisting of deuterium, amino, alkylamino, dialkylamino, alkyl, halo, cyano, haloalkyl, hydroxy, hydroxyalkyl, and alkoxy; and wherein one or more N ring members of said bicyclic heteroaryl is optionally an N-oxide; or
 (b) a five- or six-membered nitrogen-linked heterocycloalkyl ring fused to a phenyl or monocyclic heteroaryl, wherein said phenyl or heteroaryl is unsubstituted or is substituted with one or more substituent selected from the group consisting of deuterium, amino, alkylamino, dialkylamino, alkyl, halo, cyano, haloalkyl, hydroxy, hydroxyalkyl, and alkoxy; 
 
         R 1  is (1) R m  or -alkylenyl-R m , where R m  is cycloalkyl, heterocycloalkyl, phenyl, or monocyclic heteroaryl;
 wherein each of said cycloalkyl, heterocycloalkyl, phenyl, and heteroaryl is unsubstituted or is substituted with one or more substituents R x ;
 wherein each R x  substituent is independently selected from the group consisting of: deuterium, halo, hydroxy, hydroxyalkyl, cyano,
 —NR a R b , -alkylenyl-NR a R b , oxo, alkyl, cyanoalkyl, haloalkyl, alkoxy, —S-alkyl, haloalkoxy, alkoxyalkyl-, alkenyl, alkynyl, —C(O)alkyl, —C(O)alkyl-O-alkyl, —CO 2 alkyl, —CO 2 H, —CONH 2 , C(O)NH(alkyl), —C(O)NH(haloalkyl), —C(O)N(alkyl) 2 , —C(O)NH(cycloalkyl), arylalkyl-, arylalkoxy-, aryloxy-, cycloalkyl, cycloalkyloxy, (cycloalkyl)alkyl, heterocycloalkyl, aryl, (heterocycloalkyl)alkyl-, (heterocycloalkyl)alkoxy-, —C(O)cycloalkyl, —C(O)heterocycloalkyl, heteroaryl, (heteroaryl)alkyl-, —S(O)-alkyl, —SO 2 -alkyl, —SO 2 -aryl, —SO 2 -fluoroalkyl, —N(R c )—C(O)-alkyl, —N(R c )—C(O)-aryl, —N(R c )—CO-alkyl, —SO 2 NH 2 , —SO 2 NH(alkyl), —SO 2 N(alkyl) 2 , —SO 2 NH(cycloalkyl), and —N(H)(SO 2 alkyl), or two adjacent R x  substituents on a phenyl or heteroaryl R m  groups taken together form methylenedioxy, 
 wherein each of said cycloalkyl, heterocycloalkyl, aryl, and heteroaryl within R x  is unsubstituted or is substituted with one or more substituents independently selected from the group consisting of deuterium, alkyl, halo, hydroxy, cyano, alkoxy, amino, —C(O)alkyl, and —CO 2 alkyl; 
 wherein R a  and R b  are each independently H, alkyl, alkoxy, alkoxyalkyl, cyanoalkyl, or haloalkyl; and 
 R c  is H, alkyl or arylalkyl-; 
 
 
 (2) alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of deuterium, halo, hydroxy, cyano, alkoxy, haloalkoxy, —NR s R t , —C(O)alkyl, CO 2 alkyl, —CO 2 H, —CONR s R t , —SOalkyl, —SO 2 alkyl, and —SO 2 NR s R t ;
 where R s  and R t  are each independently H, alkyl, alkoxyalkyl, haloalkyl, —C(O)alkyl, or —CO 2 alkyl; or 
 
 (3) —N(R n )R o ,
 wherein R n  is H, R m , -alkylenyl-R m , hydroxyalkyl, cyanoalkyl, alkoxyalkyl, haloalkyl, —CONR h R i , or —C(O)R j ;
 where R m  is as defined in (1) above; 
 R h  and R i  are each independently H or alkyl, or R h  and R i  taken together with the nitrogen to which they are attached form a monocyclic heterocycloalkyl; and 
 R j  is an alkyl unsubstituted or substituted with one or more substituents selected from the group consisting of: deuterium, halo, amino, hydroxy, alkoxy, cycloalkyl, heteroaryl, phenyl, and heterocycloalkyl; or a cycloalkyl, heterocycloalkyl, phenyl, or heteroaryl, each unsubstituted or substituted with one or more substituents selected from the group consisting of: deuterium, alkyl, halo, amino, hydroxy, and alkoxy; and 
 
 
 R o  is H or R j ; 
 
         R 2  and R are each independently selected from the group consisting of H and deuterium; 
         wherein the compound of Formula I is not 1H-pyrrolo[3,2-c]pyridine-2-carboxylic acid (5-benzenesulfonyl-pyridin-2-ylmethyl)-amide; 
         or a pharmaceutically acceptable salt thereof.