Novel pyrrolidine bicyclic compounds and its derivatives, compositions and methods of use

Abstract

N-[1-oxo-(optionally 2-aza)-2-alkyl-3-(carboxyl or thiol or hydroxyaminocarbonyl or N-hydroxyformamido)-propyl]-(aryl or heteroaryl)-azacyclo 4-7 alkanes or thiazacyclo 4-7 alkanes, salts or prodrugs thereof have interesting properties, e.g., in the treatment or prevention of disorders amenable to treatment by PDF inhibitors, such as treatment of bacterial infections.

1 . (canceled) 
     
     
         2 . A compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is an aryl or heteroaryl which is linked to either the α- or β-position to the ring nitrogen; 
         R 2  is hydrogen, halogen or hydroxy; 
         R 3  is hydrogen, halogen, C 1-10  alkyl, C 1-10  heteroalkyl or (R 2  and R 3 ) collectively form a C 4-7  cycloalkyl, provided that when R 3  is halogen, R 2  is not hydroxy; 
         X is —CH 2 —; 
         W is NR 5  or C 4 R 5 , wherein R 4  is hydrogen, halogen, C 1-10  alkyl, or C 1-10  heteroalkyl and R 5  is C 1-10  alkyl or (R 4  and R 5 ) collectively form a C 4-7  cycloalkyl, provided that when W is NR 5 , R 2  and R 3  are hydrogen, C 1-10  alkyl or heteroalkyl; 
         Y is —COOH, —SH, —N(OH)—CHO or —CO—NH(OH), provided that when Y is —N(OH)CHO or —SH, R 2  is hydrogen and R 3  is hydrogen, C 1-10  alkyl or C 1-10  heteroalkyl; 
         n is 2; 
         a pharmaceutically acceptable salt thereof or a prodrug thereof. 
       
     
     
         3 . The compound of formula (I) according to  claim 2 , wherein Y is —CO—NH(OH). 
     
     
         4 . (canceled) 
     
     
         5 . The compound of formula (I) according to  claim 2 , wherein R 1  is hydroxy. 
     
     
         6 . The compound of formula (I) according to  claim 2 , wherein R 5  is n-butyl. 
     
     
         7 . The compound of formula (I) according to  claim 2 , wherein R 1  is heteroaryl. 
     
     
         8 . The compound of formula (I) according to  claim 2 , wherein the heteroaryl is oxazolyl, thiazolyl, pyridinyl and benzimidazolyl. 
     
     
         9 . The compound of formula (I) according to  claim 2 , wherein the heteroaryl is linked to the α-position to the nitrogen of the azacycloalkane represented in formula (I). 
     
     
         10 . The compound of formula (I) according to  claim 2 , wherein the heteroaryl is oxazolyl. 
     
     
         11 . (canceled) 
     
     
         12 . The compound of formula (I) according to  claim 2 , wherein the heteroaryl is thiazolyl. 
     
     
         13 . (canceled) 
     
     
         14 . The compound of formula (I) according to  claim 2 , wherein the heteroaryl is pyridinyl. 
     
     
         15 . The compound of formula (I) according to  claim 2 , wherein the heteroaryl is benzimidazolyl. 
     
     
         16 . The compound of formula (I) according to  claim 2 , wherein R 2  is hydrogen and W is N. 
     
     
         17 . The compound of formula (I) according to  claim 16 , wherein R 5  is a substituted lower alkyl. 
     
     
         18 . The compound of formula (I) according to  claim 16 , wherein R 1  is a heteroaryl. 
     
     
         19 . The compound of formula (I) according to  claim 16 , wherein the heteroaryl is oxazolyl or thiazolyl. 
     
     
         20 . The compound of formula (I) according to  claim 16 , wherein the heteroaryl is linked to the α-position of the azacycloalkane represented in formula (I). 
     
     
         21 - 23 . (canceled) 
     
     
         24 . The compound of formula (I) according to  claim 2 , wherein R 1  is an aryl. 
     
     
         25 . (canceled) 
     
     
         26 . The compound of formula (I) according to  claim 2 , wherein R 1  is halogen. 
     
     
         27 - 34 . (canceled) 
     
     
         35 . A pharmaceutical composition comprising a compound according to  claim 2  and a pharmaceutically acceptable carrier. 
     
     
         36 - 38 . (canceled) 
     
     
         39 . A method for inhibiting bacteria comprising contacting said bacteria with a bacteria inhibiting amount of a compound according to  claim 2  or a pharmaceutically acceptable salt thereof. 
     
     
         40 - 41 . (canceled)