NOVEL PYRROLIDINE BICYCLIC COMPOUNDS AND ITS DERIVATIVES, COMPOSITIONS AND METHODS OF USE
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)