Antimicrobial Compounds

Abstract

Cyclohexane and cyclohexene derivatives and pharmaceutically acceptable derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly man.

1 . A compound selected from compounds of formula (I); pharmaceutically acceptable salts of compounds of formula (I), and pharmaceutically acceptable N-oxides of compounds of formula (I), wherein formula (I) is: 
       
         
           
           
               
               
           
         
         wherein: 
         R v  and R w  are hydrogen or R v  and R w  together are a bond; 
         R A  is an optionally substituted bicyclic carbocyclic or heterocyclic ring system of structure: 
       
       
         
           
           
               
               
           
         
         containing 0-3 heteroatoms in each ring in which:
 at least one of rings (x) and (y) is aromatic; 
 one of Z 4  and Z 5  is C or N and the other is C; 
 Z 3  is N, NR 13 , O, S(O) x , CO, CR 1  or CR 1 R 1a ; 
 Z 1  and Z 2  are independently a 2 or 3 atom linker group each atom of which is independently selected from N, NR 13 , O, S(O) x , CO, CR 1  and CR 1 R 1a ; 
 
         such that each ring is independently substituted with 0-3 groups R 1  and/or R 1a ; 
         R 1  and R 1a  are independently selected from hydrogen; hydroxy; (C 1-6 ) alkoxy optionally substituted by (C 1-6 )alkoxy, amino, piperidyl, guanidino or amidino any of which is optionally N-substituted by one or two (C 1-6 )alkyl, acyl or (C 1-6 )alkylsulphonyl groups, CONH 2 , hydroxy, (C 1-6 )alkylthio, heterocyclylthio, heterocyclyloxy, arylthio, aryloxy, acylthio, acyloxy or (C 1-6 )alkylsulphonyloxy; (C 1-6 )alkoxy-substituted (C 1-6 )alkyl; hydroxy (C 1-6 )alkyl; halogen; (C 1-6 )alkyl; (C 1-6 )alkylthio; trifluoromethyl; trifluoromethoxy; cyano; carboxy; nitro; azido; acyl; acyloxy; acylthio; 
         (C 1-6 )alkylsulphonyl; (C 1-6 )alkylsulphoxide; arylsulphonyl; arylsulphoxide or an amino, piperidyl, guanidino or amidino group optionally N-substituted by one or two (C 1-6 )alkyl, acyl or (C 1-6 )alkylsulphonyl groups, or when Z 3  and the adjacent atom are CR 1  and CR 1a , R 1  and R 1a  may together represent (C 1-2 )alkylenedioxy, 
         wherein acyl is (C 1-6 )alkoxycarbonyl, formyl, or (C 1-6 )alkylcarbonyl; 
         provided that R 1  and R 1a , on the same carbon atom are not both optionally substituted hydroxy or amino; 
         provided that 
         (i) when R A  is optionally substituted quinolin-4-yl:
 it is unsubstituted in the 6-position; or 
 it is substituted by at least one hydroxy (C 1-6 )alkyl, cyano or carboxy group at the 2-, 5-, 6-, 7- or 8-position; or 
 it is substituted by at least one trifluoromethoxy group; or 
 R 3  is halogen; 
 
         (ii) when R A  is optionally substituted quinazolin-4-yl, cinnolin-4-yl, 1,5-naphthyridin-4-yl, 1,7-naphthyridin-4-yl or 1,8-naphthyridin-4-yl:
 it is substituted by at least one hydroxy (C 1-6 )alkyl, cyano or carboxy group at the 2-, 5-, 6-, 7- or 8-position as available; or 
 it is substituted by at least one trifluoromethoxy group; or 
 R 3  is halogen; 
 
         R 2  is hydrogen, or (C 1-4 )alkyl or (C 2-4 )alkenyl optionally substituted with 1 to 3 groups selected from: 
         amino optionally substituted by one or two (C 1-4 )alkyl groups; carboxy; (C 1-4 )alkoxycarbonyl; (C 1-4 )alkylcarbonyl; (C 2-4 )alkenyloxycarbonyl; (C 2-4 )alkenylcarbonyl; aminocarbonyl wherein the amino group is optionally substituted by hydroxy, (C 1-4 )alkyl, hydroxy(C 1-4 )alkyl, aminocarbonyl(C 1-4 )alkyl, (C 2-4 )alkenyl, (C 1-4 )alkylsulphonyl, trifluoromethylsulphonyl, (C 2-4 )alkenylsulphonyl, (C 1-4 )alkoxycarbonyl, (C 1-4 )alkylcarbonyl, (C 2-4 )alkenyloxycarbonyl or (C 2-4 )alkenylcarbonyl; cyano; tetrazolyl; 2-oxo-oxazolidinyl optionally substituted by R 10 ; 3-hydroxy-3-cyclobutene-1,2-dione-4-yl; 2,4-thiazolidinedione-5-yl; tetrazol-5-ylaminocarbonyl; 1,2,4-triazol-5-yl optionally substituted by R 10 ; 5-oxo-1,2,4-oxadiazol-3-yl; halogen; (C 1-4 )alkylthio; trifluoromethyl; hydroxy optionally substituted by (C 1-4 )alkyl, (C 2-4 )alkenyl, (C 1-4 )alkoxycarbonyl, (C 1-4 )alkylcarbonyl, (C 2-4 )alkenyloxycarbonyl, (C 2-4 )alkenylcarbonyl; oxo; (C 1-4 )alkylsulphonyl; (C 2-4 )alkenylsulphonyl; or (C 1-4 )aminosulphonyl wherein the amino group is optionally substituted by (C 1-4 )alkyl or (C 2-4 )alkenyl; 
         R 3  is hydrogen; or 
         when R v  and R w  are a bond, R 3  is in the 2-, 3- or 4-position and when R v  and R w  are not a bond, R 3  is in the 1-, 2-, 3- or 4-position and R 3  is: 
         carboxy; (C 1-6 )alkoxycarbonyl; aminocarbonyl wherein the amino group is optionally substituted by hydroxy, (C 1-6 )alkyl, hydroxy(C 1-6 )alkyl, aminocarbonyl(C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )alkylsulphonyl, trifluoromethylsulphonyl, (C 2-6 )alkenylsulphonyl, (C 1-6 )alkoxycarbonyl, (C 1-6 )alkylcarbonyl, (C 2-6 )alkenyloxycarbonyl or (C 2-6 )alkenylcarbonyl and optionally further substituted by (C 1-6 )alkyl, hydroxy(C 1-6 )alkyl, aminocarbonyl(C 1-6 )alkyl or (C 2-6 )alkenyl; cyano; tetrazolyl; 2-oxo-oxazolidinyl optionally substituted by R 10 ; 3-hydroxy-3-cyclobutene-1,2-dione-4-yl; 2,4-thiazolidinedione-5-yl; tetrazol-5-ylaminocarbonyl; 1,2,4-triazol-5-yl optionally substituted by R 10 ; or 5-oxo-1,2,4-oxadiazol-3-yl; or 
         (C 1-4 )alkyl or ethenyl optionally substituted with any of the groups listed above for R 3  and/or 0 to 2 groups R 12  independently selected from:
 halogen; (C 1-6 )alkylthio; trifluoromethyl; (C 1-6 )alkoxycarbonyl; (C 1-6 )alkylcarbonyl; (C 2-6 )alkenyloxycarbonyl; (C 2-6 )alkenylcarbonyl; hydroxy optionally substituted by (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )alkoxycarbonyl, (C 1-6 )alkylcarbonyl, (C 2-6 )alkenyloxycarbonyl, (C 2-6 )alkenylcarbonyl or aminocarbonyl wherein the amino group is optionally substituted by (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )alkylcarbonyl or (C 2-6 )alkenylcarbonyl; amino optionally mono- or disubstituted by (C 1-6 )alkoxycarbonyl, (C 1-6 )alkylcarbonyl, (C 2-6 )alkenyloxycarbonyl, (C 2-6 )alkenylcarbonyl, (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )alkylsulphonyl, (C 2-6 )alkenylsulphonyl or aminocarbonyl wherein the amino group is optionally substituted by (C 1-6 )alkyl or (C 2-6 )alkenyl; aminocarbonyl wherein the amino group is optionally substituted by (C 1-6 )alkyl, hydroxy(C 1-6 )alkyl, aminocarbonyl(C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )alkoxycarbonyl, (C 1-6 )alkylcarbonyl, (C 2-6 )alkenyloxycarbonyl or (C 2-6 )alkenylcarbonyl and optionally further substituted by (C 1-6 )alkyl, hydroxy(C 1-6 )alkyl, aminocarbonyl(C 1-6 )alkyl or (C 2-6 )alkenyl; oxo; 
 
         (C 1-6 )alkylsulphonyl; (C 2-6 )alkenylsulphonyl; or (C 1-6 )aminosulphonyl wherein the amino group is optionally substituted by (C 1-6 )alkyl or (C 2-6 )alkenyl; or 
         hydroxy optionally substituted by (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )alkoxycarbonyl, (C 1-6 )alkylcarbonyl, (C 2-6 )alkenyloxycarbonyl, (C 2-6 )alkenylcarbonyl or aminocarbonyl wherein the amino group is optionally substituted by (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )alkylcarbonyl or (C 2-6 )alkenylcarbonyl; or 
         amino optionally mono- or disubstituted by (C 1-6 )alkoxycarbonyl, (C 1-6 )alkylcarbonyl, (C 2-6 )alkenyloxycarbonyl, (C 2-6 )alkenylcarbonyl, (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )alkylsulphonyl, (C 2-6 )alkenylsulphonyl or aminocarbonyl wherein the amino group is optionally substituted by (C 1-6 )alkyl or (C 2-6 )alkenyl; or halogen; 
         provided that when R 3  is in the 4-position it is not optionally substituted hydroxyl or amino or halogen; 
         in addition when R 3  is disubstituted with a hydroxy or amino containing substituent and a carboxy containing substituent these may optionally together form a cyclic ester or amide linkage, respectively; 
         R 10  is selected from (C 1-4 )alkyl and (C 2-4 )alkenyl either of which may be optionally substituted by a group R 12  as defined above; carboxy; aminocarbonyl wherein the amino group is optionally substituted by hydroxy, (C 1-6 )alkyl, (C 2-6 )alkenyl, (C 1-6 )alkylsulphonyl, trifluoromethylsulphonyl, (C 2-6 )alkenylsulphonyl, (C 1-6 )alkoxycarbonyl, (C 1-6 )alkylcarbonyl, (C 2-6 )alkenyloxycarbonyl or (C 2-6 )alkenylcarbonyl and optionally further substituted by (C 1-6 )alkyl or (C 2-6 )alkenyl; (C 1-6 )alkylsulphonyl; trifluoromethylsulphonyl; (C 2-6 )alkenylsulphonyl; (C 1-6 )alkoxycarbonyl; (C 1-6 )alkylcarbonyl; (C 2-6 )alkenyloxycarbonyl; and (C 2-6 )alkenylcarbonyl; 
         R 4  is a group —U—R 5   2  where R 5   2  includes a 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl group; a 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl group; a 3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl group; a 3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl group; a 2-oxo-2,3-dihydro-1H-pyrido[3,4-b][1,4]oxazin-7-yl group; or a 1H-pyrido[2,3-b][1,4]thiazin-2-one-7-yl group; 
         U is CO, SO 2  or CH 2 ; 
         n is 0 or 1 and AB is NR 11 CO, CONR 11 , CO—CR 8 R 9 , CR 6 R 7 —CO, O—CR 8 R 9 , CR 6 R 7 —O, NHR 11 —CR 8 R 9 , CR 6 R 7 —NHR 11 , NR 11 SO 2 , CR 6 R 7 —SO 2  or CR 6 R 7 —CR 8 R 9 , provided that when R v  and R w  are a bond and n=0, B is not NR 11 , O or SO 2 , 
         or n is 0 and AB is NH—CO—NH or NH—CO—O and R v /R w  are not a bond; 
         or n is 0 and AB is CR 6 R 7 SO 2 NR 2 , CR 6 R 7 CONR 2  or CR 6 R 7 CH 2 NR 2  and R v /R w  are not a bond; 
         provided that R 6  and R 7 , and R 8  and R 9  are not both optionally substituted hydroxy or amino; 
         and wherein: 
         each of R 6 , R 7 , R 8  and R 9  is independently selected from: H; (C 1-6 )alkoxy; (C 1-6 )alkylthio; halo; trifluoromethyl; azido; (C 1-6 )alkyl; (C 2-6 )alkenyl; (C 1-6 )alkoxycarbonyl; (C 1-6 )alkylcarbonyl; (C 2-6 )alkenyloxycarbonyl; (C 2-6 )alkenylcarbonyl; hydroxy, amino or aminocarbonyl optionally substituted as for corresponding substituents in R 3 ; (C 1-6 )alkylsulphonyl; (C 2-6 )alkenylsulphonyl; or (C 1-6 )aminosulphonyl wherein the amino group is optionally substituted by (C 1-6 )alkyl or (C 2-6 )alkenyl; 
         or R 6  and R 8  together represent a bond and R 7  and R 9  are as above defined; 
         and each R 11  is independently H; trifluoromethyl; (C 1-6 )alkyl; (C 2-6 )alkenyl; (C 1-6 )alkoxycarbonyl; (C 1-6 )alkylcarbonyl; or aminocarbonyl wherein the amino group is optionally substituted by (C 1-6 )alkoxycarbonyl, (C 1-6 )alkylcarbonyl, (C 2-6 )alkenyloxycarbonyl, (C 2-6 )alkenylcarbonyl, (C 1-6 )alkyl or (C 2-6 )alkenyl and optionally further substituted by (C 1-6 )alkyl or (C 2-6 )alkenyl; 
         or where one of R 3  and R 6 , R 7 , R 8  or R 9  contains a carboxy group and the other contains a hydroxy or amino group they may together form a cyclic ester or amide linkage or where R 3  contains a carboxy group and A or B is NH they may be condensed to form a cyclic amide. 
       
     
     
         2 . The compound according to  claim 1  wherein R A  is optionally substituted isoquinolin-5-yl, quinolin-8-yl, thieno[3,2-b]pyridin-7-yl, 2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-8-yl, quinoxalin-5-yl, isoquinolin-8-yl, [1,6]-naphthyridin-4-yl, 1,2,3,4-tetrahydroquinoxalin-5-yl or 1,2-dihydroisoquinoline-8-yl. 
     
     
         3 . The compound according to  claim 1  wherein R 1  is hydrogen, methoxy, methyl, cyano or halogen and R 1a  is H. 
     
     
         4 . The compound according to  claim 1  wherein R 2  is hydrogen. 
     
     
         5 . The compound according to  claim 1  wherein R 3  is hydrogen, fluoro or hydroxy substituted in the 1- or 3-position. 
     
     
         6 . The compound according to  claim 1  wherein n is 0 and either A and B are both CH 2 ; A is CHOH or CH 2  and B is CH 2 ; or A is NH and B is CO. 
     
     
         7 . The compound according to  claim 1  wherein R 5   2  is
 3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl;   3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl;   7-chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl; or   7-fluoro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl.   
     
     
         8 . A compound, selected from the group consisting of:
 1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid thieno[3,2-b]pyridin-7-ylamide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (2,3-dihydro-[1,4]dioxino[2,3-b]pyridin-8-yl)-amide;   trans-4-[(3-Oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid quinolin-4-ylamide;   trans-4-[(3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid isoquinolin-5-ylamide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (2-methoxy-quinolin-8-yl)-amide;   4-[(3,4-Dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-1-hydroxy-cyclohexanecarboxylic acid (2-methoxy-quinolin-8-yl)-amide;   6-({4-Hydroxy-4-[2-(2-methoxy-quinolin-8-yl)-ethyl]-cyclohexylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;   6-({4-Hydroxy-4-[2-(2-methoxy-quinolin-8-yl)-ethyl]-cyclohexylamino}-methyl)-4H-pyrido[3,2-b][1,4]thiazin-3-one;   (1R,3S,4R)-3-Hydroxy-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (2-cyano-quinolin-8-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (2-cyano-quinolin-8-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (2-cyano-quinolin-8-yl)-amide;   (1S,3R,4S)-3-Hydroxy-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (2-cyano-quinolin-8-yl)-amide;   (1S,3R,4S)-3-Hydroxy-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (2-cyano-quinolin-8-yl)-amide;   (1R,3R,4R)-3-Hydroxy-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (2-cyano-quinolin-8-yl)-amide;   (1R,3R,4R)-3-Hydroxy-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (2-cyano-quinolin-8-yl)-amide;   (1R,3S,4R)-3-Hydroxy-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (2-cyano-quinolin-8-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (2-methoxy-quinolin-8-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (2-methyl-quinolin-8-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (2-methyl-quinolin-8-yl)-amide;   (1R,3R,4R)-3-Hydroxy-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (2-methoxy-quinolin-8-yl)-amide;   7-({r-4-Hydroxy-4-[2-(2-methoxy-quinolin-8-yl)-ethyl]-c-cyclohexylamino}-methyl)-1H-pyrido[2,3-b][1,4]thiazin-2-one;   1-Hydroxy-t-4-[(2-oxo-2,3-dihydro-1H-pyrido[3,4-b][1,4]oxazin-7-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (2-methyl-quinolin-8-yl)-amide;   t-4-[(7-Fluoro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-1-hydroxy-r-cyclohexanecarboxylic acid (2-methoxy-quinolin-8-yl)-amide;   t-4-[(7-Chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-1-hydroxy-r-cyclohexanecarboxylic acid (2-methoxy-quinolin-8-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (3-methyl-quinoxalin-5-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (2-methyl-1-oxo-1,2-dihydro-isoquinolin-8-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (1-methoxy-isoquinolin-8-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (5-methoxy-quinolin-4-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid [1,6]naphthyridin-4-ylamide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (2-methyl-quinoxalin-5-yl)-amide;   (1R,3S,4R)-3-Fluoro-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b]][1,4]oxazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;   (1R,3S,4R)-3-Fluoro-4-[(7-fluoro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-ylmethyl)-amino]-c-cyclohexanecarboxylic acid (3-methyl-1,2,3,4-tetrahydro-quinoxalin-5-yl)-amide;   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2Hpyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (3-methoxy-quinoxalin-5-yl)-amide; and   1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (6-cyano-quinolin-4-yl)-amide;   or a pharmaceutically acceptable salt thereof.   
     
     
         9 . A method of treatment of bacterial infection due to  Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Haemophilus influenzae, E. coli , or  Moraxella catarrhalis  in mammals, which method comprises the administration to a mammal in need of such treatment an effective amount of the compound according to  claim 1 . 
     
     
         10 . A pharmaceutical composition comprising the compound according to  claim 1 , and a pharmaceutically acceptable excipient. 
     
     
         11 . A method of treatment of bacterial infection due to  Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Enterococcus faecalis, Haemophilus influenzae, E. coli , or  Moraxella catarrhalis  in mammals, which method comprises the administration to a mammal in need of such treatment an effective amount of the compound according to  claim 7 . 
     
     
         12 . A pharmaceutical composition comprising the compound according to  claim 11 , and a pharmaceutically acceptable excipient. 
     
     
         13 . The compound according to  claim 1  wherein R A  is 2-methyl-1-oxo-1,2-dihydro-isoquinolin-8-yl. 
     
     
         14 . The compound according to  claim 1  wherein R A  is 3-methoxy-quinoxalin-5-yl. 
     
     
         15 . The compound according to  claim 1  wherein the compound is a compound of formula (I). 
     
     
         16 . The compound according to  claim 1  wherein the compound is a pharmaceutically acceptable salt of a compound of formula (I).