Nitrogen-containing bicycle heterocycles for use as antibacterials

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 of formula (I) or a pharmaceutically acceptable salt, solvate or N-oxide thereof:  
     
       
         
         
             
             
         
       
       wherein:  
       one of Z 1 , Z 2 , Z 3 , Z 4  and Z 5  is CR 1a  and the remainder are CH;  
       R v  and R w  are hydrogen; R v  is R 3 ; or R v  and R w  together are a bond;  
       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 amino, piperidyl, guanidino or amidino is optionally N-substituted by one or two (C 1-6 )alkyl, (C 1-6 )alkoxy-carbonyl, formyl, (C 1-6 )alkylcarbonyl or (C 1-6 )alkylsulphonyl groups, CONH 2 , hydroxy, (C 1-6 )alkylthio, heterocyclylthio, heterocyclyloxy, arylthio, aryloxy, (C 1-6 )alkoxycarbonylthio, formylthio, (C 1-6 )alkylcarbonylthio, (C 1-6 )alkoxy-carbonyloxy, formyloxy, (C 1-6 )alkylcarbonyloxy or (C 1-6 )-alkylsulphonyloxy; (C 1-6 )alkoxy-substituted (C 1-6 )alkyl; halogen; (C 1-6 )alkyl; (C 1-6 )alkylthio; trifluoromethyl; nitro; azido; (C 1-6 )alkoxycarbonyl; formyl; (C 1-6 )alkylcarbonyl; (C 1-6 )alkoxycarbonylthio; formylthio; (C 1-6 )alkylcarbonylthio; (C 1-6 )alkoxycarbonyloxy; formyloxy; (C 1-6 )alkyl carbonyloxy; (C 1-6 )alkylsulphonyl; (C 1-6 )alkylsulphoxide; arylsulphonyl; arylsulphoxide or an amino, piperdinyl, guanidine or amidino group optionally N-substituted by one or two (C 1-6 )alkyl, (C 1-6 )alkoxycarbonyl, formyl, (C 1-6 )-alkylcarbonyl or (C 1-6 )alkylsulphonyl groups, or when Z 1  is CR 1a  R 1  and R 1a  may together represent (C 1-2 ) alkylenedioxy, provided that R 1  is not hydrogen;  
       or when Z 5  is CR 1a , R 1a  may instead be cyano, hydroxymethyl or carboxy;  
       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;  
       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:  
       hydrogen; 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 2-4 )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 )alkyl-carbonyl, (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;  
       provided that when R 3  is in the 4-position it is not optionally substituted hydroxyl or amino;  
       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 —CH 2 —R 5   1  in which R 5   1  is selected from: 
 (C 4-8 )alkyl; hydroxy(C 4-8 )alkyl; (C 2-4 )alkoxy(C 4-8 )alkyl; (C 2-4 )alkanoyloxy(C 4-8 )alkyl; (C 3-8 )cycloalkyl(C 4-8 )alkyl; hydroxy-, (C 1-6 )alkoxy- or (C 1-6 )alkanoyloxy-(C 3-8 )cycloalkyl(C 4-8 )alkyl; cyano(C 4-8 )alkyl; (C 4-8 )alkenyl; (C 4-8 )alkynyl; tetrahydrofuryl; mono- or di-(C 1-6 )alkylamino(C 4-8 )alkyl; acylamino(C 4-8 )alkyl; (C 1-6 )alkyl- or acyl-aminocarbonyl(C 4-8 )alkyl; mono- or di-(C 1-6 )alkylamino(hydroxy) (C 4-8 )alkyl; or  
 
       R 4  is a group —U—R 5   2  where R 5   2  is an optionally substituted bicyclic carbocyclic or heterocyclic ring system (A):  
       
         
           
           
               
               
           
         
       
        containing up to four heteroatoms in each ring in which 
 at least one of rings (a) and (b) is aromatic;  
 X 1  is C or N when part of an aromatic ring or CR 14  when part of a non aromatic ring;  
 X 2  is N, NR 13 , O, S(O) x , CO or CR 14  when part of an aromatic or non-aromatic ring or may in addition be CR 14 R 15  when part of a non aromatic ring;  
 X 3  and X 5  are independently N or C;  
 y 1  is a 0 to 4 atom linker group each atom of which is independently selected from N, NR 13 , O, S(O) x , CO and CR 14  when part of an aromatic or non-aromatic ring or may additionally be CR 14 R 15  when part of a non aromatic ring,  
 y 2  is a 2 to 6 atom linker group, each atom of y 2  being independently selected from N, NR 13 , O, S(O) x , CO and CR 14  when part of an aromatic or non-aromatic ring or may additionally be CR 14 R 15  when part of a non aromatic ring; each of R 14  and R 15  is independently selected from: H; (C 1-4 )alkylthio; halo; carboxy(C 1-4 )alkyl; halo(C 1-4 )alkoxy; halo(C 1-4 )alkyl; (C 1-4 )alkyl; (C 2-4 )alkenyl; (C 1-4 )alkoxycarbonyl; formyl; (C 1-4 )alkylcarbonyl; (C 2-4 )alkenyloxycarbonyl; (C 2-4 )alkenylcarbonyl; (C 1-4 )alkylcarbonyloxy; (C 1-4 )alkoxycarbonyl(C 1-4 )alkyl; hydroxy; hydroxy(C 1-4 )alkyl; mercapto(C 2-4 )alkyl; (C 2-4 )alkoxy; nitro; cyano; carboxy; amino or aminocarbonyl optionally substituted as for corresponding substituent in R 3 ; (C 1-4 )alkylsulphonyl; (C 2-4 )alkenylsulphonyl; or aminosulphonyl wherein the amino group is optionally substituted by (C 1-4 )alkyl or (C 2-4 )alkenyl; aryl; aryl(C 1-4 )alkyl; aryl(C 1-4 )alkoxy;  
 each R 13  is independently H; trifluoromethyl; (C 1-4 )alkyl optionally substituted by hydroxy, carboxy, (C 1-6 )alkoxycarbonyl, (C 1-6 )alkoxy, (C 1-6 )alkylthio, halo or trifluoromethyl; (C 2-4 )alkenyl; aryl; aryl (C 1-4 )alkyl; arylcarbonyl; heteroarylcarbonyl; (C 1-4 )alkoxycarbonyl; (C 2-4 )alkylcarbonyl; formyl; (C 1-6 )alkylsulphonyl; or aminocarbonyl wherein the amino group is optionally substituted by (C 1-4 )alkoxycarbonyl, (C 1-4 )alkylcarbonyl, (C 2-4 )alkenyloxycarbonyl, (C 2-4 )alkenylcarbonyl, (C 1-4 )alkyl or (C 2-4 )alkenyl and optionally further substituted by (C 1-   4 )alkyl or (C 2-4 )alkenyl;  
 each x is independently 0, 1 or 2;  
 
       U is CO, SO 2  or CH 2 ; or  
       R 4  is a group —X 1a —X 2a —X 3a —X 4a  in which: 
 X 1a  is CH 2 , CO or SO 2 ;  
 X 2a  is CR 14a R 15a ;  
 X 3a  is NR 13a , O, S, SO 2  or CR 14a R 15a ; wherein:  
 each of R 14a  and R 15a  is independently selected from the groups listed above for R 14  and R 15 , provided that R 14a  and R 15a  on the same carbon atom are not both selected from optionally substituted hydroxy and optionally substituted amino; or  
 R 14a  and R 15a  together represent oxo;  
 R 13 a is hydrogen; 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  
 two R 14a  groups or an R 13a  and an R 14a  group on adjacent atoms together represent a bond and the remaining R 13a , R 14a  and R 15a  groups are as above defined; or  
 two R 14a  groups and two R 15a  groups on adjacent atoms together represent bonds such that X 2a  and X 3a  is triple bonded;  
 X 4a  is phenyl or C or N linked monocyclic aromatic 5- or 6-membered heterocycle containing up to four heteroatoms selected from O, S and N and: optionally C-substituted by up to three groups selected from (C 1-4 )alkylthio; halo; carboxy(C 1-4 )alkyl; halo(C 1-4 )alkoxy; halo(C 1-4 )alkyl; (C 1-4 )alkyl; (C 2-4 )alkenyl; (C 1-4 )alkoxycarbonyl; formyl; (C 1-4 )alkylcarbonyl; (C 2-4 )alkenyloxycarbonyl; (C 2-4 )alkenylcarbonyl; (C 1-4 )alkylcarbonyloxy; (C 1-4 )alkoxycarbonyl(C 1-4 )alkyl; hydroxy; hydroxy(C 1-4 )alkyl; mercapto(C 1-4 )alkyl; (C 1-4 )alkoxy; nitro; cyano; carboxy; amino or aminocarbonyl optionally substituted as for corresponding substituent in R 3 ; (C 1-4 )alkylsulphonyl; (C 2-4 )alkenylsulphonyl; or aminosulphonyl wherein the amino group is optionally substituted by (C 1-4 )alkyl or (C 2-4 )alkenyl; aryl, aryl(C 1-4 )alkyl or aryl(C 1-4 )alkoxy; and  
 
       optionally N substituted by trifluoromethyl; (C 1-4 )alkyl optionally substituted by hydroxy, (C 1-6 )alkoxy, (C 1-6 )alkylthio, halo or trifluoromethyl; (C 2-4 )alkenyl; aryl; aryl(C 1-4 )alkyl; (C 1-4 )alkoxycarbonyl; (C 1-4 )alkylcarbonyl; formyl; (C 1-6 )alkylsulphonyl; or aminocarbonyl wherein the amino group is optionally substituted by (C 1-4 )alkoxycarbonyl, (C 1-4 )alkylcarbonyl, (C 2-4 )alkenyloxycarbonyl, (C 2-4 )alkenylcarbonyl, (C 1-4 )alkyl or (C 2-4 )alkenyl and optionally further substituted by (C 1-4 )alkyl or (C 2-4 )alkenyl;  
       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, NR 11 —CR 8 R 9 , CR 6 R 7 —NR 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 substituent 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.  
     
   
   
       2 . A compound according to  claim 1  wherein Z 5  is CH, Z 3  is CH or CF and Z 1 , Z 2  and Z 4  are each CH.  
   
   
       3 . A compound according to  claim 1  wherein R 1  is methoxy or fluoro and R 1a  is H or when Z 3  is CR 1a  it may be C—F.  
   
   
       4 . A compound according to  claim 1  wherein R 2  is hydrogen.  
   
   
       5 . A compound according to  claim 1  wherein R 3  is hydrogen or hydroxy substituted in the 1- or 3-position.  
   
   
       6 . A compound according to  claim 1  wherein n is 0 and either A is CHOH or CH 2  and B is CH 2  or A is NH and B is CO, and AB(CH 2 )n and NR 2 R 4  are trans.  
   
   
       7 . A compound according to  claim 1  wherein R 4  is —U—R 5   2 , the group —U— is —CH 2 —, and R 5   2  is an aromatic heterocyclic ring (A) having 8-11 ring atoms including 2-4 heteroatoms of which at least one is N or NR 13  in which y 2  contains 2-3 heteroatoms, one of which is S and 1-2 are N, with one N bonded to X 3 , or the heterocyclic ring (A) has ring (a) aromatic selected from optionally substituted benzo and pyrido and ring (b) non-aromatic and y 2  has 3-5 atoms including a heteroatom bonded to X 5  selected from NR 13 , O or S bonded to X 5 , where R 13  is other than hydrogen, and NHCO bonded via N to X 3 , or O bonded to X 3 .  
   
   
       8 . A compound according to  claim 1  wherein R 5   2  is selected from: 
 benzo[1,2,5]thiadiazol-5-yl;    3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-yl (4H-benzo[1,4]thiazin-3-one-6-yl)    2,3-dihydro-benzo[1,4]dioxin-6-yl;    benzo[1,2,3]thiadiazol-5-yl;    3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl;    7-fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-yl;    2-oxo-2,3-dihydro-1H-pyrido[2,3-b]thiazin-7-yl;    2,3-Dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl;    3-oxo-3,4-dihydro-2H-pyrido[2,3-b]oxazin-6-yl; and    [1,2,3]thiadiazolo[5,4-b]pyridin-6-yl.    
   
   
       9 . A compound selected from: 
 Trans-4-[(2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (8-fluoro-6-methoxy-quinolin-4-yl)-amide;    Trans-4-[(2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-quinolin-4-yl)-amide;    Trans-4-[(Benzo[1,2,5]thiadiazol-5-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-quinolin-4-yl)-amide;    Trans-4-[(2-Oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-quinolin-4-yl)-amide;    Trans-6-({4-[2-Hydroxy-2-(6-methoxy-quinolin-4-yl)-ethyl]-cyclohexylamino}-methyl)-4-H-benzo[1,4]thiazin-3-one;    Trans-2-{4-[(2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-cyclohexyl}-1-(6-methoxy-quinolin-4-yl)-ethanol;    Trans-2-{4-[(2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-cyclohexyl}-1-(6-methoxy-quinolin-4-yl)-ethanone;    Trans 4-[(3-Oxo-3,4-dihydro-2-H-benzo[1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-quinolin-4-yl)-amide;    Trans-4-[(3-Oxo-3,4-dihydro-2-H-benzo[1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (8-fluoro-6-methoxy-quinolin-4-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 (2,3-dihydro-[1,4]dioxino[2,3-f]quinolin-10-yl)-amide;    (1S,3S,4S)-3-Hydroxy-4-[-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6,8-difluoro-quinolin-4-yl)-amide    and (1R,3R,4R)-3-Hydroxy-4-[-4-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][]1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6,8-difluoroquinolin-4-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 (8-fluoro-6-methoxy-quinolin-4-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 (6-methoxy-quinolin-4-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 (6,8-difluoro-quinolin-4-yl)-amide; and    compounds of Table A, B and C:                TABLE A                                                                       LINKER   R                   NHCONH   (CH 2 ) 4 Me         NHCONH   (CH 2 ) 4 Me         trans stereochem.         NHCONH   quinoxalin-2-yl         CONH   quinoxalin-2-yl         NHCO   (CH 2 ) 5 Me         CH(OH)CH 2 NH   (CH 2 ) 4 Me         NHCOO   3-oxo-3,4-dihydro-2H-pyrido[3,2-             b][1,4]thiazin-6-yl                                                                                                             TABLE B                                                                   Stereochemistry   X   R           1S,3S,4S/1R,3R,4R   CH   3-Oxo-3,4-dihydro-2H-pyrido             [3,2-b][1,4]thiazin-6-yl                                                                                              TABLE C                                                               X   R           F   2,3-Dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl                                       F   2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-yl                                       H   7-Bromo-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl                                       H   2,3-Dihydro-[1,4]dioxino[2,3-c]pyridin-7-yl                                       H   3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazin-6-yl                                       OMe   3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl                                       F   7-Chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-yl                                                                                                or a pharmaceutically acceptable salt, solvate or N-oxide of any of the foregoing compounds.    
   
   
       10 . A method of treatment of bacterial infections in mammals, which method comprises the administration to a mammal in need of such treatment an effective amount of a compound according to  claim 1 .  
   
   
       11 . (canceled)  
   
   
       12 . A pharmaceutical composition comprising a compound according to  claim 1 , and a pharmaceutically acceptable carrier.  
   
   
       13 . (canceled)  
   
   
       14 . A compound of formula (VI):  
     
       
         
         
             
             
         
       
       wherein the variables R 1 , Z 1 -Z 5 , A, B, n, R v , R w  and R 3  are as described for formula (I) in  claim 1 .  
     
   
   
       15 . A compound of formula (VII):  
     
       
         
         
             
             
         
       
       wherein the variables R 1 , Z 1 -Z 5 , A, B, n, R v , R w  and R 3  are as described for formula (I) in  claim 1 .  
     
   
   
       16 . The method of  claim 10  wherein the mammal is human.