US 2004/0171620 A1Published application

Nitrogen-containing bicyclic heterocycles for use as antibacterials

AssigneeSmithKline Beecham Corporation

InventorsGerald Brooks, David Thomas Davies, Graham Elgin Jones, Roger Edward Markwell, Neil David Pearson

Life of this patent

Estimating the term…

Abstract

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

Claims15

Dependent claims

A compound of formula (I) or a pharmaceutically acceptable derivative thereof:

138
wherein:
one of Z1, Z2, Z3, Z4 and Z5 is N, one is CR1a and the remainder are CH, or one of Z1, Z2, Z3, Z4 and Z5 is CR1a and the remainder are CH;
Rv and Rw are hydrogen or Rv and Rw together are a bond;
R1 and R1a are independently selected from hydrogen;
hydroxy;
(C1-6) alkoxy optionally substituted by (C1-6)alkoxy, amino, piperidyl, guanidino or amidino any of which is optionally N-substituted by one or two (C1-6)alkyl, acyl or (C1-6)alkylsulphonyl groups, CONH2, hydroxy, (C1-6)alkylthio, heterocyclylthio, heterocyclyloxy, arylthio, aryloxy, acylthio, acyloxy or (C1-6)alkylsulphonyloxy;
(C1-6)alkoxy-substituted (C1-6)alkyl;
halogen;
(C1-6)alkyl;
(C1-6)alkylthio;
trifluromethyl;
nitro;
azido;
acyl;
acyloxy;
acylthio;
(C1-6)alkylsulphonyl;
(C1-6)alkylsulphoxide;
arylsulphonyl;
arylsulphoxide or an amino, piperidyl, guanidino or amidino group optionally N-substituted by one or two (C1-6)alkyl, acyl or (C1-6)alkylsulphonyl groups, or when Z1 is CR1a, R1 and R1a may together represent (C1-2)alkylenedioxy,
provided that when Z1, Z2, Z3, Z4 and Z5 are CR1a or CH, then R1 is not hydrogen;
R2 is hydrogen, or (C1-4)alkyl or (C2-4)alkenyl optionally substituted with 1 to 3 groups selected from:
amino optionally substituted by one or two (C1-4)alkyl groups;
carboxy;
(C1-4)alkoxycarbonyl;
(C1-4)alkylcarbonyl;
(C2-4)alkenyloxycarbonyl;
(C2-4)alkenylcarbonyl;
aminocarbonyl wherein the amino group is optionally substituted by hydroxy, (C1-4)alkyl, hydroxy(C1-4)alkyl, aminocarbonyl(C1-4)alkyl, (C2-4)alkenyl, (C1-4)alkylsulphonyl, trifluoromethylsulphonyl, (C2-4)alkenylsulphonyl, (C1-4)alkoxycarbonyl, (C1-4)alkylcarbonyl, (C2-4)alkenyloxycarbonyl or (C2-4)alkenylcarbonyl;
cyano;
tetrazolyl;
2-oxo-oxazolidinyl optionally substituted by R10;
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 R10;
5-oxo-1,2,4-oxadiazol-3-yl;
halogen;
(C1-4)alkylthio;
trifluoromethyl;
hydroxy optionally substituted by (C1-4)alkyl, (C2-4)alkenyl, (C1-4)alkoxycarbonyl, (C1-4)alkylcarbonyl, (C2-4)alkenyloxycarbonyl, (C2-4)alkenylcarbonyl;
oxo;
(C1-4)alkylsulphonyl;
(C2-4)alkenylsulphonyl;
or (C1-4)aminosulphonyl wherein the amino group is optionally substituted by (C1-4)alkyl or (C2-4)alkenyl;
R3 is hydrogen;
or
when Rv and Rw are a bond, R3 is in the 2-, 3- or 4-position and when Rv and Rw are not a bond, R3 is in the 1-, 2-, 3- or 4-position and R3 is:
carboxy;
(C1-6)alkoxycarbonyl;
aminocarbonyl wherein the amino group is optionally substituted by hydroxy, (C1-6)alkyl, hydroxy(C1-6)alkyl, aminocarbonyl(C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylsulphonyl, trifluoromethylsulphonyl, (C2-6)alkenylsulphonyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl or (C2-6)alkenylcarbonyl and optionally further substituted by (C1-6)alkyl, hydroxy(C1-6)alkyl, aminocarbonyl(C1-6)alkyl or (C2-6)alkenyl;
cyano;
tetrazolyl;
2-oxo-oxazolidinyl optionally substituted by R10;
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 R10;
or 5-oxo-1,2,4-oxadiazol-3-yl;
or
(C1-4)alkyl or ethenyl optionally substituted with any of the groups listed above for R3 and/or 0 to 2 groups R12 independently selected from:
halogen;
(C1-6)alkylthio;
trifluoromethyl;
(C1-6)alkoxycarbonyl;
(C1-6)alkylcarbonyl;
(C2-6)alkenyloxycarbonyl;
(C2-6)alkenylcarbonyl;
hydroxy optionally substituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylcarbonyl or (C2-6)alkenylcarbonyl;
amino optionally mono- or disubstituted by (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl, (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylsulphonyl, (C2-6)alkenylsulphonyl or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl or (C2-6)alkenyl;
aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl, hydroxy(C1-6)alkyl, aminocarbonyl(C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl or (C2-6)alkenylcarbonyl and optionally further substituted by (C1-6)alkyl, hydroxy(C1-6)alkyl, aminocarbonyl(C1-6)alkyl or (C2-6)alkenyl;
oxo;
(C1-6)alkylsulphonyl;
(C2-6)alkenylsulphonyl;
or (C1-6)aminosulphonyl wherein the amino group is optionally substituted by (C1-6)alkyl or (C2-6)alkenyl;
or
hydroxy optionally substituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylcarbonyl or (C2-6)alkenylcarbonyl;
or
amino optionally mono- or disubstituted by (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl, (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylsulphonyl, (C2-6)alkenylsulphonyl or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl or (C2-6)alkenyl;
provided that when R3 is in the 4-position it is not optionally substituted hydroxyl or amino;
in addition when R3 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;
R10 is selected from (C1-4)alkyl and (C2-4)alkenyl either of which may be optionally substituted by a group R12 as defined above;
carboxy;
aminocarbonyl wherein the amino group is optionally substituted by hydroxy, (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylsulphonyl, trifluoromethylsulphonyl, (C2-6)alkenylsulphonyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl or (C2-6)alkenylcarbonyl and optionally further substituted by (C1-6)alkyl or (C2-6)alkenyl;
(C1-6)alkylsulphonyl;
trifluoromethylsulphonyl;
(C2-6)alkenylsulphonyl;
(C1-6)alkoxycarbonyl;
(C1-6)alkylcarbonyl;
(C2-6)alkenyloxycarbonyl;
and (C2-6)alkenylcarbonyl;
R4 is a group —CH2—R51 in which R51 is selected from:
(C4-8)alkyl;
hydroxy(C4-8)alkyl;
(C1-4)alkoxy(C4-8)alkyl;
(C1-4)alkanoyloxy(C4-8)alkyl;
(C3-8)cycloalkyl(C4-8)alkyl;
hydroxy-, (C1-6)alkoxy- or (C1-6)alkanoyloxy-(C3-8)cycloalkyl(C4-8)alkyl;
cyano(C4-8)alkyl;
(C4-8)alkenyl;
(C4-8)alkynyl;
tetrahydrofuryl;
mono- or di-(C1-6)alkylamino(C4-8)alkyl;
acylamino(C4-8)alkyl;
(C1-6)alkyl- or acyl-aminocarbonyl(C4-8)alkyl;
mono- or di-(C1-6)alkylamino(hydroxy) (C4-8)alkyl;
or
R4 is a group —U—R52 where R52 is an optionally substituted bicyclic carbocyclic or heterocyclic ring system (A):
139
containing up to four heteroatoms in each ring in which
at least one of rings (a) and (b) is aromatic;
X1 is C or N when part of an aromatic ring or CR14 when part of a non aromatic ring;
X2 is N, NR13, O, S(O)x, CO or CR14 when part of an aromatic or non-aromatic ring or may in addition be CR14R15 when part of a non aromatic ring;
X3 and X5 are independently N or C;
Y1 is a 0 to 4 atom linker group each atom of which is independently selected from N, NR13, O, S(O)x, CO and CR14 when part of an aromatic or non-aromatic ring or may additionally be CR14R15 when part of a non aromatic ring,
Y2 is a 2 to 6 atom linker group, each atom of Y2 being independently selected from N, NR13, O, S(O)x, CO and CR14 when part of an aromatic or non-aromatic ring or may additionally be CR14R15 when part of a non aromatic ring;
each of R14 and R15 is independently selected from:
H;
(C1-4)alkylthio;
halo;
carboxy(C1-4)alkyl;
halo(C1-4)alkoxy, halo(C1-4)alkyl;
(C1-4)alkyl;
(C2-4)alkenyl;
(C1-4)alkoxycarbonyl;
formyl;
(C1-4)alkylcarbonyl;
(C2-4)alkenyloxycarbonyl;
(C2-4)alkenylcarbonyl;
(C1-4)alkylcarbonyloxy;
(C1-4)alkoxycarbonyl(C1-4)alkyl;
hydroxy;
hydroxy(C1-4)alkyl;
mercapto(C1-4)alkyl;
(C1-4)alkoxy;
nitro;
cyano;
carboxy;
amino or aminocarbonyl optionally substituted as for corresponding substituents in R3;
(C1-4)alkylsulphonyl;
(C2-4)alkenylsulphonyl;
or aminosulphonyl wherein the amino group is optionally substituted by (C1-4)alkyl or (C2-4)alkenyl;
aryl;
aryl(C1-4)alkyl;
aryl(C1-4)alkoxy;
each R13 is independently H;
trifluoromethyl;
(C1-4)alkyl optionally substituted by hydroxy, carboxy, (C1-6)alkoxycarbonyl, (C1-6)alkoxy, (C1-6)alkylthio, halo or trifluoromethyl;
(C2-4)alkenyl;
aryl;
aryl (C1-4)alkyl;
arylcarbonyl;
heteroarylcarbonyl;
(C1-4)alkoxycarbonyl;
(C1-4)alkylcarbonyl;
formyl;
(C1-6)alkylsulphonyl;
or aminocarbonyl wherein the amino group is optionally substituted by (C1-4)alkoxycarbonyl, (C1-4)alkylcarbonyl, (C2-4)alkenyloxycarbonyl, (C2-4)alkenylcarbonyl, (C1-4)alkyl or (C2-4)alkenyl and optionally further substituted by (C1-4)alkyl or (C2-4)alkenyl;
each x is independently 0, 1 or 2;
U is CO, SO2 or CH2;
or
R4 is a group —X1a—X2a—X3a—X4a in which:
X1a is CH2, CO or SO2;
X2a is CR14aR15a;
X3a is NR13a, O, S. SO2 or CR14aR15a;
wherein:
each of R14a and R15a is independently selected from the groups listed above for R14 and R15, provided that R14a and R15a on the same carbon atom are not both selected from optionally substituted hydroxy and optionally substituted amino;
or
R14a and R15a together represent oxo;
R13a is hydrogen;
trifluoromethyl;
(C1-6)alkyl;
(C2-6)alkenyl;
(C1-6)alkoxycarbonyl;
(C1-6)alkylcarbonyl;
or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl, (C1-6)alkyl or (C2-6)alkenyl and optionally further substituted by (C1-6)alkyl or (C2-6)alkenyl;
or
two R14a groups or an R13a and an R14a group on adjacent atoms together represent a bond and the remaining R13a, R14a and R15a groups are as above defined;
or
two R14a groups and two R15a groups on adjacent atoms together represent bonds such that X2a and X3a is triple bonded;
X4a 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 (C1-4)alkylthio;
halo;
carboxy(C1-4)alkyl;
halo(C1-4)alkoxy;
halo(C1-4)alkyl;
(C1-4)alkyl;
(C2-4)alkenyl;
(C1-4)alkoxycarbonyl;
formyl;
(C1-4)alkylcarbonyl;
(C2-4)alkenyloxycarbonyl;
(C2-4)alkenylcarbonyl;
(C1-4)alkylcarbonyloxy;
(C1-4)alkoxycarbonyl(C1-4)alkyl;
hydroxy;
hydroxy(C1-4)alkyl;
mercapto(C1-4)alkyl;
(C1-4)alkoxy, nitro;
cyano;
carboxy;
amino or aminocarbonyl optionally substituted as for corresponding substituents in R3;
(C1-4)alkylsulphonyl;
(C2-4)alkenylsulphonyl;
or aminosulphonyl wherein the amino group is optionally substituted by (C1-4)alkyl or (C2-4)alkenyl;
aryl, aryl(C1-4)alkyl or aryl(C1-4)alkoxy;
and
optionally N substituted by trifluoromethyl;
(C1-4)alkyl optionally substituted by hydroxy, (C1-6)alkoxy, (C1-6)alkylthio, halo or trifluoromethyl;
(C2-4)alkenyl;
aryl;
aryl(C1-4)alkyl;
(C1-4)alkoxycarbonyl;
(C1-4)alkylcarbonyl;
formyl;
(C1-6)alkylsulphonyl;
or aminocarbonyl wherein the amino group is optionally substituted by (C1-4)alkoxycarbonyl, (C1-4)alkylcarbonyl, (C2-4)alkenyloxycarbonyl, (C2-4)alkenylcarbonyl, (C1-4)alkyl or (C2-4)alkenyl and optionally further substituted by (C1-4)alkyl or (C2-4)alkenyl;
n is 0 or 1 and AB is NR11CO, CONR11, CO—CR8R9 CR6R7-CO, O—CR8R9, CR6R7—O, NHR11—CR8R9, CR6R7—NHR11, NR11SO2, CR6R7—SO2 or CR6R7—CR8R9, provided that when Rv and Rw are a bond and n=0, B is not NR11, O or SO2,
or n is 0 and AB is NH—CO—NH or NH—CO—O and Rv/Rw are not a bond;
or n is 0 and AB is CR6R7SO2NR2, CR6R7CONR2 or CR6R7CH2NR2 and Rv/Rw are not a bond;
provided that R6 and R7, and R8 and R9 are not both optionally substituted hydroxy or amino;
and wherein:
each of R6, R7, R8 and R9 is independently selected from:
H;
(C1-6)alkoxy;
(C1-6)alkylthio;
halo;
trifluoromethyl;
azido;
(C1-6)alkyl;
(C2-6)alkenyl;
(C1-6)alkoxycarbonyl;
(C1-6)alkylcarbonyl;
(C2-6)alkenyloxycarbonyl;
(C2-6)alkenylcarbonyl;
hydroxy, amino or aminocarbonyl optionally substituted as for corresponding substituents in R3;
(C1-6)alkylsulphonyl;
(C2-6)alkenylsulphonyl;
or (C1-6)aminosulphonyl wherein the amino group is optionally substituted by (C1-6)alkyl or (C2-6)alkenyl;
or R6 and R8 together represent a bond and R7 and R9 are as above defined;
and each R11 is independently H;
trifluoromethyl;
(C1-6)alkyl;
(C2-6)alkenyl;
(C1-6)alkoxycarbonyl;
(C1-6)alkylcarbonyl;
or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl, (C1-6)alkyl or (C2-6)alkenyl and optionally further substituted by (C1-6)alkyl or (C2-6)alkenyl;
or where one of R3 and R6, R7, R8 or R9 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 R3 contains a carboxy group and A or B is NH they may be condensed to form a cyclic amide.

246 more elements

A compound selected from:

Trans-4-[(8-Hydroxy-quinolin-2-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(Benzo[1,2,5]thiadiazol-5-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(1H-Pyrrolo[2,3-b]pyridin-2-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-amino]-cyclohexane carboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(Benzo[1,2,3]thiadiazol-5-yl-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(3-Methyl-2-oxo-2,3-dihydro-benzooxazol-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(3-Oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(7-Fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
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-[1,5]naphthyridin-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-4-[(3,4-Dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(Thiazolo[5,4-b]-pyridin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(8-Hydroxy-1-oxo-1,2-dihydro-isoquinolin-3-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(2,3-Dihydro-[1,4]dioxino[2,3-b]pyridin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(2,3-Dihydro-[1,4]dioxino[2,3-c]pyridin-7-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(2,3-Dihydro-[1,4]dioxino[2,3-b]pyridin-7-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-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-4-[(6-Nitro-benzo[1,3]dioxol-5-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(6-Amino-benzo[1,3]dioxol-5-ylmenthyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(Benzothiazol-5-ylmethyl)-amino]cyclohexanecarboxylic acid(6-methoxy-[1,5]naphthyridine-4-yl)amide;
Trans-4-[(4-Oxo-4H pyrido[1,2-a]pyrimidin-2-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
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-[(2,3-Dihydro-benzo[1,4]dioxin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid [6-(3-amino-propoxy)-[1,5]naphthyridin-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;
Trans-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;
Trans-4-[([1,2,3]Thiadiazolo[5,4-b]pyridin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-(3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazine-6-sulfonylamino)-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(7-Fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(8-Nitro-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy)-[1,5]naphthyridin-4-yl)-amide;
Trans-4-[(8-Amino-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy)-[1,5]naphthyridin-4-yl)-amide;
(R/S)-4-[(3-Oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-amino]-cyclohex-1-ene carboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(R/S)-4-[(Benzo[1,2,5]thiadiazol-5-ylmethyl)-amino]-cyclohexene carboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(R/S)-4-[(Benzo[1,2,3]thiadiazol-5-ylmethyl)-amino]-cyclohex-1-ene carboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)amide;
(R/S)-4-[(2-Oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-ylmethyl)-amino]-cyclohex-1-ene carboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(R/S)-4-[(7-Fluoro-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethyl)-amino]-cyclohex-1-ene carboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(R/S)-4-[(2-Oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]oxazin-7-ylmethyl)-amino]-cyclohex-1-enecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(R/S)-4-[Carboxymethyl-(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-amino]-cyclohex-1-enecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
1-Hydroxy-t-4-[(3-oxo-3,4-dihydro-2H-benzo[1,4]thiazin-6-ylmethyl)-amino]-r-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]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
1-Hydroxy-t-4-[(2-oxo-2,3-dihydro-1H-pyrido[3,4-b][1,4]thiazin-7-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
1-Hydroxy-t-4-[(2-oxo-2,3-dihydro-1H-pyrido[2,3-b][1,4]thiazin-7-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
1-Hydroxy-t-4-[(7-bromo-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-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]-r-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
1-Hydroxy-t-4-[(7-chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
1-Hydroxy-t-4-[(7-oxo-5,6,7,8-tetrahydro-[1,8]naphthyridine-2-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridine-4-yl)-amide;
1-Hydroxy-t-4-[(7-fluoro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
1-Hydroxy-t-4-[(2-oxo-2,3-dihydro-1H-pyrido[3,4-b][1,4]oxazin-7-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (6-methyl-[1,5]naphthyridin-4-yl)-amide;
1-Hydroxy-t-4-[(7-methyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
1-Hydroxy-t-4-[(7-ethyl-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
1-Hydroxy-t-4-[(6-oxo-6,7-dihydro-5H-pyridazino[3,4-b][1,4]thiazin-3-ylmethyl)-amino]-r-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]thiazin-6-ylmethyl)-amino]-r-cyclohexanecarboxylic acid [6-(2-methoxy-ethoxy)-[1,5]naphthyridin-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-[(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 and
(1R,3R,4R)-3-Hydroxy-4-[(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;
(1R,3R,4R)-3-Hydroxy-4-[(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;
(1S,3S,4S)-3-Hydroxy-4-[(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;
(1S,3S,4S)-4-[(7-Chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-3-hydroxy-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide and (1R,3R,4R)-4-[(7-chloro-3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-3-hydroxy-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(1S,3S,4S)-3-Hydroxy-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 and (1R,3R,4R)-3-Hydroxy-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;
(1S,3S,4S)-3-Hydroxy-4-[(2-oxo-2,3-dihydro-1H-pyrido[3,4-b][1,4]oxazin-7-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide and
(1R,3R,4R)-3-Hydroxy-4-[(2-oxo-2,3-dihydro-1H-pyrido[3,4-b][1,4]oxazin-7-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(1S,3S,4S)-3-Hydroxy-4-[(2-oxo-2,3-dihydro-1H-pyrido[3,4-b][1,4]thiazin-7-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide and (1R,3R,4R)-3-Hydroxy-4-[(2-oxo-2,3-dihydro-1H-pyrido[3,4-b][1,4]thiazin-7-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(1S,3S,4S)-3-Hydroxy-4-[(6-oxo-6,7-dihydro-5H-8-thia-1,2,5-triaza-naphthalen-3-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide and (1R,3R,4R)-3-hydroxy-4-[6-oxo-6,7-dihydro-5H-8-thia-1,2,5-triaza-naphthalen-3-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(1S,3S,4S)-3-Hydroxy-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-[(3-oxo-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6,8-difluoroquinolin-4-yl)-amide;
(1R,3R,4R)-3-Hydroxy-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,3R,4R)-3-Hydroxy-4-[(7-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(1R,3R,4R)-3-Hydroxy-4-[(2-oxo-2,3-dihydro-1H-pyrido[3,4-b][1,4]thiazin-7-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(1S,3S,4S)-3-Hydroxy-4-[(7-methyl-3,4-dihydro-2H-pyrido[3,2-b][1,4]thiazin-6-ylmethyl)-amino]-cyclohexanecarboxylic acid (6-methoxy-[1,5]naphthyridin-4-yl)-amide;
(1S,3S,4S)-3-Hydroxy-4-[(2-oxo-2,3-dihydro-1H-pyrido[3,4-b][1,4]thiazin-7-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]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;
6-({4-hydroxy-4-[2-(6-methoxy-[1,5]naphthyridin-4-yl)-ethyl]-cyclohexylamino}-methyl)-4H-pyrido[3,2-b][1,4]oxazin-3-one;
or a pharmaceutically acceptable derivative thereof.

76 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/478,154Filed 6 Apr 2004
Priority: GB 0112834.725 May 2001
Published: 2 Sep 2004
Term ends: Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 31/00
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 405/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links

Family

US 7,141,564 B2Related patent
US 2004/0171620 A1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

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

A compound of formula (I) or a pharmaceutically acceptable derivative thereof:

138
wherein:
one of Z1, Z2, Z3, Z4 and Z5 is N, one is CR1a and the remainder are CH, or one of Z1, Z2, Z3, Z4 and Z5 is CR1a and the remainder are CH;
Rv and Rw are hydrogen or Rv and Rw together are a bond;
R1 and R1a are independently selected from hydrogen;
hydroxy;
(C1-6) alkoxy optionally substituted by (C1-6)alkoxy, amino, piperidyl, guanidino or amidino any of which is optionally N-substituted by one or two (C1-6)alkyl, acyl or (C1-6)alkylsulphonyl groups, CONH2, hydroxy, (C1-6)alkylthio, heterocyclylthio, heterocyclyloxy, arylthio, aryloxy, acylthio, acyloxy or (C1-6)alkylsulphonyloxy;
(C1-6)alkoxy-substituted (C1-6)alkyl;
halogen;
(C1-6)alkyl;
(C1-6)alkylthio;
trifluromethyl;
nitro;
azido;
acyl;
acyloxy;
acylthio;
(C1-6)alkylsulphonyl;
(C1-6)alkylsulphoxide;
arylsulphonyl;
arylsulphoxide or an amino, piperidyl, guanidino or amidino group optionally N-substituted by one or two (C1-6)alkyl, acyl or (C1-6)alkylsulphonyl groups, or when Z1 is CR1a, R1 and R1a may together represent (C1-2)alkylenedioxy,
provided that when Z1, Z2, Z3, Z4 and Z5 are CR1a or CH, then R1 is not hydrogen;
R2 is hydrogen, or (C1-4)alkyl or (C2-4)alkenyl optionally substituted with 1 to 3 groups selected from:
amino optionally substituted by one or two (C1-4)alkyl groups;
carboxy;
(C1-4)alkoxycarbonyl;
(C1-4)alkylcarbonyl;
(C2-4)alkenyloxycarbonyl;
(C2-4)alkenylcarbonyl;
aminocarbonyl wherein the amino group is optionally substituted by hydroxy, (C1-4)alkyl, hydroxy(C1-4)alkyl, aminocarbonyl(C1-4)alkyl, (C2-4)alkenyl, (C1-4)alkylsulphonyl, trifluoromethylsulphonyl, (C2-4)alkenylsulphonyl, (C1-4)alkoxycarbonyl, (C1-4)alkylcarbonyl, (C2-4)alkenyloxycarbonyl or (C2-4)alkenylcarbonyl;
cyano;
tetrazolyl;
2-oxo-oxazolidinyl optionally substituted by R10;
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 R10;
5-oxo-1,2,4-oxadiazol-3-yl;
halogen;
(C1-4)alkylthio;
trifluoromethyl;
hydroxy optionally substituted by (C1-4)alkyl, (C2-4)alkenyl, (C1-4)alkoxycarbonyl, (C1-4)alkylcarbonyl, (C2-4)alkenyloxycarbonyl, (C2-4)alkenylcarbonyl;
oxo;
(C1-4)alkylsulphonyl;
(C2-4)alkenylsulphonyl;
or (C1-4)aminosulphonyl wherein the amino group is optionally substituted by (C1-4)alkyl or (C2-4)alkenyl;
R3 is hydrogen;
or
when Rv and Rw are a bond, R3 is in the 2-, 3- or 4-position and when Rv and Rw are not a bond, R3 is in the 1-, 2-, 3- or 4-position and R3 is:
carboxy;
(C1-6)alkoxycarbonyl;
aminocarbonyl wherein the amino group is optionally substituted by hydroxy, (C1-6)alkyl, hydroxy(C1-6)alkyl, aminocarbonyl(C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylsulphonyl, trifluoromethylsulphonyl, (C2-6)alkenylsulphonyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl or (C2-6)alkenylcarbonyl and optionally further substituted by (C1-6)alkyl, hydroxy(C1-6)alkyl, aminocarbonyl(C1-6)alkyl or (C2-6)alkenyl;
cyano;
tetrazolyl;
2-oxo-oxazolidinyl optionally substituted by R10;
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 R10;
or 5-oxo-1,2,4-oxadiazol-3-yl;
or
(C1-4)alkyl or ethenyl optionally substituted with any of the groups listed above for R3 and/or 0 to 2 groups R12 independently selected from:
halogen;
(C1-6)alkylthio;
trifluoromethyl;
(C1-6)alkoxycarbonyl;
(C1-6)alkylcarbonyl;
(C2-6)alkenyloxycarbonyl;
(C2-6)alkenylcarbonyl;
hydroxy optionally substituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylcarbonyl or (C2-6)alkenylcarbonyl;
amino optionally mono- or disubstituted by (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl, (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylsulphonyl, (C2-6)alkenylsulphonyl or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl or (C2-6)alkenyl;
aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl, hydroxy(C1-6)alkyl, aminocarbonyl(C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl or (C2-6)alkenylcarbonyl and optionally further substituted by (C1-6)alkyl, hydroxy(C1-6)alkyl, aminocarbonyl(C1-6)alkyl or (C2-6)alkenyl;
oxo;
(C1-6)alkylsulphonyl;
(C2-6)alkenylsulphonyl;
or (C1-6)aminosulphonyl wherein the amino group is optionally substituted by (C1-6)alkyl or (C2-6)alkenyl;
or
hydroxy optionally substituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylcarbonyl or (C2-6)alkenylcarbonyl;
or
amino optionally mono- or disubstituted by (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl, (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylsulphonyl, (C2-6)alkenylsulphonyl or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkyl or (C2-6)alkenyl;
provided that when R3 is in the 4-position it is not optionally substituted hydroxyl or amino;
in addition when R3 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;
R10 is selected from (C1-4)alkyl and (C2-4)alkenyl either of which may be optionally substituted by a group R12 as defined above;
carboxy;
aminocarbonyl wherein the amino group is optionally substituted by hydroxy, (C1-6)alkyl, (C2-6)alkenyl, (C1-6)alkylsulphonyl, trifluoromethylsulphonyl, (C2-6)alkenylsulphonyl, (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl or (C2-6)alkenylcarbonyl and optionally further substituted by (C1-6)alkyl or (C2-6)alkenyl;
(C1-6)alkylsulphonyl;
trifluoromethylsulphonyl;
(C2-6)alkenylsulphonyl;
(C1-6)alkoxycarbonyl;
(C1-6)alkylcarbonyl;
(C2-6)alkenyloxycarbonyl;
and (C2-6)alkenylcarbonyl;
R4 is a group —CH2—R51 in which R51 is selected from:
(C4-8)alkyl;
hydroxy(C4-8)alkyl;
(C1-4)alkoxy(C4-8)alkyl;
(C1-4)alkanoyloxy(C4-8)alkyl;
(C3-8)cycloalkyl(C4-8)alkyl;
hydroxy-, (C1-6)alkoxy- or (C1-6)alkanoyloxy-(C3-8)cycloalkyl(C4-8)alkyl;
cyano(C4-8)alkyl;
(C4-8)alkenyl;
(C4-8)alkynyl;
tetrahydrofuryl;
mono- or di-(C1-6)alkylamino(C4-8)alkyl;
acylamino(C4-8)alkyl;
(C1-6)alkyl- or acyl-aminocarbonyl(C4-8)alkyl;
mono- or di-(C1-6)alkylamino(hydroxy) (C4-8)alkyl;
or
R4 is a group —U—R52 where R52 is an optionally substituted bicyclic carbocyclic or heterocyclic ring system (A):
139
containing up to four heteroatoms in each ring in which
at least one of rings (a) and (b) is aromatic;
X1 is C or N when part of an aromatic ring or CR14 when part of a non aromatic ring;
X2 is N, NR13, O, S(O)x, CO or CR14 when part of an aromatic or non-aromatic ring or may in addition be CR14R15 when part of a non aromatic ring;
X3 and X5 are independently N or C;
Y1 is a 0 to 4 atom linker group each atom of which is independently selected from N, NR13, O, S(O)x, CO and CR14 when part of an aromatic or non-aromatic ring or may additionally be CR14R15 when part of a non aromatic ring,
Y2 is a 2 to 6 atom linker group, each atom of Y2 being independently selected from N, NR13, O, S(O)x, CO and CR14 when part of an aromatic or non-aromatic ring or may additionally be CR14R15 when part of a non aromatic ring;
each of R14 and R15 is independently selected from:
H;
(C1-4)alkylthio;
halo;
carboxy(C1-4)alkyl;
halo(C1-4)alkoxy, halo(C1-4)alkyl;
(C1-4)alkyl;
(C2-4)alkenyl;
(C1-4)alkoxycarbonyl;
formyl;
(C1-4)alkylcarbonyl;
(C2-4)alkenyloxycarbonyl;
(C2-4)alkenylcarbonyl;
(C1-4)alkylcarbonyloxy;
(C1-4)alkoxycarbonyl(C1-4)alkyl;
hydroxy;
hydroxy(C1-4)alkyl;
mercapto(C1-4)alkyl;
(C1-4)alkoxy;
nitro;
cyano;
carboxy;
amino or aminocarbonyl optionally substituted as for corresponding substituents in R3;
(C1-4)alkylsulphonyl;
(C2-4)alkenylsulphonyl;
or aminosulphonyl wherein the amino group is optionally substituted by (C1-4)alkyl or (C2-4)alkenyl;
aryl;
aryl(C1-4)alkyl;
aryl(C1-4)alkoxy;
each R13 is independently H;
trifluoromethyl;
(C1-4)alkyl optionally substituted by hydroxy, carboxy, (C1-6)alkoxycarbonyl, (C1-6)alkoxy, (C1-6)alkylthio, halo or trifluoromethyl;
(C2-4)alkenyl;
aryl;
aryl (C1-4)alkyl;
arylcarbonyl;
heteroarylcarbonyl;
(C1-4)alkoxycarbonyl;
(C1-4)alkylcarbonyl;
formyl;
(C1-6)alkylsulphonyl;
or aminocarbonyl wherein the amino group is optionally substituted by (C1-4)alkoxycarbonyl, (C1-4)alkylcarbonyl, (C2-4)alkenyloxycarbonyl, (C2-4)alkenylcarbonyl, (C1-4)alkyl or (C2-4)alkenyl and optionally further substituted by (C1-4)alkyl or (C2-4)alkenyl;
each x is independently 0, 1 or 2;
U is CO, SO2 or CH2;
or
R4 is a group —X1a—X2a—X3a—X4a in which:
X1a is CH2, CO or SO2;
X2a is CR14aR15a;
X3a is NR13a, O, S. SO2 or CR14aR15a;
wherein:
each of R14a and R15a is independently selected from the groups listed above for R14 and R15, provided that R14a and R15a on the same carbon atom are not both selected from optionally substituted hydroxy and optionally substituted amino;
or
R14a and R15a together represent oxo;
R13a is hydrogen;
trifluoromethyl;
(C1-6)alkyl;
(C2-6)alkenyl;
(C1-6)alkoxycarbonyl;
(C1-6)alkylcarbonyl;
or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl, (C1-6)alkyl or (C2-6)alkenyl and optionally further substituted by (C1-6)alkyl or (C2-6)alkenyl;
or
two R14a groups or an R13a and an R14a group on adjacent atoms together represent a bond and the remaining R13a, R14a and R15a groups are as above defined;
or
two R14a groups and two R15a groups on adjacent atoms together represent bonds such that X2a and X3a is triple bonded;
X4a 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 (C1-4)alkylthio;
halo;
carboxy(C1-4)alkyl;
halo(C1-4)alkoxy;
halo(C1-4)alkyl;
(C1-4)alkyl;
(C2-4)alkenyl;
(C1-4)alkoxycarbonyl;
formyl;
(C1-4)alkylcarbonyl;
(C2-4)alkenyloxycarbonyl;
(C2-4)alkenylcarbonyl;
(C1-4)alkylcarbonyloxy;
(C1-4)alkoxycarbonyl(C1-4)alkyl;
hydroxy;
hydroxy(C1-4)alkyl;
mercapto(C1-4)alkyl;
(C1-4)alkoxy, nitro;
cyano;
carboxy;
amino or aminocarbonyl optionally substituted as for corresponding substituents in R3;
(C1-4)alkylsulphonyl;
(C2-4)alkenylsulphonyl;
or aminosulphonyl wherein the amino group is optionally substituted by (C1-4)alkyl or (C2-4)alkenyl;
aryl, aryl(C1-4)alkyl or aryl(C1-4)alkoxy;
and
optionally N substituted by trifluoromethyl;
(C1-4)alkyl optionally substituted by hydroxy, (C1-6)alkoxy, (C1-6)alkylthio, halo or trifluoromethyl;
(C2-4)alkenyl;
aryl;
aryl(C1-4)alkyl;
(C1-4)alkoxycarbonyl;
(C1-4)alkylcarbonyl;
formyl;
(C1-6)alkylsulphonyl;
or aminocarbonyl wherein the amino group is optionally substituted by (C1-4)alkoxycarbonyl, (C1-4)alkylcarbonyl, (C2-4)alkenyloxycarbonyl, (C2-4)alkenylcarbonyl, (C1-4)alkyl or (C2-4)alkenyl and optionally further substituted by (C1-4)alkyl or (C2-4)alkenyl;
n is 0 or 1 and AB is NR11CO, CONR11, CO—CR8R9 CR6R7-CO, O—CR8R9, CR6R7—O, NHR11—CR8R9, CR6R7—NHR11, NR11SO2, CR6R7—SO2 or CR6R7—CR8R9, provided that when Rv and Rw are a bond and n=0, B is not NR11, O or SO2,
or n is 0 and AB is NH—CO—NH or NH—CO—O and Rv/Rw are not a bond;
or n is 0 and AB is CR6R7SO2NR2, CR6R7CONR2 or CR6R7CH2NR2 and Rv/Rw are not a bond;
provided that R6 and R7, and R8 and R9 are not both optionally substituted hydroxy or amino;
and wherein:
each of R6, R7, R8 and R9 is independently selected from:
H;
(C1-6)alkoxy;
(C1-6)alkylthio;
halo;
trifluoromethyl;
azido;
(C1-6)alkyl;
(C2-6)alkenyl;
(C1-6)alkoxycarbonyl;
(C1-6)alkylcarbonyl;
(C2-6)alkenyloxycarbonyl;
(C2-6)alkenylcarbonyl;
hydroxy, amino or aminocarbonyl optionally substituted as for corresponding substituents in R3;
(C1-6)alkylsulphonyl;
(C2-6)alkenylsulphonyl;
or (C1-6)aminosulphonyl wherein the amino group is optionally substituted by (C1-6)alkyl or (C2-6)alkenyl;
or R6 and R8 together represent a bond and R7 and R9 are as above defined;
and each R11 is independently H;
trifluoromethyl;
(C1-6)alkyl;
(C2-6)alkenyl;
(C1-6)alkoxycarbonyl;
(C1-6)alkylcarbonyl;
or aminocarbonyl wherein the amino group is optionally substituted by (C1-6)alkoxycarbonyl, (C1-6)alkylcarbonyl, (C2-6)alkenyloxycarbonyl, (C2-6)alkenylcarbonyl, (C1-6)alkyl or (C2-6)alkenyl and optionally further substituted by (C1-6)alkyl or (C2-6)alkenyl;
or where one of R3 and R6, R7, R8 or R9 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 R3 contains a carboxy group and A or B is NH they may be condensed to form a cyclic amide.

246 more elements

Facts

Application

10/478,154Filed 6 Apr 2004

Priority

GB 0112834.725 May 2001

Published

2 Sep 2004

Term ends

Not estimatedThe source records don’t support an estimate.

Classification10 codes

C07D 401/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
A61P 31/00
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 405/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links