US 7,622,481 B2Granted

Antibacterial compounds

AssigneeGlaxo Group Limited

InventorsJeffrey Michael Axten, Robert A Daines, David Thomas Davies, Timothy Francis Gallagher, Graham Elgin Jones, William Henry Miller, Neil David Pearson, Israil Pendrak

Life of this patent

Estimating the term…

Abstract

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

Claims24

Dependent claims

A compound selected from the 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:
RV and RW are hydrogen or RV and RW together are a bond;
RA 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 Z4 and Z5 is C or N and the other is C;
Z3 is N, NR13, O, S(O)x, CO, CR1 or CR1R1a;
Z1 and Z2 are independently a 2 or 3 atom linker group each atom of which is independently selected from N, NR13, O, S(O)x, CO, CR1 and CR1R1a;
such that each ring is independently substituted with 0-3 groups R1 and/or R1a;
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;
hydroxy (C1-6)alkyl;
halogen;
(C1-6)alkyl;
(C1-6)alkylthio;
trifluoromethyl;
trifluoromethoxy;
cyano;
carboxy;
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 Z3 and the adjacent atom are CR1 and CR1a, R1 and R1a may together represent (C1-2)alkylenedioxy,
wherein acyl is (C1-6)alkoxycarbonyl, formyl, or (C1-6)alkylcarbonyl;
provided that R1 and R1a, on the same carbon atom are not both optionally substituted hydroxyl or amino;
provided that
(i) when RA is optionally substituted quinolin-4-yl:
it is unsubstituted in the 6-position;
or
it is substituted by at least one hydroxy (C1-6)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
R3 is halogen;
(ii) when RA 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 (C1-6)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
R3 is halogen;
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;
or
halogen;
provided that when R3 is in the 4-position it is not optionally substituted hydroxyl or amino or halogen;
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 —U—R52 where R52 is a group,
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;
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 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.

195 more elements

Dependencies are inferred from the claim text.

Facts

Application: 10/518,653Filed 25 Jun 2003
Published: US 2006/0189604 A124 Aug 2006
Granted: 24 Nov 2009
Term ends: Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 493/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 417/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 513/04
In which the condensed system contains two hetero rings: ortho-condensed systems

Family

US 2006/0189604 A1Pre-grant publication · published 24 Aug 2006
US 7,622,481 B2This 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 thereof useful in methods of treatment of bacterial infections in mammals, particularly man.

A compound selected from the 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:
RV and RW are hydrogen or RV and RW together are a bond;
RA 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 Z4 and Z5 is C or N and the other is C;
Z3 is N, NR13, O, S(O)x, CO, CR1 or CR1R1a;
Z1 and Z2 are independently a 2 or 3 atom linker group each atom of which is independently selected from N, NR13, O, S(O)x, CO, CR1 and CR1R1a;
such that each ring is independently substituted with 0-3 groups R1 and/or R1a;
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;
hydroxy (C1-6)alkyl;
halogen;
(C1-6)alkyl;
(C1-6)alkylthio;
trifluoromethyl;
trifluoromethoxy;
cyano;
carboxy;
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 Z3 and the adjacent atom are CR1 and CR1a, R1 and R1a may together represent (C1-2)alkylenedioxy,
wherein acyl is (C1-6)alkoxycarbonyl, formyl, or (C1-6)alkylcarbonyl;
provided that R1 and R1a, on the same carbon atom are not both optionally substituted hydroxyl or amino;
provided that
(i) when RA is optionally substituted quinolin-4-yl:
it is unsubstituted in the 6-position;
or
it is substituted by at least one hydroxy (C1-6)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
R3 is halogen;
(ii) when RA 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 (C1-6)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
R3 is halogen;
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;
or
halogen;
provided that when R3 is in the 4-position it is not optionally substituted hydroxyl or amino or halogen;
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 —U—R52 where R52 is a group,
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;
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 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.

195 more elements

Facts

Application

10/518,653Filed 25 Jun 2003

Published

US 2006/0189604 A124 Aug 2006

Granted

24 Nov 2009

Term ends

Not estimatedThe source records don’t support an estimate.

Classification6 codes

C07D 493/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 31/04
Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics: antibacterial agents
C07D 417/12
Containing two hetero rings: linked by a chain containing hetero atoms as chain links
C07D 513/04
In which the condensed system contains two hetero rings: ortho-condensed systems