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1. US20160272601 - Antibacterial thiazolecarboxylic acids

Note: Text based on automatic Optical Character Recognition processes. Please use the PDF version for legal matters

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Claims

1. A compound of formula (I) including all polymorphs thereof:

(MOL) (CDX)
wherein
R 1 is hydrogen;
Y is a single bond, —C 1-4 alkylene- or —C 2-4 alkenylene-, either of which may be substituted with a group R 17; or
—C 1-4 alkylene-O—; —C 1-4 alkylene-N(R 8)—; —N(R 8)—; —C 1-4 alkylene-C(O)N(R 8)—; —C 1-4 alkylene-N(R 8)C(O)— or —N(R 8)C 1-4 alkylene-;
wherein R 17 is selected from OR l, NR lR m, NR lC(O)R m, C(O)NR lR m, and C(O)OR m;
each R l and R m is independently H or C 1-4 alkyl;
and R 8 is hydrogen or C 1-6 alkyl or —C(O)C 1-6 alkyl either of which is optionally substituted by one or more substituent R d; and
C 1-4 alkylene chains may optionally be substituted with one or more substituents R e;
each R d and R e is independently halo, CN, OH or OC 1-4 alkyl optionally substituted by one or more substituents selected from halo or OH;
A represents a cyclic group selected from a 6- to 10-membered aryl, 5- to 10-membered heteroaryl or a 3- to 10-membered carbocyclyl or heterocyclyl group;
n is 0 to 4;
each R 2 is independently selected from R 3; or
C 1-4 alkyl, C 2-4 alkenyl, O(C 1-4 alkyl), S(C 1-4 alkyl), SO(C 1-4 alkyl) or SO 2(C 1-4 alkyl), any of which may optionally be substituted with one or more substituent R 3; or
C(O)OR 6; C(O)R 6; OR 5, NR 4R 5; NR 4C(O)R 6, NR 4C(O)NR 5R 6 or SO 2NR 21R 22;
or when A is saturated or partially saturated, R 2 may also be oxo;
each R 3 is independently halo, nitro, CN, OH; or
—C(O)OR 14, —C(O)NR 14R 15 or —NR 14R 15; or
phenyl optionally substituted with one or more substituent R 7; or
naphthyl optionally substituted with one or more substituent R 7; or
5- to 10-membered heteroaryl optionally substituted with one or more substituent R 7; or
3- to 8-membered carbocyclyl optionally substituted with one or more substituent R 7; or
3- to 8-membered heterocyclyl optionally substituted with one or more substituents selected from oxo or R 7;
each of R 14 and R 15 is independently H, or C 1-6 alkyl optionally substituted with one or more substituents selected from halo or OH;
each R 7 is independently halo, CN, OH; or C 1-4 alkyl or OC 1-4 alkyl either of which may optionally substituted by one or more substituents selected from halo or OH; or NR jR k, wherein each R j and R k is independently H or C 1-4 alkyl;
each of R 21 and R 22 is hydrogen or C 1-4 alkyl or R 21 and R 22 together with the nitrogen atom to which they are attached may form a 5- or 6-membered heterocyclic ring, optionally containing one further heteroatom selected from N, O or S and optionally substituted with C 1-4 alkyl or halo;
R 4 is hydrogen or C 1-6 alkyl optionally substituted with halo, CN, OH, NR jR k; or OC 1-4 alkyl which may optionally substituted by one or more substituent selected from halo or OH;
wherein each R j and R k is independently H or C 1-4 alkyl;
R 5 is hydrogen, phenyl, 5- to 6-membered heteroaryl, 3- to 8-membered carbocyclyl or 3 to 8-membered heterocyclyl; or
C 1-6 alkyl optionally substituted with phenyl, 5- to 6-membered heteroaryl, 3- to 8-membered carbocyclyl or 3- to 8-membered heterocyclyl;
wherein phenyl and heteroaryl groups are optionally substituted by one or more substituent R f and carbocyclyl and heterocyclyl groups are optionally substituted by one or more substituent R g and wherein:
each R f is independently halo, CN, OH or C 1-4 alkyl or OC 1-4 alkyl either of which may optionally be substituted by one or more substituents selected from halo or OH;
each R g is independently halo, CN, OH, oxo or C 1-4 alkyl or OC 1-4 alkyl optionally substituted by one or more substituents selected from halo or OH;
R 6 is C 1-6 alkyl optionally substituted with one or more R h, or phenyl or 5- to 6-membered heteroaryl either of which is optionally substituted with one or more substituent R i;
each R h is independently halo, CN, OH, NH 2, phenyl, pyridyl, COOH or OC 1-4 alkyl optionally substituted by one or more substituents selected from halo or OH;
each R i is independently halo, CN, OH, NH 2 or C 1-4 alkyl or OC 1-4 alkyl either of which may optionally be substituted by one or more substituents selected from halo or OH;
R 11 is hydrogen, C 1-4 alkyl optionally substituted by halo or benzyl optionally substituted by halo;
or a salt thereof;
provided that the compound is not 5-(4-aminophenylsulfonamido)thiazole-4-carboxylic acid.
2. The compound according to claim 1 wherein
R 11 is hydrogen.
3. The compound according to claim 1 wherein Y is a single bond, —C 1-4 alkylene, —C 1-4 alkylene-O—, —C 1-4 alkylene-NR 8—, —NR 8— or —NR 8(C 1-4 alkylene)-; wherein R 8 is hydrogen or methyl, but especially hydrogen and wherein alkylene chains are optionally substituted with one or more substituents R e as defined in claim 1.
4. The compound according to claim 3 wherein R e is halo.
5. The compound according to claim 3 wherein Y is a single bond, —CH 2—, —(CH 2) 2—, —(CH 2) 3—, —C(CH 3)—, —CH(CH 2CH 3)—, —NH—, —N(CH 3)—, —NHCH 2— or —N(CH 3)CH 2—.
6. The compound according to claim 1 wherein A represents 6- to 10-membered aryl, 3- to 8-membered cycloalkyl, 5- to 10-membered heteroaryl or 3- to 8-membered heterocyclyl, any of which may be unsubstituted or substituted with one to four R 2 groups as defined in claim 1.
7. The compound according to claim 1 wherein A is selected from phenyl, pyridyl, pyrazole, thiophenyl, benzothiophenyl, quinolinyl or isoquinolinyl, any of which may be unsubstituted or substituted with one to four R 2 groups as defined in claim 1; or
a 5- or 6-membered carbocyclic or heterocyclic ring which may be unsubstituted or substituted with one to four R 2 groups as defined in claim 1, for example by one or two oxo groups; or
a 9- to 10-membered bicyclic aromatic ring which may be unsubstituted or substituted with one to four R 2 groups as defined in claim 1, for example with one to four substitutents selected from halo or, when the ring is partially saturated, with oxo.
8. The compound according to claim 1 wherein A represents phenyl, pyridyl, pyrazolyl, thiophenyl or benzothiophenyl; especially phenyl, 3-pyridyl, 4-pyridyl, thiophen-2-yl, thiophen-3-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, benzothiophen-2-yl or benzothiophen-3-yl, any of which may be unsubstituted or substituted with one to four R 2 groups as defined in claim 1.
9. The compound according to claim 1 wherein n is 0 to 3.
10. The compound according to claim 1 wherein each R 2 is independently selected from:
halo, nitro, cyano, OH or when A is saturated or partially saturated, oxo;
C 1-4 alkyl, C 2-4 alkenyl, O(C 1-4 alkyl) any of which may optionally be substituted with one or more substituent R 3 as defined in claim 1; or
OR 5, wherein R 5 is as defined in claim 1; or
NR 4R 5, where R 4 and R 5 are as defined in claim 1; or
NR 4C(O)R 6, where R 4 and R 6 are as defined in claim 1; or
NR 4C(O)NR 5R 6, where R 4, R 5 and R 6 are as defined in claim 1; or
C(O)R 6 or C(O)OR 6, where R 6 is as defined in claim 1; or
SO 2(C 1-4 alkyl); or
SO 2NR 21R 22, wherein each of R 21 and R 22 is hydrogen or where R 21 and R 22 together with the nitrogen atom to which they are attached form a piperidine, pyrrolidine or morpholine ring or a piperazine ring optionally substituted on the other nitrogen atom with methyl or ethyl; or
a cyclic group selected from phenyl, naphthyl, 5- to 10-membered heteroaryl or 3- to 8-membered heterocyclyl, any of which is optionally substituted with one or more substituent R 7 as defined in claim 1.
11. The compound according to claim 10 wherein:
R 2 is C 1-4 alkyl, C 2-4 alkenyl, O(C 1-4 alkyl) and is unsubstituted or is substituted by an R 3 group selected from halo, phenyl, amino, methylamino or dimethylamino; or
R 2 is OR 5, wherein R 5 is a 5-membered heterocyclic group, for example pyrrolidine; or
R 2 is NR 4R 5, wherein R 4 is hydrogen or C 1-4 alkyl and R 5 is hydrogen or a 5- or 6-membered heterocyclic group such as oxazolyl, isoxazolyl and pyrrolyl and piperidinyl; or
R 2 is NR 4C(O)R 6, wherein R 4 is hydrogen or methyl, especially hydrogen, and R 6 is C 1-4 alkyl optionally substituted with one or more R h, where each R h is independently, OH, NH 2, phenyl, or OC 1-4 alkyl; or R 6 is phenyl; or
R 2 is NR 4C(O)NR 5R 6, wherein R 4 is hydrogen or methyl, especially hydrogen; and R 5 is hydrogen and R 6 is C 1-4 alkyl, for example methyl; or
R 2 is C(O)R 6 or C(O)OR 6, wherein R 6 is C 1-4 alkyl substituted with phenyl and/or NH 2; or
R 2 is a cyclic group selected from phenyl, pyridyl, pyrazolyl, oxazolyl, isoxazolyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, diazepanyl or azetidinyl, any of which may be substituted by one or more substituents R 7, where R 7 is halo, C 1-4 haloalkyl or NH 2; and wherein pyrazolyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, diazepanyl or azetidinyl may be substituted by one or more oxo groups in addition to or instead of an R 7 group.
12. The compound according to claim 1 wherein:
A is phenyl or pyridyl;
n is 0 to 3; and
R 2 is halo, CF 3; nitro, methoxy, phenyl, SO 2—C 1-4 alkyl; or
C 1-2 alkyl or ethenyl optionally substituted with phenyl or —C(O)NR 14R 15, where R 14 and R 15 are each independently H or methyl; or
a 4- to 7-membered carbocyclic or heterocyclic ring optionally substituted with one or more substituents selected from oxo or R 7 groups, where R 7 is as defined in claim 1; NHR 4, NHR 5, NHC(O)R 6 or NR 4C(O)NR 5R 6 where R 4, R 5 and R 6 are defined in claim 1.
13. The compound according to claim 1 wherein
A is phenyl or pyridyl;
n is 0 to 3; and R 2 is:
halo, trifluoromethyl, nitro, methoxy, phenyl; or
oxazoline, morpholine, pyrrolidine, piperidine, tetrahydropyridine, piperazine, diazepan or aziridine any of which may optionally be substituted with an oxo group or with NH 2 or C 1-2 alkyl or C 1-4 haloalkyl; or
oxazole or pyrazole, either of which may optionally be substituted with methyl; or
NHC(O)C 1-2 alkyl, which may optionally be substituted by OH or methoxy: or
NHC(O)NHCH 3, NH 2, NH(CH 3), CH 2N(CH 3) 2, SO 2CH 3; or
ethenyl substituted with phenyl or C(O)N(CH 3) 2.
14. The compound according to claim 1 wherein A is phenyl optionally substituted with 1 to 3 halo substituents R 2.
15. The compound according to claim 14 wherein:
one of the halo substituents R 2 is at the 2-position; or
one of the halo substituents R 2 is at the 3-position; or
one of the halo substituents R 2 is at the 4-position.
16. The compound according to claim 1 wherein A is phenyl substituted with one halo substituent R 2 and with one or two further substituents R 2 as defined in claim 1.
17. The compound according to claim 1 wherein the phenyl group A:
(i) is substituted with two halo substituents R 2 at the 2- and 5-positions; or
(ii) is substituted with two halo substituents R 2 at the 2- and 3-positions; or
(iii) is substituted with two halo substituents R 2 at the 3- and 5-positions; or
(iv) is substituted with two halo substituents R 2 at the 3- and 4-positions; or
(v) is substituted with one or two halo substituents R 2 and an additional R 2 substituent selected from trifluoromethyl or nitro.
18. The compound according to claim 1 wherein A is phenyl substituted with at least one R 2 group selected from a trifluoromethyl group or an amino group.
19. The compound according to claim 18 wherein:
the trifluroromethyl or amino group is at the 2-position; or
the trifluroromethyl or amino group is at the 3-position; or
the trifluoromethyl or amino group is at the 4-position.
20. The compound according to claim 1 wherein A is a 3- to 6-membered carbocyclic or heterocyclic ring optionally fused to a phenyl group.
21. The compound according to claim 20 wherein, independently or in combination:
n is 0-2;
at least one R 2 is oxo, or when attached to a ring nitrogen atom is C(O)OR 6,
wherein R 6 is benzyl.
22. The compound according to claim 1 wherein A is pyazolyl or thiophenyl, especially pyrazol-4-yl, pyrazol-5-yl, thiophen-2-yl or thiophen-3-yl.
23. The compound according to claim 22 wherein independently or in any combination:
n is 1 to 3;
R 2 is halo, methyl, trifluoromethyl or phenyl or pyridyl, either of which may optionally be substituted with halo or trifluoromethyl, especially trifluoromethyl.
24. The compound according to claim 1 wherein A is quinolinyl, isoquinolinyl or benzothiophenyl especially quinolin-6-yl or benzothiophen-2-yl and n is 0.
25. The compound according to claim 1 selected from:
5-benzenesulfonamido-1,3-thiazole-4-carboxylic acid;
5-{[(3,5-dichlorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-(2,4,6-trimethylphenylsulfonamido)thiazole-4-carboxylic acid;
5-{[3-(trifluoromethyl)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-(phenylmethylsulfonamido)thiazole-4-carboxylic acid;
5-(3-methoxyphenylsulfonamido)thiazole-4-carboxylic acid;
5-(2-phenylethylsulfonamido)thiazole-4-carboxylic acid;
5-(thiophene-2-sulfonamido)thiazole-4-carboxylic acid;
5-(4,5-dichlorothiophene-2-sulfonamido)thiazole-4-carboxylic acid;
5-(2,5-dichlorothiophene-3-sulfonamido)thiazole-4-carboxylic acid;
5-(2-(trifluoromethyl)phenylsulfonamido)thiazole-4-carboxylic acid;
5-(4-(trifluoromethyl)phenylsulfonamido)thiazole-4-carboxylic acid;
5-(2-chloro-5-(trifluoromethyl)phenylsulfonamido)thiazole-4-carboxylic acid;
5-(3,5-bis(trifluoromethyl)phenylsulfonamido)thiazole-4-carboxylic acid;
5-({[2-(trifluoromethyl)phenyl]methyl}sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-{[(2-methylphenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-((2-nitrophenyl)methylsulfonamido)thiazole-4-carboxylic acid;
5-{[((2-bromophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-(5-chlorothiophene-2-sulfonamido)thiazole-4-carboxylic acid;
5-(5-phenylthiophene-2-sulfonamido)thiazole-4-carboxylic acid;
5-(thiophene-3-sulfonamido)thiazole-4-carboxylic acid;
5-(2,5-dimethylthiophene-3-sulfonamido)thiazole-4-carboxylic acid;
5-([1,1′-biphenyl]-2-ylsulfonamido)thiazole-4-carboxylic acid;
5-((2-aminophenyl)methylsulfonamido)thiazole-4-carboxylic acid;
5-((2-acetamidophenyl)methylsulfonamido)thiazole-4-carboxylic acid;
5-((2-benzamidophenyl)methylsulfonamido)thiazole-4-carboxylic acid;
(E)-5-((2-styrylphenyl)methylsulfonamido)thiazole-4-carboxylic acid;
(E)-5-((2-(3-(dimethylamino)-3-oxoprop-1-en-1-yl)phenyl)methylsulfonamido)thiazole-4-carboxylic acid;
5-([1,1′-biphenyl]-2-ylmethylsulfonamido)thiazole-4-carboxylic acid;
5-((2-(trifluoromethoxy)phenyl)methylsulfonamido)thiazole-4-carboxylic acid;
5-((3-(trifluoromethyl)phenyl)methylsulfonamido)thiazole-4-carboxylic acid;
5-((3-bromophenyl)methylsulfonamido)thiazole-4-carboxylic acid;
5-((3-cyanophenyl)methylsulfonamido)thiazole-4-carboxylic acid;
5-((2-chlorophenyl)methylsulfonamido)thiazole-4-carboxylic acid;
5-(4-nitrophenylsulfonamido)thiazole-4-carboxylic acid;
5-({5-[5-(trifluoromethyl)-1,2-oxazol-3-yl]thiophen-2-yl}sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-(1-benzothiophene-2-sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[(5-methylthiophen-2-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[(5-bromothiophen-2-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-(1-benzothiophene-3-sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[(4-bromo-2,5-dichlorothiophen-3-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-(({[(2-chlorophenyl)methyl]sulfamoyl}amino)-1,3-thiazole-4-carboxylic acid;
5-[({[3-(trifluoromethyl)phenyl]methyl}sulfamoyl)amino]-1,3-thiazole-4-carboxylic acid;
5-[(3-bromothiophen-2-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{[(2-iodophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[4-phenyl-5-(trifluoromethyl)thiophen-3-yl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[(2,3-dichlorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[(3,4-dichlorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-[(1-phenylethyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{[6-(trifluoromethyl)pyridin-3-yl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-[(2-phenoxyethyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{[2-(1,3-dioxo-2,3-dihydro-1H-isoindol-2-yl)ethyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[2-(2-chlorophenyl)ethyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-({1-[5-(trifluoromethyl)pyridin-2-yl]-1H-pyrazol-4-yl}sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[(2-chlorophenyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-(pyridine-3-sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[(2,6-dichlorophenyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-(cyclohexylmethyl)sulfonamido-1,3-thiazole-4-carboxylic acid;
5-[(4-methyl-3,4-dihydro-2H-1,4-benzoxazin-7-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[(1-phenylpropyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{[2-(4-methoxyphenyl)ethyl]sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-(2-[3-(trifluoromethyl)phenyl]ethyl})sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-{[2-(4-chlorophenyl)ethyl]sulfonamido)}-1,3-thiazole-4-carboxylic acid;
5-[(piperidine-1-sulfonyl)amino]-1,3-thiazole-4-carboxylic acid;
5-[(phenylsulfamoyl)amino]-1,3-thiazole-4-carboxylic acid;
5-{[benzyl(methyl)sulfamoyl]amino}-1,3-thiazole-4-carboxylic acid;
5-[(4-acetamidophenyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[(2-methoxyphenyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-(1,2,3,4-tetrahydronaphthalene-1-sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[(5-methyl-1-phenyl-1H-pyrazol-4-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-(cyclopropylmethyl)sulfonamido-1,3-thiazole-4-carboxylic acid;
5-{[(2-methoxyphenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[2-(2-methoxyphenyl)ethyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[2-(3-methoxyphenyl)ethyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[2-(3-chlorophenyl)ethyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-[(2-methanesulfonylphenyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{[methyl(phenyl)sulfamoyl]amino}-1,3-thiazole-4-carboxylic acid;
5-([4-(morpholin-4-yl)phenyl]sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[(4-cyanophenyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-(pyridine-2-sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[(1-methyl-1H-imidazol-2-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[(6-methoxypyridin-3-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{[4-(1H-pyrazol-1-yl)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-[(1-ethyl-5-methyl-1H-pyrazol-4-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{[(2-cyanophenyl)methyl]sulfonamido})-1,3-thiazole-4-carboxylic acid;
5-[(1-methyl-1H-pyrazol-3-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[(1-methyl-1H-pyrazol-5-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-({(1-[(benzyloxy)carbonyl]piperidin-4-yl}sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[(3-phenylpropyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-(2,3-dihydro-1H-indene-1-sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-{[4-(1-methyl-1H-pyrazol-5-yl)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[2-(1,2,3,4-tetrahydroquinolin-1-yl)ethyl]sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-([2-(N-phenylacetamido)ethyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[4-(3-oxomorpholin-4-yl)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[4-(2-oxo-1,3-oxazolidin-3-yl)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-[(1,2-dimethyl-1H-imidazol-4-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[(oxan-4-ylmethyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[(({-[(benzyloxy)carbonyl]piperidin-4-yl}methyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{([4-(2-oxopyrrolidin-1-yl)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-({1-[6-(trifluoromethyl)pyridin-3-yl]-1H-pyrazol-4-yl}sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-{[4-(1,3-oxazol-5-yl)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[4-(1H-pyrazol-4-yl)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-[(1-phenyl-1H-pyrazol-4-yl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{[4-(piperidin-4-yl)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-[(4-propanamidophenyl)sulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{[4-(2-hydroxyacetamido)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-({4-[(methylcarbamoyl)amino]phenyl}sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-{[(2,4-dichlorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[(2-fluorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[(2,3-difluorophenyl)methyl]sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-{[4-(2-methoxyacetamido)phenyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-[(2,5-dichlorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[(2,6-dichlorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[(2-chloro-6-fluorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[(2-chloro-4-fluorophenyl)methyl]sulfonamido})-1,3-thiazole-4-carboxylic acid;
5-{[2-chloro-5-(trifluoromethyl)phenyl]methyl}sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-({4-[(dimethylamino)methyl]phenyl}sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-{[(2,3,5-trichlorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-{[(2,3-dichloro-6-fluorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-({[2,3-dichloro-6-(trifluoromethyl)phenyl]methyl}sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-{[(4-bromo-2-chlorophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-((2-[methyl(phenyl)amino]ethyl) sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-{[(4-nitrophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-[6-(piperidin-1-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(methylamino)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(4-methylpiperazin-1-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-(6-acetamidopyridin-3-ylsulfonamido)-1,3-thiazole-4-carboxylic acid;
5-({4-[(5-methyl-1,2-oxazol-3-yl)amino]phenylsulfonamido}-1,3-thiazole-4-carboxylic acid;
5-(6-aminopyridin-3-ylsulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[(6-chloro-2H-1,3-benzodioxol-5-yl)methylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{[(2-chloro-6-nitrophenyl)methyl]sulfonamido}-1,3-thiazole-4-carboxylic acid;
5-(quinoline-6-sulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[(2,3-dihydroindole-1-sulfonyl)amino]-1,3-thiazole-4-carboxylic acid;
5-(4-methanesulfonylphenylsulfonamido)-1,3-thiazole-4-carboxylic acid;
5-[3-(2-oxo-1,3-oxazolidin-3-yl)phenylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[3-(2H-pyrazol-3-yl)phenylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[2-(pyridin-3-yl)ethylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[3-(3-oxomorpholin-4-yl)phenylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[3-(2-oxopyrrolidin-1-yl)phenylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(piperidin-4-ylamino)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-(6-{[2-(dimethylamino)ethyl]amino}pyridin-3-yl sulfonamido)-1, 3-thiazole-4-carboxylic acid;
5-[(4-acetamidophenyl)methylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(piperazin-1-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(4-aminopiperidin-1-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(3-aminopyrrolidin-1-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(pyrrolidin-1-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(3-aminopiperidin-1-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(1,4-diazepan-1-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[4-(pyrrolidin-3-yloxy)phenylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(3-aminoazetidin-1-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(piperidin-4-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-[6-(1,2,3,6-tetrahydropyridin-4-yl)pyridin-3-ylsulfonamido]-1,3-thiazole-4-carboxylic acid;
5-{6-[4-(2,2,2-trifluoroethyl)piperazin-1-yl]pyridin-3-ylsulfonamido}-1,3-thiazole-4-carboxylic acid;
5-[1-(2-chlorophenyl)ethylsulfonylamino]thiazole-4-carboxylic acid;
5-[1-(2-chlorophenyl)ethylsulfonylamino]thiazole-4-carboxylic acid;
5-(3-pyridylmethylsulfonylamino)thiazole-4-carboxylic acid;
5-(isoindolin-5-ylmethylsulfonylamino)thiazole-4-carboxylic acid;
5-[[4-[(2-aminoacetyl)amino]phenyl]sulfonylamino]thiazole-4-carboxylic acid;
5-[(4-acetamido-3-fluoro-phenyl)sulfonylamino]thiazole-4-carboxylic acid;
5-[[4-[(2-hydroxy-2-methyl-propanoyl)amino]phenyl]sulfonylamino]thiazole-4-carboxylic acid;
5-[[4-[(2-hydroxy-2-phenyl-acetyl)amino]phenyl]sulfonylamino]thiazole-4-carboxylic acid;
5-[[4-[(2-hydroxy-3-phenyl-propanoyl)amino]phenyl]sulfonylamino]thiazole-4-carboxylic acid;
5-[[2-(2-hydroxyethylamino)pyrimidin-5-yl]sulfonylamino]thiazole-4-carboxylic acid (X12);
5-[(2-methylpyrimidin-5-yl)sulfonylamino]thiazole-4-carboxylic acid;
5-[[2-(4-pyridyl)pyrimidin-5-yl]sulfonylamino]thiazole-4-carboxylic acid;
5-[(6-methyl-3-pyridyl)sulfonylamino]thiazole-4-carboxylic acid; and
5-[(2-chloro-3-nitro-phenyl)methylsulfonylamino]thiazole-4-carboxylic acid;
or a salt of any of the foregoing compounds.
26. A method for reducing or removing resistance of Gram-negative bacteria to antibiotics, the method comprising administering to a patient in need of such treatment an effective amount of the compound according to claim 1.
27. A product comprising (i) the compound according to claim 1, in combination with (ii) an antibiotic agent.
28. A method for the treatment of a bacterial infection, the method comprising administering to a patient in need of such treatment an effective amount of the compound according to claim 1 and an antibiotic agent.
29. The method according to claim 28 wherein the antibiotic agent is a β-lactam antibiotic.
30. The method according to claim 29 wherein the β-lactam antibiotic is selected from carbapenems, penicillins, cephalosporins or penems.
31. The method according to claim 26 wherein the Gram-negative bacteria are bacteria which produce metallo-β-lactamases.
32. The method according to claim 26 wherein the Gram-negative bacteria are selected from Enterobacteriaceae (such as Klebsiella pneumonia or Escherichia coli), Pseudomonadaceae (such as Pseudomonas aeruginosa or Burkholderia cepacia) or Acinetobacter baumannii.
33. A pharmaceutical or veterinary composition comprising the compound according to claim 1 and a pharmaceutically or veterinarily acceptable excipient or carrier.
34. The pharmaceutical or veterinary composition according to claim 33, further comprising an antibiotic agent.
35. The pharmaceutical or veterinary composition according to claim 34 wherein the antibiotic agent is a β-lactam antibiotic.
36. The pharmaceutical or veterinary composition according to claim 35 wherein the β-lactam antibiotic is selected from carbapenems, penicillins, cephalosporins, oxacephems, monobactums, or penems.