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US 2004/0024030 A1Published application
Gyrase inhibitors and uses thereof
AssigneeVertex Pharmaceuticals Incorporated
InventorsPaul Charifson, Dean Stamos, Michael Badia, Anne Laure Grillot, Steven Ronkin, Martin Trudeau
Life of this patent
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Abstract
The present invention relates to compounds of the formula I: 1 where Ring A is a thiazole, oxazole, imidazole or pyrazole and the substituents are as described in the specification, and pharmaceutically acceptable salts thereof. The compounds inhibit bacterial gyrase activity and therefore are useful for treating bacterial infections in mammals.
Claims14
A method of treating a bacterial infection in a mammal in need thereof, comprising the step of administering to said mammal a therapeutically effective amount of a compound having the formula:
- 388
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is an optionally substituted group selected from a C1-6 aliphatic group, —C(R4)2(CH2)nNNRCOR, —C(R4)═N—OR, —C(R4)═N—OC(═O) (C1-6 aliphatic), —C(R4)═NNRCO2(C1-6 aliphatic), —C(R4)═NNRCOR, —C(R4)═NN(R)2, —C(R4)2(CH2)nNRCO2 (C1-6 aliphatic), —CO2(C1-6 aliphatic), —CON(R)2, —C(R4)2(CH2)nCON(R)2, —C(R4)2(CH2)nSO2N(R)2, —CONH—OR, —SO2N(R)2, or —C(R4)2(CH2)nNRSO2 (C1-6 aliphatic);
- n is zero or one;
- each R is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group;
- R2 is selected from hydrogen or, when R1 is —CO2(C1-3 aliphatic) or —CONH(C1-3 aliphatic), R2 is further selected from -halo, —CN, —C1-4 aliphatic, a three to five-membered heterocyclyl, or a five-membered heteroaryl;
- Ring A is a heteroaryl ring selected from thiazole, oxazole, imidazole or pyrazole, wherein said imidazole is optionally attached by a C1-3 bridge from an imidazole ring nitrogen to Ar to form a five- to seven-membered fused ring;
- Z is C—R3 or N—R3;
- R3 is —(CH2)pN(R5)2 or an optionally substituted group selected from C1-8 aliphatic, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl;
- each R4 is indepependently selected from hydrogen, an optionally subtituted C1-6 aliphatic group, or two R4 taken together with the carbon to which they are attached form a three to six membered aliphatic ring;
- each R5 is independently selected from hydrogen, an optionally subtituted C1-4 aliphatic group, or two R5 taken together with the nitrogen to which they are attached form a five or six membered heterocyclic ring;
- p is an integer from zero to four when Z is C—R3 or an integer from one to four when Z is N—R3;
- and
- Ar is an optionally substituted aryl, heteroaryl, or heterocyclyl ring.
11 more elements
A compound of formula IA:
- 390
- or a pharmaceutically acceptable salt thereof, wherein
- R1 is an optionally substituted group selected from a C1-6 aliphatic group, —C(R4)2(CH2)nNRCOR, —C(R4)═N—OR, —C(R4)═N—OC(═O) (C1-6 aliphatic), —C(R4)═NNRCO2(C1-6 aliphatic), —C(R4)═NNRCOR, —C(R4)═NN(R)2, —C(R4)2(CH2)nNRCO2(C1-6 aliphatic), —CO2(C1-6 aliphatic), —CON(R)2, —C(R4)2(CH2)nCON(R)2, —C(R4)2(CH2)nSO2N(R)2, —CONH—OR, —SO2N(R)2, or —C(R4)2(CH2)nNRSO2 (C1-6 aliphatic);
- n is zero or one;
- each R is independently selected from hydrogen or an optionally substituted C1-6 aliphatic group;
- R2 is selected from hydrogen or, when R1 is —CO2(C1-3 aliphatic) or —CONH(C1-3 aliphatic), R2 is further selected from -halo, —CN, —C1-4 aliphatic, a three to five-membered heterocyclyl, or a five-membered heteroaryl;
- Ring A is a heteroaryl ring selected from thiazole, oxazole, imidazole or pyrazole, wherein said imidazole is optionally attached by a C1-3 bridge from an imidazole ring nitrogen to Ar to form a five- to seven-membered fused ring;
- Z is C—R3 or N—R3;
- R3 is —(CH2)pN(R5)2 or an optionally substituted group selected from C1-8 aliphatic, heterocyclyl, heterocyclylalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl;
- each R4 is indepependently selected from hydrogen, an optionally subtituted C1-6 aliphatic group, or two R4 taken together with the carbon to which they are attached form a three to six membered aliphatic ring;
- each R5 is independently selected from hydrogen, an optionally subtituted C1-4 aliphatic group, or two R5 taken together with the nitrogen to which they are attached form a five or six membered heterocyclic ring;
- p is an integer from zero to four when Z is C—R3 or an integer from one to four when Z is N—R3;
- and
- Ar is an optionally substituted aryl, heteroaryl, or heterocyclyl ring.
11 more elements
Dependencies are inferred from the claim text.