Substituted oxazolidinones for the treatment of mammalian infections

1. A compound of general formula (I),

or a pharmaceutically acceptable salt thereof, wherein, X is either absent or a bond;

whenever X is absent, the four membered ring is directly attached to the 6-membered piperidine ring forming spirocyclic system with the spiro carbon at position 4 of the piperidine ring and Q being beta to the spiro carbon; Q is either O or S(O)p; p=0-2 integer; Y is OH, NR2R3, or NHC(O)R4; R1 is selected from H, F, Cl, CH3, CN and OCH3; m=1-4 integer; R2 and R3 are independently selected from H, (C1-C6)alkyl, (C3-C6)cycloalkyl, aryl, heterocyclyl and heteroaryl each of which may be further optionally substituted; or Rz and R3 are taken together with the nitrogen to which they are attached to form a 4- to 8-membered heterocyclyl or heteroaryl with 1 to 3 additional heteroatoms selected from O, S, or N, which heterocyclyl or heteroaryl may be further be optionally substituted; R4 is independently selected from (C1-C6)alkyl, (C3-C6)cycloalkyl, aryl, heteroaryl and (C1-C6)alkoxy, each of which is optionally substituted; substitutions are selected from halo, hydroxyl, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)acyloxy, haloalkyl, NO2, CN and NH2.

2. The compound of formula (I) or salt thereof as claimed in claim 1 wherein the (C 1 -C 6 )alkyl group of R 2 , R 3 and R 4 is selected from methyl, ethyl, n-propyl, and iso-propyl; the (C 1 -C 6 )alkoxy group of R 2 , R 3 and R 4 is selected from methoxy and ethoxy; and the (C 3 -C 6 )cycloalkyl group of R 2 , R 3 and R 4 is selected from cyclopropyl and cyclobutyl.

3. The compound of formula (I) or salt thereof as claimed in claim 1 wherein heteroaryl group of R 4 is selected from thienyl, furyl, isoxazolyl, and triazolyl.

4. The compound of formula (I) or salt thereof as claimed in claim 1 wherein the compound is selected from

(R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3,5-difluorophenyl)oxazolidin-2-one;

(S)-3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3,5-difluorophenyl)-5-((isoxazol-3-ylamino)methyl)oxazolidin-2-one;

(S)—N-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

(S)-methyl ((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(S)—N-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

(S)—N-((3-(3,5-difluoro-4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

(S)—N-((3-(3-fluoro-4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

(S)—N-((3-(3,5-difluoro-4-(4-(oxetan-3-yl)piperidin-1-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

(S)—N-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

(S)—N-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)acetamide;

methyl (S)-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(S)-5-(aminomethyl)-3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3,5-difluorophenyl)oxazolidin-2-one;

(R)-3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3,5-difluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one;

(S)-5-(aminomethyl)-3-(3,5-difluoro-4-(4-(oxetan-3-yl)piperidin-1-yl)phenyl)oxazolidin-2-one;

(S)-5-(aminomethyl)-3-(3,5-difluoro-4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)phenyl)oxazolidin-2-one;

(S)-5-(aminomethyl)-3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3,5-difluorophenyl)oxazolidin-2-one;

(R)-3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3,5-difluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one;

(S)—N-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3,5]nonan-7-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)thiophene-2-carboxamide;

(S)—N-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)thiophene-2-carboxamide;

(S)—N-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3,5]nonan-7-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)furan-2-carboxamide;

(S)—N-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)furan-2-carboxamide;

(S)—N-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)thiophene-2-carboxamide;

(S)—N-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)thiophene-2-carboxamide;

(S)—N-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)furan-2-carboxamide;

(S)—N-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)furan-2-carboxamide;

(S)—N-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)butyramide;

(S)—N-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)butyramide;

(S)—N-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)butyramide;

(S)—N-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)butyramide;

ethyl (S)-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (S)-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (S)-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3,5-difluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

ethyl (S)-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(xazolidin-5-yl)methyl)cyclobutanecarboxamide;

(R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3-fluorophenyl)oxazolidin-2-one;

(R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3,5-difluorophenyl)oxazolidin-2-one;

(R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3-fluorophenyl)oxazolidin-2-one;

(R)-5-((1H-1,2,4-triazol-1-yl)methyl)-3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3,5-difluorophenyl)oxazolidin-2-one;

(R)-5-((1H-1,2,4-triazol-1-yl)methyl)-3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3-fluorophenyl)oxazolidin-2-one;

(S)-3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3-fluorophenyl)-5-((isoxazol-3-ylamino)methyl)oxazolidin-2-one;

(S)-3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3,5-difluorophenyl)-5-((isoxazol-3-ylamino)methyl)oxazolidin-2-one;

methyl (S)-((3-(4-(4-(1,1-dioxidothietan-3-yl)piperidin-1-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (S)-((3-(4-(2,2-dioxido-2-thia-7-azaspiro[3.5]nonan-7-yl)-3-fluorophenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

methyl (S)-((3-(3-fluoro-4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3-fluoro-4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)phenyl)oxazolidin-2-one;

methyl (S)-((3-(3,5-difluoro-4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)phenyl)-2-oxooxazolidin-5-yl)methyl)carbamate;

(R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3,5-difluoro-4-(2-oxa-7-azaspiro[3.5]nonan-7-yl)phenyl)oxazolidin-2-one; and

(R)-5-((1H-1,2,3-triazol-1-yl)methyl)-3-(3,5-difluoro-4-(4-(oxetan-3-yl)piperidin-1-yl)phenyl)oxazolidin-2-one.

5. A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) or salt thereof as claimed in claim 1 and optionally one or more pharmaceutically acceptable carriers, diluents or excipients.

6. A method of treating a tuberculosis infection in a patient comprising administering an effective amount of a compound of formula (I) as claimed in claim 1 or salt thereof or a pharmaceutical composition comprising a compound or salt of claim 1 to the patient.