US 2003/0119817 A1 · Oxazolidinone derivatives as potential antimicrobials

Abstract

The present invention relates to certain substituted phenyl oxazolidinones and to processes for the synthesis of the same. This invention also relates to pharmaceutical compositions containing the compounds of the present invention as antimicrobials. The compounds are useful antimicrobial agents, effective against a number of human and veterinary pathogens, including gram-positive aerobic bacteria such as multiply-resistant staphylococci, streptococci and enterococci as well as anaerobic organisms such as Bacterioides spp. and Clostridia spp. species, and acid fast organisms such as Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium spp.

Claims24

Dependent claims

A compound having the structure of Formula I

29
and its pharmaceutically acceptable salts, enantiomers, diastearomers, N-oxides, prodrugs or metabolites, wherein
T is five to seven membered heterocyclic ring, aryl, substituted aryl, bound to the ring C with a linker W and the heterocyclic and aryl rings are further substituted by a group represented by R,
wherein R is selected from the group consisting of alkyl (C1-6), halogen-CN, COR5, COOR5, N(R6,R7), CON(R6, R7), CH2NO2, NO2, CH2R8, CHR9, —CH═N—OR10, —C═CH—R5, wherein R5 is selected from the group consisting of H, optionally substituted C1-C12, alkyl, C3-12, cycloalkyl, aryl, heteroaryl;
R6 and R7 are independently selected from the group consisting of H, optionally substituted C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy;
R8 and R9 are independently selected from the group consisting of H, C1-6 alkyl, F, Cl, Br, C1-12 alkyl substituted with one or more of F, Cl, Br, I, OR4, SR4, N(R6,R7) wherein R4 is selected from the group consisting of H, C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl substituted with one or more F, Cl, Br, I or OH and R6 and R7 are the same as defined earlier, R10 is selected from the group consisting of H, optionally substituted from H, optionally substituted C1-12 alkyl, C3-512 cycloalkyl, C1-6, alkoxy, C1-6 alkyl, aryl, heteroaryl;
n is an integer in the range from 0 to 3;
X is CH, CH—S, CH—O and N
Y and Z are independently selected from the group consisting of hydrogen, C1-6 alkyl, C3-12 cycloalkyl, C0-3 bridging group;
U and V are independently selected from the group consisting of optionally substituted C1-6 alkyl, F, Cl, Br, C1-12 alkyl substituted with one or more of F, Cl, Br, I, preferably U and V are hydrogen or fluoro;
W is selected from the group CH2, CO, CH2NH, —NHCH2, —CH2NHCH2, —CH2—N(R11)CH2—, —CO—CO—, CH2(R11)N—, CH(R11), S, CH2(CO), N(R11) wherein R11 is hydrogen, optionally substituted C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl, aryl or heteroaryl;
R1 is selected from the group consisting of —NHC(═O)R2 wherein R2 is hydrogen, C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl substituted with one or more of F, Cl, Br, I or OH;
N(R3, R4);
—NR2C(═S)R3;
—NR2C(═S)SR3 wherein R2 is the same as defined above and R3 and R4 are independently selected from the group consisting of H, C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl substituted with one or more of F, Cl, Br, I or OH.

12 more elements

A compound having structure of Formula II

30
and its pharmaceutically acceptable salts, enantiomers, diastearomers, N-oxides, prodrugs or metabolites wherein
M=O, S, NH, N—CH3;
X is CH, CH—S, CH—O and N;
Y and Z are independently selected from the group consisting of hydrogen, C1-6 alkyl, C3-12 cycloalkyl, C0-3 bridging group;
U and V are independently selected from the group consisting of optionally substituted C1-6 alkyl, F, Cl, Br, C1-12 alkyl substituted with one or more of F, Cl, Br, I, preferably U and V are hydrogen or fluoro;
W is selected from the group consisting of CH2, CO, CH2NH, —NHCH2, —CH2NHCH2, —CH2—N(R11)CH2—, CH2(R11)N—, CH(R11), S, CH2(CO), NH wherein R11 is optionally substituted with C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl , aryl , heteroaryl except when M=S, Q=P=H, W=(C═O);
n is an integer in the range from 0 to 3;
and,
Q and P are independently selected from the group consisting of —N, COR5, COOR5, N(R6, R7), CON(R6,R7), CH2NO2, NO2, CH2R8, CHR9, —CH═N—OR10, C═CH—R5, wherein R5 is selected from the group consisting of H, optionally substituted C1-12alkyl, C3-12 cycloalkyl, aryl, heteroaryl;
R6 and R7 are independently selected from the group consisting of H, optionally substituted C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy;
R8 and R9 are independently selected from the group consisting of H, C1-6 alkyl , F, Cl, Br, C1-12 alkyl substituted with one or more of F, Cl, Br, I, OR4, SR4, wherein R4 is selected from the group consisting of H, C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl substituted with one or more F, Cl, Br, I or OH, N(R6, R7), R10 is selected from the group consisting of H, optionally substituted C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl, aryl, heteroaryl except W=(CO), Q and P=H and M=S, ring C in Formula II is 6-8 membered or of larger size and the larger rings have either two or three carbons between each nitrogen atom, comprising of
31
and may be bridged to form a bicyclic system as shown below,
32
ring C is optionally substituted by Y and Z with alkyl groups, cycloalkyl groups, fluoro group, carboxylic and corresponding esters, amides, substituted alkyls or bridging alkyl groups are as shown below:
33
six membered ring C with X=—CH—(NR11), (wherein R11 is the same as defined earlier) is selected from the group consisting of the following rings;
34
wherein M=Sulphur and Oxygen as shown by Formulae II and IV respectively,
35
wherein P, Q, U, V, X, Y, Z, W and n in Formulae III and IV as defined earlier for Formula I.

19 more elements

A compound selected from the group consisting of

1. (S)-N-[[3-[3-Fluoro-4-[N-1-[4-(2-furoyl)piperazinyl]]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
2. (S)-N-[[3-[3-Fluoro-4-[N-1[4-{2-furyl(5-formyl)methyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
3. (S)-N-[[3-Fluoro-4-[N-1[4-(2-furyl-(5-carboxyethyl)methyl)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
4. (S)-N-[[3-Fluoro-4-[N-1[4-(5-bromo-2-furoyl)]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
5. (S)-N-[[3-Fluoro-4-[N-1[4-(5-chloromethyl-2-furoyl)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
6. (S)-N-[[3-Fluoro-4-[N-1[4-(5-nitro-2-furoyl)piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
7. (S)-N[[3-[3-Fluoro-4-[N-1[4-{2-(2-thienyl)dicarbonyl}]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
8. (S)-N[[3-[3-Fluoro-4-[N-1[4-(3-furoyl)]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
9. (S)-N[[3-[3-Fluoro-4-[N-1[4-{2-furyl(5-bromo)methyl}]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
10. (S)-N[[3-[3-Fluoro-4-[N-1[4-{2-thienyl(5-chloro)methyl}]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
11. (S)-N[[3-[3-Fluoro-4-[N-1[4-(2-furylmethyl)]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
12. (S)-N-[[3-[3-Fluoro-4-[N-1[4-(2-thienylmethyl)]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
13. (S)-N[[3-[3-Fluoro-4-[N-1[4-(2-thienylacetyl)]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
14. (S)-N-[[3-[3-Fluoro-4-[N-1[4-{2-thienyl(4-bromo)methyl}]piperazinyl]phenyl]-2oxo-5-oxazolidinyl]methyl]acetamide
15. (S)-N-[[3-[3-fluoro-4-[N-1-[4-{2-furyl-(5-nitro)methyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide.
16. Hydrochloric salt of (S)-N-[[3-Fluoro-4-[N-1[4-{2-furyl(5-nitro)methyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
17. Citrate salt of (S)-N-[[3-Fluoro-4-[N-1[4-{2-furyl(5-nitro)methyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
18. (S)-N[[3-[3-Fluoro-4-[N-1[4-(2-pyrrolylmethyl)]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
19. (S)-N[[3-[3-Fluoro-4-[N-1[4-{2-thienyl(3-methyl)methyl}]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
20. (S)-N[[3-[3-Fluoro-4-[N-1[4-(3-furylmethyl)]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
21. (S)-N[[3-[3-Fluoro-4-[N-1[4-{2-thienyl(5-methyl)methyl}]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
22. (S)-N[[3-[3-Fluoro-4-[N-1[4-{2-pyrrole(1-methyl)methyl}]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
23. (S)-N[[3-[3-Fluoro-4-[N-1[4-{2-thienyl(5-nitro)methyl}]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
24. (S)-N[[3-[3-Fluoro-4-[N-1[4-[2-furyl{5-(N-thiomorpholinyl)methyl}methyl]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
25. (S)-N[[3-[3-Fluoro-4-[N-1[4-[2-furyl{5-(N-morpholinyl)methyl}methyl]]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
26. (S)-N-[[3-Fluoro-4-[N-1[4-{2-furyl(5-acetoxymethyl)methyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
27. (S)-N-[[3-Fluoro-4-[N-1[4-{2-thienyl(5-bromo)methyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
28. (S)-N-[[3-Fluoro-4-[N-1[4-(5-nitro-2-furylmethyl)piperazinyl]phenyl]-2-oxo oxazolidinyl]methyl]dichloroacetamide
29. (S)-N[[3-[3-Fluoro-4-[N-1[4-(5-nitro-2-thienoyl)]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide hydrochloride
30. (S)-N[[3-[3-Fluoro-4-[N-1[4-(2′,2′-diphenyl-2′hydroxy acetyl)]piperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
31. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(5-nitro-2-furoyl-N-methyl]amino]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
32. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(3-furoyl)-N-methyl]amino]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
33. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(5-bromo-2-furoyl)-N-methyl]amino]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
34. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(5-nitro-2-thienylmethyl)-N-methyl]amino]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
35. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(5-nitro-2-furylmethyl)-N-methyl]amino]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
36. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(5-formyl-2-furylmethyl)-N-methyl]aminomethyl]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
37. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(5-carboxyethyl-2-furylmethyl)-N-methyl]aminomethyl]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
38. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(2-thiopheneacetyl)-N-methyl]aminomethyl]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
39. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(5-nitro-2-thienylmethyl)-N-methyl]amino-methyl]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
40. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(5-nitro-2-furylmethyl)-N-methyl]amino-methyl]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
41. (S)-N-[[3-[4-[4-(N-methyl-N-2furyl(5formyl)methylaminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide
42. (S)-N-[[3-[4-[4-(N-methyl-N-(3,5-difluorobenzoyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide.
43. (S)-N-[[3-[4-[4-(N-methyl-N-(5-bromo-2-furoyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide
44. (S)-N-[[3-[4-[4-(N-methyl-N-(5-nitro-2-furoyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide
45. (S)-N-[[3-[4-[4-(N-methyl-N-3-furoyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide.
46. (S)-N-{3-[4-[4-(N-methyl,N-2-furoyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl methyl]acetamide
47. (S)-N-{3-[4-[4-(N-methyl,2-thiopheneacetyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo oxazolidin-5-yl methyl]acetamide
48. (S)-N-[[3-[4-[4-(N-methyl-N-2furylmethyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide
49. (S)-N-[[3-[4-[4-(N-methyl-N-3-furyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide.
50. (S)-N-[[3-[4-[4-(N-methyl-N-2-furyl(5-nitro)methyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide.
51. (S)-N-[[3-[4-[4-(N-methyl-N-2-thienyl(5-nitro)methyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide.
52. (S)-N-[[3-[4-[4-(N-methyl-N-2-thienylmethyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide.
53. (S)-N-[[3-[4-[4-(N-methyl-N-(5-methyl-2-thienylmethyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl]methyl]acetamide
54. (S)-N-{3-[4-[4-(N-methyl,2-(5-bromo)thienylmethyl)aminopiperidine-1-yl]-3-fluorophenyl]-2-oxo-oxazolidin-5-yl methyl]acetamide
55. (S)-N[[3-[3-Fluoro-4-[N-1[4-{2-furyl(5-formyl)methyl}]homopiperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
56. (S)-N[[3-[3-Fluoro-4-[N-1[4-(2-thienylacetyl)]homopiperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
57. (S)-N[[3-[3-Fluoro-4-[N-1[4-{2-thienyl(5-nitro)methyl}]homopiperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
58. (S)-N[[3-[3-Fluoro-4-[N-1[4-(3-furylmethyl)]homopiperazinyl]phenyl]2-oxo-5-oxazolidinyl]methyl]acetamide
59. Preparation of (S)-N-[[3-[3-fluoro-4-[N-1{2-furyl-[4-(5-difluoromethyl)methyl}]piperazinyl]-2-oxo-5-oxazolidinyl]-methyl]acetamide.
60. (S)-N-[[3-[3-Fluoro-4-[N-1-[4-(2-furyl-(5-aldoxime)methyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
61. (S)-N-[[3-[3-Fluoro-4-[N-1[4-{2-furyl(5-aldoxime(methyl-4-(N-carboxyaminophenyl acetate)methyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
62. (S)-N-[[3-[3-Fluoro-4[N-1-[4-{2-furyl-(5-hydrazone)-methyl}]-piperazinyl]-phenyl]-2-oxo-5-oxazolidinyl]-methyl]acetamide
63. Preparation of (S)-N-[[3-[3-Fluoro-4-[N-1{2-furyl-[4-(5-hydroxymethyl)methyl}]piperazinyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
64. (S)-N-[[3-[3-Fluoro-4-[N-1[4-{2-furyl(5-cyano)methyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
65. (S)-N-[[3-Fluoro-4-[N-1[4-{2-furyl(5-carboxy)methyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
66. (S)-N-[[3-Fluoro-4-[N-1[5-(1,3-dioxane)-2-furylmethyl]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
67. (S)-N-[[3-Fluoro-4-[N-1[5-(formamido)-2-furylmethyl]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
68. (S)-N-[[3-Fluoro-4-[N-1[5-(morpholine-1-carbonyl)-2-furylmethyl]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
69. (S)-N-[[3-Fluoro-4-[N-1[5-(4-(tertbutoxycarbonyl)amino piperidine)-2-furylmethyl]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
70. (S)-N-[[3-Fluoro-4-[N-1[4-{(Z)-2-methoxyimino-2-(2-furyl)acetyl}]piperazinyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
71. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(2-thiopheneacetyl)-N-methyl]amino]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
72. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(5-formyl-2-furylmethyl)-N-methyl]amino]-3-azabicyclo-[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
73. (S)-N-[[3-[3-Fluoro[4-[3-(1α,5α,6α)-6-[N-(3-thienoyl)-N-methyl]amino]-3-azabicyclo[3.1.0]hexane]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide
74. (S)-N-[[3-[3-fluoro-4-[N-1{2-furyl-[4-(5-fluoromethyl)methyl}]piperazinyl]-2-oxo-5-oxazolidinyl]-methyl]acetamide.

71 more elements

A process for preparing a compound of Formula I

36
and its pharmaceutically acceptable salts, enantiomers, diastearomers, N-oxides, prodrugs or metabolites, wherein
T is five to seven membered heterocyclic ring, aryl, substituted aryl, bound to the ring C with a linker w and the heterocyclic and aryl rings are further substituted by a group represented by R,
wherein R is selected from the group consisting of —CN, COR5, COOR5, N(R6,R7), CON(R6, R7), CH2NO2, NO2, CH2R8, CHR9, —CH═N—OR10, —C═CH—R5, wherein R5 is selected from the group consisting of H, optionally substituted C1-C12, alkyl, C3-12, cycloalkyl, aryl, heteroaryl, R6 and R7, are independently selected from the group consisting of H, optionally substituted C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy;
R8 and R9 are independently selected from the group consisting of H, C1-6 alkyl, F, Cl, Br, C1-12 alkyl substituted with one or more of F, Cl, Br, I, OR4, SR4, N(R6,R7) wherein R4 is selected from the group consisting of H, C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl substituted with one or more F, Cl, Br, I or OH and R6 and R7 are the same as defined earlier, R10 is selected from the group consisting of H, optionally substituted from H, optionally substituted C1-12 alkyl, C3-512 cycloalkyl, C1-6, alkoxy, C1-6 alkyl, aryl, heteroaryl;
n is an integer in the range from 0 to 3;
X is CH, CH—S, CH—O and N;
Y and Z are independently selected from the group consisting of hydrogen, C1-6 alkyl, C3-12 cycloalkyl, C0-3 bridging group;
U and V are independently selected from the group consisting of optionally substituted C1-6 alkyl, F, Cl, Br, C1-12 alkyl substituted with one or more of F, Cl, Br, I, preferably U and V are hydrogen or fluoro;
W is selected from the group consisting of CH2, CO, CH2NH, —NHCH2, —CH2NHCH2,—CH2—N(R11)CH2—, CH2(R11)N—, CH(R11), S, CH2(CO)NH wherein R11 is optionally substituted with C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl, aryl, heteroaryl;
and
R1 is selected from the group consisting of —NHC(═O)R2 wherein R2 is hydrogen, C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl substituted with one or more of F, Cl, Br, I or OH;
N(R3, R4);
—NR2C(═S)R3:
—NR2C(═S)SR3 wherein R2 is the same as defined above and R3 and R4 are independently selected from the group consisting of H, C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl substituted with one or more of F, Cl, Br, I or OH, which comprises reacting an amine compound of Formula V
37
with a heterocyclic compound of Formula R-T-W-R12 wherein G in amines of Formula V is defined as NH, CH(NHR13), —CH—CH2NHR13 wherein R13 is H, ethyl, methyl, isopropyl, acetyl, cyclopropyl, alkoxy or acetyl and Y, Z, U, V, R1, n, R, T and W are the same as defined earlier and R12 is a suitable leaving group selected from the group comprising of fluoro, chloro, bromo, SCH3, —SO2CH3, —SO2CF3 or OC6H5.

14 more elements

A process for the preparation of compound of Formula II

38
wherein
n is an integer in the range from 0 to 3;
X is CH, CH—S, CH—O and N;
Y and Z are independently selected from the group consisting of hydrogen, C1-6 alkyl, C3-12 cycloalkyl, C0-3 bridging group;
U and V are independently selected from the group consisting of optionally substituted C1-6 alkyl, F, Cl, Br, C1-12 alkyl substituted with one or more of F, Cl, Br, I, preferably U and V are hydrogen or fluoro;
W is selected from the group consisting of CH2, CO, CH2NH, —NHCH2, —CH2NHCH2, —CH2—N(R11)CH2—, CH2(R11)N—, CH(R11), S, CH2(CO), NH wherein R11 is optionally substituted with C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl, aryl, heteroaryl;
and
Q and P are independently selected from the group consisting of —CN, COR5, COOR5, N(R6, R7), CON(R6,R7), CH2NO2, NO2, CH2R8, CHR9, —CH═N—OR10, C═CH—R5, wherein R5 is selected from the group consisting of H, optionally substituted C1-12alkyl, C3-12 cycloalkyl, aryl, heteroaryl;
R6 and R7 are independently selected from the group consisting of H, optionally substituted C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy;
R8 and R9 are independently selected from the group consisting of H, C1-6 alkyl, F, Cl, Br, C1-12 alkyl substituted with one or more of F, Cl, Br, I, OR4, SR4, wherein R4 is the same as defined before, N(R6, R7), R10 is selected from the group consisting of H, optionally substituted C1-12 alkyl, C3-12 cycloalkyl, C1-6 alkoxy, C1-6 alkyl, aryl, heteroaryl except W=(CO), Q and P=H.
Ring C in Formula II is 6-8 membered or of larger size and the larger rings have either two or three carbons between each nitrogen atom, comprising of
39
and may be bridged to form a bicyclic system as shown below,
40
ring C is optionally substituted by Y and Z with alkyl groups, cycloalkyl groups, fluoro group, carboxylic and corresponding esters, amides, substituted alkyls or bridging alkyl groups are as shown below:
41
six membered ring C with X=—CH—(NHR11), (wherein R11 is the same as defined earlier) is selected from the group consisting of the following rings;
42
wherein M=Sulphur is shown by compounds of Formula III,
43
wherein P, Q, U, V, X, Y, Z, W and n in Formula III are the same as previously defined, wherein the process comprising reacting a compound of Formula V
44
with a compound of Formula VI
45
wherein P, Q, R12, Y, Z, G, n, U and V are the same as defined earlier.

23 more elements

Dependencies are inferred from the claim text.

Oxazolidinone derivatives as potential antimicrobials

Life of this patent

Oxazolidinone derivatives as potential antimicrobials

Life of this patent

Abstract

Claims24