Claims
- 1. A compound of structural Formula I:
- or pharmaceutically acceptable salts thereof wherein: X is S, SO, SO.sub.2 SNR.sup.10 or S(O)NR.sup.10 ;
- R is (a) hydrogen,
- (b) C.sub.1 -C.sub.8 alkyl optionally substituted with one or more of the following: F, Cl, hydroxy, C.sub.1 -C.sub.8 alkoxy, C.sub.1 -C.sub.8 acyloxy or --O--CH.sub.2 --Ph,
- (c) C.sub.3 -C.sub.6 cycloalkyl,
- (d) amino,
- (e) C.sub.1 -C.sub.8 alkylamino,
- (f) C.sub.1 -C.sub.8 dialkylamino or
- (g) C.sub.1 -C.sub.8 alkoxy;
- R.sup.1 is H;
- R.sup.2 is independently H, F or Cl;
- R.sup.3 is H; R.sup.10 is independently H, C .sub.1 -C.sub.4 alkyl (optionally substituted with chloro, fluoro, hydroxy, C.sub.1 -C.sub.8 alkoxy, amino, C.sub.1 -C.sub.8 alkylamino, or C.sub.1 -C.sub.8 dialkylamino) or p-toluenesulfonyl; and
- n is 0, 1 or 2.
- 2. The compound of claim 1 wherein X is S, SO or SO.sub.2.
- 3. The compound of claim 2 wherein each R.sup.2 is fluorine.
- 4. The compound of claim 1 wherein n is 1 and X is S, SO or SO.sub.2.
- 5. The compound of claim 1 which is an optically pure enantiomer having the S-configuration at C5 of the oxazolidinone ring.
- 6. The compound of claim 1 wherein one R.sup.2 is hydrogen and the other is fluorine.
- 7. The compound of claim 1 wherein R is methyl, OCH.sub.3, CHCl.sub.2, CH.sub.2 OH or hydrogen.
- 8. The compound of claim 1 which is:
- (a) (S)--N--��3-�3-fluoro-4-(4-thiomorpholinyl)phenyl!-2-oxo-5-oxazolidinyl!methyl!acetamide;
- (b) (S)--N--��3-�3-fluoro-4-(1,1-dioxothiomorpholin-4-yl)phenyl!-2-oxo-5-oxazolidinyl!methyl!acetamide;
- (c) (S)--N--��3-�3-fluoro-4-(1-oxothiomorpholin-4-yl)phenyl! -2-oxo-5-oxazolidinyl!methyl!acetamide; and
- (d) (S)--N--��3-�3-fluoro-4-�1-�(p-toluenesulfonyl)imino!thiomorpholin-4-yl!phenyl!-2-oxo-5-oxazolidinyl!methyl!acetamide.
- 9. The compound of claim 1 where n is O and X is S, SO or SO.sub.2.
- 10. The compound of claim 9 wherein one R.sup.2 is hydrogen and the other is fluorine.
- 11. The compound of claim 9 which is:
- (a) (S)--N--��3-�3-fluoro-4-(3-thiazolidinyl)phenyl!-2-oxo-5-oxazolidinyl!methyl!acetamide;
- (b) (S)--N--��3-�3-fluoro-4-(1,1-dioxothiazolidin-3-yl)phenyl!-2-oxo-5-oxazolidinyl! methyl! acetamide; or
- (c) (S)--N--��3-�3-fluoro-4-(1-oxothiazolidin-3-yl)phenyl!-2-oxo-5-oxazolidinyl!methyl!acetamide.
- 12. The compound of claim 1 where n is 2 and X is S, SO or SO.sub.2.
- 13. The compound of claim 12 wherein one R.sup.2 is hydrogen and the other is fluorine.
- 14. The compound of claim 12 which is:
- (a) (S)--N--��3-�3-fluoro-4-(hexahydrothiazepin-4-yl)phenyl!-2-oxo-5-oxazolidinyl!methyl!acetamide;
- (b) (S)--N--��3-�3-fluoro-4-(1,1-dioxohexahydrothiazepin-4-yl)phenyl!-2-oxo-5-oxazolidinyl!methyl!acetamide; or
- (c) (S)--N--��3-�3-fluoro-4-(l-oxohexahydlrothiazepin-4-yl)phenyl!-2-oxo-5-oxazolidinyl!methyl!acetamide.
- 15. A method useful in treating microbial infections in patients comprising:
- administering to a patient in need thereof an effective amount of a compound of Formula I as shown in claim 1.
- 16. The method of claim 15 wherein said compound of Formula I is administered orally, parenterally or topically in a pharmaceutical composition.
- 17. The method of claim 15 wherein said compound is administered in an amount of from about 0.1 to about 100 mg/kg of body weight/day.
- 18. The method of claim 17 wherein said compound is administered in an amount of from about 3.0 to about 50 mg/kg of body weight/day.
- 19. The method of claim 15 wherein said microbial infection is caused by staphylococci, streptococci, enterococci, Bacteroides spp., Clostridia spp., Mycobacterium tuberculosis, Mycobacterium avium or Mycobacterium spp..
- 20. A compound selected from the group consisting of:
- (a) (S)--N--��3-�3-fluoro-4-(3-oxazolidinyl)!phenyl!-2-oxo-5-oxazolidinyl! methyl!acetamide; and
- (b) (S)--N--��3-�3-fluoro-4-(hexahydrooxazepin-4-yl)!phenyl!-2-oxo-5-oxazolidinyl!methyl!acetamide.
Parent Case Info
This application is a divisional of U.S. Ser. No. 08/617,877, filed Mar. 5, 1996, now issued as U.S. Pat. No. 5,688,792; which is the national stage of international application PCT/US94/08904, filed August 16, 1994, which designated the U.S., now abandoned; which is a continuation-in-part of U.S. Ser. No. 08/226,158, filed Apr. 11, 1994, now abandoned; which is a continuation-in-part of U.S. Ser. No. 08/119,279, filed Sep. 9, 1993, now abandoned.
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Divisions (1)
|
Number |
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Country |
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617877 |
Mar 1996 |
|
Continuation in Parts (2)
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Number |
Date |
Country |
Parent |
226158 |
Apr 1994 |
|
Parent |
119279 |
Sep 1993 |
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