Claims
- 1. A compound of the formula: ##STR199## (a) X is selected from the group consisting of --C(O)--, --O--C(O)--, --NH--C(O) --, --S(O.sub.2)--, --O--S(O.sub.2)--, --NH--S(O.sub.2)-- and --N(R')--S(O.sub.2)--, wherein R' is alkyl of 1 to about 4 carbon atoms, aryl of about 6 to about 14 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms;
- (b) R.sub.1 is selected from the group consisting of:
- (1) ##STR200## where X is not --O--C(O)--, NH--C(O)--, --O--S(O.sub.2)--, --NH--S(O.sub.2)-- or --N(R')--S(O.sub.2)--,
- (2) a substituted group of the formula ##STR201## wherein the aryl ring is substituted with Y.sub.1, and X is not --O--C(O)--, NH--C(O)--, --O--S(O.sub.2)--, --NH--S(O.sub.2)-- or --N(R ')--S(O.sub.2)--, and
- (3) a substituted group of the formula ##STR202## wherein the aryl ring is substituted with Y.sub.1 and Y.sub.2, and X is not --O--C(O)--, NH--C(O)--, --O--S(O.sub.2)--, --NH--S(O.sub.2)-- or --N(R')--S(O.sub.2)--,
- wherein
- Y.sub.1, Y.sub.2 and Y.sub.3 are independently selected from the group consisting of bromo, chloro, fluoro, --Z.sub.1, --OH, --OZ.sub.1, --NH.sub.2, --NHZ.sub.1, --NZ.sub.1 Z.sub.2, --NH--C(O)--Z.sub.1, --N(Z.sub.1)--C(O)--Z.sub.2, --NH--C(O)--OZ.sub.1, --N(Z.sub.1)--C(O)--OZ.sub.2, --NH--C(O)--NH.sub.2, --NH--C(O)--NHZ.sub.1, NH--C(O)--NZ.sub.1 Z.sub.2, --N(Z.sub.1)--C(O)--NHZ.sub.2, --N(Z.sub.1)--C(O)--NZ.sub.2 Z.sub.3, --C(O)--OH, --C(O)--OZ.sub.1, --C(O)--NHZ.sub.1, --C(O)--NZ.sub.1 Z.sub.2, --SH, --SZ.sub.1, --S(O)--Z.sub.1, --S(O.sub.2)--Z.sub.1, --S(O.sub.2)--OH, --S(O.sub.2) --OZ.sub.1, --S(O.sub.2)--NH.sub.2, --S(O.sub.2)--NHZ.sub.1, --S(O.sub.2)--NZ.sub.1 Z.sub.2 and ##STR203## wherein Z.sub.1, Z.sub.2 and Z.sub.3 are independently selected from the group consisting of trifluoromethyl, pentafluoroethyl, alkyl of 1 to about 12 carbon atoms, aryl of about 6 to about 14 carbon atoms, and aralkyl of about 6 to about 15 carbon atoms,
- R" is alkyl of 1 to about 4 carbon atoms, aryl of about 6 to about 14 carbon atoms, or aralkyl of about 6 to about 15 carbon atoms,
- (c) R.sub.2 is selected from the group consisting of
- --CH.sub.2 --S(O).sub.q --CH.sub.3,
- --CH.sub.2 --S(O).sub.q --(CH.sub.2)m--C(O)--OH,
- --CH.sub.2 --S(O).sub.q --(CH.sub.2)m--C(O)--OR',
- --CH.sub.2 --S(O).sub.q --(CH.sub.2)m--C(O)--NH.sub.2,
- --CH.sub.2 --S(O).sub.q --(CH.sub.2)m--C(O)--NHR',
- --CH.sub.2 --S(O).sub.q --(CH.sub.2)m--C(O)--NR'R", ##STR204## --CH.sub.2 --S(O).sub.q --(CH.sub.2).sub.m --Ar--C(O) OH, --CH.sub.2 --S(O).sub.q --(CH.sub.2).sub.m --Ar--C(O) OR',
- --CH.sub.2 --S(O).sub.q --(CH.sub.2).sub.m --Ar--C(O) NH.sub.2,
- --CH.sub.2 --S(O).sub.q --(CH.sub.2).sub.m --Ar--C(O) NHR',
- --CH.sub.2 --S(O).sub.q --(CH.sub.2).sub.m --Ar--C(O) NR'R",
- --CH.sub.2 --S(O).sub.q --(CH.sub.2).sub.m --Ar--CN.sub.4 H,
- --S(O).sub.q --CH.sub.3,
- --S(O).sub.q --(CH.sub.2).sub.m --C(O)--OH,
- --S(O).sub.q --(CH.sub.2).sub.m --C(O)--OR',
- --S(O).sub.q --(CH.sub.2).sub.m --C(O)--NH.sub.2,
- --S(O).sub.q --(CH.sub.2).sub.m --C(O)--NHR',
- --S(O).sub.q --(CH.sub.2).sub.m --C(O).sub.m --NR'R", ##STR205## --S(O).sub.q --(CH.sub.2).sub.m --Ar--C(O) OH, --S(O).sub.q --(CH.sub.2).sub.m --Ar--C(O) OR',
- --S(O).sub.q --(CH.sub.2).sub.m --Ar--C(O) NH.sub.2,
- --S(O).sub.q --(CH.sub.2).sub.m --Ar--C(O) NHR',
- --S(O).sub.q --Ar--C(O)NR'R", and
- --S(O).sub.q --Ar--CN.sub.4 H,
- wherein m is 1, 2, 3, 4, 5 or 6; q is 0, 1 or 2 and Ar is a divalent aryl group of 6 to 14 carbon atoms and
- (d) n is 1, 2 or 3; or pharmaceutically acceptable salts thereof.
- 2. A compound of claim 1, wherein n is 2.
- 3. A compound of claim 2, wherein R.sub.2 is --CH.sub.2 --S(O.sub.2)--CH.sub.3.
- 4. A compound of claim 3, wherein X is --S(O.sub.2)-- or --C(O)--.
- 5. A compound of claim 4, wherein X is --S(O.sub.2)--.
- 6. A compound of claim 4, wherein X is --C--(O)--.
- 7. A compound of claim 2, wherein R.sub.2 is --S(O.sub.2)--CH.sub.3.
- 8. A compound of claim 7, wherein X is --S(O.sub.2)-- or --C(O)--.
- 9. A compound of claim 8, wherein X is --S(O.sub.2)--.
- 10. A compound of claim 2, wherein R.sub.2 is --S(O.sub.2)--CH.sub.2 --C(O)--OH.
- 11. A compound of claim 10, wherein X is --S(O.sub.2)-- or --C(O)--.
- 12. A compound of claim 11, wherein X is --S(O.sub.2)--.
- 13. A compound of claim 11, wherein X is --C(O)--.
- 14. A compound of claim 2, wherein R.sub.2 is --S(O.sub.2)--CH.sub.2 --C(O)--OR'.
- 15. A compound of claim 14, wherein R' is methyl, ethyl or propyl.
- 16. A compound of claim 15, wherein R' is methyl.
- 17. A compound of claim 16, wherein X is --S(O.sub.2)-- or --C(O)--.
- 18. A compound of claim 17, wherein X is --S(O.sub.2)--.
- 19. A compound of claim 17, wherein X is --C(O)--.
- 20. A compound of claim 2 wherein X is --S(O.sub.2)-- or --C(O)--.
- 21. A compound of claim 20 wherein R.sub.2 is
- --S(O)q--(CH.sub.2)m--Ar--C(O) OH,
- --S(O)q--(CH.sub.2)m--Ar--C(O) OR',
- --S(O)q--(CH.sub.2)m--Ar--C(O) NH.sub.2,
- --S(O)q--(CH.sub.2)m--Ar--C(O)--NHR',
- --S(O)q--(CH.sub.2)m--Ar--C(O)--NHR'R", or,
- --S(O)q--(CH.sub.2)m--Ar--C(O)--CHN.sub.4.
- 22. A pharmaceutical composition for the prevention of thrombosis in a mammal suspected of having a condition characterized by abnormal thrombosis, comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of the compound of claim 1, 2, 3, 7, 10, 16 or 21.
- 23. A method for the prevention of thrombosis in a mammal suspected of having a condition characterized by abnormal thrombosis, comprising administering to said mammal a therapeutically effective amount of the compound of 1, 2, 3, 7, 10, 16 or 21.
- 24. A method for the prevention of thrombosis in a mammal suspected of having a condition characterized by abnormal thrombosis, comprising administering to said mammal a therapeutically effective amount of the pharmaceutical composition of claim 22.
RELATED APPLICATIONS
This application is a continuation-in-part of U.S. Ser. No. 08/234,811, filed Apr. 28, 1994 which is a continuation-in-part of U.S. Ser. No. 08/229,298, filed Apr. 18, 1994 the disclosures of which are hereby incorporated by reference herein, including the drawings attached thereto.
US Referenced Citations (2)
Number |
Name |
Date |
Kind |
5153176 |
Abe et al. |
Oct 1992 |
|
5254546 |
Ardecky et al. |
Oct 1993 |
|
Foreign Referenced Citations (2)
Number |
Date |
Country |
WO9315756 |
Aug 1993 |
WOX |
WO9528420 |
Oct 1995 |
WOX |
Non-Patent Literature Citations (1)
Entry |
Carini et al., "Nonpeptide Angiotensin II Receptor Antagonist: The Discovery of a Series of N-(Biphenylylmethyl)imidazoles as Potent, Orally Active Antihypertensives," J. Med. Chem. 34:2525-2547 (1991). |
Continuation in Parts (2)
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Number |
Date |
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Parent |
234811 |
Apr 1994 |
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Parent |
229298 |
Apr 1994 |
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