Claims for Patent: 6,376,515

Summary for Patent: 6,376,515

Title:	Benzamides and related inhibitors of factor Xa
Abstract:	Novel benzamide compounds including their pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives having activity against mammalian factor Xa are described. Compositions containing such compounds are also described. The compounds and compositions are useful in vitro or in vivo for preventing or treating coagulation disorders.
Inventor(s):	Zhu; Bing-Yan (Belmont, CA), Zhang; Penglie (Foster City, CA), Wang; Lingyan (Chatham, NJ), Huang; Wenrong (Cupertino, CA), Goldman; Erick A. (San Francisco, CA), Li; Wenhao (South San Francisco, CA), Zuckett; Jingmei (Glendale, AZ), Song; Yonghong (Foster City, CA), Scarborough; Robert M. (Half Moon Bay, CA)
Assignee:	COR Therapeutics, Inc. (South San Francisco, CA)
Application Number:	09/794,225
Patent Claims:	1. A compound of formula VI: ##STR571## wherein: Z' and Z" are each independently a C.sub.1 -C.sub.6 alkyl which is optionally substituted with a hydroxyl, carboxylic acid or carboxylic acid ester group; R.sup.1a is a member selected from the group of H, --F, --Cl and Br; R.sup.1d2 and R.sup.1d4 are each H; R.sup.1d1 and R.sup.1d3 are each independently a member selected from the group of H, --Cl, --F, --Br, --OH and --OMe; R.sup.1e is a member selected from the group of --F, --Cl, --Br, --OH, --Me and --OMe, and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives thereof. 2. A compound of claim 1 wherein Z' is --Me and Z" is --CH.sub.2 OH, --CH.sub.2 CO.sub.2 H, or --CH.sub.2 CO.sub.2 CH.sub.3. 3. A compound of claim 1 having the following structure: ##STR572## 4. A compound of claim 1 having the following structure: ##STR573## 5. A compound of claim 1 having the following structure: ##STR574## 6. A compound of claim 1 having the following structure: ##STR575## 7. A compound of claim 1 having the following structure: ##STR576## 8. A compound of claim 1 having the following structure: ##STR577## 9. A compound of claim 1 having the following structure: ##STR578## 10. A compound of claim 1 having the following structure: ##STR579## 11. A compound of claim 1 having the following structure: ##STR580## 12. A compound of claim 1 having the following structure: ##STR581## 13. A compound of claim 1 having the following structure: ##STR582## 14. A compound of claim 1 having the following structure: ##STR583## 15. A compound of claim 1 having the following structure: ##STR584## 16. A compound of claim 1 having the following structure: ##STR585## 17. A compound of claim 1 having the following structure: ##STR586## 18. A compound of claim 1 having the following structure: ##STR587## 19. A pharmaceutical composition for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of one of claims 1-18. 20. A method for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of one of claims 1-18. 21. The method of claim 20, wherein the condition is selected from the group consisting of: acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, occlusive coronary thrombus occurring post-thrombolytic therapy or post-coronary angioplasty, a thrombotically mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, transient ischemic attacks, venous thrombosis, deep venous thrombosis, pulmonary embolus, coagulopathy, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, thromboangiitis obliterans, thrombotic disease associated with heparin-induced thrombocytopenia, thrombotic complications associated with extracorporeal circulation, thrombotic complications associated with instrumentation, and thrombotic complications associated with the fitting of prosthetic devices. 22. A method for inhibiting the coagulation of a biological sample comprising the step of administering a compound of one of claims 1-18. 23. A compound formula VII: ##STR588## wherein: A-Q is a member selected from the group of: ##STR589## where Z' is a C.sub.1 -C.sub.6 alkyl which is optionally substituted with a hydroxyl, carboxylic acid or carboxylic acid ester group; R.sup.1a is a member selected from the group of H, --F, --Cl and Br; R.sup.1d2 and R.sup.1d4 are each H; R.sup.1d1 and R.sup.1d3 are each independently a member selected from the group of H, --Cl, --F, --Br, --OH and --OMe; R.sup.1e is a member selected from the group of --F, --Cl, --Br, --OH, --Me and --OMe; and all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug derivatives thereof. 24. A compound of claim 23, wherein A-Q is: ##STR590## and Z' is --Me, --CH.sub.2 OH, --CH.sub.2 CO.sub.2 H, or --CH.sub.2 CO.sub.2 CH.sub.3. 25. A compound of claim 24 having the following structure: ##STR591## 26. A compound of claim 24 having the following structure: ##STR592## 27. A compound of claim 24 having the following structure: ##STR593## 28. A compound of claim 24 having the following structure: ##STR594## 29. A compound of claim 24 having the following structure: ##STR595## 30. A compound of claim 24 having the following structure: ##STR596## 31. A compound of claim 24 having the following structure: ##STR597## 32. A compound of claim 24 having the following structure: ##STR598## 33. A compound of claim 24 having the following structure: ##STR599## 34. A compound of claim 24 having the following structure: ##STR600## 35. A compound of claim 24 having the following structure: ##STR601## 36. A compound of claim 24 having the following structure: ##STR602## 37. A compound of claim 24 having the following structure: ##STR603## 38. A compound of claim 24 having the following structure: ##STR604## 39. A compound of claim 24 having the following structure: ##STR605## 40. A compound of claim 24 having the following structure: ##STR606## 41. A compound of claim 23 having the following formula: ##STR607## 42. A compound of claim 23 having the following formula: ##STR608## 43. A compound of claim 23 having the following structure: ##STR609## 44. A compound of claim 23 having the following structure: ##STR610## 45. A compound of claim 23 having the following structure: ##STR611## 46. A compound of claim 23 having the following structure: ##STR612## 47. A compound of claim 23 having the following structure: ##STR613## 48. A compound of claim 23 having the following structure: ##STR614## 49. A compound of claim 23 having the following structure: ##STR615## 50. A compound of claim 23 having the following structure: ##STR616## 51. A compound of claim 23 having the following structure: ##STR617## 52. A compound of claim 23 having the following structure: ##STR618## 53. A compound of claim 23 having the following structure: ##STR619## 54. A compound of claim 23 having the following structure: ##STR620## 55. A compound of claim 23 having the following structure: ##STR621## 56. A compound of claim 23 having the following structure: ##STR622## 57. A compound of claim 23 having the following structure: ##STR623## 58. A compound of claim 23 having the following structure: ##STR624## 59. A compound of claim 23 having the following structure: ##STR625## 60. A compound of claim 23 having the following structure: ##STR626## 61. A compound of claim 23 having the following structure: ##STR627## 62. A compound of claim 23 having the following structure: ##STR628## 63. A compound of claim 23 having the following structure: ##STR629## 64. A compound of claim 23 having the following structure: ##STR630## 65. A compound of claim 23 having the following structure: ##STR631## 66. A compound of claim 23 having the following structure: ##STR632## 67. A compound of claim 23 having the following structure: ##STR633## 68. A compound of claim 23 having the following structure: ##STR634## 69. A pharmaceutical composition for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of one of claims 23-68. 70. A method for preventing or treating a condition in a mammal characterized by undesired thrombosis comprising administering to said mammal a therapeutically effective amount of a compound of one of claims 23-68. 71. The method of claim 70, wherein the condition is selected from the group consisting of: acute coronary syndrome, myocardial infarction, unstable angina, refractory angina, occlusive coronary thrombus occurring post-thrombolytic therapy or post-coronary angioplasty, a thrombotically mediated cerebrovascular syndrome, embolic stroke, thrombotic stroke, transient ischemic attacks, venous thrombosis, deep venous thrombosis, pulmonary embolus, coagulopathy, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, thromboanglitis obliterans, thrombotic disease associated with heparin-induced thrombocytopenia, thrombotic complications associated with extracorporeal circulation, thrombotic complications associated with instrumentation, and thrombotic complications associated with the fitting of prosthetic devices. 72. A method for inhibiting the coagulation of a biological sample comprising the step of administering a compound of one of claims 23-68.