Claims
- 1. A compound having the structure:
- 2. The compound of claim 1 wherein Z1 is C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl, the alkyl, alkenyl, or alkynyl being optionally substituted at any substitutable position with fluorine;
Z3 comprises a substituted phenyl or substituted thienyl ring, the phenyl or thienyl ring being substituted with an amidine or derivatized amidine, and optionally further substituted with fluorine or hydroxy; R44 is hydrocarbyl, substituted hydrocarbyl, heterocyclo, halogen, or a substituted or unsubstituted heteroatom selected from nitrogen, oxygen, sulfur and phosphorus; and X5, L1, L3, Z4 and R42 are as defined in claim 1;provided, however, one of the following conditions exist: (a) Z1 is other than cyclobutyl when X5 is CH; (b) Z1 is other than isopropyl when (i) X5 is CH and (ii) Z4 is 3,5-diaminophenyl or 3-amino-5-(2,2,2-trifluoroacetamide)phenyl; or (c) Z3 is other than 4-amidinobenzyl, 4-amidino-2-fluorobenzyl, or 4-amidino-3-fluorobenzyl.
- 3. The compound of claims 1 or 2 wherein L1 is a bond.
- 4. The compound of claims 1 or 2 wherein Z1 is C1-C5 alkyl optionally substituted at any substitutable position with fluorine.
- 5. The compound of claim 3 wherein Z1 is selected from the group consisting of cyclopropyl, isopropyl, methyl, ethyl, cyclobutyl, isobutyl, tert-butyl and sec-butyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy, or alkoxycarbonyl.
- 6. The compound of claim 3 wherein Z1 is selected from the group consisting of cyclopropyl, isopropyl, methyl, ethyl, cyclobutyl, isobutyl, and sec-butyl.
- 7. The compound of claim 1 wherein Z1 is isopropyl or cyclobutyl substituted with fluorine, hydroxy, carboxy, or alkoxycarbonyl.
- 8. The compound of claim 3 wherein Z3 is a phenyl ring substituted with an amidine group.
- 9. The compound of claim 1 wherein Z3 is a phenyl, thienyl, or furanyl ring substituted with a derivatized amidine which, upon hydrolysis, oxidation, reduction, or elimination, or any combination thereof, under physiological conditions yields an amidine group.
- 10. The compound of claim 2 wherein Z3 is a phenyl or thienyl ring substituted with a derivatized amidine which, upon hydrolysis, oxidation, reduction or elimination under physiological conditions yields an amidine group.
- 11. The compound of any of claims 8-10 wherein Z3 is further substituted at any position with fluorine or hydroxy.
- 12. The compound of claim 1 wherein Z3 is
- 13. The compound of claim 1 or 2 wherein Z4 is
- 14. The compound of claim 13 wherein R42 is as defined in claim 1, R44 is as defined in claim 13, and R41, R43 and R45 are independently hydrogen, halogen, alkoxy, or alkyl, optionally substituted with halogen or alkoxy.
- 15. The compound claim 13 wherein R44 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, carboxy, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 16. The compound of claim 15 wherein R44 is selected from the group consisting of hydroxy, carboxy, carboxamido, alkoxy, alkylsulfonyl, sulfonamido, or alkoxycarbonyl.
- 17. The compound of claim 16 wherein R44 is sec-butylamide, carboxy, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isopropylamide or hydroxy.
- 18. The compound of claim 15 wherein R44 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 19. The compound of claim 16 wherein L1 is a bond, Z1 is isopropyl or cyclopropyl, Z3 is phenyl substituted with an amidine group, and R44 is as defined in claim 16.
- 20. The compound of claim 13 wherein Z41, Z43 or Z45 is substituted with fluorine or chlorine.
- 21. The compound of claim 1 wherein Z4 is
- 22. The compound of claim 1 wherein Z4 is
- 23. The compound of claim 1 wherein Z4 is
- 24. The compound of claim 1 wherein L1 is a bond; Z1 is selected from the group consisting of cyclopropyl, isopropyl, methyl, ethyl, cyclobutyl, isobutyl, tert-butyl, and sec-butyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy, or alkoxycarbonyl; Z3 is phenyl substituted with an amidine group and optionally substituted by hydrogen, fluorine, hydroxy, carboxy, alkoxycarbonyl, or hydrocarbyloxy; and one of R41, R43, R44 or R45 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, carboxy, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 25. The compound of claim 2 wherein L1 is a bond; Z1 is selected from the group consisting of cyclopropyl, isopropyl, methyl, ethyl, cyclobutyl, isobutyl, and sec-butyl optionally substituted at any substitutable position with fluorine; and R44 is selected from the group consisting of hydroxy, alkylsulfonyl, haloalkyl, haloalkoxy, haloalkylthio, carboxamidoalkyl, and carboxamidoalkylaryl.
- 26. The compound of claim 1 having the structure:
- 27. The compound of claim 1 having the structure:
- 28. The compound of claim 2 having the structure:
- 29. The compound of claim 2 having the structure:
- 30. The compound of claim 2 having the structure:
- 31. The compound of claim 2 having the structure:
- 32. The compound of claim 1 having the structure:
- 33. The compound of claim 2 having the structure:
- 34. The compound of claim 2 having the structure:
- 35. The compound of claim 2 having the structure:
- 36. The compound of claim 2 having the structure:
- 37. The compound of claim 2 having the structure:
- 38. The compound of claim 2 having the structure:
- 39. The compound of claim 2 having the structure:
- 40. The compound of claim 2 having the structure:
- 41. The compound of claim 2 having the structure:
- 42. A compound having the structure:
- 43. The compound of claim 42 wherein Z1 is C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl, the alkyl, alkenyl, or alkynyl being optionally substituted at any substitutable position with fluorine;
Z3 comprises a substituted phenyl or substituted thienyl ring, the phenyl or thienyl ring being substituted with an amidine or derivatized amidine, and optionally further substituted with fluorine or hydroxy; R44 is hydrocarbyl, substituted hydrocarbyl, heterocyclo, halogen, or a substituted or unsubstituted heteroatom selected from nitrogen, oxygen, sulfur and phosphorus; and X5, L1, L3, Z4 and R42 are as defined in claim 39;provided, however, one of the following conditions exist: (a) Z3 is other than 4-amidinobenzyl, 4-amidino-2-fluorobenzyl, and 4-amidino-3-fluorobenzyl; or (b) (i) Z1 is other than cyclobutyl and isopropyl when X5 is CH or C(Cl) and (ii) neither Z41 nor Z45 is sulfur when Z4 is thienyl;
- 44. The compound of claims 42 or 43 wherein L1 is a bond.
- 45. The compound of claims 42 or 43 wherein Z1 is C1-C5 alkyl optionally substituted at any substitutable position with fluorine.
- 46. The compound of claim 44 wherein Z1 is selected from the group consisting of cyclopropyl, isopropyl, methyl, ethyl, cyclobutyl, isobutyl, tert-butyl and sec-butyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy, or alkoxycarbonyl.
- 47. The compound of claim 44 wherein Z1 is selected from the group consisting of cyclopropyl, isopropyl, methyl, ethyl, cyclobutyl, isobutyl, and sec-butyl.
- 48. The compound of claim 42 wherein Z1 is isopropyl or cyclobutyl substituted with fluorine, hydroxy, carboxy, or alkoxycarbonyl.
- 49. The compound of claim 44 wherein Z3 is a phenyl ring substituted with an amidine group.
- 50. The compound of claim 42 wherein Z3 is a phenyl, thienyl, or furanyl ring substituted with a derivatized amidine which, upon hydrolysis, oxidation, reduction, or elimination, or any combination thereof, under physiological conditions yields an amidine group.
- 51. The compound of claim 43 wherein Z3 is a phenyl or thienyl ring substituted with a derivatized amidine which, upon hydrolysis, oxidation, reduction or elimination under physiological conditions yields an amidine group.
- 52. The compound of any of claims 49-51 wherein Z3 is further substituted at any position with fluorine or hydroxy.
- 53. The compound of claim 42 wherein Z3 is
- 54. The compound of claim 42 or 43 wherein Z4 is
- 55. The compound of claim 54 wherein R42 is as defined in claim 42, R44 is as defined in claim 54, and R41, R43 and R45 are independently hydrogen, halogen, alkoxy, or alkyl, optionally substituted with halogen or alkoxy.
- 56. The compound claim 54 wherein R44 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, carboxy, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 57. The compound of claim 56 wherein R44 is selected from the group consisting of hydroxy, carboxy, carboxamido, alkoxy, alkylsulfonyl, sulfonamido, or alkoxycarbonyl.
- 58. The compound of claim 57 wherein R44 is sec-butylamide, carboxy, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isopropylamide or hydroxy.
- 59. The compound of claim 56 wherein R44 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 60. The compound of claim 57 wherein L1 is a bond, Z1 is isopropyl or cyclopropyl, Z3 is phenyl substituted with an amidine group, and R44 is as defined in claim 57.
- 61. The compound of claim 54 wherein Z41, Z43 or Z45 is substituted with fluorine or chlorine.
- 62. The compound of claim 42 wherein Z4 is
- 63. The compound of claim 42 wherein Z4 is
- 64. The compound of claim 42 wherein Z4 is
- 65. The compound of claim 42 wherein L1 is a bond; Z1 is selected from the group consisting of cyclopropyl, isopropyl, methyl, ethyl, cyclobutyl, isobutyl, tert-butyl, and sec-butyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy, or alkoxycarbonyl; Z3 is phenyl substituted with an amidine group and optionally substituted by hydrogen, fluorine, hydroxy, carboxy, alkoxycarbonyl, or hydrocarbyloxy; and one of R41, R43, R44 or R45 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, carboxy, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 66. The compound of claim 43 wherein L1 is a bond; Z1 is selected from the group consisting of cyclopropyl, isopropyl, methyl, ethyl, cyclobutyl, isobutyl, and sec-butyl optionally substituted at any substitutable position with fluorine; and R44 is selected from the group consisting of hydroxy, alkylsulfonyl, haloalkyl, haloalkoxy, haloalkylthio, carboxamidoalkyl, and carboxamidoalkylaryl.
- 67. A compound having the structure:
- 68. The compound of claim 67 wherein X6 is CH;
Z1 is C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl, the alkyl, alkenyl, or alkynyl being optionally substituted at any substitutable position with fluorine, provided that Z1 is other than cyclobutyl or isopropyl; Z3 comprises a substituted phenyl or substituted thienyl ring, the phenyl or thienyl ring being substituted with an amidine or a derivatized amidine group, and optionally further substituted with fluorine or hydroxy; R44 is hydrocarbyl, substituted hydrocarbyl, heterocyclo, halogen, or a substituted or unsubstituted heteroatom selected from nitrogen, oxygen, sulfur and phosphorus; and L1, L3, Z4 and R42 are as defined in claim 62.
- 69. The compound of claims 67 or 68 wherein L1 is a bond.
- 70. The compound of claims 67 or 68 wherein Z1 is C1-C5 alkyl optionally substituted at any substitutable position with fluorine.
- 71. The compound of claim 69 wherein Z1 is selected from the group consisting of cyclopropyl, methyl, ethyl, isobutyl, tert-butyl and sec-butyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy or alkoxycarbonyl.
- 72. The compound of claim 69 wherein Z1 is selected from the group consisting of cyclopropyl, methyl, ethyl, isobutyl, and sec-butyl.
- 73. The compound of claim 67 wherein Z1 is isopropyl or cyclobutyl substituted with fluorine, hydroxy, carboxy or alkoxycarbonyl.
- 74. The compound of claim 69 wherein Z3 is a phenyl ring substituted with an amidine group.
- 75. The compound of claim 67 wherein Z3 is a phenyl, thienyl, or furanyl ring substituted with a derivatized amidine which, upon hydrolysis, oxidation, reduction, or elimination, or any combination thereof, under physiological conditions yields an amidine group.
- 76. The compound of claim 68 wherein Z3 is a phenyl or thienyl ring substituted with a derivatized amidine which, upon hydrolysis, oxidation, reduction or elimination under physiological conditions yields an amidine group.
- 77. The compound of any of claims 74-76 wherein Z3 is further substituted at any position with fluorine or hydroxy.
- 78. The compound of claim 67 wherein Z3 is
- 79. The compound of claim 67 or 68 wherein Z4 is
- 80. The compound of claim 79 wherein R42 is as defined in claim 67, R44 is as defined in claim 79, and R41, R43 and R45 are independently hydrogen, halogen, alkoxy, or alkyl, optionally substituted with halogen or alkoxy.
- 81. The compound claim 79 wherein R44 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, carboxy, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 82. The compound of claim 81 wherein R44 is selected from the group consisting of hydroxy, carboxy, carboxamido, alkoxy, alkylsulfonyl, sulfonamido, or alkoxycarbonyl.
- 83. The compound of claim 82 wherein R44 is sec-butylamide, carboxy, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isopropylamide or hydroxy.
- 84. The compound of claim 81 wherein R44 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 85. The compound of claim 82 wherein L1 is a bond, Z1 is isopropyl or cyclopropyl, Z3 is phenyl substituted with an amidine group, and R44 is as defined in claim 82.
- 86. The compound of claim 79 wherein Z41, Z43 or Z45 is substituted with fluorine or chlorine.
- 87. The compound of claim 67 wherein Z4 is
- 88. The compound of claim 67 wherein Z4 is
- 89. The compound of claim 67 wherein Z4 is
- 90. The compound of claim 67 wherein L1 is a bond; Z1 is selected from the group consisting of cyclopropyl, methyl, ethyl, isobutyl, tert-butyl, and sec-butyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy, or alkoxycarbonyl; Z3 is phenyl substituted with an amidine group and optionally substituted by hydrogen, fluorine, hydroxy, carboxy, alkoxycarbonyl, or hydrocarbyloxy; and one of R41, R43, R44 or R45 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, carboxy, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 91. The compound of claim 68 wherein L1 is a bond; Z1 is selected from the group consisting of cyclopropyl, methyl, ethyl, isobutyl, and sec-butyl optionally substituted at any substitutable position with fluorine; and R44 is selected from the group consisting of hydroxy, alkylsulfonyl, haloalkyl, haloalkoxy, haloalkylthio, carboxamidoalkyl, and carboxamidoalkylaryl.
- 92. A compound having the structure:
- 93. The compound of claim 92 wherein Z1 is C1-C8 alkyl, C2-C8 alkenyl, or C2-C8 alkynyl, the alkyl, alkenyl, or alkynyl being optionally substituted at any substitutable position with fluorine, provided that Z1 is other than cyclobutyl or isopropyl;
Z3 comprises a substituted phenyl or substituted thienyl ring, the phenyl or thienyl ring being substituted with an amidine or a derivatized amidine group, and optionally further substituted with fluorine or hydroxy; R44 is hydrocarbyl, substituted hydrocarbyl, heterocyclo, halogen, or a substituted or unsubstituted heteroatom selected from nitrogen, oxygen, sulfur and phosphorus; and L1, L3, Z4 and R42 are as defined in claim 62.
- 94. The compound of claims 92 or 93 wherein L1 is a bond.
- 95. The compound of claims 92 or 93 wherein Z1 is C1-C5 alkyl optionally substituted at any substitutable position with fluorine.
- 96. The compound of claim 94 wherein Z1 is selected from the group consisting of cyclopropyl, methyl, ethyl, isobutyl, tert-butyl and sec-butyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy or alkoxycarbonyl.
- 97. The compound of claim 94 wherein Z1 is selected from the group consisting of cyclopropyl, methyl, ethyl, isobutyl, and sec-butyl.
- 98. The compound of claim 92 wherein Z1 is isopropyl or cyclobutyl substituted with fluorine, hydroxy, carboxy or alkoxycarbonyl.
- 99. The compound of claim 94 wherein Z3 is a phenyl ring substituted with an amidine group.
- 100. The compound of claim 92 wherein Z3 is a phenyl, thienyl, or furanyl ring substituted with a derivatized amidine which, upon hydrolysis, oxidation, reduction, or elimination, or any combination thereof, under physiological conditions yields an amidine group.
- 101. The compound of claim 93 wherein Z3 is a phenyl or thienyl ring substituted with a derivatized amidine which, upon hydrolysis, oxidation, reduction or elimination under physiological conditions yields an amidine group.
- 102. The compound of any of claims 99-101 wherein Z3 is further substituted at any position with fluorine or hydroxy.
- 103. The compound of claim 92 wherein Z3 is
- 104. The compound of claim 92 or 93 wherein Z4 is
- 105. The compound of claim 104 wherein R42 is as defined in claim 1, R44 is as defined in claim 106, and R411 R43 and R45 are independently hydrogen, halogen, alkoxy, or alkyl, optionally substituted with halogen or alkoxy.
- 106. The compound claim 104 wherein R44 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, carboxy, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 107. The compound of claim 106 wherein R44 is selected from the group consisting of hydroxy, carboxy, carboxamido, alkoxy, alkylsulfonyl, sulfonamido, or alkoxycarbonyl.
- 108. The compound of claim 107 wherein R44 is sec-butylamide, carboxy, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isopropylamide or hydroxy.
- 109. The compound of claim 106 wherein R44 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 110. The compound of claim 107 wherein L1 is a bond, Z1 is isopropyl or cyclopropyl, Z3 is phenyl substituted with an amidine group, and R44 is as defined in claim 107.
- 111. The compound of claim 92 wherein Z41, Z43 or Z4S is substituted with fluorine or chlorine.
- 112. The compound of claim 92 wherein Z4 is
- 113. The compound of claim 92 wherein Z4 is
- 114. The compound of claim 92 wherein Z4 is
- 115. The compound of claim 92 wherein L1 is a bond; Z1 is selected from the group consisting of cyclopropyl, methyl, ethyl, isobutyl, tert-butyl, and sec-butyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy, or alkoxycarbonyl; Z3 is phenyl substituted with an amidine group and optionally substituted by hydrogen, fluorine, hydroxy, carboxy, alkoxycarbonyl, or hydrocarbyloxy; and one of R41, R43, R44 or R45 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, carboxy, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 116. The compound of claim 93 wherein L1 is a bond; Z1 is selected from the group consisting of cyclopropyl, methyl, ethyl, isobutyl, and sec-butyl optionally substituted at any substitutable position with fluorine; and R44 is selected from the group consisting of hydroxy, alkylsulfonyl, haloalkyl, haloalkoxy, haloalkylthio, carboxamidoalkyl, and carboxamidoalkylaryl
- 117. A compound having the structure:
- 118. A compound having the structure:
- 119. The compound of claims 117 or 118 wherein L1 is a bond.
- 120. The compound of claim 119 wherein Z1 is C1-C5 alkyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy, or alkoxycarbonyl.
- 121. The compound of claim 119 wherein Z1 is selected from the group consisting of cyclopropyl, isopropyl, methyl, ethyl, cyclobutyl, isobutyl, tert-butyl and sec-butyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy, or alkoxycarbonyl.
- 122. The compound of claim 119 wherein Z3 is
- 123. The compound of claim 118 wherein Z3 is
- 124. The compound of claim 123 wherein at least one of R304, R305 R306, and R307 is hydroxy or carboxy.
- 125. The compound of claims 117 or 118 wherein Z3 is a phenyl, thienyl or furanyl ring substituted with a derivatized amidine which, upon hydrolysis, oxidation, reduction, or elimination, or any combination thereof, under physiological conditions yields an amidine group.
- 126. The compound of claim 117 or 118 wherein Z4 is
- 127. The compound of claim 126 wherein R42 is as defined in claim 1, R44 is as defined in claim 13, and R41, R43 and R45 are independently hydrogen, halogen, alkoxy, or alkyl, optionally substituted with halogen or alkoxy.
- 128. The compound of claim 127 wherein R44 is selected from the group consisting of hydroxy, carboxy, carboxamido, alkoxy, alkylsulfonyl, sulfonamido, or alkoxycarbonyl.
- 129. The compound of claim 128 wherein R44 is sec-butylamide, carboxy, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isopropylamide or hydroxy.
- 130. The compound of claim 126 wherein R44 is selected from the group consisting of hydrocarbyl, substituted hydrocarbyl, acetamidyl, alkoxy, hydroxy, amino, alkylsulfonyl, haloalkoxy, haloalkythio, alkoxycarbonyl, sulfonamido, carboxamido and sulfonamidyl, optionally substituted with fluorine.
- 131. The compound of claim 126 wherein Z41, Z43 or Z45 is substituted with fluorine or chlorine.
- 132. The compound of claims 117 or 118 wherein Z4 is
- 133. The compound of claims 117 or 118 wherein Z4 is
- 134. The compound of claims 117 or 118 wherein Z4 is
- 135. The compound of claim 117 having the structure:
- 136. A compound having the structure:
- 137. The compound of claim 136 having the structure:
- 138. The compound of claim 137 wherein X7 and X8 are carbon.
- 139. The compound of claims 136 or 137 wherein Z4 is
- 140. The compound of claim 137 wherein Z1 is methyl, ethyl, isopropyl, cyclopropyl, sec-butyl, tert-butyl, and cyclobutyl optionally substituted at any substitutable position with fluorine, hydroxy, carboxy or alkoxycarbonyl.
- 141. The compound of claim 137 wherein Z3 is
- 142. A compound having the structure:
- 143. A compound having the structure:
- 144. A composition for inhibiting thrombotic conditions in blood comprising a compound of any of claims 1, 42, 67, 92, 117, or 118 and a pharmaceutically acceptable carrier.
- 145. A method for inhibiting thrombotic conditions in blood comprising adding to blood a therapeutically effective amount of the composition of claim 144.
- 146. A method for inhibiting formation of blood platelet aggregates in blood comprising adding to blood a therapeutically effective amount of the composition of claim 144.
- 147. A method for inhibiting thrombus formation in blood comprising adding to blood a therapeutically effective amount of the composition of claim 144.
- 148. A method for treating or preventing venuous thromboembolism and pulmonary embolism in a mammal comprising administering to the mammal a therapeutically effective amount of the composition of claim 144.
- 149. A method for treating or preventing deep vein thrombosis in a mammal comprising administering to the mammal a therapeutically effective amount of the composition of claim 144.
- 150. A method for treating or preventing cardiogenic thromboembolism in a mammal comprising administering to the mammal a therapeutically effective amount of the composition of claim 144.
- 151. A method for treating or preventing thromboembolic stroke in mammals comprising administering to the mammal a therapeutically effective amount of the composition of claim 144.
- 152. A method for treating or preventing thrombosis associated with cancer and cancer chemotherapy in mammals comprising administering to the mammal a therapeutically effective amount of the composition of claim 144.
- 153. A method for treating or preventing unstable angina in mammals comprising administering to the mammal a therapeutically effective amount of the composition of claim 144.
- 154. A method for inhibiting thrombus formation in blood comprising adding to blood a therapeutically effective amount of the composition of claim 144 with a therapeutically effective amount of fibrinogen receptor antagonist.
- 155. A composition comprising a compound of each of claims 1, 42, 67, 92, 117 or 118 or a pharmaceutically acceptable salt or prodrug thereof and a thrombolytic agent.
- 156. The composition of claim 155 wherein the thrombolytic agent is selected from the group consisting of anti-platelet agents, anticoagulation agents and cardiovascular agents.
- 157. The composition of claim 155 wherein the thrombolytic agent is an anti-platelet agent.
- 158. The composition of claim 157 wherein the anti-platelet agent is selected from the group consisting of a salicylate compound, ticlopidine, clopidrogel, and a GP IIa/IIIa inhibitor.
- 159. The composition of claim 158 wherein the anti-platelet agent is a salicylate compound.
- 160. The composition of claim 159 wherein the salicylate compound is aspirin.
- 161. The composition of claim 157 wherein the anti-platelet agent substantially inhibits prostaglandin synthesis.
- 162. A method for the treatment or prevention of a thrombolytic condition in a subject, the method comprising administering to the subject a compound of each of claims 1, 42, 67, 92, 117 or 118 or a pharmaceutically acceptable salt or prodrug thereof and a thrombolytic agent.
- 163. The method of claim 162 wherein the thrombolytic agent is selected from the group consisting of anti-platelet agents, anticoagulation agents and cardiovascular agents.
- 164. The method of claim 163 wherein the thrombolytic agent is an anti-platelet agent.
- 165. The method of claim 164 wherein the anti-platelet agent is selected from the group consisting of a salicylate compound, ticlopidine, clopidrogel, and a GP IIa/IIIa inhibitor.
- 166. The method of claim 165 wherein the anti-platelet agent is a salicylate compound.
- 167. The method of claim 166 wherein the salicylate compound is aspirin.
- 168. The method of claim 164 wherein the anti-platelet agent substantially inhibits prostaglandin synthesis.
- 169. The method of claim 162 wherein the thrombolytic condition is selected from the group consisting of myocardial infarction, stroke, amaurosis fugax, aortic stenosis, cardiac stenosis, coronary stenosis and pulmonary stenosis.
- 170. The method of claim 162 wherein the compound of claim 1, 42, 67, 92, 117 or 118 and the thrombolytic agent are administered in a substantially simultaneous manner.
- 171. The method of claim 162 wherein the compound of claim 1, 42, 67, 92, 117 or 118 and the thrombolytic agent are administered sequentially.
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims priority from Provisional Application Serial No. 60/326,721 filed Oct. 3, 2001, No. 60/338,623 filed Oct. 24, 2001, No. 60/332,857 filed Nov. 6, 2001, No. 60/333,292 filed on Nov. 14, 2001, and No. 60/332,107 and 60/331,891 both filed on Nov. 21, 2001, which are all hereby incorporated by reference in their entirety.
Provisional Applications (6)
|
Number |
Date |
Country |
|
60326721 |
Oct 2001 |
US |
|
60338623 |
Oct 2001 |
US |
|
60332857 |
Nov 2001 |
US |
|
60333292 |
Nov 2001 |
US |
|
60332107 |
Nov 2001 |
US |
|
60332014 |
Nov 2001 |
US |