Claims
- 1. A compound represented by A:
- 2. The compound of claim 1, wherein X is C(R3)2, O, or NR2.
- 3. The compound of claim 1, wherein X is C(R3)2.
- 4. The compound of claim 1, wherein Z is O or NR.
- 5. The compound of claim 1, wherein m is 2 or 3.
- 6. The compound of claim 1, wherein n is 1.
- 7. The compound of claim 1, wherein y is 1.
- 8. The compound of claim 1, wherein R1 represents aryl.
- 9. The compound of claim 1, wherein R3 represents independently for each occurrence H or alkyl.
- 10. The compound of claim 1, wherein R4 represents cycloalkyl, aryl, or heteroaryl.
- 11. The compound of claim 1, wherein R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 12. The compound of claim 1, wherein R8 and R9 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 13. The compound of claim 1, wherein X is C(R3)2, O, or NR2; and Z is O or NR.
- 14. The compound of claim 1, wherein X is C(R3)2, O, or NR2; Z is O or NR; and m is 2 or 3.
- 15. The compound of claim 1, wherein X is C(R3)2, O, or NR2; Z is O or NR; and n is 1.
- 16. The compound of claim 1, wherein X is C(R3)2, O, or NR2; Z is O or NR; and y is 1.
- 17. The compound of claim 1, wherein X is C(R3)2, O, or NR2; Z is O or NR; m is 2 or 3; n is 1; and y is 1.
- 18. The compound of claim 1, wherein X is C(R3)2, O, or NR2; Z is O or NR; m is 2 or 3; n is 1; y is 1; and R1 is aryl.
- 19. The compound of claim 1, wherein X is C(R3)2, O, or NR2; Z is O or NR; m is 2 or 3; n is 1; y is 1; R1 is aryl; and R3 is H or alkyl.
- 20. The compound of claim 1, wherein X is C(R3)2, O, or NR2; Z is O or NR; m is 2 or 3; n is 1; y is 1; R1 is aryl; R3 is H or alkyl; and R4 is cycloalkyl, aryl, or heteroaryl.
- 21. The compound of claim 1, wherein X is C(R3)2, O, or NR2; Z is O or NR; m is 2 or 3; n is 1; y is 1; R1 is aryl; R3 is H or alkyl; R4 is cycloalkyl, aryl, or heteroaryl; and R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 22. The compound of claim 1, wherein X is C(R3)2, O, or NR2; Z is O or NR; m is 2 or 3; n is 1; y is 1; R1 is aryl; R3 is H or alkyl; R4 is cycloalkyl, aryl, or heteroaryl; R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F; and R8 and R9 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 23. The compound of claim 1, wherein X is CH2; Z is O; m is 2; n is 1; y is 1; R1 is 4-trifluoromethylphenyl or 3,4-methylenedioxyphenyl; R3 is H; R is 4-chlorophenyl; R5 and R6 are selected independently for each occurrence from the group consisting of H and alkyl; and R8 and R9 are H.
- 24. The compound of claim 1, wherein X is CH2; Z is O; m is 3; n is 1; y is 1; R1 is 4-trifluoromethylphenyl; R3 is H; R4 is 4-chlorophenyl; R5 and R6 are selected independently for each occurrence from the group consisting of H, OH, and alkyl; and R8 and R9 are H.
- 25. The compound of claim 1, wherein said compound has an EC50 less than 1 μM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 26. The compound of claim 1, wherein said compound has an EC50 less than 100 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 27. The compound of claim 1, wherein said compound has an EC50 less than 10 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 28. The compound of claim 1, wherein said compound has an EC50 less than 1 μM in an assay based on a mammalian dopamine receptor or transporter.
- 29. The compound of claim 1, wherein said compound has an EC50 less than 100 nM in an assay based on a mammalian dopamine receptor or transporter.
- 30. The compound of claim 1, wherein said compound has an EC50 less than 10 nM in an assay based on a mammalian dopamine receptor or transporter.
- 31. The compound of claim 1, wherein said compound has an IC50 less than 1 μM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 32. The compound of claim 1, wherein said compound has an IC50 less than 100 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 33. The compound of claim 1, wherein said compound has an IC50 less than 10 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 34. The compound of claim 1, wherein said compound has an IC50 less than 1 μM in an assay based on a mammalian dopamine receptor or transporter.
- 35. The compound of claim 1, wherein said compound has an IC50 less than 100 nM in an assay based on a mammalian dopamine receptor or transporter.
- 36. The compound of claim 1, wherein said compound has an IC50 less than 10 nM in an assay based on a mammalian dopamine receptor or transporter.
- 37. A compound represented by B:
- 38. The compound of claim 37, wherein Z is O or NR.
- 39. The compound of claim 37, wherein m is 3.
- 40. The compound of claim 37, wherein y is 1.
- 41. The compound of claim 37, wherein R1 represents aryl.
- 42. The compound of claim 37, wherein R3 represents independently for each occurrence H or alkyl.
- 43. The compound of claim 37, wherein R4 represents cycloalkyl, aryl, or heteroaryl.
- 44. The compound of claim 37, wherein R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 45. The compound of claim 37, wherein R8 and R9 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 46. The compound of claim 37, wherein Z is O or NR; and m is 3.
- 47. The compound of claim 37, wherein Z is O or NR; and y is 1.
- 48. The compound of claim 37, wherein Z is O or NR; m is 3; and y is 1.
- 49. The compound of claim 37, wherein Z is O or NR; m is 3; y is 1; and R1 is aryl.
- 50. The compound of claim 37, wherein Z is O or NR; m is 3; y is 1; R1 is aryl; and R3 is H or alkyl.
- 51. The compound of claim 37, wherein Z is O or NR; m is 3; y is 1; R1 is aryl; R3 is H or alkyl; and R4 is cycloalkyl, aryl, or heteroaryl.
- 52. The compound of claim 37, wherein Z is O or NR; m is 3; y is 1; R1 is aryl; R3 is H or alkyl; R4 is cycloalkyl, aryl, or heteroaryl; and R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 53. The compound of claim 37, wherein Z is O or NR; m is 3; y is 1; R1 is aryl; R3 is H or alkyl; R4 is cycloalkyl, aryl, or heteroaryl; R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F; and R8 and R9 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 54. The compound of claim 37, wherein said compound has an EC50 less than 1 μM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 55. The compound of claim 37, wherein said compound has an EC50 less than 100 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 56. The compound of claim 37, wherein said compound has an EC50 less than 10 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 57. The compound of claim 37, wherein said compound has an EC50 less than 1 μM in an assay based on a mammalian dopamine receptor or transporter.
- 58. The compound of claim 37, wherein said compound has an EC50 less than 100 nM in an assay based on a mammalian dopamine receptor or transporter.
- 59. The compound of claim 37, wherein said compound has an EC50 less than 10 nM in an assay based on a mammalian dopamine receptor or transporter.
- 60. The compound of claim 37, wherein said compound has an IC50 less than 1 μM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 61. The compound of claim 37, wherein said compound has an IC50 less than 100 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 62. The compound of claim 37, wherein said compound has an IC50 less than 10 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 63. The compound of claim 37, wherein said compound has an IC50 less than 1 μM in an assay based on a mammalian dopamine receptor or transporter.
- 64. The compound of claim 37, wherein said compound has an IC50 less than 100 nM in an assay based on a mammalian dopamine receptor or transporter.
- 65. The compound of claim 37, wherein said compound has an IC50 less than 10 nM in an assay based on a mammalian dopamine receptor or transporter.
- 66. A compound represented by C:
- 67. The compound of claim 66, wherein Z is O or NR.
- 68. The compound of claim 66, wherein m is 3.
- 69. The compound of claim 66, wherein y is 1.
- 70. The compound of claim 66, wherein R1 represents aryl.
- 71. The compound of claim 66, wherein R3 represents independently for each occurrence H or alkyl.
- 72. The compound of claim 66, wherein R4 represents cycloalkyl, aryl, or heteroaryl.
- 73. The compound of claim 66, wherein R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 74. The compound of claim 66, wherein R8 and R9 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 75. The compound of claim 66, wherein Z is O or NR; and m is 3.
- 76. The compound of claim 66, wherein Z is O or NR; and y is 1.
- 77. The compound of claim 66, wherein Z is O or NR; m is 3; and y is 1.
- 78. The compound of claim 66, wherein Z is O or NR; m is 3; y is 1; and R1 is aryl.
- 79. The compound of claim 66, wherein Z is O or NR; m is 3; y is 1; R1 is aryl; and R3 is H or alkyl.
- 80. The compound of claim 66, wherein Z is O or NR; m is 3; y is 1; R1 is aryl; R3 is H or alkyl; and R4 is cycloalkyl, aryl, or heteroaryl.
- 81. The compound of claim 66, wherein Z is O or NR; m is 3; y is 1; R1 is aryl; R3 is H or alkyl; R4 is cycloalkyl, aryl, or heteroaryl; and R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 82. The compound of claim 66, wherein Z is O or NR; m is 3; y is 1; R1 is aryl; R3 is H or alkyl; R4 is cycloalkyl, aryl, or heteroaryl; R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F; and R8 and R9 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 83. The compound of claim 66, wherein said compound has an EC50 less than 1 μM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 84. The compound of claim 66, wherein said compound has an EC50 less than 100 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 85. The compound of claim 66, wherein said compound has an EC50 less than 10 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 86. The compound of claim 66, wherein said compound has an EC50 less than 1 μM in an assay based on a mammalian dopamine receptor or transporter.
- 87. The compound of claim 66, wherein said compound has an EC50 less than 100 nM in an assay based on a mammalian dopamine receptor or transporter.
- 88. The compound of claim 66, wherein said compound has an EC50 less than 10 nM in an assay based on a mammalian dopamine receptor or transporter.
- 89. The compound of claim 66, wherein said compound has an IC50 less than 1 μM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 90. The compound of claim 66, wherein said compound has an IC50 less than 100 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 91. The compound of claim 66, wherein said compound has an IC50 less than 10 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 92. The compound of claim 66, wherein said compound has an IC50 less than 1 μM in an assay based on a mammalian dopamine receptor or transporter.
- 93. The compound of claim 66, wherein said compound has an IC50 less than 100 nM in an assay based on a mammalian dopamine receptor or transporter.
- 94. The compound of claim 66, wherein said compound has an IC50 less than 10 nM in an assay based on a mammalian dopamine receptor or transporter.
- 95. A compound represented by D:
- 96. The compound of claim 95, wherein X is O or NR2.
- 97. The compound of claim 95, wherein Z is O or NR.
- 98. The compound of claim 95, wherein m is 3.
- 99. The compound of claim 95, wherein y is 1.
- 100. The compound of claim 95, wherein R1 represents aryl.
- 101. The compound of claim 95, wherein R3 represents independently for each occurrence H or alkyl.
- 102. The compound of claim 95, wherein R4 represents cycloalkyl, aryl, or heteroaryl.
- 103. The compound of claim 95, wherein R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 104. The compound of claim 95, wherein R8 and R9 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 105. The compound of claim 95, wherein X is O or NR2; and Z is O or NR.
- 106. The compound of claim 95, wherein X is O or NR2; Z is O or NR; and m is 3.
- 107. The compound of claim 95, wherein X is O or NR2; Z is O or NR; and y is 1.
- 108. The compound of claim 95, wherein X is O or NR2; Z is O or NR; m is 3; and y is 1.
- 109. The compound of claim 95, wherein X is O or NR2; Z is O or NR; m is 3; y is 1; and R1 is aryl.
- 110. The compound of claim 95, wherein X is O or NR2; Z is O or NR; m is 3; y is 1; R1 is aryl; and R3 is H or alkyl.
- 111. The compound of claim 95, wherein X is O or NR2; Z is O or NR; m is 3; y is 1; R1 is aryl; R3 is H or alkyl; and R4 is cycloalkyl, aryl, or heteroaryl.
- 112. The compound of claim 95, wherein X is O or NR2; Z is O or NR; m is 3; y is 1; R1 is aryl; R3 is H or alkyl; R4 is cycloalkyl, aryl, or heteroaryl; and R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 113. The compound of claim 95, wherein X is O or NR2; Z is O or NR; m is 3; y is 1; R1 is aryl; R3 is H or alkyl; R4 is cycloalkyl, aryl, or heteroaryl; R5 and R6 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F; and R8 and R9 are selected independently for each occurrence from the group consisting of H, alkyl, OR2, aryl, heteroaryl, and F.
- 114. The compound of claim 95, wherein said compound has an EC50 less than 1 μM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 115. The compound of claim 95, wherein said compound has an EC50 less than 100 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 116. The compound of claim 95, wherein said compound has an EC50 less than 10 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 117. The compound of claim 95, wherein said compound has an EC50 less than 1 μM in an assay based on a mammalian dopamine receptor or transporter.
- 118. The compound of claim 95, wherein said compound has an EC50 less than 100 nM in an assay based on a mammalian dopamine receptor or transporter.
- 119. The compound of claim 95, wherein said compound has an EC50 less than 10 nM in an assay based on a mammalian dopamine receptor or transporter.
- 120. The compound of claim 95, wherein said compound has an IC50 less than 1 μM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 121. The compound of claim 95, wherein said compound has an IC50 less than 100 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 122. The compound of claim 95, wherein said compound has an IC50 less than 10 nM in an assay based on a mammalian dopamine, serotonin, or norepinephrine receptor or transporter.
- 123. The compound of claim 95, wherein said compound has an IC50 less than 1 μM in an assay based on a mammalian dopamine receptor or transporter.
- 124. The compound of claim 95, wherein said compound has an IC50 less than 100 nM in an assay based on a mammalian dopamine receptor or transporter.
- 125. The compound of claim 95, wherein said compound has an IC50 less than 10 nM in an assay based on a mammalian dopamine receptor or transporter.
- 126. The compound of claim 1, 37, 66, or 95, wherein said compound is a single stereoisomer.
- 127. A formulation, comprising a compound of claim 1, 37, 66, or 95; and a pharmaceutically acceptable excipient.
- 128. A method of modulating the activity of a dopamine, serotonin, or norepinephrine receptor or transporter in a mammal, comprising the step of:
administering to said mammal a therapeutically effective amount of a compound of claim 1, 37, 66, or 95.
- 129. The method of claim 128, wherein said mammal is a primate, equine, canine or feline.
- 130. The method of claim 128, wherein said mammal is a human.
- 131. The method of claim 128, wherein said compound is administered orally.
- 132. The method of claim 128, wherein said compound is administered intravenously.
- 133. The method of claim 128, wherein said compound is administered sublingually.
- 134. The method of claim 128, wherein said compound is administered ocularly.
- 135. The method of claim 128, wherein said compound is administered transdermally.
- 136. The method of claim 128, wherein said compound is administered rectally.
- 137. The method of claim 128, wherein said compound is administered vaginally.
- 138. The method of claim 128, wherein said compound is administered topically.
- 139. The method of claim 128, wherein said compound is administered intramuscularly.
- 140. The method of claim 128, wherein said compound is administered subcutaneously.
- 141. The method of claim 128, wherein said compound is administered buccally.
- 142. The method of claim 128, wherein said compound is administered nasally.
- 143. A method of modulating the activity of a dopamine receptor or transporter in a mammal, comprising the step of:
administering to said mammal a therapeutically effective amount of a compound of claim 1, 37, 66, or 95.
- 144. The method of claim 143, wherein said mammal is a primate, equine, canine or feline.
- 145. The method of claim 143, wherein said mammal is a human.
- 146. The method of claim 143, wherein said compound is administered orally.
- 147. The method of claim 143, wherein said compound is administered intravenously.
- 148. The method of claim 143, wherein said compound is administered sublingually.
- 149. The method of claim 143, wherein said compound is administered ocularly.
- 150. The method of claim 143, wherein said compound is administered transdermally.
- 151. The method of claim 143, wherein said compound is administered rectally.
- 152. The method of claim 143, wherein said compound is administered vaginally.
- 153. The method of claim 143, wherein said compound is administered topically.
- 154. The method of claim 143, wherein said compound is administered intramuscularly.
- 155. The method of claim 143, wherein said compound is administered subcutaneously.
- 156. The method of claim 143, wherein said compound is administered buccally.
- 157. The method of claim 143, wherein said compound is administered nasally.
- 158. A method of treating a mammal suffering from addiction, anxiety, depression, sexual dysfunction, hypertension, migraine, Alzheimer's disease, obesity, emesis, psychosis, analgesia, schizophrenia, Parkinson's disease, restless leg syndrome, sleeping disorders, attention deficit hyperactivity disorder, irritable bowel syndrome, premature ejaculation, menstrual dysphoria syndrome, urinary incontinence, inflammatory pain, neuropathic pain, Lesche-Nyhane disease, Wilson's disease, or Tourette's syndrome, comprising the step of:
administering to said mammal a therapeutically effective amount of a compound of claim 1, 37, 66, or 95.
- 159. The method of claim 158, wherein said mammal is a primate, equine, canine or feline.
- 160. The method of claim 158, wherein said mammal is a human.
- 161. The method of claim 158, wherein said compound is administered orally.
- 162. The method of claim 158, wherein said compound is administered intravenously.
- 163. The method of claim 158, wherein said compound is administered sublingually.
- 164. The method of claim 158, wherein said compound is administered ocularly.
- 165. The method of claim 158, wherein said compound is administered transdermally.
- 166. The method of claim 158, wherein said compound is administered rectally.
- 167. The method of claim 158, wherein said compound is administered vaginally.
- 168. The method of claim 158, wherein said compound is administered topically.
- 169. The method of claim 158, wherein said compound is administered intramuscularly.
- 170. The method of claim 158, wherein said compound is administered subcutaneously.
- 171. The method of claim 158, wherein said compound is administered buccally.
- 172. The method of claim 158, wherein said compound is administered nasally.
RELATED APPLICATIONS
[0001] This application claims the benefit of priority to: U.S. Provisional Patent Application serial No. 60/231,667, filed Sep. 11, 2000; U.S. Provisional Patent Application serial No. 60/273,530, filed Mar. 5, 2001; and U.S. Provisional Patent Application serial No. 60/298,057, filed Jun. 13, 2001.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60273530 |
Mar 2001 |
US |
|
60298057 |
Jun 2001 |
US |
Divisions (1)
|
Number |
Date |
Country |
Parent |
09951130 |
Sep 2001 |
US |
Child |
10607457 |
Jun 2003 |
US |