5-HT受体的调节剂和其使用方法

摘要

本申请涉及式(I)的芳基和杂芳基稠合的十氢吡咯并氮杂                                               、八氢噁庚英并吡咯、八氢吡咯并硫氮杂二氧化物、十氢环庚烷并[c]吡咯和八氢环庚烷并[c]吡咯衍生物其中R¹、R²、R³、R⁴、R⁵、A、Y¹、Y²和Y³如说明书所定义。本申请还涉及包含这种化合物的组合物、制备这种化合物的方法和使用这种化合物和组合物治疗疾病症状的方法和鉴定这种化合物的方法。

主权项

选自下列的化合物：反式‑8‑甲氧基‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7‑氟‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑9‑(三氟甲氧基)‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7,9‑二氟‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；顺式‑9‑氟‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7‑(三氟甲氧基)‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑9‑氟‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑10‑氟‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；顺式‑7,10‑二氟‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7,10‑二氟‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑9‑甲基‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7‑甲基‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑8‑(3,5‑二甲基‑1,2‑噁唑‑4‑基)‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑{3‑[(1S)‑1‑羟基乙基]苯基}‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑{3‑[(1R)‑1‑羟基乙基]苯基}‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；顺式‑7‑氯‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑8‑(5‑乙酰基‑2‑噻吩基)‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(异丁基氨基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑2‑甲基‑8‑(哌啶‑1‑基)‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(4‑氟‑2‑甲氧基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(5‑氟‑2‑甲氧基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(5‑异丙基‑2‑甲氧基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(2‑甲氧基‑4‑甲基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(2,4‑二甲氧基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑[3‑(1‑羟基‑2‑甲基丙基)苯基]‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑[(E)‑2‑环丙基乙烯基]‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑2‑甲基‑8‑(3‑氧代‑2,3‑二氢‑1H‑茚‑5‑基)‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑[4‑氟‑3‑(1‑羟基乙基)苯基]‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aR,10bS)‑8‑异丁氧基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bR)‑8‑异丁氧基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑(3‑羟基‑2,3‑二氢‑1H‑茚‑5‑基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑[3‑(1‑羟基丙基)苯基]‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑[3‑(1‑羟基‑3‑甲基丁基)苯基]‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑[3‑(1‑羟基丁基)苯基]‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(4‑氟‑3‑甲基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(4‑甲氧基‑3‑甲基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(3‑氟‑4‑甲氧基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(4‑甲氧基‑3,5‑二甲基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑(6‑甲氧基吡啶‑3‑基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑(3‑氯‑4‑甲氧基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(4‑氟‑3‑甲氧基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(2,3‑二氢‑1‑苯并呋喃‑5‑基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑2‑甲基‑8‑(3,4,5‑三氟苯基)‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(2‑氟‑5‑甲氧基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(2,3‑二氢‑1‑苯并呋喃‑6‑基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑(2‑氟‑4‑甲氧基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑(4‑氟‑2‑甲氧基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑6‑甲基‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂；1‑[反式‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][1]苯并氮杂‑6(1H)‑基]乙酮；反式‑6‑苄基‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂；反式‑2,6‑二甲基‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂；反式‑8‑(2,4‑二氟苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；顺式‑7‑溴‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；1‑[反式‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][1]苯并氮杂‑6(1H)‑基]‑2‑甲基丙‑1‑酮；反式‑6‑[(3,4‑二氯苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑{[4‑(二氟甲氧基)苯基]磺酰基}‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(3‑甲氧基苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(3‑氟苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑(苯磺酰基)‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(5‑氯‑2‑噻吩基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(4‑氯苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(2‑甲基苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(3‑氯‑2‑甲基苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(2,5‑二甲氧基苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(4‑叔丁基苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑{[3‑(三氟甲基)苯基]磺酰基}‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(4‑甲氧基苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑{[4‑(三氟甲基)苯基]磺酰基}‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(3‑甲基苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑{[4‑(三氟甲氧基)苯基]磺酰基}‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑7‑[3‑(甲磺酰)苯基]‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；1‑{3‑[反式‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯‑7‑基]苯基}乙酮；(3aS,10bS)‑8‑{4‑氟‑3‑[(1S)‑1‑羟基乙基]苯基}‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑8‑{4‑氟‑3‑[(1R)‑1‑羟基乙基]苯基}‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑6‑[(2‑甲氧基苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；2‑[反式‑7,7a,8,9,10,10a‑六氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂‑6(5H)‑基磺酰基]苄腈；反式‑6‑[(4‑甲基苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(4‑氟苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑(2‑噻吩基磺酰基)‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(3‑氯苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(5‑溴‑2‑噻吩基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(2‑氟苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑[(2‑氯苯基)磺酰基]‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑(基磺酰基)‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑{[2‑(三氟甲氧基)苯基]磺酰基}‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑{[2‑(三氟甲基)苯基]磺酰基}‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；反式‑6‑{[3‑(三氟甲氧基)苯基]磺酰基}‑5,6,7,7a,8,9,10,10a‑八氢吡啶并[3,2‑c]吡咯并[3,4‑e]氮杂；1‑{3‑[反式‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯‑7‑基]苯基}乙醇；反式‑7‑(吡啶‑3‑基)‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7‑(吡啶‑4‑基)‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑2‑甲基‑7‑(吡啶‑3‑基)‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；4‑[反式‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯‑7‑基]‑N‑甲基苯甲酰胺；反式‑7‑甲氧基‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑8‑甲基‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯‑10‑醇；反式‑7‑氯‑6‑甲基‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂；反式‑7‑氯‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑10‑溴‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑8‑(3‑异丙基苯基)‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(3‑异丙基苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑2‑(2‑氟乙基)‑8‑异丁氧基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；N‑甲基‑3‑[反式‑6‑氧代‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][2]苯并氮杂‑8‑基]苯甲酰胺；N‑甲基‑3‑[反式‑2‑甲基‑6‑氧代‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][2]苯并氮杂‑8‑基]苯甲酰胺；反式‑7‑溴‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑2‑(2‑氟乙基)‑8‑(4‑氟苯基)‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(2‑氯‑3‑噻吩基)‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(3‑氯‑1H‑吡咯‑2‑基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮和反式‑8‑(5‑氯‑1H‑吡咯‑2‑基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑8‑(2‑氯‑3‑噻吩基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；(3aS,10bS)‑2‑甲基‑8‑(吡啶‑2‑基)‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂；反式‑2‑甲基‑8‑(4‑氧代‑3,4‑二氢‑2H‑苯并吡喃‑6‑基)‑2,3,3a,4,5,10b‑六氢吡咯并[3,4‑d][2]苯并氮杂‑6(1H)‑酮；反式‑9‑氯‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂；反式‑7‑氯‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂；顺式‑7‑溴‑9‑氯‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7‑溴‑9‑氯‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑9‑氯‑2,6‑二甲基‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂；反式‑9‑溴‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂；反式‑7‑苯基‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7‑[(4‑氟苄基)氧基]‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7‑(4‑氟苯基)‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7‑(4‑氟苯基)‑2‑甲基‑2,3,3a,4,5,10b‑六氢‑1H‑[1]苯并噁庚英并[4,5‑c]吡咯；反式‑7‑(4‑氟苯基)‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂；和反式‑1,2,3,3a,4,5,6,10b‑八氢吡咯并[3,4‑d][1]苯并氮杂‑7‑甲酸甲酯；或其可药用盐。