[发明专利]氘化氨基缩水甘油基化合物

摘要

本发明提供了式(1)的取代氨基缩水甘油基化合物、其制备方法和其药物组合物及其用于治疗、预防或改善社交焦虑障碍、焦虑症、甲状腺机能亢进、震颤、青光眼、高血压、冠状动脉旁路移植、慢性稳定性心绞痛、房性心律失常、偏头痛、出血性食管静脉曲张、肥厚性主动脉瓣下狭窄、心力衰竭、心肌梗死后、近期心肌梗死后出现的左心室功能下降和/或通过β肾上腺素能受体调节剂改善的任何病症的一种或多种症状的方法。

主权项

1.下式1的化合物或其单一对映体、其(+)-对映体和其(-)-对映体的混合物、约90重量％或更多的其(-)-对映体与约10重量％或更少的其(+)-对映体的混合物、约90重量％或更多的其(+)-对映体与约10重量％或更少的其(-)-对映体的混合物、其单一非对映体或其非对映体的混合物；或其药学上可接受的盐、其溶剂化物或其前药：其中：R₃独立地选自由氢、氘和组成的组；R₄和R₅各自独立地为氢或氘，或R₄和R₅连接在一起以形成从而产生萘环体系；且R₁、R₂、R₆、R₇、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀独立地为氢或氘；条件为在所述式1的化合物中R₁、R₂、R₃、R₄、R₅、R₆、R₇、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个独立地为氘；条件为，当R₄和R₅连接在一起以形成时：1)如果R₁和R₃为氘，则R₂、R₆、R₇、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且2)如果R₃为氘，则R₁、R₂、R₆、R₇、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且3)如果R₁、R₂、R₃、R₂₇、R₂₈、R₂₉和R₃₀为氘，则R₆、R₇、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅和R₂₆中至少一个为氘；且4)如果R₁₆为氘，则R₁、R₂、R₃、R₆、R₇、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且5)如果R₁₃、R₁₄、R₁₅、R₁₇、R₁₈和R₁₉为氘，则R₁、R₂、R₃、R₆、R₇、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₆、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且6)如果R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈和R₁₉为氘，则R₁、R₂、R₃、R₆、R₇、R₈、R₉、R₁₀、R₁₁、R₁₂、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且7)如果R₁₀和R₁₁为氘，则R₁、R₂、R₃、R₆、R₇、R₈、R₉、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且8)如果R₆和R₇为氘，则R₁、R₂、R₃、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且9)如果R₆、R₇、R₈、R₁₀和R₁₁为氘，则R₁、R₂、R₃、R₉、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；条件为，当R₃为时：1)如果R₁₃、R₁₄、R₁₅、R₁₇、R₁₈和R₁₉为氘，则R₁、R₂、R₄、R₅、R₆、R₇、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₆、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且2)如果R₆和R₇为氘，则R₁、R₂、R₄、R₅、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且3)如果R₁和R₅为氘，则R₂、R₄、R₆、R₇、R₈、R₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且条件为，当R₃为氢时：1)如果R₈为氘，则R₁、R₂、R₄、R₅、R₆、R₇、R₉、R₁₀、R₁₁、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘；且2)如果R₁₀和R₁₁为氘，则R₁、R₂、R₄、R₅、R₆、R₇、R₈、R₉、R₁₂、R₁₃、R₁₄、R₁₅、R₁₆、R₁₇、R₁₈、R₁₉、R₂₀、R₂₁、R₂₂、R₂₃、R₂₄、R₂₅、R₂₆、R₂₇、R₂₈、R₂₉和R₃₀中至少一个为氘。