[发明专利]用于治疗肥胖的MAO－B抑制剂

摘要

本发明提供式(I)和(II)的新型化合物，其为单胺氧化酶－B抑制剂，可用于治疗肥胖、糖尿病和/或心脏代谢紊乱(例如过度紧张、血脂异常、高血压和胰岛素抗性)。

主权项

1.式I或II的新型化合物，或其立体异构体或制药上可接受的盐：其中：R，在各种情况下，独立地选自H、C_1-6烷基、C_2-6链烯基和C_2-6炔基；R¹选自H、C_1-6烷基、C_2-6链烯基、C_2-6炔基、(CH₂)_mCO₂R、C_2-6链烯基-CO₂R、CH₂CH(NHAc)CO₂R、CH₂CH(NHR)CO₂R和(CH₂)_nPO(OR)₂；A^-是抗衡离子；V选自O^-、C_1-4烷基、C_2-4链烯基和C_2-4炔基；X、X¹、X²和X³独立地选自H、OR、C_1-6烷基、C_2-6链烯基、C_2-6炔基、卤素、CF₃、硝基、-CN、N(R)₂、(CH₂)_m-四唑、(CH₂)_nCO₂R、(CH₂)_nCONR₂、(CH₂)_nCN、O(CH₂)_nCN、O(CH₂)_n-四唑、O(CH₂)_nCO₂R、O(CH₂)_nCON(R)₂、O-C_2-6链烯基-CO₂R、O(CH₂)_nPO(OR)₂、NR-C_2-4链烯基、NRSO₂CH₃、NR(CH₂)_nCO₂R、NR(CH₂)_nCON(R)₂、NR-C_2-4链烯基-CO₂R、NR(CH₂)_nPO(OR)₂、NR(CH₂)_nSO₂OR、NR(CH₂)_n-四唑、SO₂NRCH₃、OCH₂CHMCONRCH₂CO₂R、CH₂-芳基、O(CH₂)_nPO(OR)₂、O(CH₂)_nSO₂OR、OCH₂(CH₂)_nN⁺(CH₃)₃A^-、O(CH₂)_n-联苯基、O(CH₂)_n-联苯基-(CH₂)_mCO₂R、O(CH₂)_n-联苯基-(CH₂)_m四唑、O(CH₂)_n-联苯基-(CH₂)_mCN、O(CH₂)_n-联苯基-(CH₂)_mCON(R)₂、NR(CH₂)_n-联苯基、NR(CH₂)_n-联苯基-(CH₂)_mCO₂R、NR(CH₂)_n-联苯基-(CH₂)_m四唑、NR(CH₂)_n-联苯基-(CH₂)_mCN、NR(CH₂)_n-联苯基-(CH₂)_mCON(R)₂、O(CH₂)_n-芳基、O(CH₂)_n-杂芳基、NR(CH₂)_n-芳基、NR(CH₂)_n-杂芳基、O(CH₂)_n-芳基(CH₂)_mCO₂R、O(CH₂)_n-芳基-C_2-6链烯基-CO₂R、O(CH₂)_n-芳基(CH₂)_m-四唑、O(CH₂)_n-芳基(CH₂)_mCN、O(CH₂)_n-芳基(CH₂)_mCON(R)₂、O(CH₂)_n-芳基(CH₂)_m-PO(OR)₂、O(CH₂)_n-芳基-O(CH₂)_nCO₂R、O(CH₂)_n-芳基-O-C_2-6链烯基-CO₂R、O(CH₂)_n-芳基O(CH₂)_n-四唑、O(CH₂)_n-芳基O(CH₂)_nCN、O(CH₂)_n-芳基O(CH₂)_nCON(R)₂、O(CH₂)_n-芳基O(CH₂)_n-PO(OR)₂、O(CH₂)_n-芳基-NR(CH₂)_nCO₂R、O(CH₂)_n-芳基-NRC_2-6链烯基-CO₂R、O(CH₂)_n-芳基-NR(CH₂)_n-四唑、O(CH₂)_n-芳基-NR(CH₂)_nCN、O(CH₂)_n-芳基-NR(CH₂)_nCON(R)₂、O(CH₂)_n-芳基-NR(CH₂)_n-PO(OR)₂、NR(CH₂)_n-芳基(CH₂)_mCO₂R、NR(CH₂)_n-芳基-C_2-6链烯基-CO₂R、NR(CH₂)_n-芳基(CH₂)_m-四唑、NR(CH₂)_n-芳基(CH₂)_mCN、NR(CH₂)_n-芳基(CH₂)_mCON(R)₂、NR(CH₂)_n-芳基(CH₂)_m-PO(OR)₂、NR(CH₂)_n-芳基-NR(CH₂)_nCO₂R、NR(CH₂)_n-芳基-NR-C_2-6链烯基-CO₂R、NR(CH₂)_n-芳基-NR(CH₂)_n-四唑、NR(CH₂)_n-芳基-NR(CH₂)_nCN、NR(CH₂)_n-芳基-NR(CH₂)_nCON(R)₂、NR(CH₂)_n-芳基-NR(CH₂)_nPO(OR)₂、NR(CH₂)_n-芳基O(CH₂)_nCO₂R、NR(CH₂)_n-芳基-O-C_2-6链烯基-CO₂R、NR(CH₂)_n-芳基-O(CH₂)_n-四唑、NR(CH₂)_n-芳基O(CH₂)_nCN、NR(CH₂)_n-芳基-O(CH₂)_nCON(R)₂、NR(CH₂)_n-芳基O(CH₂)_nPO(OR)₂、O(CH₂)_n-杂芳基(CH₂)_mCO₂R、O(CH₂)_n-杂芳基-C_2-6链烯基-CO₂R、O(CH₂)_n-杂芳基(CH₂)_m-四唑、O(CH₂)_n-杂芳基-O(CH₂)_mCN、O(CH₂)_n-杂芳基(CH₂)_mCON(R)₂、O(CH₂)_n-杂芳基(CH₂)_m-PO(OR)₂、O(CH₂)_n-杂芳基-O(CH₂)_nCO₂R、O(CH₂)_n-杂芳基-O-C_2-6链烯基-CO₂R、O(CH₂)_n-杂芳基O(CH₂)_n-四唑、O(CH₂)_n-杂芳基O(CH₂)_nCN、O(CH₂)_n-杂芳基O(CH₂)_nCON(R)₂、O(CH₂)_n-杂芳基O(CH₂)_n-PO(OR)₂、O(CH₂)_n-杂芳基-NR(CH₂)_nCO₂R、O(CH₂)_n-杂芳基-NR-C_2-6链烯基-CO₂R、O(CH₂)_n-杂芳基-NR(CH₂)_n-四唑、O(CH₂)_n-杂芳基-NR(CH₂)_nCN、O(CH₂)_n-杂芳基-NR(CH₂)_nCON(R)₂、O(CH₂)_n-杂芳基-NR(CH₂)_n-PO(OR)₂，、NR(CH₂)_n-杂芳基(CH₂)_mCO₂R、NR(CH₂)_n-杂芳基-C_2-6链烯基-CO₂R、NR(CH₂)_n-杂芳基(CH₂)_m-四唑、NR(CH₂)_n-杂芳基(CH₂)_mCN、NR(CH₂)_n-杂芳基(CH₂)_mCON(R)₂、NR(CH₂)_n-杂芳基(CH₂)_m-PO(OR)₂、NR(CH₂)_n-杂芳基-NR(CH₂)_nCO₂R、NR(CH₂)_n-杂芳基-NR-C_2-6链烯基-CO₂R、NR(CH₂)_n-杂芳基-NR(CH₂)_n-四唑、NR(CH₂)_n-杂芳基-NR(CH₂)_nCN、NR(CH₂)_n-杂芳基-NR(CH₂)_nCON(R)₂、NR(CH₂)_n-杂芳基-NR(CH₂)_nPO(OR)₂、NR(CH₂)_n-杂芳基-O(CH₂)_nCO₂R、NR(CH₂)_n-杂芳基-O-C_2-6链烯基-CO₂R、NR(CH₂)_n-杂芳基-O(CH₂)_n-四唑、NR(CH₂)_n-杂芳基-O(CH₂)_nCN、NR(CH₂)_n-杂芳基-O(CH₂)_nCON(R)₂、NR(CH₂)_n-杂芳基O(CH₂)_nPO(OR)₂，其中杂芳基是5-12元环体系，所述环体系由碳原子和1-4个杂原子组成，所述杂原子选自N、O和S，并且其中芳基和杂芳基被1-2个X⁴取代以及四唑被0-1个R取代；X⁴选自H、OR、O-C_2-6链烯基、C_1-6烷基、C_2-6链烯基、C_2-6炔基、卤素、CF₃、硝基、-CN、C(O)NR₂、NRSO₂CH₃和SO₂N(R)C_1-6烷基；Q选自H、OH、C_1-6烷氧基、O(CH₂)_nCO₂R、O(CH₂)_nCON(R)₂、O-C_2-6链烯基、O-C_2-6链烯基-CO₂R、OCH₂CH₂CONRCH₂CO₂R、OCH₂CHMCONRCH₂CO₂R、O(CH₂)_nPO(OR)₂、O(CH₂)_nSO₂OR、OCH₂CH(NHAc)CO₂R、OCH₂CH(NHR)CO₂R、O(CH₂)_n-芳基和O(CH₂)_n-5-12元杂芳基，所述杂芳基由碳原子和1-4个杂原子组成，所述杂原子选自N、O和S；W选自H、CO₂R、CON(R)₂、CH₂OH、CH₂OC_1-6烷基、CH₂OC_2-6链烯基、CH₂O(CH₂)_nCO₂R、CH₂O(CH₂)_nCON(R)₂、CH₂O-C_2-6链烯基-CO₂R、CH₂OCH₂CH₂CONRCH₂CO₂R、CH₂OCH₂CHMCONRCH₂CO₂R、CH₂O(CH₂)_nPO(OR)₂、CH₂O(CH₂)_nSO₂OR、CH₂OCH₂CH(NHAc)CO₂R、CH₂OCH₂CH(NHR)CO₂R、CH₂O-C_2-6链烯基和CH₂O(CH₂)_nCONH₂、CH₂O(CH₂)_n-芳基和CH₂O(CH₂)_n-5-12元杂芳基，所述杂芳基由碳原子和1-4个杂原子组成，所述杂原子选自N、O和S，并且其中杂芳基被1-2个X⁴取代；M独立地选自H、C_1-6烷基、C_3-8环烷基、C_2-6链烯基、C_2-6炔基、芳基、(CH₂)_n-芳基、杂芳基和(CH₂)_n-杂芳基，其中杂芳基是5-12元环体系，所述环体系由碳原子和1-4个杂原子组成，所述杂原子选自N、O和S，并且其中芳基和杂芳基被1-2个X⁴取代；m独立地选自0、1、2、3和4；和n独立地选自1、2、3.和4；条件是：X、X¹、X²和X³中至少一个不是H、烷基、烷氧基、羟基和卤。