发明名称 PYRIDO [4,3-B]INDOLE AND PYRIDO [3,4-B] INDOLE DERIVATIVES AND METHODS OF USE
摘要 This disclosure is directed to tetracyclic pyrido[4,3-b]indole and pyrido[3,4-b]indoles. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.
申请公布号 US2016030446(A1) 申请公布日期 2016.02.04
申请号 US201514882303 申请日期 2015.10.13
申请人 Medivation Technologies, Inc. 发明人 CHAKRAVARTY Sarvajit;HART Barry Patrick;JAIN Rajendra Parasmal
分类号 A61K31/55;A61K31/4709;A61K31/519;A61K31/439;A61K31/4985;A61K31/437;A61K31/506 主分类号 A61K31/55
代理机构 代理人
主权项 1. A method of treating a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder or a neuronal disorder in an individual comprising administering to an individual in need thereof an effective amount of a compound of the formula (IA):or a salt or solvate thereof; wherein: R1 is H, hydroxyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, perhaloalkyl, acyl, acyloxy, carbonylalkoxy, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted aralkyl, C1-C8perhaloalkoxy, alkoxy, aryloxy, thiol, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl or carbonylalkylenealkoxy, or R1 and R2a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R1 and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R1 and R4a are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety; each R2a and R2b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R2a and R2b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R2a and R1 are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R2a and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety, or R2a and R4a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety; each R3a and R3b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, hydroxyl, alkoxy, nitro or R3a and R3b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R3a and R1 are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety, or R3a and R2a are taken together to form a propylene (—CH2CH2CH2—) moiety, or R3a and R4a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety; each R4a and R4b is independently H, substituted or unsubstituted C1-C8 alkyl, halo, cyano, nitro, substituted or unsubstituted amino, hydroxyl, alkoxy, acyloxy, acylamino, aryl, heteroaryl, cycloalkyl, heterocyclyl, or R4a and R4b are taken together with the carbon to which they are attached to form a carbonyl moiety or a cycloalkyl moiety, or R4a and R1 are taken together to form an ethylene (—CH2CH2—) moiety or a propylene (—CH2CH2CH2—) moiety, or R4a and R2a are taken together to form a methylene (—CH2—) moiety or an ethylene (—CH2CH2—) moiety, or R4a and R3a are taken together to form a propylene (—CH2CH2CH2—) moiety or a butylene (—CH2CH2CH2CH2—) moiety; each X1, X2, X3 and X4 is independently N, CH or CR6; Q is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted of unsubstituted aralkyl, wherein the aralkyl is a fused ring system where at least one cycloalkyl moiety is fused with at least one aryl moiety and wherein the aralkyl is attached to the parent structure via the cycloalkyl moiety or the aryl moiety; and R6 is hydroxyl, nitro, cyano, halo, C1-C8 perhaloalkyl, substituted or unsubstituted C1-C8 alkyl, substituted or unsubstituted C2-C8 alkenyl, substituted or unsubstituted C2-C8 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, C1-C8 perhaloalkoxy, substituted or unsubstituted C1-C8 alkoxy, substituted or unsubstituted aryloxy, carboxyl, carbonylalkoxy, thiol, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aralkyl, thioalkyl, substituted or unsubstituted amino, acylamino, aminoacyl, aminocarbonylamino, aminocarbonyloxy, aminosulfonyl, sulfonylamino, sulfonyl, carbonylalkylenealkoxy, alkylsulfonylamino or acyl, provided that: (1) at least one of X1, X2, X3 and X4 is CH or CR6; (2) when each X1, X2, X3 and X4 is independently CH or CR6, none of R1, R2a, R2b, R3a, R3b, R4a and R4b are taken together to form a ring and Q is an unsubstituted 6-membered aryl or an unsubstituted 6-membered heteroaryl, then Q is other than unsubstituted phenyl, unsubstituted pyridyl and unsubstituted pyrimidyl; (3) when each X1, X2, X3 and X4 is independently CH or CR6, none of R1, R2a, R2b, R3a, R3b, R4a and R4b are taken together to form a ring and Q is a substituted phenyl, then Q is a phenyl substituted with a substituent selected from the group consisting of substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, and substituted or unsubstituted aralkyl.
地址 San Francisco CA US