9H-PYRROLO[2,3-B: 5,4-C'] DIPYRIDINE AZACARBOLINE DERIVATIVES, PREPARATION THEREOF, AND THERAPEUTIC USE THEREOF
申请人:Babin Didier
公开号:US20120208809A1
公开(公告)日:2012-08-16
The invention relates to novel 9H-pyrrolo[2,3-b:5,4-c′]dipyridine azacarbolines of formula (I), where: Z2, Z3, and Z4 are CH, CRa, CRs, or N; R3 is H, Hal; CF3, CHF2; OH, alkoxy; NH2, NH (alkyl), N(alkyl)2; C(O)O alkyl; CONH(alkyl), CON(alkyl)2; C1-C10 alkyl; aryl; heteroaryl; R6 is heteroaryl; Ra is CONH2, CONH alkyl, CONH cycloalkyl; CONH heterocycloalkyl; CON(alkyl)2; CON(alkyl)(heterocycloalkyl); CONHN(alkyl)2; C(O)heterocycloalkyl; Rs is H; Hal, OH; O-alkyl(C1-C10); NH2; N(alkyl(C1-C10) or cycloalkyl(C3-C7))2; NHC(O)R3a; N(alkyl(C1-C10)C(O)R3a; NHS(O2)R3a; N(alkyl)(C1-C10)S(O2)R3a; CO2R3a; SR3a; S(O)R3a; S(O2)R3a; Ra and Rs optionally form a cycle; R3a is selected from among Hal, CF3, C1-C10 alkyl; C3-C7 cycloalkyl; C2-C6 alkenyl; C2-C6 alkynyl; OH; O-alkyl(C1-C10); (C3-C7); heterocycloalkyl (C3-C7); NH2; NH-(alkyl(C1-C10) or cycloalkyl(C3-C7)); N(alkyl(C1-C10) or cycloalkyl(C3-C7))2; NH-(alkyl(C1-C10) or heterocycloalkyl(C3-C7)); N(alkyl(C1-C10) or heterocycloalkyl(C3-C7))2, as well as to the isomers and salts of said substances of formula (I) and to the therapeutic use thereof for treating cancer.
该发明涉及公式(I)的新型9H-吡咯[2,3-b:5,4-c′]二吡啶氮杂碳醇,其中:Z2、Z3和Z4为CH、CRa、CRs或N;R3为H、Hal、CF3、CHF2、OH、烷氧基、NH2、NH(烷基)、N(烷基)2、C(O)O烷基、CONH(烷基)、CON(烷基)2、C1-C10烷基、芳基、杂环芳基;R6为杂环芳基;Ra为CONH2、CONH烷基、CONH环烷基、CONH杂环烷基、CON(烷基)2、CON(烷基)(杂环烷基)、CONHN(烷基)2、C(O)杂环烷基;Rs为H、Hal、OH、O-烷基(C1-C10)、NH2、N(烷基(C1-C10)或环烷基(C3-C7))2、NHC(O)R3a、N(烷基(C1-C10)C(O)R3a、NHS(O2)R3a、N(烷基)(C1-C10)S(O2)R3a、CO2R3a、SR3a、S(O)R3a、S(O2)R3a;Ra和Rs可选择形成环;R3a从Hal、CF3、C1-C10烷基、C3-C7环烷基、C2-C6烯基、C2-C6炔基、OH、O-烷基(C1-C10)、(C3-C7)、杂环烷基(C3-C7)、NH2、NH-(烷基(C1-C10)或环烷基(C3-C7))、N(烷基(C1-C10)或环烷基(C3-C7))2、NH-(烷基(C1-C10)或杂环烷基(C3-C7))、N(烷基(C1-C10)或杂环烷基(C3-C7))2中选择,以及所述公式(I)的异构体和盐,以及其治疗用途,用于治疗癌症。