公开(公告)号：US08772272B2

公开(公告)日：2014-07-08

申请号：US12724203

申请日：2010-03-15

申请人： Eddy Jean Edgard Freyne ,  Marc Willems ,  Pierre Henri Storck ,  Virginie Sophie Poncelet ,  Kristof Van Emelen ,  Peter Jacobus Johnnes Antonius Buijnsters ,  Werner Constant Johan Embrechts ,  Timothy Pietro Suren Perera

发明人： Eddy Jean Edgard Freyne ,  Marc Willems ,  Pierre Henri Storck ,  Virginie Sophie Poncelet ,  Kristof Van Emelen ,  Peter Jacobus Johnnes Antonius Buijnsters ,  Werner Constant Johan Embrechts ,  Timothy Pietro Suren Perera

IPC分类号： A61K31/33 ,  A61K31/519 ,  C07D487/00 ,  C07D487/18

CPC分类号： C07D498/16 ,  C07D471/04 ,  C07D487/04 ,  C07D487/16 ,  C07D487/22

摘要： The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein a1-a2=a3-a4 represents a divalent radical selected from N—CH═CH—CH, N—CH═N—CH or CH—CH═N—CH; Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR13—C1-5alkyl-, —C1-6alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O— or —NR11—; X2 represents —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen; R4 represents hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or R4 represents C1-4alkyloxy substituted with one or where possible two or more substituents selected from C1-4alkyloxy- or Het2-; R11 represents hydrogen; R12 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R13 represents Het14-C1-4alkyl, in particular morpholinyl-C1-4alkyl; Het2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C1-4alkyl-, preferably methyl; Het14 represents morpholinyl; Het16 represents a heterocycle selected from morpholinyl or pyrrolidinyl; Ar4 represents phenyl; Ar5 represents phenyl optionally substituted with cyano.

摘要翻译： 本发明涉及N-氧化物形式的化合物，其药学上可接受的加成盐和立体化学异构体，其中a1-a2 = a3-a4表示选自N-CH = CH-CH，N- CH = N-CH或CH-CH = N-CH; Z表示NH; Y表示-C3-9烷基 - ，-C1-5烷基-NR13-C1-5烷基 - ，C1-6烷基-NH-CO-或-CO-NH-C1-6烷基 - ; X1表示-O-或-NR11-; X2表示-C1-2烷基 - ， - O-C1-2烷基，-O-或-O-CH2-; R1表示氢或卤素; R 2表示氢，氰基，卤素，羟基羰基 - ，C 1-4烷氧基羰基 - ，Het 16 - 羰基 - 或Ar 5; R3表示氢; R 4表示羟基，C 1-4烷氧基 - ，Ar 4 -C 1-4烷氧基或R 4表示被一个或多个可能的两个或多个选自C 1-4烷氧基或Het 2-的取代基取代的C 1-4烷氧基; R11表示氢; R 12表示氢，C 1-4烷基 - 或C 1-4烷基 - 氧基 - 羰基 - ; R13表示Het14-C1-4烷基，特别是吗啉基-C 1-4烷基; Het2表示选自任选被C 1-4烷基，优选甲基取代的吗啉基或哌啶基的杂环; Het14代表吗啉基; Het16表示选自吗啉基或吡咯烷基的杂环; Ar4表示苯基; Ar 5表示任选被氰基取代的苯基。