Patent EP-0645379-B1 (EP)
Inventor: TAKAYANAGI HISAO
IPC: C07D213/30
Filed: 1994-07-29
Granted: 1999-03-17
Abstract: A compound of the following formula (I) <CHEM> wherein R<1>  SIMILAR  R<5> are independently hydrogen; -OR<7> wherein R<7> is hydrogen, C1  SIMILAR  C5 alkyl optionally substituted by halogen or phenyl, or -COR<8> wherein R<8> is phenyl or C1  SIMILAR  C5 alkyl optionally substituted by phenyl; halogen; C1  SIMILAR  C5 alkyl optionally substituted by halogen; -NR<9>R<1><0> wherein R<9> and R<1><0> are independently hydrogen, phenyl, C1  SIMILAR  C5 alkyl optionally substituted by phenyl, benzoyl, or acetyl; -SOpR<1><1> wherein p is 0, 1 or 2, R<1><1> is C1  SIMILAR  C5 alkyl or phenyl; cyano; or nitro; or when adjacent substituents are taken together, they may represent C1  SIMILAR  C3 oxyalkylene having one or two oxygen atoms,  R<6> is hydrogen; C1  SIMILAR  C5 alkyl; <CHEM> wherein Y<1>, Y<2> and Y<3> are independently hydrogen, pyridyl, C1 SIMILAR C5 alkyl, phenyl or halogen; <CHEM> wherein Z<1>, Z<2> and Z<3> are independently hydrogen, C1  SIMILAR C5 alkyl or halogen; C3  SIMILAR  C12 trialkylsilyl; -COR<1><2> wherein R<1><2> is C1 SIMILAR  C5 alkyl, phenyl, C1  SIMILAR  C5 alkoxy optionally substituted by phenyl, or -NR<1><3>R<1><4> wherein R<1><3> and R<1><4> are independently hydrogen, C1  SIMILAR C5 alkyl optionally substituted by phenyl, or phenyl optionally substituted by halogen; or -CR<1><5>R<1><6>X wherein R<1><5> and R<1><6> are independently hydrogen, phenyl, C1  SIMILAR  C5 alkyl optionally substituted by phenyl, or C3  SIMILAR  C8 cycloalkyl, or when taken together to be C3  SIMILAR  C7 alkylene optionally substituted by C1  SIMILAR  C5 alkyl, X is -OR<1><7> wherein R<1><7> is hydrogen, C1  SIMILAR  C5 alkyl optionally substituted by phenyl, or -COR<1><8> wherein R<1><8> is phenyl or C1  SIMILAR  C5 alkyl optionally substituted by phenyl, -COR<1><9> wherein R<1><9> is hydroxyl, phenyl optionally substituted by C1  SIMILAR  C5 alkyl, C1  SIMILAR  C5 alkyl optionally substituted by phenyl, C1  SIMILAR  C5 alkoxy optionally substituted by phenyl, or -NR<2><0>R<2><1> wherein R<2><0> and R<2><1> are independently hydrogen, C1  SIMILAR C5 alkyl or phenyl optionally substituted by halogen, -SOpR<2><2> wherein p is 0, 1 or 2, R<2><2> is C1  SIMILAR  C5 alkyl or phenyl, or -NR<2><3>R<2><4> wherein R<2><3> and R<2><4> are independently hydrogen, phenyl optionally substituted by halogen or C1  SIMILAR  C5 alkyl, or C1  SIMILAR  C5 alkyl optionally substituted by hydroxyl, phenyl, C1  SIMILAR  C5 alkylamino, C2  SIMILAR  C6 dialkylamino or indolyl, C3  SIMILAR  C8 cycloalkyl, pyridyl, -SO2R<2><7> wherein R<2><7> is phenyl optionally substituted by C1  SIMILAR  C3 alkoxy, or -COR<2><5> wherein R<2><5> is C1  SIMILAR  C5 alkyl, phenyl, or C1  SIMILAR C5 alkoxy optionally substituted by pyridyl, N-methylpyridyl, N-oxopyridyl or phenyl optionally substituted by carboxyl or sodium carboxylate, or when R<2><3> and R<2><4> are taken together, they are C3  SIMILAR  C6 alkylene optionally containing therein -O-, <CHEM>  or -NR<2><6>- wherein R<2><6> is hydrogen, phenyl or C1  SIMILAR  C5 alkyl, or C3 SIMILAR  C6 alkylene optionally substituted by C1  SIMILAR  C5 alkyl with a proviso that when R<6> is hydrogen, R<2> and R<3> are not methoxy, or its salt, and a pharmaceutical composition containing at least one of these compounds, which is useful as a tyrosine kinase inhibitor and useful for suppressing the growth of cancer cells.