Patent EP-0645379-A2 (EP)
Inventor: TAKAYANAGI HISAO
IPC: C07D213/30
Filed: 1994-07-29
Abstract: A compound of the following formula (I)
     
     wherein R 1  ~ R 5  are independently hydrogen; -OR 7  wherein R 7  is hydrogen, C 1  ~ C 5  alkyl optionally substituted by halogen or phenyl, or -COR 8  wherein R 8  is phenyl or C 1  ~ C 5  alkyl optionally substituted by phenyl; halogen;   C 1  ~ C 5  alkyl optionally substituted by halogen; -NR 9 R 10  wherein R 9  and R 10  are independently hydrogen, phenyl,   C 1  ~ C 5  alkyl optionally substituted by phenyl, benzoyl, or acetyl;   -SOpR 11  wherein p is 0, 1 or 2, R 11  is C 1  ~ C 5  alkyl or phenyl; cyano; or nitro; or when adjacent substituents are taken together, they may represent C 1  ~ C 3  oxyalkylene having one or two oxygen atoms,   R 6  is hydrogen; C 1  ~ C 5  alkyl;
         wherein Y 1 , Y 2  and Y 3  are independently hydrogen, pyridyl, C 1  ~ C 5  alkyl, phenyl or halogen;
         wherein Z 1 , Z 2  and Z 3  are independently hydrogen, C 1  ~ C 5  alkyl or halogen;   C 3  - C 12  trialkylsilyl; -COR 12  wherein R 12  is C 1  ~ C 5  alkyl, phenyl, C 1  ~ C 5  alkoxy optionally substituted by phenyl, or -NR 13 R 14  wherein R 13  and R 14  are independently hydrogen, C 1  ~ C 5  alkyl optionally substituted by phenyl, or phenyl optionally substituted by halogen; or -CR 15 R 16 X wherein R 15  and R 16  are independently hydrogen, phenyl, C 1  ~ C 5  alkyl optionally substituted by phenyl, or C 3  - C 8  cycloalkyl, or when taken together to be C 3  - C 7  alkylene optionally substituted by C 1  ~ C 5  alkyl, X is -OR 17  wherein R 17  is hydrogen, C 1  ~ C 5  alkyl optionally substituted by phenyl, or -COR 18  wherein R 18  is phenyl or C 1  ~ C 5  alkyl optionally substituted by phenyl, -COR 19  wherein R 19  is hydroxyl, phenyl optionally substituted by C 1  ~ C 5  alkyl, C 1  ~ C 5  alkyl optionally substituted by phenyl, C 1  ~ C 5  alkoxy optionally substituted by phenyl, or   -NR 20 R 21  wherein R 20  and R 21  are independently hydrogen, C 1  ~ C 5  alkyl or phenyl optionally substituted by halogen, -SOpR 22  wherein p is 0, 1 or 2, R 22  is   C 1  ~ C 5  alkyl or phenyl, or -NR 23 R 24  wherein R 23  and R 24  are independently hydrogen, phenyl optionally substituted by halogen or C 1  ~ C 5  alkyl, or C 1  ~ C 5  alkyl optionally substituted by hydroxyl, phenyl, C 1  ~ C 5  alkylamino, C 2  ~ C 6  dialkylamino or indolyl, C 3  - C 8  cycloalkyl, pyridyl, -SO 2 R 27  wherein R 27  is phenyl optionally substituted by C 1  ~ C 3  alkoxy, or -COR 25  wherein R 25  is C 1  ~ C 5  alkyl, phenyl, or C 1  ~ C 5  alkoxy optionally substituted by pyridyl, N-methylpyridyl, N-oxopyridyl or phenyl optionally substituted by carboxyl or sodium carboxylate, or when R 23  and R 24  are taken together, they are C 3  - C 6  alkylene optionally containing therein -O-,
     or -NR 26 -   wherein R 26  is hydrogen, phenyl or C 1  ~ C 5  alkyl, or C 3  - C 6  alkylene optionally substituted by C 1  ~ C 5  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.