Quinazoline derivatives and pharmaceutical compositions containing them
View Patent ↗A compound of general formula I wherein: R a is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group; R b is a dimethylamino, N-methyl-N-ethylamino, diethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetrahydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetrahydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and R c is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group, or a tautomer, stereoisomer, or salt thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases which have valuable pharmacological properties, in particular an inhibitory effect on signal transduction mediated by tyrosine kinases, their use in the treatment of diseases, especially tumoral diseases and diseases of the lungs and airways, and the preparation thereof.
1. A compound of formula I
wherein
R a is a benzyl, 1-phenylethyl, or 3-chloro-4-fluorophenyl group;
R b is a dimethylamino, N-methyl-N-ethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetrahydrofuran-3-yl)amino, N-methyl-N-(tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetrahydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and
R c is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group,
or a stereoisomer or physiologically acceptable salt thereof.
2. The compound of claim 1 , wherein Rb is a dimethylamino or a stereoisomer or physiologically acceptable salt thereof.
3. The compound of formula I according to claim 1 , wherein:
R a is a 1-phenylethyl or 3-chloro-4-fluorophenyl group;
R b is a dimethylamino, N-methyl-N-ethylamino, N-methyl-N-isopropylamino, N-methyl-N-cyclopropylamino, N-methyl-N-(2-methoxyethyl)amino, N-ethyl-N-(2-methoxyethyl)amino, bis(2-methoxyethyl)amino, morpholino, N-methyl-N-(tetrahydrofuran-3-yl)amino, N-methyl-N- (tetrahydrofuran-2-ylmethyl)amino, N-methyl-N-(tetrahydrofuran-3-ylmethyl)amino, N-methyl-N-(tetrahydropyran-4-yl)amino, or N-methyl-N-(tetrahydropyran-4-ylmethyl)amino group; and
R c is a cyclopropylmethoxy, cyclobutyloxy, cyclopentyloxy, tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetradrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group,
or a stereoisomer or physiologically acceptable salt thereof.
4. The compounds of claim 3 , wherein
R b is a dimethylamino,
or a stereoisomer or physiologically acceptable salt thereof.
5. The compounds of claim 3 , wherein
R a is a 3-chloro-4-fluorohenyl group and
R b is a dimethylamino group,
or a stereoisomer or physiologically acceptable salt thereof.
6. The compound of formula I according to claim 1 , wherein:
R a is a 3-chloro-4-fluorophenyl group;
R b is a dimethylaminno group; and
R c is a tetrahydrofuran-3-yloxy, tetrahydrofuran-2-ylmethoxy, tetrahydrofuran-3-ylmethoxy, tetrahydropyran-4-yloxy, or tetrahydropyran-4-ylmethoxy group,
or a steroisomer or physiologically acceptable salt thereof.