Quinazoline derivatives useful as anti-tumor medicament
The present invention relates to quinazoline derivatives of the formula (I) useful as anti-tumor medicaments, or a pharmaceutically acceptable salt thereof, the definition of the substituents R 1 , R 1 ′, R 2 , R 2 ′ are as defined in the description. It also relates to a pharmaceutical composition containing same, and a method for the preparation of quinazoline derivatives of formula (I) or a pharmaceutically acceptable salt thereof.
1. A compound of formula I, or a pharmaceutically acceptable salt, thereof,
wherein
R 1 is acylamino of the formula:
wherein R 3 is selected from hydrogen, N,N-dimethylaminomethyl, N,N-diethylaminomethyl, N,N-dipropylaminomethyl and N-morpholinomethyl;
R 1 ′ is selected from hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted by halogens, C 1 -C 4 alkoxy, or C 1 -C 4 alkoxy substituted by halogens, and
R 2 is selected from benzyloxy, mono-, di- and tri-halobenzyloxy; and
R 2 ′ is halogen.
2. A compound of claim 1 or a pharmaceutically acceptable salt, thereof, wherein
R 3 is selected from hydrogen and N,N-dimethylaminomethyl.
3. The compound of claim 1 , or a pharmaceutically acceptable salt, thereof, which is selected from the group consisting of:
N-{4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-quinazolin -6 -yl}-acrylamide;
N-{4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-quinazolin -6 -yl}-E, 4-(dimethylamino)-but-2-enamide;
N-[4-(3-chloro-4-benzyloxy-phenylamino)-quinazolin-6-yl]-E,4 (dimethylamino)-but-2-enamide;
N-{4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-7-trifluoro ethoxy-quinazolin-6-yl}-E,4-(dimethylamino)-but-2-enamide;
N-{4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-7-methoxy -quinazolin-6-yl}-E,4-(dimethylamino)-but-2-enamide;
N-{4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-7-methoxy-quinazolin-6-yl}-acrylamide.
4. A pharmaceutical composition, comprising 0.05-100mg of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, excipient or diluent.