4-phenylamino-quinazolin-6-yl-amides
View Patent ↗This invention provides quinazoline compounds of the formula: wherein: R 1 is halo; R 2 is H or halo; R 3 is a) C 1 -C 3 alkyl, optionally substituted by halo; or b) —(CH 2 ) n -morpholino, —(CH 2 ) n -piperidine, —(CH 2 ) n -piperazine, —(CH 2 ) n -piperazine-N(C 1 -C 3 alkyl), —(CH 2 ) n -pyrrolidine, or —(CH 2 ) n -imidazole; n is 1 to 4; R 4 is —(CH 2 ) m -Het; Het is morpholine, piperidine, piperazine, piperazine-N(C 1 -C 3 alkyl), imidazole, pyrrolidine, azepane, 3,4-dihydro-2H-pyridine, or 3,6-dihydro-2H-pyridine, each optionally substituted by alkyl, halo, OH, NH 2 , NH(C 1 -C 3 alkyl) or N(C 1 -C 3 alkyl) 2 ; m is 1-3; and X is O, S or NH; or a pharmaceutically acceptable salt thereof, as well as processes and intermediate compounds for making them, useful pharmaceutical compositions and methods of using the compounds in the treatment of proliferative diseases.
1. A compound of the formula:
wherein:
Y is NH 2 , NO 2 or the moiety R 4 —(CH 2 ) m —CH═CH—C(O)—NH 2 —; and m is an integer from 1 to 3;
R 3 is selected from:
a) C 1 -C 3 straight or branched alkyl, optionally substituted by halogen; or
b) —(CH 2 ) n -morpholino, —(CH 2 ) n -piperidine, —(CH 2 ) n -piperazine, —(CH 2 ) n -piperazine-N(C 1 -C 3 alkyl), —(CH 2 ) n -pyrrolidine, or —(CH 2 ) n -imidazole;
n is an integer from 1 to 4;
R 4 is —(CH 2 ) m -Het;
Het is a heterocyclic moiety selected from the group of morpholine, piperidine, piperazine, piperazine-N(C 1 -C 3 alkyl), imidazole, pyrrolidine, azepane,
3,4-dihydro-2H-pyridine, or 3,6-dihydro-2H-pyridine, wherein each heterocyclic moiety is optionally substituted by from 1 to 3 groups selected from C 1 -C 3 alkyl, halogen, OH, NH 2 , NH(C 1 -C 3 alkyl) or N (C 1 -C 3 alkyl) 2 ;
m is an integer from 1 to 3; and
X is 0, S or NH.
2. A compound of the formula:
wherein:
Y is NO 2 , NH 2 , or the moiety halo-(CH 2 ) m —CH═CH—C(O)-NH 2 -;
halo is F, CI, Br or I;
m is an integer from 1 to 3;
R 3 is selected from:
a) a mono-, di- or tri-halogenated methyl group;
b) C 2 -C 3 straight or branched alkyl, optionally substituted by halogen; or
c) —(CH 2 ) n -morpholino, —(CH 2 ) n -piperidine, —(CH 2 ) n -piperazine, —(CH 2 ) n -piperazine-N(C 1 -C 3 alkyl), —(CH 2 ) n -pyrrolidine, or —(CH 2 ) n -imidazole.