Quinazoline derivatives useful as anti-tumor medicament

1. A method for treating a tumor chosen from breast cancer, squamous carcinoma, cell lung cancer, ovarian cancer, stomach cancer, and pancreatic cancer, the method comprising the step of administering to a patient in need of treatment 0.05-100 mg/kg of bodyweight daily a compound of formula I, or a pharmaceutically acceptable salt thereof:

wherein, R 1 is selected from:

(a) C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted by halogens, C 1 -C 4 alkoxy, C 1 -C 4 alkoxy substituted by halogens, methoxyethoxy, N-morpholinopropoxy, formate, acetate, propionate, butyrate, acylamino or sulfonamide group;

(b) Unsubstituted or substituted phenyl, wherein the substituents are 1-3 substituents selected from the group consisting of halogen, —OH, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 1 -C 4 alkyl-OH, C 1 -C 4 alkoxymethyl, acetate, propionate, butyrate, and sulfonate;

(c) Unsubstituted or substituted furyl, and unsubstituted or substituted thienyl, wherein the substituents are 1-3 substituents selected from the group consisting of halogen, —OH, —NH 2 , C 1 -C 4 alkyl, C 1 -C 4 alkoxy, alkoxymethyl, formate, acetate, propionate, butyrate, and sulfonate;

or R 1 is

wherein R 1 is attached to the ring via oxygen, and X is selected from furyl, pyrrolidyl, pyridyl, oxazoline, thiazolyl, and thienyl;

R 1 ′ is selected from hydrogen, C 1 -C 4 alkyl, C 1 -C 4 alkyl substituted by halogens, C 1 -C 4 alkoxy, and C 1 -C 4 alkoxy substituted by halogens;

R 2 is selected from benzyl, mono-, di- or tri-halobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, benzyloxy, mono-, di, -or tri-halobenzyloxy or mono-, di- or tri-halophenylsulfonyl, furylmethyl, pyrrolylmethyl, pyrrolylmethoxy, halogen, C 1 -C 4 alkyl and C 1 -C 4 alkoxy, wherein said phenyl, benzyl, pyridyl, furyl or pyrrolyl may have 1-3 substituents selected from the group consisting of halogen, —OH, —NH 2 , C 1 -C 4 alkyl and C 1 -C 4 alkoxy;

R 2 ′ is selected from benzyl, mono-, di- or tri-halobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, mono-, di- or tri-halophenoxy or mono-, di-, or tri-halophenylsulfonyl, furylmethyl, pyrrolylmethyl, pyrrolylmethoxy, halogen, C 1 -C 4 alkyl and C 1 -C 4 alkoxy, wherein said phenyl, benzyl, pyridyl, furyl or pyrrolyl may have 1-3 substituents selected from the group consisting of halogen, —OH, —NH 2 , C 1 -C 4 alkyl and C 1 -C 4 alkoxyl.

2. The method according to claim 1 , wherein

R 2 is selected from benzyloxy, mono-, di- or tri-halobenzyloxy; and

R 2 ′ is halogen.

3. The method according to claim 2 , wherein

R 1 is selected from C 1 -C 4 alkoxy, C 1 -C 4 alkoxy

Substituted by halogens, methoxyethoxy, N-morpholinopropoxy, formate, acetate, propionate, butyrate, acylamino, sulfonamide group, phenyl, furyl,

or R 1 is

 wherein X is furyl.

4. The method according to claim 3 , wherein

R 1 is acylamino:

wherein R 3 is selected from hydrogen, N,N-dimethyl aminomethyl, N,N-diethylaminomethyl, N,N-dipropylaminomethyl and N-morpholinomethyl.

5. The method according to claim 4 , wherein

R 1 is acylamino:

wherein R 3 is selected from hydrogen and N,N-dimethylaminomethyl.

6. The method according to claim 1 , wherein the compound of formula I 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}-4-methylbenzenesulfonamide;

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-trifluoroethoxy-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;

N-{4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-7-chloro-quinazolin-6-yl}-E,4-(dimethylamino)-but-2-enamide;

N-{4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-7-chloro-quinazolin-6-yl}-acrylamide;

O-{4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-quinazolin-6-yl}-acetate;

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6-(3-oxo-butoxy)-quinazoline;

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6-[3-(4-morpholino)-propoxy]-quinazoline;

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6,7-dimethoxy-quinazoline;

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6-(4-methoxy-phenyl)-quinazoline;

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6-(3-hydroxymethyl-phenyl)-quinazoline;

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6-(3-acetoxymethyl-phenyl)-quinazoline;

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6-[3-(3-oxo-butoxymethyl)-phenyl]-quinazoline;

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6-(5-hydroxymethylfuran-2-yl)-quinazoline;

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6-(5-methanesulfonyloxymethylene-furan-2-yl)-quinazoline;

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6-(5-dimethylaminomethyl-furan-2-yl-methoxy)-quinazoline; and

4-[3-chloro-4-(3-fluorobenzyloxy)-phenylamino]-6-[3-(4-morpholino)propoxy)-7-methoxy-quinazoline.