Quinazoline compounds as kinase inhibitors

A compound having a structure represented by formula (II)

• wherein X is CH;
• Y is NH;
• wherein the heteroaryl attached to Y is selected from:
• wherein each of R5, R6, and R7, independently, is H, halo, nitro, cyano, aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, —ORa, —C(O)Ra, —C(O)NRaRb, —NRaC(O)Rb, —NRaRb, —S(O)2Ra, —S(O)2NRaRb, —NRaS(O)2Rb, —N═CRaRb, or —NRaC(O)NHRb, wherein each of Ra and Rb, independently, is H, alkyl, alkenyl, alkynyl, aryl, aryloxy, alkoxy, hydroxy, heteroaryl, cycloalkyl, heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, or Ra and Rb, together with the nitrogen atom to which they are bonded, form heteroaryl, heterocycloalkyl, or heterocycloalkenyl;
• one of R and R2 is —OH or —ORa and the other of R1 and R2 is —H, OH, or —ORa,
• R3, and R4 are independently H or —ORa, wherein Ra is alkyl.

A compound of Formula (A),

• wherein X is N;
• Y is NH:
• Z is
• or a heteroaryl selected from
• wherein each of R5, R6, and R7, independently, is H, halo, nitro, cyano, aryl, heteroaryl, alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, cycloalkenyl, heterocycloalkenyl, —ORa, —C(O)Ra, —C(O)NRaRb, —NRaC(O)Rb, —NRaRb, —S(O)2Ra, —S(O)2NRaRb, —NRaS(O)2Rb, —N═CRaRb, or —NRaC(O)NHRb, wherein each of Ra and Rb, independently, is H, alkyl, alkenyl, alkynyl, aryl, aryloxy, alkoxy, hydroxy, heteroaryl, cycloalkyl heterocycloalkyl, cycloalkenyl, or heterocycloalkenyl, or Ra and Rb, together with the nitrogen atom to which they are bonded, form heteroaryl, heterocycloalkyl, or heterocycloalkenyl;
• one of R1 and R2 is —OH or —ORa and the other of R1 and R2 is —H, OH, or —ORa,
• R3, and R4 are independently H or —ORa, wherein Ra is alkyl,
• wherein the compound is:
• 2-methoxy-4-(4-(phenylamino)quinazolin-6-yl)phenol;
• 6-(3-fluoro-4-methoxyphenyl)-N-phenylquinazolin-4-amine;
• 6-(3-methoxyphenyl)-N-phenylquinazolin-4-amine;
• 4-(4-(phenylamino)quinazolin-6-yl)phenol;
• 6-(4-aminophenyl)-N-phenylquinazolin-4-amine;
• 2-methoxy-4-(4-(phenylamino)quinazolin-6-yl)phenyl phenylcarbamate;
• 4-(4-(3-hydroxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 2-methoxy-4-(4-(phenylamino)quinazolin-6-yl)phenyl ethylcarbamate;
• 6-(4-methoxyphenyl)-N-phenylquinazolin-4-amine;
• 4-(4-(3,4-dimethoxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(3-chloro-4-fluorophenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(4-fluorophenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(4-chloro-2-fluorophenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(2-fluoro-4-methylphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 2-methoxy-4-(4-(3-(trifluoromethyl)phenylamino)quinazolin-6-yl)phenol;
• 4-(4-(4-hydroxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(2,4-difluorophenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(4-chloro-2-hydroxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 2-methoxy-4-(4-(3-methoxyphenylamino)quinazolin-6-yl)phenol;
• 4-(4-(2-hydroxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• N-(4-(4-(phenylamino)quinazolin-6-yl)phenyl)ethanesulfonamide;
• 4-(4-(3-hydroxy-4-methoxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)benzene sulfonamide;
• 4-(4-(3-hydroxy-4-methylphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 2-methoxy-4-(7-methoxy-4-(phenylamino)quinazolin-6-yl)phenol;
• 4-(4-(3-hydroxyphenylamino)-7-methoxyquinazolin-6-yl)-2-methoxyphenol;
• 3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)benzoic acid;
• 2-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)benzamide;
• 3-hydroxy-4-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)benzoic acid;
• 3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)benzamide;
• 2-methoxy-4-(4-(3-nitrophenylamino)quinazolin-6-yl)phenol;
• 4-(4-(3-aminophenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(benzo[d][1,3]dioxol-5-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(1H-indazol-6-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(1H-indol-6-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(3-hydroxy-4-methylphenylamino)-7-methoxyquinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(3-hydroxy-4-methoxyphenylamino)-7-methoxyquinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(2-chloro-5-hydroxyphenylamino)-7-methoxyquinazolin-6-yl)-2-methoxyphenol;
• N-(3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenyl)acetamide;
• 2,2,2-trifluoro-N-(3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenyl)acetamide;
• 4-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)benzenesulfonamide;
• 4-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)benzamide;
• 2-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)-4-methoxybenzoic acid;
• 3-(6-(4-hydroxyphenyl)-7-methoxyquinazolin-4-ylamino)phenol;
• 2-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)benzoic acid;
• 4-(4-(1H-indazol-4-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(3-fluorophenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)-2-methylphenol;
• 4-(4-(1H-benzo[d]imidazol-6-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(5-hydroxy-2-methoxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• N-(3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenyl)methanesulfonamide;
• 4-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)benzoic acid;
• 4-(4-(2-fluoro-5-hydroxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(2-chloro-5-hydroxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 2-chloro-3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenol;
• 2,4-dichloro-5-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenol;
• 3-(6-(4-hydroxyphenyl)quinazolin-4-ylamino)phenol;
• 3-(6-(3-hydroxyphenyl)quinazolin-4-ylamino)phenol;
• 3-(6-(4-methoxyphenyl)quinazolin-4-ylamino)phenol;
• 1,1,1-trifluoro-N-(3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenyl)methanesulfonamide;
• 4-(4-(1H-benzo[d][1,2,3]triazol-5-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• 3-(6-(3-methoxyphenyl)quinazolin-4-ylamino)phenol;
• 6-(2-fluoro-3-methoxyphenyl)-N-(1H-indazol-4-yl)quinazolin-4-amine;
• 6-(3-fluoro-4-methoxyphenyl)-N-(1H-indazol-4-yl)quinazolin-4-amine;
• 6-(3-chloro-4-methoxyphenyl)-N-(1H-indazol-4-yl)quinazolin-4-amine;
• N-(1H-indazol-4-yl)-6-(4-methoxy-2-methylphenyl)quinazolin-4-amine;
• N-(1H-indazol-4-yl)-6-(4-methoxy-3-methylphenyl)quinazolin-4-amine;
• 4-(4-(1H-benzo[d][1,2,3]triazol-4-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(1H-indol-4-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• 6-(4-fluoro-3-methoxyphenyl)-N-(1H-indazol-4-yl)quinazolin-4-amine;
• 6-(3,4-dimethoxyphenyl)-N-(1H-indazol-4-yl)quinazolin-4-amine;
• 6-(4-ethoxyphenyl)-N-(1H-indazol-4-yl)quinazolin-4-amine;
• 5-(4-(1H-indazol-4-ylamino)quinazolin-6-yl)-2-methoxybenzaldehyde;
• 2-methoxy-4-(4-(1-methyl-1H-indazol-4-ylamino)quinazolin-6-yl)phenol;
• 4-(4-(3-hydroxyphenylamino)quinolin-6-yl)-2-methoxyphenol;
• 4-(4-(2-fluoro-5-hydroxyphenylamino)quinolin-6-yl)-2-methoxyphenol;
• 4-(4-(1H-indazol-4-ylamino)quinolin-6-yl)-2-methoxyphenol;
• 6-(2,3-dimethoxyphenyl)-N-(1H-indazol-4-yl)quinazolin-4-amine;
• 6-(2-fluoro-3-methoxyphenyl)-N-(1H-indazol-4-yl)quinolin-4-amine;
• 6-(3-fluoro-4-methoxyphenyl)-N-(1H-indazol-4-yl)quinolin-4-amine;
• 6-(3,4-dimethoxyphenyl)-N-(1H-indazol-4-yl)quinolin-4-amine;
• 6-(3-chloro-4-methoxyphenyl)-N-(1H-indazol-4-yl)quinolin-4-amine;
• 5-(4-(1H-indazol-4-ylamino)quinolin-6-yl)-2-methoxybenzaldehyde;
• 4-(4-(3-(difluoromethoxy)phenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(4-(2-fluorophenylamino)quinazolin-6-yl)-2-methoxyphenol;
• N-(1H-indazol-4-yl)-6-(4-(methylsulfonyl)phenyl)quinolin-4-amine;
• N-(1H-indazol-4-yl)-6-(3-methoxyphenyl)quinolin-4-amine;
• 4-(4-(1H-indazol-4-ylamino)quinolin-6-yl)phenol;
• 4-(4-(3-chloro-1H-indazol-4-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)-1H-benzo[d]imidazol-2(3H)-one;
• N-(4-fluoro-3-(6-(4-hydroxy-3-methoxyphenyl)quinolin-4-ylamino)phenyl)methanesulfonamide;
• N-(4-fluoro-3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenyl)methanesulfonamide;
• N-(2-fluoro-5-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenyl)methanesulfonamide;
• 4-(4-(1H-indazol-4-ylamino)quinazolin-6-yl)phenol;
• 3-(6-phenylquinazolin-4-ylamino)phenol;
• 4-(4-(2,6-difluorophenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 4-(1H-indazol-4-ylamino)-6-(4-hydroxy-3-methoxyphenyl)quinoline-3-carbonitrile;
• 4-(4-(5-fluoro-1H-indazol-4-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• N-(4-chloro-3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenyl)methanesulfonamide;
• N-(2-chloro-5-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenyl)methanesulfonamide;
• N-(2-chloro-5-(6-(4-hydroxy-3-methoxyphenyl)quinolin-4-ylamino)phenyl)methanesulfonamide;
• 3-(4-(1H-indazol-4-ylamino)quinazolin-6-yl)phenol;
• N-(1H-indazol-4-yl)-6-(3-methoxyphenyl)quinazolin-4-amine;
• N-(2-fluoro-5-(6-(4-hydroxy-3-methoxyphenyl)quinolin-4-ylamino)phenyl)methanesulfonamide;
• N-(1H-indazol-4-yl)-6-(3-methoxyphenyl)quinolin-4-amine;
• N-(1H-indazol-4-yl)-6-(4-methoxyphenyl)quinazolin-4-amine;
• 3-(4-(1H-indazol-4-ylamino)quinolin-6-yl)phenol;
• 4-(4-(5-fluoro-1H-indazol-4-ylamino)quinazolin-6-yl)-2-methoxyphenol;
• N-(2,4-difluoro-5-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenyl)methanesulfonamide;
• N-(3-ethynylphenyl)-6-(4-methoxyphenyl)quinazolin-4-amine;
• 3-(6-(4-methoxyphenyl)quinazolin-4-yloxy)phenol;
• 4-(4-(5-hydroxy-2-methylphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 2-methoxy-4-(4-(5-methyl-1H-indazol-4-ylamino)quinazolin-6-yl)phenol;
• 4-fluoro-5-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)-2-methylphenol;
• 4-(4-(4-chloro-3-hydroxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 2,4-difluoro-5-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenol;
• 2-chloro-4-fluoro-5-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenol;
• 5-(6-(4-chlorophenyl)quinazolin-4-ylamino)-2,4-difluorophenol;
• 4-(4-(4-fluoro-3-hydroxyphenylamino)quinazolin-6-yl)-2-methoxyphenol;
• 2,6-difluoro-3-(6-(4-hydroxy-3-methoxyphenyl)quinazolin-4-ylamino)phenol;
• 3-(6-(1H-indazol-5-yl)quinazolin-4-ylamino)-2,6-difluorophenol;
• or
• 3-(6-(4-chlorophenyl)quinazolin-4-ylamino)-2,6-difluorophenol.