Preventives and/or remedies for subjects with the expression or activation of her2 and/or egfr

1 . A Her2 and/or EGFR inhibitor to be administered to a subject determined to show overexpression or activation of Her2 and/or EGFR as a result of a diagnosis of the subject for the expression or activity of Her2 and/or EGFR based on a test for detecting the expression or activity of Her2 and/or EGFR.

2 . The inhibitor of claim 1 to be administered to a subject determined to show activation of Her2 and/or EGFR as a result of a diagnosis of the subject for the activity of Her2 and/or EGFR based on a test for detecting the activity of Her2 and/or EGFR.

3 . The inhibitor of claim 1 to be administered to a subject determined to show overexpression or activation of Her2 and EGFR as a result of a diagnosis of the subject for the expression or activity of Her2 and EGFR based on a test for detecting the expression or activity of Her2 and EGFR.

4 . The inhibitor of claim 3 to be administered to a subject determined to show activation of Her2 and EGFR as a result of a diagnosis of the subject for the activity of Her2 and EGFR based on a test for detecting the activity of Her2 and EGFR.

5 . The inhibitor of claim 1 , wherein the subject is a patient expected to suffer from a disease caused by overexpression or activation of Her2 and/or EGFR.

6 . The inhibitor of claim 1 , wherein the subject is a patient expected to suffer from a disease caused by overexpression or activation of Her2 and EGFR.

7 . The inhibitor of any of claim 1 , wherein the subject is a human.

8 . The inhibitor of claim 1 , wherein the test for detecting the expression or activity of Her2 and/or EGFR is an extracorporeal test.

9 . The inhibitor of claim 1 , wherein the test for detecting the expression or activity of Her2 and EGFR is an extracorporeal test.

10 . The inhibitor of claim 3 , which is a mixture of a Her2 inhibitor and an EGFR inhibitor.

11 . The inhibitor of any one of claims 1 to 9 , which is used for administering a Her2 inhibitor and/or an EGFR inhibitor simultaneously, separately or at time intervals.

12 . The inhibitor of claim 8 or 9 , wherein the extracorporeal test is an immunological method using an antibody, or a hybridization method using a nucleic acid and a nucleic acid derivative.

13 . The inhibitor of claim 12 , wherein the immunological method using an antibody is selected from the group consisting of an enzyme-linked immunosorbent assay, an enzyme-linked immunoassay, a radioimmunoassay, an immunohistochemical method and western blotting.

14 . The inhibitor of claim 12 , wherein the hybridization method using a nucleic acid and a nucleic acid derivative is selected from the group consisting of an RT-PCR method, an ISH method, a FISH method, northern blotting and southern blotting method.

15 . The inhibitor of any one of claims 1 to 14 , which is a substituted heteroaromatic compound represented by the following formula (I)

wherein X is N or CH; Y is CR 1 and V is N; or Y is N and V is CR 1 ; or Y is CR 1 and V is CR 2 ; or Y is CR 2 and V is CR 1 ; R 1 is C 1-4 alkyl, C 1-4 alkoxy, CH 3 SO 2 CH 2 CH 2 NHCH 2 —Ar— (wherein Ar is selected from phenyl, furan, thiophene, pyrrole and thiazole, each of which is optionally substituted by 1 or 2 halogens, C 1-4 alkyl or C 1-4 alkoxy on demand) or —C≡C—C(R 6 )(R 7 )(R 8 ) (wherein R 6 , R 7 and R 8 are each independently a hydrogen atom, hydroxy, halogen, C 1-4 alkyl or C 1-4 alkoxy, or C 3-6 cycloalkyl wherein the ring is optionally substituted by hydrogen atom or C 1-4 alkyl and optionally contains 1 or 2 hetero atoms selected from O, S and N therein; R 2 is selected from the group consisting of hydrogen, halogen, hydroxy, C 1-4 alkyl, C 1-4 alkoxy, C 1-4 alkylamino, di[C 1-4 alkyl]amino and —NHCO—R 9 (wherein R 9 is C 1-4 alkyl, C 1-4 alkoxy, C 2-4 alkenyl or C 2-4 alkynyl); U is phenyl, pyridyl, 3H-imidazolyl, indolyl, isoindolyl, indolinyl, isoindolinyl, 1H-indazolyl, 2,3-dihydro-1H-indazolyl, 1H-benzimidazolyl, 2,3-dihydro-1H-benzimidazolyl or 1H-benzotriazolyl group, each of which is substituted by R 3 group and optionally substituted on demand by at least one R 4 group selected independently; R 3 is selected from the group consisting of benzyl, halo-, dihalo- and trihalobenzyl, benzoyl, pyridylmethyl, pyridylmethoxy, phenoxy, benzyloxy, halo-, dihalo- and tribenzyloxy and benzenesulfonyl; or R 3 is trihalomethylbenzyl or trihalomethylbenzyloxy; or R 3 is a group of the above-mentioned formula (a) (wherein each R 5 is independently selected from halogen, C 1-4 alkyl and C 1-4 alkoxy; and n is 0-3); each R 4 is independently hydroxy, halogen, C 1-4 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-4 alkoxy, amino, C 1-4 alkylamino, di[C 1-4 alkyl]amino, C 1-4 alkylthio, C 1-4 alkylsulfinyl, C 1-4 alkylsulfonyl, C 1-4 alkylcarbonyl, carboxy, carbamoyl, C 1-4 alkoxycarbonyl, C 1-4 alkanoylamino, N-(C 1-4 alkyl)carbamoyl, N,N-di(C 1-4 alkyl)carbamoyl, cyano, nitro or trifluoromethyl, or a pharmaceutically acceptable salt thereof, a hydrate or solvate thereof, an optically active substance or a racemate thereof, or a mixture of diastereomers thereof.

16 . The inhibitor of claim 15 , which is (4-(3-fluorobenzyloxy)-phenyl)-(6-(5-((2-methanesulfonyl-ethylamino)methyl)-furan-2-yl)-pyrido[3,4-d]pyrimidin-4-yl)-amine;

(4-benzyloxyphenyl)-(6-(5-((2-methanesulfonyl-ethylamino)-methyl)-furan-2-yl)-quinazolin-4-yl)-amine;

N-{4-[(3-fluorobenzyl)oxy]phenyl }-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-}2-furyl]-4-quinazolinamine;

N-[4-(benzyloxy)phenyl]-7-methoxy-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine;

N-(1-benzyl-1H-indazol-5-yl)-7-methoxy-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)- 2-furyl]-4-quinazolinamine;

N-{3-fluoro-4-[(3-fluorobenzyl)oxy]phenyl }-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine;

N-[1-(3-fluorobenzyl)-1H-indazol-5-yl]-6-[2-({[2-(methylsulfonyl)ethyl]amino}methyl)-1,3-thiazol-4-yl]-4-quinazolinamine;

6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-N-[4-(phenylsulfonyl)phenyl]-4-quinazolinamine;

N-{3-fluoro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[2-({[2-(methylsulfonyl)ethyl]amino}methyl)-1,3-thiazol-4-yl]-4-quinazolinamine;

N-(1-benzyl-1H-indazol-5-yl)-6-[2-({[2-(methylsulfonyl)ethyl]amino}methyl)-1,3-thiazol-4-yl]-4-quinazolinamine;

N-(3-fluoro-4-benzyloxyphenyl)-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-4-furyl]-4-quinazolinamine;

N-(3-chloro-4-benzyloxyphenyl)-6-[2-({[2-(methylsulfonyl)ethyl]amino}methyl)-4-furyl]-4-quinazolinamine;

N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine;

N-(1-benzyl-1H-indazol-5-yl)-7-fluoro-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine;

N-(3-trifluoromethyl-4-benzyloxyphenyl)-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-4-furyl]-4-quinazolinamine;

N-[4-(3-chloro-4-fluorophenyl)amino-7-[3-(4-morpholinyl)propoxy]quinazolin-6-yl]acrylamide;

N-{4-[(3-chloro-4-fluorophenyl)amino]-7-[3-methyl-3-(4-methyl-1-piperazinyl)-1-butynyl]-6-quinazolinyl}acrylamide; or

N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methanesulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine, or a pharmaceutically acceptable salt thereof, a hydrate or a solvate thereof, an optically active substance or a racemate thereof, or a mixture of diastereomers thereof.

17 . The inhibitor of claim 15 , which is N-[4-(3-chloro-4-fluorophenyl)amino]-7-[3-(4-morpholinyl)propoxy]quinazolin-6-yl]acrylamide, or N-{3-chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methanesulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine or a pharmaceutically acceptable salt thereof, a hydrate or a solvate thereof, an optically active substance or a racemate thereof, or a mixture of diastereomers thereof.

18 . A pharmaceutical composition comprising an inhibitor of any one of claims 1 to 17 as an active ingredient and a pharmaceutically acceptable carrier.

19 . The pharmaceutical composition of claim 18 , which is an agent for the prophylaxis and/or treatment of a disease caused by overexpression or activation of Her2 and/or EGFR.

20 . The pharmaceutical composition of claim 19 , wherein the disease caused by the overexpression or activation of Her2 and/or EGFR is cancer, angiogenesis associated with the growth of cancer or sarcoma, angiogenesis associated with cancer metastasis, angiogenesis associated with diabetic retinopathy, arteriosclerosis or psoriasis.

21 . An agent for the prophylaxis and/or treatment of a disease caused by overexpression or activation of Her2 and/or EGFR, which is to be administered to a subject determined to show overexpression or activation of Her2 and/or EGFR as a result of a diagnosis of the subject for the expression or activity of Her2 and/or EGFR based on a test for detecting the expression or activity of Her2 and/or EGFR.

22 . The agent of claim 21 , wherein the disease caused by overexpression or activation of Her2 and/or EGFR is cancer, angiogenesis associated with the growth of cancer or sarcoma, angiogenesis associated with cancer metastasis, angiogenesis associated with diabetic retinopathy, arteriosclerosis or psoriasis.

23 . A method for the prophylaxis and/or treatment of a disease caused by overexpression or activation of Her2 and/or EGFR, which comprises administering an effective dose of a Her2 and/or an EGFR inhibitor to a subject determined to show overexpression or activation of Her2 and/or EGFR as a result of a diagnosis of the subject for the expression or activity of Her2 and/or EGFR based on a test for detecting the expression or activity of Her2 and/or EGFR.

24 . The method of claim 23 , wherein the disease caused by overexpression or activation of Her2 and/or EGFR is cancer, angiogenesis associated with the growth of cancer or sarcoma, angiogenesis associated with cancer metastasis, angiogenesis associated with diabetic retinopathy, arteriosclerosis or psoriasis.

25 . A commercial package comprising the pharmaceutical composition of any one of claims 18 to 20 and a written matter associated therewith, the written matter stating that the pharmaceutical composition can or should be used for the prophylaxis and/or treatment of a disease caused by overexpression or activation of Her2 and/or EGFR.

26 . The commercial package of claim 25 , wherein the disease caused by overexpression or activation of Her2 and/or EGFR is cancer, angiogenesis associated with the growth of cancer or sarcoma, angiogenesis associated with cancer metastasis, angiogenesis associated with diabetic retinopathy, arteriosclerosis or psoriasis.