JP2000508657A - チロシンキナーゼの不可逆的阻害剤 - Google Patents
チロシンキナーゼの不可逆的阻害剤Info
- Publication number
- JP2000508657A JP2000508657A JP9537173A JP53717397A JP2000508657A JP 2000508657 A JP2000508657 A JP 2000508657A JP 9537173 A JP9537173 A JP 9537173A JP 53717397 A JP53717397 A JP 53717397A JP 2000508657 A JP2000508657 A JP 2000508657A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- amide
- phenylamino
- quinazolin
- pyrido
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 title claims abstract description 19
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 title claims abstract description 19
- 239000003112 inhibitor Substances 0.000 title abstract description 18
- 230000002427 irreversible effect Effects 0.000 title abstract description 16
- 150000001875 compounds Chemical class 0.000 claims abstract description 164
- 238000000034 method Methods 0.000 claims abstract description 47
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 43
- 208000037803 restenosis Diseases 0.000 claims abstract description 25
- 201000011510 cancer Diseases 0.000 claims abstract description 19
- 201000004681 Psoriasis Diseases 0.000 claims abstract description 15
- 201000001320 Atherosclerosis Diseases 0.000 claims abstract description 11
- 201000009273 Endometriosis Diseases 0.000 claims abstract description 11
- -1 C1-C6Perfluo Loalkyl Chemical group 0.000 claims description 331
- 150000001408 amides Chemical class 0.000 claims description 167
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 151
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 118
- 239000002253 acid Substances 0.000 claims description 102
- 125000004547 quinazolin-6-yl group Chemical group N1=CN=CC2=CC(=CC=C12)* 0.000 claims description 91
- 229910052739 hydrogen Inorganic materials 0.000 claims description 86
- 239000001257 hydrogen Substances 0.000 claims description 86
- 239000000460 chlorine Substances 0.000 claims description 80
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 79
- 125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 claims description 74
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 55
- 239000000203 mixture Substances 0.000 claims description 55
- 150000002431 hydrogen Chemical class 0.000 claims description 44
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 40
- 229910052736 halogen Inorganic materials 0.000 claims description 40
- 150000002367 halogens Chemical class 0.000 claims description 40
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 36
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 24
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 23
- XVOUMQNXTGKGMA-UHFFFAOYSA-N glutaconic acid Chemical compound OC(=O)CC=CC(O)=O XVOUMQNXTGKGMA-UHFFFAOYSA-N 0.000 claims description 23
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
- QHFKHIQMXKHBKV-UHFFFAOYSA-N 7-(dimethylamino)-4,4-difluorohept-2-enoic acid Chemical compound CN(C)CCCC(F)(F)C=CC(O)=O QHFKHIQMXKHBKV-UHFFFAOYSA-N 0.000 claims description 16
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 15
- 229910052731 fluorine Inorganic materials 0.000 claims description 15
- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 14
- 150000002148 esters Chemical class 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 239000000651 prodrug Substances 0.000 claims description 13
- 229940002612 prodrug Drugs 0.000 claims description 13
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 12
- ROFBGEBOZYQKEF-UHFFFAOYSA-N 8-(dimethylamino)-4,4-difluorooct-2-enoic acid Chemical compound CN(C)CCCCC(F)(F)C=CC(O)=O ROFBGEBOZYQKEF-UHFFFAOYSA-N 0.000 claims description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 230000005764 inhibitory process Effects 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 9
- YKROIMGVWWTHPL-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N1=CN=C2C=NC(N)=CC2=C1NC1=CC=C(F)C(Cl)=C1 YKROIMGVWWTHPL-UHFFFAOYSA-N 0.000 claims description 9
- JYIZGZWUTAZSBA-UHFFFAOYSA-N 5-morpholin-4-ylpent-2-ynoic acid Chemical compound OC(=O)C#CCCN1CCOCC1 JYIZGZWUTAZSBA-UHFFFAOYSA-N 0.000 claims description 9
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
- KWEDUNSJJZVRKR-UHFFFAOYSA-N carbononitridic azide Chemical compound [N-]=[N+]=NC#N KWEDUNSJJZVRKR-UHFFFAOYSA-N 0.000 claims description 9
- 239000011737 fluorine Substances 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 229910052801 chlorine Chemical group 0.000 claims description 8
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 8
- 125000002950 monocyclic group Chemical group 0.000 claims description 8
- 239000005483 tyrosine kinase inhibitor Substances 0.000 claims description 8
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 claims description 8
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 7
- HJAGRTPTIMMQPY-UHFFFAOYSA-N 4-n-(3-chloro-4-fluorophenyl)quinazoline-4,6-diamine Chemical compound C12=CC(N)=CC=C2N=CN=C1NC1=CC=C(F)C(Cl)=C1 HJAGRTPTIMMQPY-UHFFFAOYSA-N 0.000 claims description 6
- RRKPTFVGWKHCJO-UHFFFAOYSA-N 5-imidazol-1-ylpent-2-ynoic acid Chemical compound OC(=O)C#CCCN1C=CN=C1 RRKPTFVGWKHCJO-UHFFFAOYSA-N 0.000 claims description 6
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 6
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
- 239000006187 pill Substances 0.000 claims description 5
- 229940124530 sulfonamide Drugs 0.000 claims description 5
- DEDFTIYIQKMIGJ-UHFFFAOYSA-N 4-N-(1-phenylethyl)pyrido[3,4-d]pyrimidine-4,6-diamine Chemical compound N=1C=NC2=CN=C(N)C=C2C=1NC(C)C1=CC=CC=C1 DEDFTIYIQKMIGJ-UHFFFAOYSA-N 0.000 claims description 4
- MBOVYSREMPLTQZ-UHFFFAOYSA-N CN(C)CCCN.NC(C=C12)=CC=C1N=CN=C2NC(C=C1Cl)=CC=C1F Chemical compound CN(C)CCCN.NC(C=C12)=CC=C1N=CN=C2NC(C=C1Cl)=CC=C1F MBOVYSREMPLTQZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- UGKRCKRGEISAKC-UHFFFAOYSA-N n-[4-(3-bromoanilino)pyrido[3,4-d]pyrimidin-6-yl]-2-methylprop-2-enamide Chemical compound N1=CN=C2C=NC(NC(=O)C(=C)C)=CC2=C1NC1=CC=CC(Br)=C1 UGKRCKRGEISAKC-UHFFFAOYSA-N 0.000 claims description 4
- OLYVUTGQXNIQQG-UHFFFAOYSA-N n-[4-(3-bromoanilino)pyrido[3,4-d]pyrimidin-6-yl]prop-2-enamide Chemical compound BrC1=CC=CC(NC=2C3=CC(NC(=O)C=C)=NC=C3N=CN=2)=C1 OLYVUTGQXNIQQG-UHFFFAOYSA-N 0.000 claims description 4
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 claims description 4
- FQBVFXSRGBEWNP-RKMMXNITSA-N (1Z)-1-[(E)-[4-(3-bromophenyl)iminoquinazolin-6-ylidene]amino]buta-1,3-dien-1-ol Chemical compound C=C/C=C(/N=C/1\C=CC2=NC=NC(=NC3=CC(=CC=C3)Br)C2=C1)\O FQBVFXSRGBEWNP-RKMMXNITSA-N 0.000 claims description 3
- GDVYZGMAXSNLGM-OWOJBTEDSA-N (e)-3-chloroprop-2-enamide Chemical compound NC(=O)\C=C\Cl GDVYZGMAXSNLGM-OWOJBTEDSA-N 0.000 claims description 3
- DQNQKAFBQJVRTG-UHFFFAOYSA-N CC(C1=CC=CC=C1)NC(C1=C2)=NC=NC1=CC=C2N.NCCCCN1C=NC=C1 Chemical compound CC(C1=CC=CC=C1)NC(C1=C2)=NC=NC1=CC=C2N.NCCCCN1C=NC=C1 DQNQKAFBQJVRTG-UHFFFAOYSA-N 0.000 claims description 3
- SGKJBBKCSQJVIH-UHFFFAOYSA-N CN1CCN(CC1)C(C#CC(=O)O)C Chemical compound CN1CCN(CC1)C(C#CC(=O)O)C SGKJBBKCSQJVIH-UHFFFAOYSA-N 0.000 claims description 3
- BVMWIXWOIGJRGE-UHFFFAOYSA-N NP(O)=O Chemical compound NP(O)=O BVMWIXWOIGJRGE-UHFFFAOYSA-N 0.000 claims description 3
- 239000007983 Tris buffer Substances 0.000 claims description 3
- LDHQCZJRKDOVOX-NSCUHMNNSA-N crotonic acid Chemical compound C\C=C\C(O)=O LDHQCZJRKDOVOX-NSCUHMNNSA-N 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- OYRRZWATULMEPF-UHFFFAOYSA-N pyrimidin-4-amine Chemical compound NC1=CC=NC=N1 OYRRZWATULMEPF-UHFFFAOYSA-N 0.000 claims description 3
- 150000003456 sulfonamides Chemical class 0.000 claims description 3
- APEJMQOBVMLION-VOTSOKGWSA-N trans-cinnamamide Chemical compound NC(=O)\C=C\C1=CC=CC=C1 APEJMQOBVMLION-VOTSOKGWSA-N 0.000 claims description 3
- PCRKFWDIMUJRAW-DUXPYHPUSA-N (e)-n-[4-(3-bromoanilino)pyrido[3,4-d]pyrimidin-6-yl]but-2-enamide Chemical compound N1=CN=C2C=NC(NC(=O)/C=C/C)=CC2=C1NC1=CC=CC(Br)=C1 PCRKFWDIMUJRAW-DUXPYHPUSA-N 0.000 claims description 2
- JPHUTKJINPEEPQ-DUXPYHPUSA-N (e)-n-[4-(3-bromoanilino)quinazolin-6-yl]but-2-enamide Chemical compound C12=CC(NC(=O)/C=C/C)=CC=C2N=CN=C1NC1=CC=CC(Br)=C1 JPHUTKJINPEEPQ-DUXPYHPUSA-N 0.000 claims description 2
- MPRUXYYTYPLCAL-UHFFFAOYSA-N 2-(4-methylpiperazin-1-yl)ethyl 5-[[4-(3-bromoanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-5-oxopent-3-enoate Chemical compound C1CN(C)CCN1CCOC(=O)CC=CC(=O)NC(N=CC1=NC=N2)=CC1=C2NC1=CC=CC(Br)=C1 MPRUXYYTYPLCAL-UHFFFAOYSA-N 0.000 claims description 2
- CHAURNBMHQWZQC-UHFFFAOYSA-N 2-imidazol-1-ylethyl 5-[[4-(3-chloro-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-5-oxopent-3-enoate Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CN=C2NC(=O)C=CCC(=O)OCCN1C=NC=C1 CHAURNBMHQWZQC-UHFFFAOYSA-N 0.000 claims description 2
- OQUVFQFGEKAJGD-UHFFFAOYSA-N 2-morpholin-4-ylethyl 5-[[4-(3-chloro-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-5-oxopent-3-enoate Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CN=C2NC(=O)C=CCC(=O)OCCN1CCOCC1 OQUVFQFGEKAJGD-UHFFFAOYSA-N 0.000 claims description 2
- GVOAYRZCKFVXQR-UHFFFAOYSA-N 4,4-difluoro-7-morpholin-4-yl-n-[4-(1-phenylethylamino)quinazolin-6-yl]hept-2-enamide Chemical compound C=1C=CC=CC=1C(C)NC(C1=C2)=NC=NC1=CC=C2NC(=O)C=CC(F)(F)CCCN1CCOCC1 GVOAYRZCKFVXQR-UHFFFAOYSA-N 0.000 claims description 2
- UCYLNNOFRVPIKP-UHFFFAOYSA-N 4,4-difluoro-7-morpholin-4-ylhept-2-enoic acid Chemical compound OC(=O)C=CC(F)(F)CCCN1CCOCC1 UCYLNNOFRVPIKP-UHFFFAOYSA-N 0.000 claims description 2
- MADHKJASELWHCT-UHFFFAOYSA-N 5-[[4-(3-chloro-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]amino]-5-oxopent-3-enoic acid Chemical compound N1=CN=C2C=NC(NC(=O)C=CCC(=O)O)=CC2=C1NC1=CC=C(F)C(Cl)=C1 MADHKJASELWHCT-UHFFFAOYSA-N 0.000 claims description 2
- KLDUXDFAXMMTEL-UHFFFAOYSA-N 7-imidazol-1-ylhept-2-enoic acid Chemical compound N1(C=NC=C1)CCCCC=CC(=O)O KLDUXDFAXMMTEL-UHFFFAOYSA-N 0.000 claims description 2
- JSMMEWSCFUNLLJ-UHFFFAOYSA-N CC(C1=CC=CC=C1)NC(C1=C2)=NC=NC1=CN=C2N.NCCCCN1C=NC=C1 Chemical compound CC(C1=CC=CC=C1)NC(C1=C2)=NC=NC1=CN=C2N.NCCCCN1C=NC=C1 JSMMEWSCFUNLLJ-UHFFFAOYSA-N 0.000 claims description 2
- UAUPGXZLERMBCC-UHFFFAOYSA-N CN(C)CCCN.NC(C=C12)=CC=C1N=CN=C2NC1=CC=CC(Br)=C1 Chemical compound CN(C)CCCN.NC(C=C12)=CC=C1N=CN=C2NC1=CC=CC(Br)=C1 UAUPGXZLERMBCC-UHFFFAOYSA-N 0.000 claims description 2
- LHXKDABTJCUTTN-UHFFFAOYSA-N CN(C)CCCN.NC1=CC2=C(NC3=CC=CC(Br)=C3)N=CN=C2C=N1 Chemical compound CN(C)CCCN.NC1=CC2=C(NC3=CC=CC(Br)=C3)N=CN=C2C=N1 LHXKDABTJCUTTN-UHFFFAOYSA-N 0.000 claims description 2
- JXCWZUONVRULJC-UHFFFAOYSA-N NCCCN1C=NC=C1.NC(C=C12)=CC=C1N=CN=C2NC1=CC=CC(Br)=C1 Chemical compound NCCCN1C=NC=C1.NC(C=C12)=CC=C1N=CN=C2NC1=CC=CC(Br)=C1 JXCWZUONVRULJC-UHFFFAOYSA-N 0.000 claims description 2
- NQVHELJXYAFNRV-UHFFFAOYSA-N ethyl 4-amino-4-oxobut-2-enoate Chemical compound CCOC(=O)C=CC(N)=O NQVHELJXYAFNRV-UHFFFAOYSA-N 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 2
- BWMCLQKGZYSIQG-UHFFFAOYSA-N n-(3-bromophenyl)-6-(5-morpholin-4-ylpent-1-enylsulfonyl)pyrido[3,4-d]pyrimidin-4-amine Chemical compound BrC1=CC=CC(NC=2C3=CC(=NC=C3N=CN=2)S(=O)(=O)C=CCCCN2CCOCC2)=C1 BWMCLQKGZYSIQG-UHFFFAOYSA-N 0.000 claims description 2
- YXCOROLRANQGRV-UHFFFAOYSA-N n-(3-bromophenyl)-6-[2-[4-(4-methylpiperazin-1-yl)butylamino]ethenylsulfonyl]pyrido[3,4-d]pyrimidin-4-amine Chemical compound C1CN(C)CCN1CCCCNC=CS(=O)(=O)C(N=CC1=NC=N2)=CC1=C2NC1=CC=CC(Br)=C1 YXCOROLRANQGRV-UHFFFAOYSA-N 0.000 claims description 2
- BERMKBBVKIVRJO-UHFFFAOYSA-N n-(3-chloro-4-fluorophenyl)-6-[2-[4-(4-methylpiperazin-1-yl)butylamino]ethylsulfonyl]quinazolin-4-amine Chemical compound C1CN(C)CCN1CCCCNCCS(=O)(=O)C1=CC=C(N=CN=C2NC=3C=C(Cl)C(F)=CC=3)C2=C1 BERMKBBVKIVRJO-UHFFFAOYSA-N 0.000 claims description 2
- DKBAOZZHNYPUBZ-UHFFFAOYSA-N n-[4-(3-bromoanilino)-7-[4-(dimethylamino)butoxy]quinazolin-6-yl]prop-2-enamide Chemical compound C=12C=C(NC(=O)C=C)C(OCCCCN(C)C)=CC2=NC=NC=1NC1=CC=CC(Br)=C1 DKBAOZZHNYPUBZ-UHFFFAOYSA-N 0.000 claims description 2
- IRYRQLCQMYKEJF-UHFFFAOYSA-N n-[4-(3-bromoanilino)pyrido[3,4-d]pyrimidin-6-yl]-4,4-difluoro-7-morpholin-4-ylhept-2-enamide Chemical compound C=1C2=C(NC=3C=C(Br)C=CC=3)N=CN=C2C=NC=1NC(=O)C=CC(F)(F)CCCN1CCOCC1 IRYRQLCQMYKEJF-UHFFFAOYSA-N 0.000 claims description 2
- RCWLMTHCAVCUFY-UHFFFAOYSA-N n-[4-(3-bromoanilino)pyrido[3,4-d]pyrimidin-6-yl]-n-methylprop-2-enamide Chemical compound N1=CN=C2C=NC(N(C(=O)C=C)C)=CC2=C1NC1=CC=CC(Br)=C1 RCWLMTHCAVCUFY-UHFFFAOYSA-N 0.000 claims description 2
- DECUBVXBHCLQNY-UHFFFAOYSA-N n-[4-(3-bromoanilino)pyrido[3,4-d]pyrimidin-6-yl]ethenesulfonamide Chemical compound BrC1=CC=CC(NC=2C3=CC(NS(=O)(=O)C=C)=NC=C3N=CN=2)=C1 DECUBVXBHCLQNY-UHFFFAOYSA-N 0.000 claims description 2
- OMYOVWAUIIJSPG-UHFFFAOYSA-N n-[4-(3-bromoanilino)pyrido[3,4-d]pyrimidin-6-yl]prop-2-ynamide Chemical compound BrC1=CC=CC(NC=2C3=CC(NC(=O)C#C)=NC=C3N=CN=2)=C1 OMYOVWAUIIJSPG-UHFFFAOYSA-N 0.000 claims description 2
- FUWHUKWESOYWPK-UHFFFAOYSA-N n-[4-(3-bromoanilino)pyrido[4,3-d]pyrimidin-7-yl]-n-(3-morpholin-4-ylpropyl)prop-2-enamide Chemical compound BrC1=CC=CC(NC=2C3=CN=C(C=C3N=CN=2)N(CCCN2CCOCC2)C(=O)C=C)=C1 FUWHUKWESOYWPK-UHFFFAOYSA-N 0.000 claims description 2
- LBTKBOXSMBAAAQ-UHFFFAOYSA-N n-[4-(3-bromoanilino)pyrido[4,3-d]pyrimidin-7-yl]prop-2-enamide Chemical compound BrC1=CC=CC(NC=2C3=CN=C(NC(=O)C=C)C=C3N=CN=2)=C1 LBTKBOXSMBAAAQ-UHFFFAOYSA-N 0.000 claims description 2
- WAIUKOGAHBATEN-UHFFFAOYSA-N n-[4-(3-bromoanilino)quinazolin-6-yl]-4,4-difluoro-7-morpholin-4-ylhept-2-enamide Chemical compound C=1C=C2N=CN=C(NC=3C=C(Br)C=CC=3)C2=CC=1NC(=O)C=CC(F)(F)CCCN1CCOCC1 WAIUKOGAHBATEN-UHFFFAOYSA-N 0.000 claims description 2
- QSLXJIOCLJPHTB-UHFFFAOYSA-N n-[4-(3-bromoanilino)quinazolin-6-yl]-4,4-difluoro-8-morpholin-4-yloct-2-enamide Chemical compound C=1C=C2N=CN=C(NC=3C=C(Br)C=CC=3)C2=CC=1NC(=O)C=CC(F)(F)CCCCN1CCOCC1 QSLXJIOCLJPHTB-UHFFFAOYSA-N 0.000 claims description 2
- FZFZJPJZBIPWBC-UHFFFAOYSA-N n-[4-(3-bromoanilino)quinazolin-6-yl]-5-(4-methylpiperazin-1-yl)pent-2-ynamide Chemical compound C1CN(C)CCN1CCC#CC(=O)NC1=CC=C(N=CN=C2NC=3C=C(Br)C=CC=3)C2=C1 FZFZJPJZBIPWBC-UHFFFAOYSA-N 0.000 claims description 2
- UANMHGQOMLCKBI-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]-5-imidazol-1-ylpent-2-ynamide Chemical compound C1=C(Cl)C(F)=CC=C1NC(C1=C2)=NC=NC1=CN=C2NC(=O)C#CCCN1C=NC=C1 UANMHGQOMLCKBI-UHFFFAOYSA-N 0.000 claims description 2
- FOYSJZHYJSDHFX-UHFFFAOYSA-N n-[4-(3-chloro-4-fluoroanilino)pyrido[3,4-d]pyrimidin-6-yl]-n-methylprop-2-enamide Chemical compound N1=CN=C2C=NC(N(C(=O)C=C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 FOYSJZHYJSDHFX-UHFFFAOYSA-N 0.000 claims description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000003566 phosphorylation assay Methods 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229920002643 polyglutamic acid Polymers 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
- 229920001451 polypropylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
- 229960004063 propylene glycol Drugs 0.000 description 1
- HCJTYESURSHXNB-UHFFFAOYSA-N propynamide Chemical compound NC(=O)C#C HCJTYESURSHXNB-UHFFFAOYSA-N 0.000 description 1
- UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
- 238000001243 protein synthesis Methods 0.000 description 1
- 230000001185 psoriatic effect Effects 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- PLZDHJUUEGCXJH-UHFFFAOYSA-N pyrido[4,3-d]pyrimidine Chemical group C1=NC=C2C=NC=CC2=N1 PLZDHJUUEGCXJH-UHFFFAOYSA-N 0.000 description 1
- 229940048084 pyrophosphate Drugs 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 108091006082 receptor inhibitors Proteins 0.000 description 1
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 1
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 239000013037 reversible inhibitor Substances 0.000 description 1
- 102220240796 rs553605556 Human genes 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000008054 signal transmission Effects 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 208000000587 small cell lung carcinoma Diseases 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical compound [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
- 229910000080 stannane Inorganic materials 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 125000004963 sulfonylalkyl group Chemical group 0.000 description 1
- OBTWBSRJZRCYQV-UHFFFAOYSA-N sulfuryl difluoride Chemical compound FS(F)(=O)=O OBTWBSRJZRCYQV-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229910052714 tellurium Inorganic materials 0.000 description 1
- PORWMNRCUJJQNO-UHFFFAOYSA-N tellurium atom Chemical compound [Te] PORWMNRCUJJQNO-UHFFFAOYSA-N 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical compound C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 230000002885 thrombogenetic effect Effects 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000006208 topical dosage form Substances 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000014616 translation Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- 231100000588 tumorigenic Toxicity 0.000 description 1
- 230000000381 tumorigenic effect Effects 0.000 description 1
- 229940070710 valerate Drugs 0.000 description 1
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 1
- 210000004509 vascular smooth muscle cell Anatomy 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910000166 zirconium phosphate Inorganic materials 0.000 description 1
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
- C07D239/94—Nitrogen atoms
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- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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Abstract
Description
Claims (1)
- 【特許請求の範囲】 1.式I [式中、Xは−D−E−FでありそしてYは-SR4、-OR4、-NHR3または水素で あるか、またはXは-SR4、-OR4、-NHR3または水素でありそしてYは−D−E− Fであり; R1は水素、ハロゲンまたはC1-C6アルキルであり; R2、R3およびR4は独立して、水素、C1-C6アルキル、 −(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジニル、−(CH2)n−N1−ピ ペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N−ピロリジル、−(CH2)n −N−ピリジニル、−(CH2)n−N−イミダゾイル、−(CH2)n−イミダゾイル、− (CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ、−(CH2)n−N−ヘキ サヒドロアゼピンまたは置換され 択され、AおよびBは独立して、水素、C1-C6アルキル、−(CH2)nOH、−(CH2)n −N−ピペリジニル、−(CH2)n−N−ピペラジニル、−(CH2)n−N1−ピペラジ ニル[N4−(C1-C6)アルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−N− ピリジル、−(CH2)n−イミダゾイル、または−(CH2)n−N−イミダゾイルであり ; Z1、Z2またはZ3は独立して、水素、ハロゲン、C1-C6アルキル、C3-C8シクロア ルキル、C1-C6アルコキシ、C3-C8シクロアルコキシ、ニトロ、C1-C6ペルフルオ ロアルキル、ヒドロキシ、C1-C6アシルオキシ、-NH2、−NH(C1-C6アルキル) 、−N(C1-C6アルキル)2、−NH(C3-C8シクロアルキル)、−N(C3-C8シクロ アルキル)2、ヒドロキシメチル、C1-C6アシル、シアノ、アジド、C1-C6チオアル キル、C1-C6スルフィニルアルキル、C1-C6スルホニルアルキル、C3-C8チオシク ロアルキル、C3-C8スルフィニルシクロアルキル、C3-C8スルホニルシクロアルキ ル、メルカ プト、C1-C6アルコキシカルボニル、C3-C8シクロアルコキシカルボニル、C2-C4 アルケニル、C4-C8シクロアルケニル、またはC2-C4アルキニルであり; R5は水素、ハロゲン、C1-C6ペルフルオロアルキル、1,1−ジフルオロ(C1-C6 )アルキル、C1-C6アルキル、−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピ ペラジニル、−(CH2)n−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N −ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N−イミダゾイル、−(CH2)n −N−モルホリノ、−(CH2)n−N−ヘキサヒドロアゼピン、−(CH2)n-NH2、-(CH2)n-NH(C1-C6アルキル)、−( CH2)n−N(C1-C6アルキル)2、−1−オキソ(C1-C6アルキル)、カルボキシ、(C1 -C6)アルキルオキシカルボニル、N−(C1-C6)アルキルカルバモイル、フェ ニルまたは置換フェニルであり、ここで置換フェニルはZ1、Z2、Z3または単環式 ヘテロアリール基から独立して選択される1〜3個の置換基を有することができ 、そしてそれぞれのC1-C6アルキル基は-OH、-NH2または-NAB(ここでAおよびB は前述の定義を有する)で置換されることができ; R6は水素またはC1-C6アルキルであり;そして nは1〜4、pは0または1である]で表される化合物およびその医薬的に 許容し得る塩、エステル、アミド並びにそのプロドラッグ。 2.Z1およびZ2が水素でありそしてZ3がハロゲンである請求項1記載の化合物。 3.Z3が臭素である請求項2記載の化合物。 4.その臭素がフェニル環の3位またはメタ位に存在する請求項3記載の化合物 。 5.Z1が水素であり、Z2がFでありそしてZ3がClである請求項1記載の化 合物。 6.フッ素がフェニル環の4位にありそして塩素がフェニル環の3位にある請求 項5記載の化合物。 7.Xが でありそしてYが水素であるか、またはXが水素でありそしてYが である請求項1記載の化合物。 8.Yが−D−E−Fでありそして−D−E−Fは である請求項1記載の化合物。 9.Xが−D−E−Fでありそして−D−E−Fは である請求項1記載の化合物。 10.R2が水素である請求項8記載の化合物。 11.R2が水素である請求項9記載の化合物。 12.R2が−(CH2)n−モルホリノである請求項8記載の化合物。 13.R2が−(CH2)n−モルホリノである請求項9記載の化合物。 14.R5がカルボキシ、(C1-C6)アルキルオキシカルボニルまたはC1-C6アルキル である請求項8記載の化合物。 15.Yが−D−E−FでありそしてXが−O(CH2)n−モルホリノである請求項1 記載の化合物。 16.Yが−D−E−FでありそしてXが−O(CH2)n−N1−ピペラジニル[N4− (C1-C6)アルキル]である請求項1記載の化合物。 17.Yが−D−E−FでありそしてXが−O(CH2)n−イミダゾイルである請求項 1記載の化合物。 18.式II [式中Qは Xは−D−E−Fであり、そしてYは-SR4、-OR4、-NHR3または水素であるか 、またはxは-SR4、-OR4、-NHR3または水素であり、そしてYは−D−E−Fで あり; R1は水素、ハロゲンまたはC1-C6アルキルであり; R2、R3およびR4は独立して、水素、C1-C6アルキル、−(CH2)n−N−ピペリジ ニル、−(CH2)n−N−ピペラジニル、−(CH2)n−N1−ピペラジニル[N4−(C1 -C6)アルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−ピリジニル、−(CH2)n −N−イミダゾイル、−(CH2)n−イミダゾイル、−(CH2)n−N−モルホリノ、 −(CH2)n−N−チオモルホリノ、−(CH2)n−N−ヘキサヒドロアゼピンまたは置 換されたC1-C6ア AおよびBは独立して、水素、C1-C6アルキル、−(CH2)nOH、−(CH2)n−N−ピ ペリジニル、−(CH2)n−N−ピペラジニル、−(CH2)n−N1−ピペラジニル[N4 −(C1-C6)アルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−N−ピリジル 、−(CH2)n−イミダゾイル、または−(CH2)n−N−イミダゾイルであり; E1、E2またはE3は独立して、ハロゲン、C1-C6アルキル、C3-C8シクロアルキル 、C1-C6アルコキシ、C3-C8シクロアルコキシ、ニトロ、C1-C6ペルフルオロアル キル、ヒドロキシ、C1-C6アシルオキシ、-NH2、-NH(C1-C6アルキル)、−N(C1 -C6アルキル)2、-NH(C3−C8シクロアルキル)、−N(C3−C8シクロアルキ ル)2、ヒドロキシメチル、C1-C6アシル、シアノ、アジド、C1-C6チオアルキル 、C1-C6スルフィニルアルキル、C1-C6スルホニルアルキル、C3-C8チオシクロア ルキル、C3-C8スルフィニルシクロアルキル、C3-C8スルホニルシクロアルキル、 メルカプト、C1-C6アルコキシカルボニル、C3-C8シクロアルコキシカルボニル、 C2-C4アルケニル、C4-C8シクロアルケニル、またはC2-C4アルキニルであり; R5は水素、ハロゲン、C1-C6ペルフルオロアルキル、1,1−ジフルオロ(C1-C6 )アルキル、C1-C6アルキル、−(CH2)n−N−ピペリジニル、 −(CH2)n−ピペラジニル、−(CH2)n−ピペラジニル[N4−(C1-C6)アルキル] 、−(CH2)n−N−ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N−イミダゾ イル、−(CH2)n−N−モルホリノ、−(CH2)n− N−ヘキサヒドロアゼピン、−(CH2)n−NH2、−(CH2)n−NH(C1-C6アルキル)、 −(CH2)n−N(C1-C6アルキル)2、−1−オキソ(C1-C6アルキル)、カルボキシ、( C1-C6)アルキルオキシカルボニル、N−(C1-C6)アルキルカルバモイル、フェ ニルまたは置換フェニルであり、ここで置換フェニルはZ1、Z2、Z3または単環式 ヘテロアリール基から独立して選択される1〜3個の置換基を有することができ 、そしてそれぞれのC1-C6アルキル基は-OH、-NH2または-NAB(ここでAおよびB は前述の定義を有する)で置換されることができ; R6は水素またはC1-C6アルキルであり;そして nは1〜4、pは0または1である]で表される化合物およびその医薬的に 許容し得る塩、エステル、アミド並びにそのプロドラッグ。 19.E1およびE2が水素でありそしてE3がハロゲンである請求項18記載の化合物。 20.ハロゲンは臭素である請求項19記載の化合物。 21.その臭素はフェニル環の3位またはメタ位に存在する請求項20記載の化合物 。 22.Qが である請求項18記載の化合物。 23.Qが である請求項18記載の化合物。 24.Qが である請求項18記載の化合物。 25.Qが である請求項18記載の化合物。 26.Xが である請求項23記載の化合物。 27.Xが である請求項24記載の化合物。 28.Xが である請求項24記載の化合物。 29.Xが でありそしてYが水素である請求項22記載の化合物。 30.式III [式中Qは Xは−D−E−Fであり、そしてYは-OR4、-NHR3または水素であるか、また はXは-OR4、-NHR3または水素であり、そしてYは−D−E−Fであり; R1は水素、ハロゲンまたはC1-C6アルキルであり; R2、R3およびR4は独立して、水素、C1-C6アルキル、−(CH2)n−N−ピペリジ ニル、-(CH2)n−N−ピペラジニル、−(CH2)n−N1−ピペラジニル[N4−(C1-C6 )アルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−ピリジニル、−(CH2)n− N−イミダゾイル、−(CH2)n−イミダゾイル、−(CH2)n−N−モルホリノ、−(C H2)n−N−チオモルホリノ、−(CH2)n−N−ヘキサヒドロアゼピンまたは置換さ れたC1-C6アルキル びBは独立して、水素、C1-C6アルキル、−(CH2)nOH、−(CH2)n−N−ピペリジ ニル、−(CH2)n−N−ピペラジニル、−(CH2)n−N1−ピペラジニル[N4−(C1- C6)アルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−N−ピリジル、−(CH2)n −イミダゾイル、または−(CH2)n−N−イミダゾイルであり; E1、E2またはE3は独立して、ハロゲン、C1-C6アルキル、C3-C8シクロアルキル 、C1-C6アルコキシ、C3-C8シクロアルコキシ、ニトロ、C1-C6 ペルフルオロアルキル、ヒドロキシ、C1-C6アシルオキシ、−NH2、−NH(C1-C6ア ルキル)、−N(C1-C6アルキル)2、−NH(C3-C8シクロアルキル)、−N(C3-C8シク ロアルキル)2、ヒドロキシメチル、C1-C6アシル、シアノ、アジド、C1-C6チオ アルキル、C1-C6スルフィニルアルキル、C1-C6スルホニルアルキル、C3-C8チオ シクロアルキル、C3-C8スルフィニルシクロアルキル、C3-C8スルホニルシクロア ルキル、メルカプト、C1-C6アルコキシカルボニル、C3-C8シクロアルコキシカル ボニル、C2-C4アルケニル、C4-C8シクロアルケニルまたはC2-C4アルキニルであ り; R5は水素、ハロゲン、C1-C6ペルフルオロアルキル、1,1−ジフルオロ(C1-C6 )アルキル、C1-C6アルキル、−(CH2)n−N−ピペリジニル、−(CH2)n−ピペラ ジニル、−(CH2)n−ピペラジニル[N4−(C1-C6)アル キル]、−(CH2)n−N− ピロリジル、−(CH2)n−ピリジニル、−(CH2)n −N−イミダゾイル、−(CH2)n −N−モルホリノ、−(CH2)n− N−ヘキサヒドロアゼピン、−(CH2)n−NH2、−(CH2)n−NH(C1-C6アルキル) 、−(CH2)n−N(C1-C6アルキル)2、−1−オキソ(C1-C6アルキル)、カルボキ シ、(C1-C6)アルキルオキシカルボニル、N−(C1-C6)アルキルカルバモイル、 フェニルまたは置換フェニルであり、ここで置換フェニルはZ1、Z2、Z3または単 環式ヘテロアリール基から独立して選択される1〜3個の置換基を有することが でき、そしてそれぞれのC1-C6アルキル基は-OH、-NH2または-NAB(ここでAおよ びBは前述の定義を有する)で置換されることができ; R6は水素またはC1-C6アルキルであり;そして nは1〜4、pは0または1である]で表される化合物およびその医薬的に 許容し得る塩、エステル、アミド並びにそのプロドラッグ。 31.Qが である請求項30記載の化合物。 32.Qが である請求項30記載の化合物。 33.Xが である請求項31記載の化合物。 34.E1およびE2が水素でありそしてE3が臭素である請求項30記載の化合物。 35.Xが である請求項32記載の化合物。 36.請求項1記載の化合物からなる医薬的に許容し得る組成物。 37.請求項18記載の化合物からなる医薬的に許容し得る組成物。 38.請求項30記載の化合物からなる医薬的に許容し得る組成物。 39.ガン患者に治療的に有効な量の請求項1記載の化合物を投与することからな るガンの治療方法。 40.再発狭窄または再発狭窄の危険のある患者に治療的に有効な量の請求項1記 載の化合物を投与することからなる再発狭窄の予防または治療方法。 41.ガン患者に治療的に有効な量の請求項18記載の化合物を投与することからな るガンの治療方法。 42.再発狭窄または再発狭窄の危険のある患者に治療的に有効な量の請求項18記 載の化合物を投与することからなる再発狭窄の予防または治療方法。 43.ガン患者に治療的に有効な量の請求項30記載の化合物を投与することからな るガンの治療方法。 44.再発狭窄または再発狭窄の危険のある患者に治療的に有効な量の請求項30記 載の化合物を投与することからなる再発狭窄の予防または治療方法。 45.チロシンキナーゼ阻害を必要とする患者にチロシンキナーゼ阻害量の請求項 1記載の化合物を投与することからなるチロシンキナーゼを不可逆的に阻害する 方法。 46.チロシンキナーゼ阻害を必要とする患者にチロシンキナーゼ阻害量の請求項 18記載の化合物を投与することからなるチロシンキナーゼを不可逆的に阻害する 方法。 47.チロシンキナーゼ阻害を必要とする患者にチロシンキナーゼ阻害量の請求項 30記載の化合物を投与することからなるチロシンキナーゼを不可逆的に阻害する 方法。 48.下記の化合物: N−[4−(3−ブロモ−フェニルアミノ)−キナゾリン−7−イル]−ア クリルアミド; 3−[4−(3−ブロモ−フェニルアミノ)−キナゾリン−7−イル−カル バモイル]−アクリル酸; 3−[4−(3−ブロモ−フェニルアミノ)−キナゾリン−7−イル−カル バモイル]−アクリル酸エチルエステル; ブタ−2−エン酸[4−(3−ブロモ−フェニルアミノ)−キナゾリ ン−7−イル]−アミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]−アク リルアミド; N−[4−(3−メチル−フェニルアミノ)−キナゾリン−7−イル]−アク リルアミド; N−[4−(3−クロロ−フェニルアミノ)−キナゾリン−7−イル]−アク リルアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−7−イル]−メタ クリルアミド; N−[4−[(3−ブロモ−フェニルアミノ)−キナゾリン−7−イル]エテ ニルスルホンアミド; N−[4−[(3−クロロフェニル)アミノ]キナゾリン−6−イル]−アク リルアミド; N−[4−[(3−メチルフェニル)アミノ]キナゾリン−6−イル]−アク リルアミド; N−[4−[(3−(トリフルオロメチル)フェニル)アミノ]キナゾリン− 6−イル]−アクリルアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]−メタ クリルアミド; N−[4−[(3−ブロモ−フェニルアミノ)−キナゾリン−7−イル]エテ ニルスルホンアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]−E− ブタ−2−エンアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]−4,4, 4−トリフルオロ−E−ブタ−2−エンアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]プロピ ンアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]ブタ− 2−インアミド; N−[4−(3−ブロモ−フェニルアミノ)−ピリド[4,3-d]ピリミジン−7 −イル]−アクリルアミド; N−[4−(3−ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]−アクリルアミド; N−[4−(3−メチル−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]−アクリルアミド; N−[4−(3−ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]−N−メチルアクリルアミド; N−[4−(3−ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]−メタクリルアミド; N−[4−(3−ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]−エテニルスルホンアミド; N−[4−(3−ブロモ−フェニルアミノ)−ベンゾ[b]チエノ[3,2-d]ピ リミジン−8−イル]−アクリルアミド; N−[4−(3−ブロモ−フェニルアミノ)−ベンゾ[b]チエノ[3,2-d]ピ リミジン−6−イル]−アクリルアミド; N−[4−(3−ブロモ−フェニルアミノ)−ベンゾ[b]チエノ[3,2-d]ピ リミジン−7−イル]−アクリルアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]−ブタ −2,3−ジエンアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]−E,4 −オキソペンタ−2−エンアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]−E,4 −エトキシ−4−オキソブタ−2−エンアミド; N−[4−(3−ブロモフェニルアミノ)−ピリド[3,4-d]ピリミジ ン−6−イル]ペンタ−2,4−ジエンアミド; N−[4−(3−ブロモフェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]−E−ブタ−2−エンアミド; N−[4−(3−ブロモフェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]シンナミド; N−[4−(3−ブロモフェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]−E,3−クロロアクリルアミド; N−[4−(3−ブロモフェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]−プロピンアミド; 3−[4−(3−ブロモ−フェニルアミノ)−キナゾリン−6−イルカルバ モイル]−アクリル酸(Z);および 4−[(3−ブロモー−ニル)アミノ]−6−(エテンスルホニル)−ピリ ド[3,4-d]ピリミジン。 49.乾癬症の患者に治療的に有効な量の請求項1記載の化合物を投与することか らなる乾癬症の治療方法。 50.乾癬症の患者に治療的に有効な量の請求項18記載の化合物を投与するとから なる乾癬症の治療方法。 51.乾癬症の患者に治療的に有効な量の請求項30記載の化合物を投与することか らなる乾癬症の治療方法。 52.アテローム性動脈硬化症の患者に治療的に有効な量の請求項1記載の化合物 を投与することからなるアテローム性動脈硬化症の治療方法。 53.アテローム性動脈硬化症の患者に治療的に有効な量の請求項18記載の化合物 を投与することからなるアテローム性動脈硬化症の治療方法。 54.アテローム性動脈硬化症の患者に治療的に有効な量の請求項30記載の化合物 を投与することからなるアテローム性動脈硬化症の治療方法。 55.子宮内膜症の患者に治療的に有効な量の請求項1記載の化合物を投与するこ とからなる子宮内膜症の治療方法。 56.子宮内膜症の患者に治療的に有効な量の請求項18記載の化合物を投与するこ とからなる子宮内膜症の治療方法。 57.子宮内膜症の患者に治療的に有効な量の請求項30記載の化合物を投与するこ とからなる子宮内膜症の治療方法。 58.下記の化合物。 1−[4−(3−ブロモ−フェニルアミノ)−キナゾリン−6−イル]ピロ ール−2,5−ジオン; 1−[4−(3−ブロモ−フェニルアミノ)−キナゾリン−6−イル]プロ パ−2−エン−1−オン; アクリル酸4−(3−ブロモ−フェニルアミノ)−キナゾリン−6−イルエ ステル; メチルN−[4−[(3−ブロモフェニル)アミノ]−P−エテニル−ピリ ド[3,4-d]ピリミジン−6−イル]ホスホンアミデート; アクリル酸4−(3−ブロモ−フェニルアミノ)−キナゾリン−7−イルエ ステル; 1−[4−(3−ブロモ−フェニルアミノ)−キナゾリン−6−イル]−ブ タ−3−エン−2−オン; アクリル酸4−(3−クロロ−4−フルオロ−フェニルアミノ)−7 −メ トキシ−キナゾリン−6−イルエステル: ペンタ−2,3−ジエン酸[4−(3−ブロモ−フェニルアミノ)−キナゾリ ン−6−イル]アミド; プロパ−1,2−ジエン−1−スルホン酸[4−(3−ブロモーフェニルアミ ノ)-キナゾリン-6-イル]アミド; メチルN−[4−[(3−ブロモフェニル)アミノ]−6−キナゾリニル] −P−(1,2−プロパンジエニル)ホスホンアミデート; N−[1−(3−ブロモ−フェニルアミノ)−9H−2,4,9−トリアザフルオ レン−7−イル]アクリルアミド; N−[4−(3−ブロモ−フェニルアミノ)−9H−1,3,9−トリアザフ ルオレン−6−イル]アクリルアミド; N−[4−(3−クロロ−4−フルオロ−フェニルアミノ)−キナゾリン− 6−イル]アクリルアミド; N−(4−フェニルメチルアミノ−キナゾリン−6−イル)−アクリルアミ ド; (S)−N−[4−(1−フェニル−エチルアミノ)−キナゾリン−6−イ ル]−アクリルアミド; (R)−N−[4−(1−フェニル−エチルアミノ)−キナゾリン−6−イ ル]−アクリルアミド; N−[4−(3−クロロ−4−フルオロ−フェニルアミノ)−ピリド[3,4-d ]ピリミジン−6−イル]−アクリルアミド; N−[4−(3−クロロ−4−フルオロ−フェニルアミノ)−ピリド[3,4-d ]ピリミジン−6−イル]−N−メチルアクリルアミド; (3−クロロ−4−フルオロ−フェニル)−(6−エテンスルフィニル−ピ リド[3,4-d]ピリミジン−4−イル]−アミン;および (3−ブロモ−フェニル)−(6−エテンスルフィニル−ピリド[3,4-d]ピ リミジン−4−イル]−アミン。 59.E1が水素であり、E2がフッ素であり、そしてE3が塩素である請求項18記載の 化合物。 60.フッ素がフェニル環の4−位、そして塩素がフェニル環の3−位に存在する 請求項59記載の化合物。 61.E1が水素であり、E2がフッ素であり、そしてE3が塩素である請求項30記載の 化合物。 62.フッ素がフェニル環の4−位、そして塩素がフェニル環の3−位に存在する 請求項61記載の化合物。 63.下記の化合物。 N−[4−(3−ブロモ−フェニルアミノ)−ピリド[4,3-d]ピリミジン−7 −イル]−N−(3−モルホリン−4−イル−プロピル)−アクリルアミド; N−[4−(3−ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]−N−(3−モルホリン−4−イル−プロピル)−アクリルアミド; N−[4−(3−ブロモフェニル)アミノ]キナゾリン−7−イル]−N−( 3−モルホリノプロピル)−アクリルアミド; N−[4−(3−ブロモーフェニルアミノ)−6−(3−モルホリン−4−イ ル−プロピルアミノ)−キナゾリン−7−イル]−アクリルアミド; N−[4−(3−ブロモフェニル)アミノ]−7−[3−(4−モルホリノ) プロポキシ]キナゾリン−6−イル]アクリルアミド; N−[4−(3−メチルフェニル)アミノ]−7−[3−(4−モルホリノ) プロポキシ]キナゾリン−6−イル]アクリルアミド; N−[4−[(3−メチルフェニル)アミノ]−7−[3−(4,N−メチル−1 ,N−ピペラジノ)プロポキシ]キナゾリン−6−イル]アクリルアミド; N−[4−[(3−ブロモフェニル)アミノ]−7−[3−(4,N−メチル−1 ,N−ピペラジノ)プロポキシ]キナゾリン−6−イル]アクリルアミド; N−[4−[(3−ブロモフェニル)アミノ]−7−[3−(1,N−イミダジ ル)プロポキシ]キナゾリン−6−イル]アクリルアミド; N−[4−[(3−ブロモフェニル)アミノ]−7−[4−(N,N−ジメチル アミノ)ブトキシ]キナゾリン−6−イル]アクリルアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]−N− [3−モルホリノプロピル]アクリルアミド; N−[4−(3−ブロモフェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]−N−[2−(N,N−ジメチルアミノ)エチル)アクリルアミド; N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]−E, 4−(3−(N,N−ジメチルアミノ)プロポキシ−4−オキソブタ−2−エンアミ ド トリス トリフルオロアセテート;および N−[4−[(3−ブロモフェニル)アミノ]キナゾリン−6−イル]− E,4−(3−(N,N−ジメチルアミノ)プロピルアミノ−4−オキソブタ−2−エ ンアミド。 64.下記の化合物。 N−[4−(3−ブロモ−フェニルアミノ)−7−(3−モルホリン−4− イル−プロポキシ)−ピリド[3,2-d]ピリミジン−6−イル]−アクリルアミド ; ブタ−2−エン二酸[4−(3−クロロ−4−フルオロ−フェニルアミノ) −キナゾリン−6−イル]−アミド(3−ジメチルアミノ−プロピル)−アミド ; ブタ−2−エン二酸[4−(3−クロロ−4−フルオロ−フェニルアミノ) −ピリド[3,4-d]ピリミジン−6−イル]−アミド(3−ジメチルアミノ−プロ ピル)−アミド; ブタ−2−エン二酸[4−(3−クロロ−4−フルオロ−フェニルアミノ) −ピリド[3,4-d]ピリミジン−6−イル]−アミド(3−イミダゾール−1−イ ル−プロピル)−アミド; 4,4−ジフルオロ−8−モルホリン−4−イル−オクタ−2−エン酸[4− (3−クロロ−4−フルオロ−フェニルアミノ)−ピリド[3,4-d]ピリミジン− 6−イル]−アミド; 8−ジメチルアミノ−4,4−ジフルオロ−オクタ−2−エン酸[4−(3− クロロ−4−フルオロ−フェニルアミノ)−ピリド[3,4-d]ピリ ミジン−6−イル]−アミド; 7−ジメチルアミノ−4,4−ジフルオロ−ヘプタ−2−エン酸[4−(3−ク ロロ−4−フルオロ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル ]アミド; 4,4−ジフルオロ−7−モルホリン−4−イル−ヘプタ−2−エン酸[4−( 3−クロロ−4−フルオロ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]アミド; 6−ジメチルアミノ−ヘキサ−2−イン酸[4−(3−クロロ−4−フルオロ −フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 6−モルホリン−4−イル−ヘキサ−2−イン酸[4−(3−クロロ−4−フ ルオロ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 7−ジメチルアミノ−ヘプタ−2−イン酸[4−(3−クロロ−4−フルオロ −フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 7−モルホリン−4−イル−ヘプタ−2−イン酸[4−(3−クロロ−4−フ ルオロ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 5−ジメチルアミノ−ペンタ−2−イン酸[4−(3−クロロ−4−フルオロ −フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 5−モルホリン−4−イル−ペンタ−2−イン酸[4−(3−クロロ−4−フ ルオロ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 5−イミダゾール−1−イル−ペンタ−2−イン酸[4−(3−クロロ−4− フルオロ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イル]アミド; 5−(4−メチル−ピペラジン−1−イル−ペンタ−2−イン酸[4−(3− クロロ−4−フルオロ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イ ル]アミド; 4−[4−(3−クロロ−4−フルオロ−フェニルアミノ)−ピリド[3,4-d] ピリミジン−6−イルカルバモイル]−ブタ−3−エン酸2−(4−メチルピペ ラジン−1−イル)−エチルエステル; 4−[4−(3−クロロ−4−フルオロ−フェニルアミノ)−ピリド[3,4-d] ピリミジン−6−イルカルバモイル]−ブタ−3−エン酸2−(イミダゾ−ル− 1−イル)−エチルエステル; ペンタ−2−エン二酸1−{[4−(3−クロロ−4−フルオロ−フェニルア ミノ)−ピリド[3,4-d]ピリミジン−6−イル]−アミド}5−[3−モルホリ ン−4−イル−プロピル)−アミド]; ペンタ−2−エン二酸1−{[4−(3−クロロ−4−フルオロ−フェニルア ミノ)−ピリド[3,4-d]ピリミジン−6−イル]−アミド}5−[3−ジエチル アミノ−プロピル)−アミド]; 4−[4−(3−クロロ−4−フルオロ−フェニルアミノ)−ピリド[3,4-d] ピリミジン−6−イルカルバモイル]−ブタ−3−エン酸2−モルホリン−4− イル−エチルエステル; ペンタ−2−エン二酸1−{[4−(3−クロロ−4−フルオロ−フェニルア ミノ)-ピリド[3,4-d]ピリミジン−6−イル]−アミド}5−[3−4−メチル −ピペラジン−1)−プロピル]−アミド}; (3−クロロ−4−フルオロ−フェニル)−{6−[2−(3−ジメチルアミ ノプロポキシ]−エテンスルホニル]−ピリド[3,4-d]ピリミジン−4−イル} −アミン; (3−クロロ−4−フルオロ−フェニル)−{6−{2−[4−(4−メチル ピペラジン−1−イル)−ブチルアミノ]−エテンスルホニル} −ピリド[3,4-d]ピリミジン−4−イル}−アミン; 3−[4−(1−フェニル−エチルアミノ)−キナゾリン−6−イルカルバモ イル]−アクリル酸2−モルホリン−4−イル−エチルエステル; ブタ−2−エン二酸(4−イミダゾール−1−イル−ブチル)−アミド [4 −(1−フェニル−エチルアミノ)−キナゾリン−6−イル]−アミド; 4−[4−(1−フェニル−エチルアミノ)−キナゾリン−6−イルカルバモ イル]−ブタ−3−エン酸3−ジエチルアミノ−プロピルエステル; ペンタ−2−エン二酸5−{[2−(4−メチル−1−ピペラジン−1−イル )−エチル]−アミド}1−{[4−(1−フェニル-エチルアミノ)−キナゾ リン−6−イル]−アミド}; 4,4−ジフルオロ−7−モルホリン−4−イル−ヘプタ−2−エン酸[4−( 1−フェニル−エチルアミノ)−キナゾリン−6−イル]−アミド; 7−ジメチルアミノ−4,4−ジフルオロ−ヘプタ−2−エン酸[4−(1−フ ェニル−エチルアミノ)−キナゾリン−6−イル]−アミド; 7−イミダゾール−1−イル−ヘプタ−2−エン酸[4−(1−フェニル−エ チルアミノ)−キナゾリン−6−イル]−アミド; 6−ジメチルアミノ−ヘキサ−2−イン酸[4−(1−フェニル−エチルアミ ノ)−キナゾリン−6−イル]−アミド; ブタ−2−エンジ酸[4−(3−ブロモ−フェニルアミノ)−ピリド[3,4-d] ピリミジン−6−イル]アミド(3−ジメチルアミノプロピル)−アミド; ブタ−2−エン二酸[4−(3−ブロモ−フェニルアミノ)−ピリド[3,4-d] ピリミジン−6−イル]アミド(3−イミダゾール−1−イル −プロピル)−アミド; 4,4−ジフルオロ−8−モルホリン−4−イル−オクタ−2−エンジ酸[4− (3−ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミ ド; 8−ジメチルアミノ−4,4−ジフルオロ−オクタ−2−エン酸[4−(3−ブ ロモ-フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 7−ジメチルアミノ−4,4−ジフルオロ−ヘプタ−2−エン酸[4−(3−ブ ロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 4,4−ジフルオロ−7−モルホリン−4−イル−ヘプタ−2−エン酸[4−( 3−ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド ; 6−ジメチルアミノ−ヘキサ−2−イン酸[4−(3−ブロモ−フェニルアミ ノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 6−モルホリン−4−イル−ヘキサ−2−イン酸[4−(3−ブロモ−フェニ ルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 7−ジメチルアミノ−ヘプタ−2−イン酸[4−(3−ブロモ−フェニルアミ ノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 7−モルホリン−4−イル−ヘプタ−2−イン酸[4−(3−ブロモ−フェニ ルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 5−ジメチルアミノ−ペンタ−2−イン酸[4−(3−ブロモ−フェニルアミ ノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 5−モルホリン−4−イル−ペンタ−2−イン酸[4−(3−ブロモ−フェニ ルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 5−イミダゾール−1−イル−ペンタ−2−イン酸[4−(3−ブロモ−フェ ニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 5−(4−メチル−ピペラジン−1−イル−ペンタ−2−イン酸[4−(3− ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 4−[4−(3−ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イルカルバモイル]−ブタ−3−エン酸2−(4−メチル−ピペラジン−1− イル)−エチルエステル; 4−[4−(3−ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イルカルバモイル]−ブタ−3−エン酸2−イミダゾール−1−イル−エチル エステル; ペンタ−2−エン二酸1−{[4−(3−ブロモ−フェニルアミノ)−ピリド [3,4-d]ピリミジン−6−イル]アミド}5−[(3−モルホリン−4−イル− プロピル)−アミド]; ペンタ−2−エン二酸1−{[4−(3−ブロモ−フェニルアミノ)−ピリド [3,4-d]ピリミジン−6−イル]アミド}5−[(3−ジエチルアミノプロピル )−アミド]; 4−[4−(3−ブロモ−フェニルアミノ)−ピリド[3,4-d]ピリミジン−6 −イルカルバモイル]−ブタ−3−エン酸2−モルホリン−4−イル−エチルエ ステル; ペンタ−2−エン二酸1−{[4−(3−ブロモ−フェニルアミノ)−ピリド [3,4-d]ピリミジン−6−イル]アミド}5−{3−(4−メチルピペラジン− 1−イル)−プロピル]−アミド}; (3−ブロモ−フェニル)−{6−[2−(3−ジメチルアミノ−プロポキシ )−エテンスルホニル]−ピリド[3,4-d]ピリミジン−4−イル}−アミン; (3−ブロモ−フェニル)−(6−{2−[4−(4−メチル−ピペラジン− 1−イル)−ブチルアミノ]−エテンスルホニル}−ピリド[3,4-d]ピリミジン −4−イル)−アミン; (3−ブロモ−フェニル)−[6−(5−モルホリン−4−イル−ペンタ−1 −エン−1−スルホニル)−ピリド[3,4-d]ピリミジン−4−イル]−アミン; (3−ブロモ−フェニル)−(6−エテンスルフィニル−ピリド[3,4-d]ピリ ミジン−4−イル]−アミン; ブタ−2−エン二酸[4−(3−クロロ−4−フルオロ−フェニルアミノ)− キナゾリン−6−イル]−アミド(3−ジメチルアミノプロピル)−アミド; ブタ−2−エン二酸[4−(3−クロロ−4−フルオロ−フェニルアミノ)− キナゾリン−6−イル]−アミド(3−イミダゾール−1−イル−プロピル)− アミド; 4,4−ジフルオロ−8−モルホリン−4−イル−オクタ−2−エン酸[4−( 3−クロロ−4−フルオロ−フェニルアミノ)−キナゾリン−6−イル]アミド ; 8−ジメチルアミノ−4,4−ジフルオロ−オクタ−2−エン酸[4−(3−ク ロロ−4−フルオロ−フェニルアミノ)−キナゾリン−6−イル]アミド; 7−ジメチルアミノ−4,4−ジフルオロ−ヘプタ−2−エン酸[4−(3−ク ロロ−4−フルオロ−フェニルアミノ)−キナゾリン−6−イル]アミド; 4,4−ジフルオロ−7−モルホリン−4−イル−ヘプタ−2−エン酸[4−( 3−クロロ−4−フルオロ−フェニルアミノ)−キナゾリン−6−イル]アミド ; 6−ジメチルアミノ−ヘキサ−2−イン酸[4−(3−クロロ−4−フルオロ -フェニルアミノ)−キナゾリン−6−イル]アミド; 6−モルホリン−4−イル−ヘキサ−2−イン酸[4−(3−クロロ−4−フ ルオロ−フェニルアミノ)−キナゾリン−6−イル]アミド; 7−ジメチルアミノ−ヘプタ−2−イン酸[4−(3−クロロ−4−フルオロ −フェニルアミノ)−キナゾリン−6−イル]アミド; 7−モルホリン−4−イル−ヘプタ−2−イン酸[4−(3−クロロ−4−フ ルオロ−フェニルアミノ)−キナゾリン−6−イル]アミド; 5−ジメチルアミノ−ペンタ−2−イン酸[4−(3−クロロ−4−フルオロ −フェニルアミノ)−キナゾリン−6−イル]アミド; 5−モルホリン−4−イル−ペンタ−2−イン酸[4−(3−クロロ−4−フ ルオロ−フェニルアミノ)−キナゾリン−6−イル]アミド; 5−イミダゾール−1−イル−ペンタ−2−イン酸 [4−(3−クロロ−4 −フルオロ−フェニルアミノ)−キナゾリン−6−イル]アミド; 5−(4−メチル−ピペラジン−1−イル)−ペンタ−2−イン酸[4−(3 −クロロ−4−フルオロ−フェニルアミノ)−キナゾリン−6−イル]アミド; ペンタ−2−エン二酸1−{[4−(3−クロロ−4−フルオロ−フェニルア ミノ)−キナゾリン−6−イル]アミド}5−[{3−モルホリン−4−イル− プロピル)−アミド]; ペンタ−2−エン二酸1−{[4−(3−クロロ−4−フルオロ−フェニルア ミノ)−キナゾリン−6−イル]アミド}5−[(3−ジエチルアミノ−プロピ ル)−アミド]; 4−[4−(3−クロロ−4−フルオロ−フェニルアミノ)−キナゾリン−6 −イルカルバモイル]−ブタ−3−エン酸2−モルホリン−4−イル−エチルエ ステル; ペンタ−2−エン二酸1-{[4−(3−クロロ−4−フルオロ−フェニルア ミノ)−キナゾリン−6−イル]アミド}5−{[3−(4−メチルピペラジン −1−イル)−プロピル]−アミド}; (3−クロロ−4−フルオロ−フェニル)−{6−[2−(3−ジメチルアミ ノプロポキシ)−エタンスルホニル]−キナゾリン−4−イル} −アミン; (3−クロロ−4−フルオロ−フェニル)−(6−(2−[4−(4−メチル ピペラジン−1−イル)−ブチルアミノ]−エタンスルホニル}−キナゾリン− 4−イル}−アミン; ブタ−2−エン二酸[4−(3−ブロモ−フェニルアミノ)−キナゾリン−6 −イル]アミド(3−ジメチルアミノ−プロピル)−アミド; ブタ−2−エン二酸[4−(3−ブロモ−フェニルアミノ)−キナゾリン−6 −イル]アミド(3−イミダゾール−1−イル−プロピル)−アミド; 4,4−ジフルオロ−8−モルホリン−4−イル−オクタ−2−エン酸[4−( 3−ブロモ−フェニルアミノ)−キナゾリン−6−イル]アミド; 8−ジメチルアミノ−4,4−ジフルオロ−オクタ−2−エン酸[4−(3−ブ ロモ−フェニルアミノ)−キナゾリン−6−イル]アミド; 7−ジメチルアミノ−4,4−ジフルオロ−ヘプタ−2−エン酸[4−(3−ブ ロモ−フェニルアミノ)−キナゾリン−6−イル]アミド; 4,4−ジフルオロ−7−モルホリン−4−イル−ヘプタ−2−エン酸[4−( 3−ブロモ−フェニルアミノ)−キナゾリン−6−イル]アミド; 6−ジメチルアミノ−ヘキサ−2−イン酸[4−(3−ブロモ−フェニルアミ ノ)−キナゾリン−6−イル]アミド; 6−モルホリン−4−イル−ヘキサ−2−イン酸[4−(3−ブロモ−フェニ ルアミノ)−キナゾリン−6−イル]アミド; 7−ジメチルアミノ−ヘプタ−2−イン酸[4−(3−ブロモ−フェニルアミ ノ)−キナゾリン−6−イル]アミド: 7−モルホリン−4−イル−ヘプタ−2−イン酸[4−(3−ブロモ−フェニ ルアミノ)−キナゾリン−6−イル]アミド; 5−ジメチルアミノ−ペンタ−2−イン酸[4−(3−ブロモ−フェニルアミ ノ)−キナゾリン−6−イル]アミド; 5−モルホリン−4−イル−ペンタ−2−イン酸[4−(3−ブロモ−フェニ ルアミノ)−キナゾリン−6−イル]アミド; 5−イミダゾ−ル−1−イル−ペンタ−2−イン酸[4−(3−ブロモ−フェ ニルアミノ)−キナゾリン−6−イル]アミド; 5−(4−メチル−ピペラジン−1−イル)−ペンタ−2−イン酸[4−(3 −ブロモ−フェニルアミノ)−キナゾリン−6−イル]アミド; 4−[4−(3−ブロモ−フェニルアミノ)−キナゾリン−6−イルカルバモ イル]−ブタ−3−エン酸2−(4−メチルピペラジン−1−イル)−エチルエ ステル; 4−[4−(3−ブロモ−フェニルアミノ)−キナゾリン−6−イルカルバモ イル]−ブタ−3−エン酸2−イミダゾール−1−イル−エチルエステル; ペンタ−2−エン二酸1−{[4−(3−ブロモ−フェニルアミノ)−キナゾ リン−6−イル]アミド}5−{[3−(モルホリン−4−イル)−プロピル] −アミド}; ペンタ−2−エン二酸1−{[4−(3−ブロモ−フェニルアミノ)−キナゾ リン−6−イル]アミド}5−{[3−ジメチルアミノ−プロピル]−アミド} ; 4−[4−(3−ブロモ−フェニルアミノ)−キナゾリン−6−イルカルバモ イル]−ブタ−3−エン酸2−モルホリン−4−イル−エチルエステル; ペンタ−2−エン二酸1−{[4−(3−ブロモ−フェニルアミノ)−キナゾ リン−6−イル]アミド}5−{[3−(4−メチル−ピペラジン−1−イル) −プロピル]−アミド}; 3−[4−(1−フェニル−エチルアミノ)−ピリド[3,4-d]ピリミ ジン−6−イルカルバモイル]−アクリル酸2−モルホリン−4−イル−エチ ルエステル; ブタ−2−エン二酸(4−イミダゾール−1−イル−ブチル)−アミド[4 −(1−フェニル−エチルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]− アミド; 4−[4−(1−フェニル−エチルアミノ)−ピリド[3,4-d]ピリミジン− 6−イルカルバモイル]−ブタ−3−エン酸3−ジエチルアミノ−プロピルエス テル; ペンタ−2−エン二酸5−{[2−(4−メチル−ピペラジン−1−イル) −エチル]−アミド}1−{[4−(1−フェニル−エチルアミノ)−ピリド[3 ,4-d]ピリミジン−6−イル]アミド; 4,4−ジフルオロ−7−モルホリン−4−イル−ヘプタ−2−エン酸[4− (1−フェニル−エチルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミ ド; 7−ジメチルアミノ−4,4−ジフルオロ−ヘプタ−2−エン酸[4−(1− フェニル−エチルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; 7−イミダゾール−1−イル−ヘプタ−2−イン酸[4−(1−フェニル− エチルアミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド; (3−クロロ−4−フルオロフェニルアミノ)−[6−(5−モルホリン− 4−イル−ペンタ−1−エン−1−スルホニル)−ピリド[3,4-d]ピリミジン− 4−イル]アミン;および 6−ジメチルアミノ−ヘキサ−2−イン酸[4−(1−フェニル−エチルア ミノ)−ピリド[3,4-d]ピリミジン−6−イル]アミド。 65.Xが−D−E−FでありそしてFが であり、 R5が1,1−ジフルオロ(C1-C6)アルキル、C1-C6アルキル、−(CH2)n−N−ピペ リジニル、−(CH2)n−ピペラジニル、−(CH2)n−ピペラジニル[N4−(C1-C6)ア ルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N− イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ、− CH=CH−(C1-C6)アルキル、−(CH2)n−N−ヘキサヒドロアゼピン、−(CH2)n−NH2 、−(CH2)n−NH(C1-C6アルキル)、−(CH2)n−N(C1-C6アルキル)2、−1−オ キソ(C1-C6アルキル)、カルボキシ、(C1-C6)アルキルオキシカルボニル、N− (C1-C6)アルキルカルバモイルであり、そして1,1−ジフルオロ(C1-C6)アルキ ル、C1-C6アルキル、−CH=CH-(C1-C6)アルキル、−1−オキソ(C1-C6)アルキル 、(C1-C6)アルキルオキシカルボニルまたは−N−(C1-C6)アルキルカルバモイ ルのそれぞれのC1-C6アルキル基は-OH、-NH2または-NAB(ここでAおよびBは前 述の定義を有する)で置換されることができる;かまたは Yが−D−E−FでありそしてFが であり、 R5が1,1−ジフルオロ(C1-C6)アルキル、C1-C6アルキル、−(CH2)n−N−ピペ リジニル、−(CH2)n−ピペラジニル、−(CH2)n−ピペラジニル[N4−(C1-C6)ア ルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N− イミダゾイル、−(CH2)n−N−モルホリノ、 −(CH2)n−N−チオモルホリノ、-CH=CH−(C1-C6)アルキル、−(CH2)n−N−ヘ キサヒドロアゼピン、−(CH2)n−NH2、−(CH2)n−NH(C1-C6アルキル)、−(CH2 )n−N(C1-C6アルキル)2、−1−オキソ(C1-C6)アルキル、カルボキシ、(C1- C6)アルキルオキシカルボニル、N−(C1-C6)アルキルカルバモイルであり、 そして1,1−ジフルオロ(C1-C6)アルキル、C1-C6アルキル、−CH=CH−(C1-C6) アルキル、−1−オキソ(C1-C6)アルキル、(C1-C6)アルキルオキシカルボニル または−N−(C1-C6)アルキルカルバモイルのそれぞれのC1-C6アルキル基は-O H、-NH2または-NAB(ここでAおよびBは前述の定義を有する)で置換されるこ とができる、請求項1記載の化合物。 66.Xが−D−E−FでありそしてFが であり、 R5が1,1−ジフルオロ(C1-C6)アルキル、C1-C6アルキル、−(CH2)n−N−ピ ペリジニル、−(CH2)n−ピペラジニル、−(CH2)n−ピペラジニル[N4−(C1-C6) アルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N −イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ、 -CH=CH−(C1-C6)アルキル、−(CH2)n−N−ヘキサヒドロアゼピン、−(CH2)n−N H2、−(CH2)n−NH(C1-C6アルキル)、−(CH2)n−N(C1-C6アルキル)2、−1− オキソ(C1-C6アルキル)、カルボキシ、(C1-C6)アルキルオキシカルボニル、N −(C1-C6)アルキルカルバモイルであり、そして1,1−ジフルオロ(C1-C6)ア ルキル、C1-C6アルキル、−CH=CH−(C1-C6)アルキル、−1−オキソ(C1-C6)ア ルキル、(C1-C6)アルキルオキシカルボニルまたは−N−(C1-C6)アルキルカル バモイルのそれぞれのC1-C6アルキル基は-OH、-NH2ま たは-NAB(ここでAおよびBは前述の定義を有する)で置換されることができる ;かまたは Yが−D−E−FでありそしてFが であり、 R5が1,1−ジフルオロ(C1-C6)アルキル、C1-C6アルキル、−(CH2)n−N−ピ ペリジニル、−(CH2)n−ピペラジニル、−(CH2)n−ピペラジニル[N4−(C1-C6) アルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N −イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ、 −CH=CH−(C1-C6)アルキル、−(CH2)nN−ヘキサヒドロアゼピン、−(CH2)n−NH2 、−(CH2)n−NH(C1-C6アルキル)、−(CH2)n−N(C1-C6アルキル)2、−1−オ キソ(C1-C6)アルキル、カルボキシ、(C1-C6)アルキルオキシカルボニル、N− (C1-C6)アルキルカルバモイルであり、そして1,1−ジフルオロ(C1-C6)アルキ ル、C1-C6アルキル、−CH=CH−(C1-C6)アルキル、−1−オキソ(C1-C6)アルキ ル、(C1-C6)アルキルオキシカルボニルまたは−N−(C1-C6)アルキルカルバ モイルのそれぞれのC1-C6アルキル基は-OH、-NH2または-NAB(ここでAおよびB は前述の定義を有する)で置換されることができる、請求項18記載の化合物。 67.Xが−D−E−FでありそしてFが であり、 R5が1,1−ジフルオロ(C1-C6)アルキル、C1-C6アルキル、−(CH2)n− N−ピペリジニル、−(CH2)n−ピペラジニル、−(CH2)n−ピペラジニル[N4−( C1-C6)アルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−ピリジニル、−(CH2 )n−N−イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホ リノ、−CH=CH−(C1-C6)アルキル、−(CH2)n−N−ヘキサヒドロアゼピン、−(C H2)n-NH2、−(CH2)n−NH(C1-C6アルキル)、−(CH2)n−N(C1-C6アルキル)2、− 1−オキソ(C1-C6)アルキル、カルボキシ、(C1-C6)アルキルオキシカルボニ ル、N−(C1-C6)アルキルカルバモイルであり、そして1,1−ジフルオロ(C1-C6) アルキル、C1-C6アルキル、−CH=CH−(C1-C6)アルキル、−1−オキソ(C1-C6)ア ルキル、(C1-C6)アルキルオキシカルボニルまたは−N−(C1-C6)アルキルカ ルバモイルのそれぞれのC1-C6アルキル基は-OH、-NH2または-NAB(ここでAおよ びBは前述の定義を有する)で置換されることができる;かまたは Yが−D−E−FでありそしてFが であり、 R5が1,1−ジフルオロ(C1-C6)アルキル、C1-C6アルキル、−(CH2)n−N−ピペ リジニル、−(CH2)n−ピペラジニル、−(CH2)n−ピペラジニル[N4−(C1-C6) アルキル]、−(CH2)n−N−ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N −イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ、 −CH=CH−(C1-C6)アルキル、−(CH2)n−N−ヘキサヒドロアゼピン、−(CH2)n-N H2、−(CH2)n−NH(C1-C6アルキル)、−(CH2)n−N(C1-C6アルキル)2、−1− オキソ(C1-C6)アルキル、カルボキシ、(C1-C6)アルキルオキシカルボニル、N −(C1-C6)アルキルカルバモイルであり、そして1,1−ジフルオロ(C1-C6)アル キ ル、C1-C6アルキル、−CH=CH−(C1-C6)アルキル、−1−オキソ(C1-C6アルキル )、(C1-C6アルキル)アルキルオキシカルボニルまたは−N−(C1-C6)アルキ ルカルバモイルのそれぞれのC1-C6アルキル基は-OH、-NH2または-NAB(ここでA およびBは前述の定義を有する)で置換されることができる、請求項30記載の化 合物。 68.Xが−D−E−Fであり; Yが-SR4、−OR4または-NHR3であり; そしてR3およびR4が−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジニ ル、−(CH2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N −ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N−イミダゾイル、−(CH2)n −イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ、 −(CH2)n−N−ヘキサヒドロアゼピンまたは置換されたC1-C6アルキルであり、 ここで置換基は-OH、-NH2、また −(CH2)nOH、−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジニル、−(C H2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N−ピロリジ ル、−(CH2)n−N−ピリジル、−(CH2)n−イミダゾイル、または−(CH2)n−N− イミダゾイルである;かまたは Yが−D−E−Fであり; Xが-SR4、-OR4または-NHR3であり; そしてR3およびR4が−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジ ニル、−(CH2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N −ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N−イミダゾイル、−(CH2)n −イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ、 −(CH2)n−N−ヘキサヒドロアゼピンまたは置換されたC1-C6アルキルであり、 ここで置換基は-OH、-NH2、ま −(CH2)nOH、−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジニル、−(C H2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N−ピロリジ ル、−(CH2)n−N−ピリジル、−(CH2)n−イミダゾイル、または−(CH2)n−N− イミダゾイルである;請求項1記載の化合物。 69.Xが−D−E−Fであり; Yが-SR4、-OR4または-NHR3であり; そしてR3およびR4が−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジ ニル、−(CH2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n− N−ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N−イミダゾイル、−(CH2 )n−イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ 、−(CH2)n−N−ヘキサヒドロアゼピンまたは置換されたC1-C6アルキルであり 、ここで置換基は-OH、-NH2、また −(CH2)nOH、−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジニル、−(C H2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N−ピロリジ ル、−(CH2)n−N−ピリジル、−(CH2)n−イミダゾイル、または−(CH2)n−N− イミダゾイルである;かまたは Yが−D−E−Fであり; Xが-SR4、-OR4または-NHR3であり; そしてR3およびR4が−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジ ニル、−(CH2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n− N−ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N−イミダゾイル、−(CH2 )n−イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ 、−(CH2)n−N−ヘキサヒドロアゼピン または置換されたC1-C6アルキルであり、ここで置換基は-OH、-NH2、ま −(CH2)nOH、−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジニル、−(C H2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N−ピロリジ ル、−(CH2)n−N−ピリジル、−(CH2)n−イミダゾイル、または−(CH2)n−N− イミダゾイルである;請求項18記載の化合物。 70.Xが−D−E−Fであり; Yが−SR4、-OR4または-NHR3であり; そしてR3およびR4が−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジニ ル、−(CH2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N −ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N−イミダゾイル、−(CH2)n −イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ、 −(CH2)n−N−ヘキサヒドロアゼピンまたは置換されたC1-C6アルキルであり、 ここで置換基は-OH、-NH2、ま −(CH2)nOH、−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジニル、−(C H2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N−ピロリジ ル、−(CH2)n−N−ピリジル、−(CH2)n−イミダゾイル、または−(CH2)n−N− イミダゾイルである;かまたは Yが−D−E−Fであり; Xが-SR4、-OR4または-NHR3であり; そしてR3およびR4が−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジ ニル、−(CH2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N −ピロリジル、−(CH2)n−ピリジニル、−(CH2)n−N−イミダゾイル、−(CH2)n −イミダゾイル、−(CH2)n−N−モルホリノ、−(CH2)n−N−チオモルホリノ、 −(CH2)n−N−ヘキサヒドロアゼピン または置換されたC1-C6アルキルであり、ここで置換基は-OH、-NH2、ま −(CH2)nOH、−(CH2)n−N−ピペリジニル、−(CH2)n−N−ピペラジニル、−(C H2)n−N1−ピペラジニル[N4−(C1-C6)アルキル]、−(CH2)n−N−ピロリジ ル、−(CH2)n−N−ピリジル、−(CH2)n−イミダゾイル、または−(CH2)n−N− イミダゾイルである;請求項30記載の化合物。
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- 1997-04-08 HU HU9901207A patent/HU228446B1/hu unknown
- 1997-04-08 GE GEAP19974568A patent/GEP20012442B/en unknown
- 1997-04-08 CN CNB97194458XA patent/CN1145614C/zh not_active Expired - Lifetime
- 1997-04-08 EA EA199800887A patent/EA001595B1/ru not_active IP Right Cessation
- 1997-04-08 PT PT97920213T patent/PT892789E/pt unknown
- 1997-04-08 EP EP97920213A patent/EP0892789B2/en not_active Expired - Lifetime
- 1997-04-08 AU AU24463/97A patent/AU725533B2/en not_active Expired
- 1997-04-08 CN CNB2003101141263A patent/CN100503580C/zh not_active Expired - Lifetime
- 1997-04-08 CN CNA2006101018277A patent/CN1923818A/zh active Pending
- 1997-04-08 IL IL12635197A patent/IL126351A0/xx not_active IP Right Cessation
- 1997-04-08 JP JP53717397A patent/JP3370340B2/ja not_active Expired - Lifetime
- 1997-04-08 PL PL97329391A patent/PL190489B1/pl unknown
- 1997-04-08 WO PCT/US1997/005778 patent/WO1997038983A1/en active IP Right Grant
- 1997-04-08 RO RO98-01475A patent/RO121900B1/ro unknown
- 1997-04-08 DE DE69710712T patent/DE69710712T3/de not_active Expired - Lifetime
- 1997-04-08 AT AT97920213T patent/ATE213730T1/de active
- 1997-04-08 SK SK1417-98A patent/SK284073B6/sk not_active IP Right Cessation
- 1997-04-08 SI SI9730304T patent/SI0892789T2/sl unknown
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- 1997-04-08 CZ CZ19983244A patent/CZ295468B6/cs not_active IP Right Cessation
- 1997-04-08 EE EE9800328A patent/EE05289B1/xx unknown
- 1997-04-08 DK DK97920213.2T patent/DK0892789T4/da active
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- 1997-04-08 US US09/155,501 patent/US6344459B1/en not_active Expired - Lifetime
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2000
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2003
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