DE60105295T2 - Chinazolinderivate zur behandlung von tumoren - Google Patents
Chinazolinderivate zur behandlung von tumoren Download PDFInfo
- Publication number
- DE60105295T2 DE60105295T2 DE60105295T DE60105295T DE60105295T2 DE 60105295 T2 DE60105295 T2 DE 60105295T2 DE 60105295 T DE60105295 T DE 60105295T DE 60105295 T DE60105295 T DE 60105295T DE 60105295 T2 DE60105295 T2 DE 60105295T2
- Authority
- DE
- Germany
- Prior art keywords
- alkyl
- group
- ethoxy
- pyrrolidin
- formula
- 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.)
- Expired - Lifetime
Links
- 206010028980 Neoplasm Diseases 0.000 title claims description 19
- 238000011282 treatment Methods 0.000 title claims description 10
- -1 cyano, isocyano, nitro, hydroxy, mercapto, amino, formyl Chemical group 0.000 claims description 1584
- 125000000217 alkyl group Chemical group 0.000 claims description 499
- 125000000623 heterocyclic group Chemical group 0.000 claims description 231
- 125000001424 substituent group Chemical group 0.000 claims description 227
- 239000001257 hydrogen Substances 0.000 claims description 219
- 229910052739 hydrogen Inorganic materials 0.000 claims description 219
- 229910052757 nitrogen Inorganic materials 0.000 claims description 217
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 214
- 229910052760 oxygen Inorganic materials 0.000 claims description 188
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 147
- 125000003118 aryl group Chemical group 0.000 claims description 126
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 120
- 125000001072 heteroaryl group Chemical group 0.000 claims description 112
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 103
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 103
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 94
- 229910052736 halogen Inorganic materials 0.000 claims description 93
- 150000002367 halogens Chemical class 0.000 claims description 93
- 239000000460 chlorine Substances 0.000 claims description 89
- 150000001875 compounds Chemical class 0.000 claims description 89
- 229910052801 chlorine Inorganic materials 0.000 claims description 79
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 75
- 229910052717 sulfur Inorganic materials 0.000 claims description 73
- 239000011737 fluorine Substances 0.000 claims description 68
- 229910052731 fluorine Inorganic materials 0.000 claims description 68
- 125000003545 alkoxy group Chemical group 0.000 claims description 66
- 125000006620 amino-(C1-C6) alkyl group Chemical group 0.000 claims description 64
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 59
- 150000002431 hydrogen Chemical class 0.000 claims description 59
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 56
- 150000003839 salts Chemical class 0.000 claims description 56
- 125000004432 carbon atom Chemical group C* 0.000 claims description 55
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 54
- 125000006619 (C1-C6) dialkylamino group Chemical group 0.000 claims description 52
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 52
- 229910052794 bromium Inorganic materials 0.000 claims description 52
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 51
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 43
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 43
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 39
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 37
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 37
- 229920002554 vinyl polymer Polymers 0.000 claims description 37
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 36
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 35
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 35
- 238000003780 insertion Methods 0.000 claims description 35
- 230000037431 insertion Effects 0.000 claims description 35
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 35
- 125000002947 alkylene group Chemical group 0.000 claims description 33
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 33
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 claims description 32
- 125000004738 (C1-C6) alkyl sulfinyl group Chemical group 0.000 claims description 31
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 30
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 30
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 29
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 29
- LCIYFINKFGDAHD-UHFFFAOYSA-N azepane;3-nitrobenzoic acid Chemical compound C1CCCNCC1.OC(=O)C1=CC=CC([N+]([O-])=O)=C1 LCIYFINKFGDAHD-UHFFFAOYSA-N 0.000 claims description 29
- 125000004423 acyloxy group Chemical group 0.000 claims description 28
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 27
- 239000002253 acid Substances 0.000 claims description 27
- 125000005153 alkyl sulfamoyl group Chemical group 0.000 claims description 27
- 125000001589 carboacyl group Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 26
- 125000006239 protecting group Chemical group 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 24
- 125000000304 alkynyl group Chemical group 0.000 claims description 24
- 125000001153 fluoro group Chemical group F* 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 20
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 125000000524 functional group Chemical group 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 19
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 19
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 18
- 125000002619 bicyclic group Chemical group 0.000 claims description 18
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 18
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
- 241000282414 Homo sapiens Species 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 10
- MJPPGVVIDGQOQT-UHFFFAOYSA-N 2-bromo-5-(2-bromo-2-nitroethenyl)furan Chemical compound [O-][N+](=O)C(Br)=CC1=CC=C(Br)O1 MJPPGVVIDGQOQT-UHFFFAOYSA-N 0.000 claims description 9
- 125000005133 alkynyloxy group Chemical group 0.000 claims description 9
- 125000001246 bromo group Chemical group Br* 0.000 claims description 9
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 claims description 9
- 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 8
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 6
- 150000001412 amines Chemical class 0.000 claims description 6
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 claims description 6
- 230000008569 process Effects 0.000 claims description 5
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- MDNWOSOZYLHTCG-UHFFFAOYSA-N Dichlorophen Chemical compound OC1=CC=C(Cl)C=C1CC1=CC(Cl)=CC=C1O MDNWOSOZYLHTCG-UHFFFAOYSA-N 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000002560 therapeutic procedure Methods 0.000 claims description 3
- CSRHUAMWMPNCLJ-VWLOTQADSA-N (2s)-1-[2-[4-(2-bromo-5-methoxyanilino)-5-(oxan-4-yloxy)quinazolin-7-yl]oxyethyl]-n,n-dimethylpyrrolidine-2-carboxamide Chemical compound COC1=CC=C(Br)C(NC=2C3=C(OC4CCOCC4)C=C(OCCN4[C@@H](CCC4)C(=O)N(C)C)C=C3N=CN=2)=C1 CSRHUAMWMPNCLJ-VWLOTQADSA-N 0.000 claims description 2
- VCVITBJRYVJDMQ-DEOSSOPVSA-N (2s)-1-[2-[4-(2-bromo-5-methoxyanilino)-5-(oxan-4-yloxy)quinazolin-7-yl]oxyethyl]-n-methylpyrrolidine-2-carboxamide Chemical compound CNC(=O)[C@@H]1CCCN1CCOC1=CC(OC2CCOCC2)=C(C(NC=2C(=CC=C(OC)C=2)Br)=NC=N2)C2=C1 VCVITBJRYVJDMQ-DEOSSOPVSA-N 0.000 claims description 2
- NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 claims description 2
- 239000004593 Epoxy Substances 0.000 claims description 2
- 230000001740 anti-invasion Effects 0.000 claims description 2
- VSCFUBQXHXHWBU-UHFFFAOYSA-N n-(2,4-dichloro-5-methoxyphenyl)-5-(oxan-4-yloxy)-7-(2-piperidin-1-ylethoxy)quinazolin-4-amine Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=C(OC4CCOCC4)C=C(OCCN4CCCCC4)C=C3N=CN=2)=C1Cl VSCFUBQXHXHWBU-UHFFFAOYSA-N 0.000 claims description 2
- RIDMECZKUSOYKF-UHFFFAOYSA-N n-(2,4-dichloro-5-methoxyphenyl)-5-(oxan-4-yloxy)-7-(2-pyrrolidin-1-ylethoxy)quinazolin-4-amine Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=C(OC4CCOCC4)C=C(OCCN4CCCC4)C=C3N=CN=2)=C1Cl RIDMECZKUSOYKF-UHFFFAOYSA-N 0.000 claims description 2
- BLIYFWIFLLWOIW-UHFFFAOYSA-N n-(2,4-dichloro-5-methoxyphenyl)-7-(2-morpholin-4-ylethoxy)-5-(oxan-4-yloxy)quinazolin-4-amine Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=C(OC4CCOCC4)C=C(OCCN4CCOCC4)C=C3N=CN=2)=C1Cl BLIYFWIFLLWOIW-UHFFFAOYSA-N 0.000 claims description 2
- PEZRZHSAIHVJIJ-UHFFFAOYSA-N n-(2,4-dichloro-5-methoxyphenyl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine Chemical compound C1=C(Cl)C(OC)=CC(NC=2C3=C(OC4CCOCC4)C=C(OCCN4CCN(C)CC4)C=C3N=CN=2)=C1Cl PEZRZHSAIHVJIJ-UHFFFAOYSA-N 0.000 claims description 2
- LWYABZMGKZJVCX-UHFFFAOYSA-N n-(2,4-dichloro-5-methoxyphenyl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C(=CC(Cl)=C(OC)C=3)Cl)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 LWYABZMGKZJVCX-UHFFFAOYSA-N 0.000 claims description 2
- WCGMYDZBHJUBAI-UHFFFAOYSA-N n-(2,5-dimethoxyphenyl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound COC1=CC=C(OC)C(NC=2C3=C(OC4CCN(C)CC4)C=C(OC)C=C3N=CN=2)=C1 WCGMYDZBHJUBAI-UHFFFAOYSA-N 0.000 claims description 2
- AUPJMWGAXBDLAF-UHFFFAOYSA-N n-(2-bromo-5-methoxyphenyl)-5-(oxan-4-yloxy)-7-(2-piperidin-1-ylethoxy)quinazolin-4-amine Chemical compound COC1=CC=C(Br)C(NC=2C3=C(OC4CCOCC4)C=C(OCCN4CCCCC4)C=C3N=CN=2)=C1 AUPJMWGAXBDLAF-UHFFFAOYSA-N 0.000 claims description 2
- AIRJDVWSRXGZLJ-UHFFFAOYSA-N n-(2-bromo-5-methoxyphenyl)-5-(oxan-4-yloxy)-7-(2-pyridin-4-yloxyethoxy)quinazolin-4-amine Chemical compound COC1=CC=C(Br)C(NC=2C3=C(OC4CCOCC4)C=C(OCCOC=4C=CN=CC=4)C=C3N=CN=2)=C1 AIRJDVWSRXGZLJ-UHFFFAOYSA-N 0.000 claims description 2
- RWCQVHHBOZOVOB-UHFFFAOYSA-N n-(2-bromo-5-methoxyphenyl)-5-(oxan-4-yloxy)-7-(2-pyrrolidin-1-ylethoxy)quinazolin-4-amine Chemical compound COC1=CC=C(Br)C(NC=2C3=C(OC4CCOCC4)C=C(OCCN4CCCC4)C=C3N=CN=2)=C1 RWCQVHHBOZOVOB-UHFFFAOYSA-N 0.000 claims description 2
- GSPWGVNZNBSDPZ-UHFFFAOYSA-N n-(2-bromo-5-methoxyphenyl)-5-cyclopentyloxy-7-(2-pyrrolidin-1-ylethoxy)quinazolin-4-amine Chemical compound COC1=CC=C(Br)C(NC=2C3=C(OC4CCCC4)C=C(OCCN4CCCC4)C=C3N=CN=2)=C1 GSPWGVNZNBSDPZ-UHFFFAOYSA-N 0.000 claims description 2
- RWICHPXUBOMASG-UHFFFAOYSA-N n-(2-bromo-5-methoxyphenyl)-7-(3-methylsulfonylpropoxy)-5-piperidin-4-yloxyquinazolin-4-amine Chemical compound COC1=CC=C(Br)C(NC=2C3=C(OC4CCNCC4)C=C(OCCCS(C)(=O)=O)C=C3N=CN=2)=C1 RWICHPXUBOMASG-UHFFFAOYSA-N 0.000 claims description 2
- LXCFBQWFFIUKPN-UHFFFAOYSA-N n-(2-bromo-5-methoxyphenyl)-7-[2-(4-methylpiperazin-1-yl)ethoxy]-5-(oxan-4-yloxy)quinazolin-4-amine Chemical compound COC1=CC=C(Br)C(NC=2C3=C(OC4CCOCC4)C=C(OCCN4CCN(C)CC4)C=C3N=CN=2)=C1 LXCFBQWFFIUKPN-UHFFFAOYSA-N 0.000 claims description 2
- KBCHXRRWXCXHDE-UHFFFAOYSA-N n-(2-bromo-5-methoxyphenyl)-7-methoxy-5-(piperidin-4-ylmethoxy)quinazolin-4-amine Chemical compound COC1=CC=C(Br)C(NC=2C3=C(OCC4CCNCC4)C=C(OC)C=C3N=CN=2)=C1 KBCHXRRWXCXHDE-UHFFFAOYSA-N 0.000 claims description 2
- KFRSXMUSYAQULP-UHFFFAOYSA-N n-(2-bromo-5-methoxyphenyl)-7-phenylmethoxy-5-piperidin-4-yloxyquinazolin-4-amine Chemical compound COC1=CC=C(Br)C(NC=2C3=C(OC4CCNCC4)C=C(OCC=4C=CC=CC=4)C=C3N=CN=2)=C1 KFRSXMUSYAQULP-UHFFFAOYSA-N 0.000 claims description 2
- JNYZPLVVZJKPNU-UHFFFAOYSA-N n-(2-chloro-5-methoxyphenyl)-5,7-bis(3-morpholin-4-ylpropoxy)quinazolin-4-amine Chemical compound COC1=CC=C(Cl)C(NC=2C3=C(OCCCN4CCOCC4)C=C(OCCCN4CCOCC4)C=C3N=CN=2)=C1 JNYZPLVVZJKPNU-UHFFFAOYSA-N 0.000 claims description 2
- VCVHFPAOHFDEOW-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-5-(oxan-4-yloxy)-7-(2-piperidin-1-ylethoxy)quinazolin-4-amine Chemical compound ClC1=CC=C2OCOC2=C1NC(C1=C(OC2CCOCC2)C=2)=NC=NC1=CC=2OCCN1CCCCC1 VCVHFPAOHFDEOW-UHFFFAOYSA-N 0.000 claims description 2
- UUUXOMVMDSIRMB-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-5-(oxan-4-yloxy)-7-(2-pyridin-4-yloxyethoxy)quinazolin-4-amine Chemical compound ClC1=CC=C2OCOC2=C1NC(C1=C(OC2CCOCC2)C=2)=NC=NC1=CC=2OCCOC1=CC=NC=C1 UUUXOMVMDSIRMB-UHFFFAOYSA-N 0.000 claims description 2
- QPKZNXSXCNZSDC-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-5-(oxan-4-yloxy)-7-(2-pyrrolidin-1-ylethoxy)quinazolin-4-amine Chemical compound ClC1=CC=C2OCOC2=C1NC(C1=C(OC2CCOCC2)C=2)=NC=NC1=CC=2OCCN1CCCC1 QPKZNXSXCNZSDC-UHFFFAOYSA-N 0.000 claims description 2
- HLILQABBLFGERM-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-5-(oxan-4-yloxy)-7-(3-pyrrolidin-1-ylpropoxy)quinazolin-4-amine Chemical compound ClC1=CC=C2OCOC2=C1NC(C1=C(OC2CCOCC2)C=2)=NC=NC1=CC=2OCCCN1CCCC1 HLILQABBLFGERM-UHFFFAOYSA-N 0.000 claims description 2
- UTOOQZAPEDMMFY-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-5-(oxan-4-yloxy)-7-(piperidin-4-ylmethoxy)quinazolin-4-amine Chemical compound ClC1=CC=C2OCOC2=C1NC(C1=C(OC2CCOCC2)C=2)=NC=NC1=CC=2OCC1CCNCC1 UTOOQZAPEDMMFY-UHFFFAOYSA-N 0.000 claims description 2
- WETSNLOXQAQKPO-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-5-cyclopentyloxy-7-(2-pyrrolidin-1-ylethoxy)quinazolin-4-amine Chemical compound ClC1=CC=C2OCOC2=C1NC(C1=C(OC2CCCC2)C=2)=NC=NC1=CC=2OCCN1CCCC1 WETSNLOXQAQKPO-UHFFFAOYSA-N 0.000 claims description 2
- QLPARMMDOPNDPN-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-5-piperidin-4-yloxyquinazolin-4-amine Chemical compound ClC1=CC=C2OCOC2=C1NC(C=12)=NC=NC2=CC=CC=1OC1CCNCC1 QLPARMMDOPNDPN-UHFFFAOYSA-N 0.000 claims description 2
- YQPAFFIGFWEPLF-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-7-[(1-methylpiperidin-4-yl)methoxy]-5-(oxan-4-yloxy)quinazolin-4-amine Chemical compound C1CN(C)CCC1COC1=CC(OC2CCOCC2)=C(C(NC=2C(=CC=C3OCOC3=2)Cl)=NC=N2)C2=C1 YQPAFFIGFWEPLF-UHFFFAOYSA-N 0.000 claims description 2
- NNTCPBYVAUSUOH-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-7-[3-(4-methylpiperazin-1-yl)propoxy]-5-(oxan-4-yloxy)quinazolin-4-amine Chemical compound C1CN(C)CCN1CCCOC1=CC(OC2CCOCC2)=C(C(NC=2C(=CC=C3OCOC3=2)Cl)=NC=N2)C2=C1 NNTCPBYVAUSUOH-UHFFFAOYSA-N 0.000 claims description 2
- VVKSFHCTJLSWTD-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C(=CC=C4OCOC4=3)Cl)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 VVKSFHCTJLSWTD-UHFFFAOYSA-N 0.000 claims description 2
- QQZMLTXRSKBBOH-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-7-methoxy-5-(piperidin-4-ylmethoxy)quinazolin-4-amine Chemical compound C=12C(NC=3C(=CC=C4OCOC4=3)Cl)=NC=NC2=CC(OC)=CC=1OCC1CCNCC1 QQZMLTXRSKBBOH-UHFFFAOYSA-N 0.000 claims description 2
- RHICODWVWUTRSH-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-7-methoxy-5-piperidin-4-yloxyquinazolin-4-amine Chemical compound C=12C(NC=3C(=CC=C4OCOC4=3)Cl)=NC=NC2=CC(OC)=CC=1OC1CCNCC1 RHICODWVWUTRSH-UHFFFAOYSA-N 0.000 claims description 2
- AWTKDKXDACFEHT-UHFFFAOYSA-N n-(5-chloronaphthalen-1-yl)-7-methoxy-5-(1-methylpiperidin-4-yl)oxyquinazolin-4-amine Chemical compound C=12C(NC=3C4=CC=CC(Cl)=C4C=CC=3)=NC=NC2=CC(OC)=CC=1OC1CCN(C)CC1 AWTKDKXDACFEHT-UHFFFAOYSA-N 0.000 claims description 2
- OUKYUETWWIPKQR-UHFFFAOYSA-N saracatinib Chemical compound C1CN(C)CCN1CCOC1=CC(OC2CCOCC2)=C(C(NC=2C(=CC=C3OCOC3=2)Cl)=NC=N2)C2=C1 OUKYUETWWIPKQR-UHFFFAOYSA-N 0.000 claims description 2
- 150000003246 quinazolines Chemical class 0.000 claims 20
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- QHSJVBSZHSXNSA-UHFFFAOYSA-N n-(2-bromo-5-methoxyphenyl)-5-(oxan-4-yloxy)-7-(pyridin-4-ylmethoxy)quinazolin-4-amine Chemical compound COC1=CC=C(Br)C(NC=2C3=C(OC4CCOCC4)C=C(OCC=4C=CN=CC=4)C=C3N=CN=2)=C1 QHSJVBSZHSXNSA-UHFFFAOYSA-N 0.000 claims 1
- PVOAJSAAENFMPF-UHFFFAOYSA-N n-(5-chloro-1,3-benzodioxol-4-yl)-7-fluoro-5-(oxan-4-yloxy)quinazolin-4-amine Chemical compound C=12C(NC=3C(=CC=C4OCOC4=3)Cl)=NC=NC2=CC(F)=CC=1OC1CCOCC1 PVOAJSAAENFMPF-UHFFFAOYSA-N 0.000 claims 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 172
- 125000002294 quinazolinyl group Chemical class N1=C(N=CC2=CC=CC=C12)* 0.000 description 47
- 210000004027 cell Anatomy 0.000 description 24
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (7)
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| EP00401581 | 2000-06-06 | ||
| EP00401581 | 2000-06-06 | ||
| EP01400297 | 2001-02-07 | ||
| EP01400297 | 2001-02-07 | ||
| EP01400565 | 2001-03-05 | ||
| EP01400565 | 2001-03-05 | ||
| PCT/GB2001/002424 WO2001094341A1 (en) | 2000-06-06 | 2001-06-01 | Quinazoline derivatives for the treatment of tumours |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60105295D1 DE60105295D1 (de) | 2004-10-07 |
| DE60105295T2 true DE60105295T2 (de) | 2005-09-15 |
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| DE60105295T Expired - Lifetime DE60105295T2 (de) | 2000-06-06 | 2001-06-01 | Chinazolinderivate zur behandlung von tumoren |
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| NO (1) | NO324838B1 (enExample) |
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| US6849625B2 (en) | 2000-10-13 | 2005-02-01 | Astrazeneca Ab | Quinazoline derivatives with anti-tumour activity |
| AU2001292137A1 (en) | 2000-10-13 | 2002-04-22 | Astrazeneca Ab | Quinazoline derivatives |
| ATE502928T1 (de) | 2000-11-01 | 2011-04-15 | Millennium Pharm Inc | Stickstoffhaltige heterozyklische verbindungen und verfahren zu deren herstellung |
| MXPA03008658A (es) * | 2001-03-23 | 2005-04-11 | Bayer Ag | Inhibidores de rho-cinasa. |
| UY27225A1 (es) * | 2001-03-23 | 2002-10-31 | Bayer Corp | Inhibidores de la rho-quinasa |
| ES2312557T3 (es) | 2001-04-19 | 2009-03-01 | Astrazeneca Ab | Derivados de quinazolina. |
| JP4326328B2 (ja) | 2001-07-16 | 2009-09-02 | アストラゼネカ アクチボラグ | キノリン誘導体及びそれらのチロシンキナーゼ阻害薬としての使用 |
| JP2005515176A (ja) * | 2001-11-03 | 2005-05-26 | アストラゼネカ アクチボラグ | 抗腫瘍剤としてのキナゾリン誘導体 |
| GB0126433D0 (en) * | 2001-11-03 | 2002-01-02 | Astrazeneca Ab | Compounds |
| GB0128108D0 (en) | 2001-11-23 | 2002-01-16 | Astrazeneca Ab | Therapeutic use |
| WO2003047582A1 (en) * | 2001-12-05 | 2003-06-12 | Astrazeneca Ab | Quinoline derivatives as antitumour agents |
| CN1625555A (zh) * | 2002-02-01 | 2005-06-08 | 阿斯特拉曾尼卡有限公司 | 喹唑啉化合物 |
| US6924285B2 (en) | 2002-03-30 | 2005-08-02 | Boehringer Ingelheim Pharma Gmbh & Co. | Bicyclic heterocyclic compounds, pharmaceutical compositions containing these compounds, their use and process for preparing them |
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| DE60327323D1 (de) | 2002-07-09 | 2009-06-04 | Astrazeneca Ab | Chinazoline derivative und ihre anwendung in der krebsbehandlung |
| US7576074B2 (en) | 2002-07-15 | 2009-08-18 | Rice Kenneth D | Receptor-type kinase modulators and methods of use |
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