JP2005525356A5 - - Google Patents

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Publication number

JP2005525356A5

JP2005525356A5 JP2003571255A JP2003571255A JP2005525356A5 JP 2005525356 A5 JP2005525356 A5 JP 2005525356A5 JP 2003571255 A JP2003571255 A JP 2003571255A JP 2003571255 A JP2003571255 A JP 2003571255A JP 2005525356 A5 JP2005525356 A5 JP 2005525356A5

Authority

JP

Japan

Prior art keywords

group

substituted

alkyl

substituents

compound

Prior art date

2003-02-25

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.)

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• 150000001875 compounds Chemical class 0.000 claims description 477
• 125000000217 alkyl group Chemical group 0.000 claims description 398
• 125000001424 substituent group Chemical group 0.000 claims description 376
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 300
• 239000003112 inhibitor Substances 0.000 claims description 179
• 125000001072 heteroaryl group Chemical group 0.000 claims description 169
• 229910052799 carbon Inorganic materials 0.000 claims description 144
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 142
• 238000011282 treatment Methods 0.000 claims description 140
• 206010028980 Neoplasm Diseases 0.000 claims description 117
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 111
• 150000001721 carbon Chemical group 0.000 claims description 105
• 239000002246 antineoplastic agent Substances 0.000 claims description 102
• BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 98
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 97
• -1 R 31 Chemical compound 0.000 claims description 94
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 90
• 125000003386 piperidinyl group Chemical group 0.000 claims description 89
• 201000011510 cancer Diseases 0.000 claims description 88
• 229910052739 hydrogen Inorganic materials 0.000 claims description 87
• 125000003118 aryl group Chemical group 0.000 claims description 86
• 229910052736 halogen Inorganic materials 0.000 claims description 86
• 125000005843 halogen group Chemical group 0.000 claims description 85
• 229940034982 antineoplastic agent Drugs 0.000 claims description 82
• 150000002367 halogens Chemical class 0.000 claims description 81
• VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 79
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 73
• RCINICONZNJXQF-MZXODVADSA-N taxol Chemical compound O([C@@H]1[C@@]2(C[C@@H](C(C)=C(C2(C)C)[C@H](C([C@]2(C)[C@@H](O)C[C@H]3OC[C@]3([C@H]21)OC(C)=O)=O)OC(=O)C)OC(=O)[C@H](O)[C@@H](NC(=O)C=1C=CC=CC=1)C=1C=CC=CC=1)O)C(=O)C1=CC=CC=C1 RCINICONZNJXQF-MZXODVADSA-N 0.000 claims description 73
• 229930012538 Paclitaxel Natural products 0.000 claims description 72
• 229960001592 paclitaxel Drugs 0.000 claims description 72
• 229960004562 carboplatin Drugs 0.000 claims description 68
• 125000005842 heteroatom Chemical group 0.000 claims description 66
• 229910052757 nitrogen Inorganic materials 0.000 claims description 66
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 62
• 125000002883 imidazolyl group Chemical group 0.000 claims description 61
• 239000003814 drug Substances 0.000 claims description 60
• 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 58
• 125000005346 substituted cycloalkyl group Chemical group 0.000 claims description 57
• 125000003107 substituted aryl group Chemical group 0.000 claims description 56
• 229940123237 Taxane Drugs 0.000 claims description 51
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 51
• 229910052697 platinum Inorganic materials 0.000 claims description 49
• 150000003384 small molecules Chemical group 0.000 claims description 49
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 47
• ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 claims description 45
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 43
• DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 40
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 40
• DKPFODGZWDEEBT-QFIAKTPHSA-N taxane Chemical class C([C@]1(C)CCC[C@@H](C)[C@H]1C1)C[C@H]2[C@H](C)CC[C@@H]1C2(C)C DKPFODGZWDEEBT-QFIAKTPHSA-N 0.000 claims description 40
• 229960004316 cisplatin Drugs 0.000 claims description 39
• 125000003342 alkenyl group Chemical group 0.000 claims description 37
• 125000003545 alkoxy group Chemical group 0.000 claims description 35
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 34
• 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 34
• 230000000259 anti-tumor effect Effects 0.000 claims description 33
• 150000003833 nucleoside derivatives Chemical class 0.000 claims description 33
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 31
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 31
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 29
• SDUQYLNIPVEERB-QPPQHZFASA-N gemcitabine Chemical compound O=C1N=C(N)C=CN1[C@H]1C(F)(F)[C@H](O)[C@@H](CO)O1 SDUQYLNIPVEERB-QPPQHZFASA-N 0.000 claims description 29
• 229960005277 gemcitabine Drugs 0.000 claims description 29
• 229960003668 docetaxel Drugs 0.000 claims description 28
• 150000003839 salts Chemical class 0.000 claims description 26
• 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 24
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 23
• 239000001257 hydrogen Substances 0.000 claims description 23
• 239000003795 chemical substances by application Substances 0.000 claims description 20
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 20
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• 229940043355 kinase inhibitor Drugs 0.000 claims description 18
• 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 18
• 125000004447 heteroarylalkenyl group Chemical group 0.000 claims description 17
• 102000016914 ras Proteins Human genes 0.000 claims description 17
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• 229940063683 taxotere Drugs 0.000 claims description 17
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• 239000002525 vasculotropin inhibitor Substances 0.000 claims description 16
• 102000007399 Nuclear hormone receptor Human genes 0.000 claims description 15
• 108020005497 Nuclear hormone receptor Proteins 0.000 claims description 15
• KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 claims description 15
• 102000006495 integrins Human genes 0.000 claims description 15
• 108010044426 integrins Proteins 0.000 claims description 15
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 15
• 229940095743 selective estrogen receptor modulator Drugs 0.000 claims description 15
• 239000000333 selective estrogen receptor modulator Substances 0.000 claims description 15
• 239000005517 L01XE01 - Imatinib Substances 0.000 claims description 14
• 102000004357 Transferases Human genes 0.000 claims description 14
• 108090000992 Transferases Proteins 0.000 claims description 14
• 125000004030 farnesyl group Chemical group [H]C([*])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])C([H])([H])C([H])=C(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 14
• 229940080856 gleevec Drugs 0.000 claims description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims description 14
• 208000034578 Multiple myelomas Diseases 0.000 claims description 13
• 208000015914 Non-Hodgkin lymphomas Diseases 0.000 claims description 13
• 206010035226 Plasma cell myeloma Diseases 0.000 claims description 13
• 125000004429 atom Chemical group 0.000 claims description 13
• 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 12
• XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 claims description 12
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 12
• UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 claims description 11
• 108010050904 Interferons Proteins 0.000 claims description 11
• 102000014150 Interferons Human genes 0.000 claims description 11
• 229940045799 anthracyclines and related substance Drugs 0.000 claims description 11
• AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 claims description 11
• 229960003433 thalidomide Drugs 0.000 claims description 11
• 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 10
• 229940102550 Estrogen receptor antagonist Drugs 0.000 claims description 10
• 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 10
• 229940122803 Vinca alkaloid Drugs 0.000 claims description 10
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 10
• 239000003534 dna topoisomerase inhibitor Substances 0.000 claims description 10
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• 150000003883 epothilone derivatives Chemical class 0.000 claims description 10
• 125000001188 haloalkyl group Chemical group 0.000 claims description 10
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• 229940079322 interferon Drugs 0.000 claims description 10
• 201000005202 lung cancer Diseases 0.000 claims description 10
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• 125000005017 substituted alkenyl group Chemical group 0.000 claims description 10
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• 239000005411 L01XE02 - Gefitinib Substances 0.000 claims description 9
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• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 9
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• 125000004104 aryloxy group Chemical group 0.000 claims description 7
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• 239000005551 L01XE03 - Erlotinib Substances 0.000 claims description 6
• 229940123934 Reductase inhibitor Drugs 0.000 claims description 6
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• 125000005251 aryl acyl group Chemical group 0.000 claims description 6
• 125000005312 heteroarylalkynyl group Chemical group 0.000 claims description 6
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