JP2013528610A5 - - Google Patents
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- JP2013528610A5 JP2013528610A5 JP2013512850A JP2013512850A JP2013528610A5 JP 2013528610 A5 JP2013528610 A5 JP 2013528610A5 JP 2013512850 A JP2013512850 A JP 2013512850A JP 2013512850 A JP2013512850 A JP 2013512850A JP 2013528610 A5 JP2013528610 A5 JP 2013528610A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- alkoxy
- halo
- imidazo
- amino
- 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
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- -1 cyano - Chemical class 0.000 claims description 95
- 150000001875 compounds Chemical class 0.000 claims description 50
- 125000001072 heteroaryl group Chemical group 0.000 claims description 50
- 125000003118 aryl group Chemical group 0.000 claims description 47
- 229910052799 carbon Inorganic materials 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 206010028980 Neoplasm Diseases 0.000 claims description 16
- 239000001257 hydrogen Substances 0.000 claims description 16
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 14
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 11
- 238000000034 method Methods 0.000 claims description 10
- 201000010099 disease Diseases 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 230000024932 T cell mediated immunity Effects 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 230000004083 survival effect Effects 0.000 claims description 6
- 238000011282 treatment Methods 0.000 claims description 6
- 230000028709 inflammatory response Effects 0.000 claims description 5
- 208000032839 leukemia Diseases 0.000 claims description 5
- 229960001592 paclitaxel Drugs 0.000 claims description 5
- 230000035755 proliferation Effects 0.000 claims description 5
- 235000013772 propylene glycol Nutrition 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 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 5
- 230000004222 uncontrolled growth Effects 0.000 claims description 5
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 claims description 4
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 claims description 4
- 229930012538 Paclitaxel Natural products 0.000 claims description 4
- 230000001413 cellular effect Effects 0.000 claims description 4
- 229960002949 fluorouracil Drugs 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- 229960004063 propylene glycol Drugs 0.000 claims description 4
- 229960004641 rituximab Drugs 0.000 claims description 4
- WYWHKKSPHMUBEB-UHFFFAOYSA-N 6-Mercaptoguanine Natural products N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 claims description 3
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 3
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 claims description 3
- 206010027476 Metastases Diseases 0.000 claims description 3
- 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 3
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 3
- 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 3
- 229960004562 carboplatin Drugs 0.000 claims description 3
- 229960004316 cisplatin Drugs 0.000 claims description 3
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 3
- 229960004397 cyclophosphamide Drugs 0.000 claims description 3
- 229960000684 cytarabine Drugs 0.000 claims description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 229930013356 epothilone Natural products 0.000 claims description 3
- 229960005420 etoposide Drugs 0.000 claims description 3
- VJJPUSNTGOMMGY-MRVIYFEKSA-N etoposide Chemical compound COC1=C(O)C(OC)=CC([C@@H]2C3=CC=4OCOC=4C=C3[C@@H](O[C@H]3[C@@H]([C@@H](O)[C@@H]4O[C@H](C)OC[C@H]4O3)O)[C@@H]3[C@@H]2C(OC3)=O)=C1 VJJPUSNTGOMMGY-MRVIYFEKSA-N 0.000 claims description 3
- 229960001101 ifosfamide Drugs 0.000 claims description 3
- HOMGKSMUEGBAAB-UHFFFAOYSA-N ifosfamide Chemical compound ClCCNP1(=O)OCCCN1CCCl HOMGKSMUEGBAAB-UHFFFAOYSA-N 0.000 claims description 3
- 229960001156 mitoxantrone Drugs 0.000 claims description 3
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 claims description 3
- CPTBDICYNRMXFX-UHFFFAOYSA-N procarbazine Chemical compound CNNCC1=CC=C(C(=O)NC(C)C)C=C1 CPTBDICYNRMXFX-UHFFFAOYSA-N 0.000 claims description 3
- 229960000624 procarbazine Drugs 0.000 claims description 3
- 229960003087 tioguanine Drugs 0.000 claims description 3
- 229960003048 vinblastine Drugs 0.000 claims description 3
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 3
- 229960004528 vincristine Drugs 0.000 claims description 3
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 3
- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 claims description 2
- 108010006654 Bleomycin Proteins 0.000 claims description 2
- GAGWJHPBXLXJQN-UORFTKCHSA-N Capecitabine Chemical compound C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1[C@H]1[C@H](O)[C@H](O)[C@@H](C)O1 GAGWJHPBXLXJQN-UORFTKCHSA-N 0.000 claims description 2
- GAGWJHPBXLXJQN-UHFFFAOYSA-N Capecitabine Natural products C1=C(F)C(NC(=O)OCCCCC)=NC(=O)N1C1C(O)C(O)C(C)O1 GAGWJHPBXLXJQN-UHFFFAOYSA-N 0.000 claims description 2
- PTOAARAWEBMLNO-KVQBGUIXSA-N Cladribine Chemical compound C1=NC=2C(N)=NC(Cl)=NC=2N1[C@H]1C[C@H](O)[C@@H](CO)O1 PTOAARAWEBMLNO-KVQBGUIXSA-N 0.000 claims description 2
- 208000002699 Digestive System Neoplasms Diseases 0.000 claims description 2
- 208000001976 Endocrine Gland Neoplasms Diseases 0.000 claims description 2
- 208000009849 Female Genital Neoplasms Diseases 0.000 claims description 2
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 claims description 2
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 claims description 2
- 206010061218 Inflammation Diseases 0.000 claims description 2
- 206010025323 Lymphomas Diseases 0.000 claims description 2
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 2
- 206010029098 Neoplasm skin Diseases 0.000 claims description 2
- 208000000453 Skin Neoplasms Diseases 0.000 claims description 2
- 229940123237 Taxane Drugs 0.000 claims description 2
- 235000018936 Vitellaria paradoxa Nutrition 0.000 claims description 2
- 229960001561 bleomycin Drugs 0.000 claims description 2
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 claims description 2
- 229960001467 bortezomib Drugs 0.000 claims description 2
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 claims description 2
- 229960004117 capecitabine Drugs 0.000 claims description 2
- 229960004630 chlorambucil Drugs 0.000 claims description 2
- JCKYGMPEJWAADB-UHFFFAOYSA-N chlorambucil Chemical compound OC(=O)CCCC1=CC=C(N(CCCl)CCCl)C=C1 JCKYGMPEJWAADB-UHFFFAOYSA-N 0.000 claims description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 claims description 2
- 229960000975 daunorubicin Drugs 0.000 claims description 2
- 229960003668 docetaxel Drugs 0.000 claims description 2
- 201000011523 endocrine gland cancer Diseases 0.000 claims description 2
- HESCAJZNRMSMJG-KKQRBIROSA-N epothilone A Chemical class C/C([C@@H]1C[C@@H]2O[C@@H]2CCC[C@@H]([C@@H]([C@@H](C)C(=O)C(C)(C)[C@@H](O)CC(=O)O1)O)C)=C\C1=CSC(C)=N1 HESCAJZNRMSMJG-KKQRBIROSA-N 0.000 claims description 2
- 229960000390 fludarabine Drugs 0.000 claims description 2
- GIUYCYHIANZCFB-FJFJXFQQSA-N fludarabine phosphate Chemical compound C1=NC=2C(N)=NC(F)=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@@H]1O GIUYCYHIANZCFB-FJFJXFQQSA-N 0.000 claims description 2
- 229960002074 flutamide Drugs 0.000 claims description 2
- MKXKFYHWDHIYRV-UHFFFAOYSA-N flutamide Chemical compound CC(C)C(=O)NC1=CC=C([N+]([O-])=O)C(C(F)(F)F)=C1 MKXKFYHWDHIYRV-UHFFFAOYSA-N 0.000 claims description 2
- 125000000524 functional group Chemical group 0.000 claims description 2
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 2
- 208000024200 hematopoietic and lymphoid system neoplasm Diseases 0.000 claims description 2
- 229960000908 idarubicin Drugs 0.000 claims description 2
- 230000004054 inflammatory process Effects 0.000 claims description 2
- FABUFPQFXZVHFB-CFWQTKTJSA-N ixabepilone Chemical compound C/C([C@@H]1C[C@@H]2O[C@]2(C)CCC[C@@H]([C@@H]([C@H](C)C(=O)C(C)(C)[C@H](O)CC(=O)N1)O)C)=C\C1=CSC(C)=N1 FABUFPQFXZVHFB-CFWQTKTJSA-N 0.000 claims description 2
- 229960002014 ixabepilone Drugs 0.000 claims description 2
- 210000003734 kidney Anatomy 0.000 claims description 2
- 230000001404 mediated effect Effects 0.000 claims description 2
- 229960001924 melphalan Drugs 0.000 claims description 2
- SGDBTWWWUNNDEQ-LBPRGKRZSA-N melphalan Chemical compound OC(=O)[C@@H](N)CC1=CC=C(N(CCCl)CCCl)C=C1 SGDBTWWWUNNDEQ-LBPRGKRZSA-N 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 208000023958 prostate neoplasm Diseases 0.000 claims description 2
- 201000004477 skin sarcoma Diseases 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims 56
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims 51
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 47
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 34
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 33
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 29
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims 21
- 125000004093 cyano group Chemical group *C#N 0.000 claims 21
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims 14
- 125000004944 pyrazin-3-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 12
- 150000001204 N-oxides Chemical class 0.000 claims 10
- 239000012453 solvate Substances 0.000 claims 10
- KXDAEFPNCMNJSK-UHFFFAOYSA-N benzene carboxamide Natural products NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims 9
- 125000005418 aryl aryl group Chemical group 0.000 claims 5
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 claims 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims 2
- 125000002877 alkyl aryl group Chemical group 0.000 claims 2
- 150000004677 hydrates Chemical class 0.000 claims 2
- 230000036571 hydration Effects 0.000 claims 2
- 238000006703 hydration reaction Methods 0.000 claims 2
- 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims 2
- 206010061289 metastatic neoplasm Diseases 0.000 claims 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims 2
- 125000005505 thiomorpholino group Chemical group 0.000 claims 2
- 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 claims 1
- WSHPFVZKPKNXLP-UHFFFAOYSA-N 2-(1-methylcyclopropyl)benzamide Chemical compound C=1C=CC=C(C(N)=O)C=1C1(C)CC1 WSHPFVZKPKNXLP-UHFFFAOYSA-N 0.000 claims 1
- VOXBZHOHGGBLCQ-UHFFFAOYSA-N 2-amino-3,7-dihydropurine-6-thione;hydrate Chemical compound O.N1C(N)=NC(=S)C2=C1N=CN2.N1C(N)=NC(=S)C2=C1N=CN2 VOXBZHOHGGBLCQ-UHFFFAOYSA-N 0.000 claims 1
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 claims 1
- GMMFTXWDTNSPRY-UHFFFAOYSA-N 3-[3-[4-(2-cyclopropyl-1h-imidazol-5-yl)phenyl]-8-(2-methylprop-2-enylamino)imidazo[1,2-a]pyrazin-6-yl]prop-2-yn-1-ol Chemical compound C=1N=C2C(NCC(=C)C)=NC(C#CCO)=CN2C=1C(C=C1)=CC=C1C(N1)=CN=C1C1CC1 GMMFTXWDTNSPRY-UHFFFAOYSA-N 0.000 claims 1
- SLIXJNVGBFXHJA-UHFFFAOYSA-N 3-[3-[4-(2-cyclopropyl-1h-imidazol-5-yl)phenyl]-8-(4,4,4-trifluorobutylamino)imidazo[1,2-a]pyrazin-6-yl]prop-2-yn-1-ol Chemical compound C=1N=C2C(NCCCC(F)(F)F)=NC(C#CCO)=CN2C=1C(C=C1)=CC=C1C(N1)=CN=C1C1CC1 SLIXJNVGBFXHJA-UHFFFAOYSA-N 0.000 claims 1
- YQPHGJXCHXNTMG-UHFFFAOYSA-N 3-[8-(cyclobutylmethylamino)-3-[4-(2-cyclopropyl-1h-imidazol-5-yl)phenyl]imidazo[1,2-a]pyrazin-6-yl]prop-2-yn-1-ol Chemical compound N=1C(C#CCO)=CN2C(C=3C=CC(=CC=3)C=3NC(=NC=3)C3CC3)=CN=C2C=1NCC1CCC1 YQPHGJXCHXNTMG-UHFFFAOYSA-N 0.000 claims 1
- LOPVAUAMTOQZMH-UHFFFAOYSA-N 4-[2-[3-[4-(cyclopropylcarbamoyl)phenyl]-8-(2-methylpropylamino)imidazo[1,2-a]pyrazin-6-yl]ethynyl]benzamide Chemical compound C=1N=C2C(NCC(C)C)=NC(C#CC=3C=CC(=CC=3)C(N)=O)=CN2C=1C(C=C1)=CC=C1C(=O)NC1CC1 LOPVAUAMTOQZMH-UHFFFAOYSA-N 0.000 claims 1
- NECFVPYNODMISP-UHFFFAOYSA-N 4-[6-(2-cyclohexylethynyl)-8-(2-methylpropylamino)imidazo[1,2-a]pyrazin-3-yl]-n-cyclopropylbenzamide Chemical compound C=1N=C2C(NCC(C)C)=NC(C#CC3CCCCC3)=CN2C=1C(C=C1)=CC=C1C(=O)NC1CC1 NECFVPYNODMISP-UHFFFAOYSA-N 0.000 claims 1
- PNNPELOXIAYGKY-UHFFFAOYSA-N 4-[6-(2-cyclopentylethynyl)-8-(2-methylpropylamino)imidazo[1,2-a]pyrazin-3-yl]-n-cyclopropylbenzamide Chemical compound C=1N=C2C(NCC(C)C)=NC(C#CC3CCCC3)=CN2C=1C(C=C1)=CC=C1C(=O)NC1CC1 PNNPELOXIAYGKY-UHFFFAOYSA-N 0.000 claims 1
- VHQGSJZKTKAZKM-UHFFFAOYSA-N 4-[6-(3-aminoprop-1-ynyl)-8-(2-methylpropylamino)imidazo[1,2-a]pyrazin-3-yl]-n-cyclopropylbenzamide Chemical compound C=1N=C2C(NCC(C)C)=NC(C#CCN)=CN2C=1C(C=C1)=CC=C1C(=O)NC1CC1 VHQGSJZKTKAZKM-UHFFFAOYSA-N 0.000 claims 1
- NZRVNQXILCXBFD-UHFFFAOYSA-N 4-[6-(5-cyanopent-1-ynyl)-8-(2-methylpropylamino)imidazo[1,2-a]pyrazin-3-yl]-n-cyclopropylbenzamide Chemical compound C=1N=C2C(NCC(C)C)=NC(C#CCCCC#N)=CN2C=1C(C=C1)=CC=C1C(=O)NC1CC1 NZRVNQXILCXBFD-UHFFFAOYSA-N 0.000 claims 1
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| TWI541243B (zh) | 2010-09-10 | 2016-07-11 | 拜耳知識產權公司 | 經取代咪唑并嗒 |
| WO2012080236A1 (en) * | 2010-12-17 | 2012-06-21 | Bayer Pharma Aktiengesellschaft | 6-substituted imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| US9212184B2 (en) * | 2010-12-17 | 2015-12-15 | Bayer Intellectual Property Gmbh | 6-thio-substituted imidazo[1,2-a]pyrazines as Mps-1 inhibitors |
| WO2012080230A1 (en) * | 2010-12-17 | 2012-06-21 | Bayer Pharma Aktiengesellschaft | 6 substituted imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| WO2012080234A1 (en) * | 2010-12-17 | 2012-06-21 | Bayer Pharma Aktiengesellschaft | Substituted 6-imidazopyrazines for use as mps-1 and tkk inhibitors in the treatment of hyperproliferative disorders |
| US9512126B2 (en) | 2012-03-14 | 2016-12-06 | Bayer Intellectual Property Gmbh | Substituted imidazopyridazines |
| WO2014020043A1 (en) | 2012-08-02 | 2014-02-06 | Bayer Pharma Aktiengesellschaft | Combinations for the treatment of cancer |
| WO2014020041A1 (en) | 2012-08-02 | 2014-02-06 | Bayer Pharma Aktiengesellschaft | Combinations for the treatment of cancer |
| JP6377068B2 (ja) | 2012-11-16 | 2018-08-22 | ユニバーシティ・ヘルス・ネットワーク | ピラゾロピリミジン化合物 |
| JP6095857B2 (ja) * | 2013-11-15 | 2017-03-15 | ユニバーシティ・ヘルス・ネットワーク | ピラゾロピリミジン化合物 |
| CA2981844A1 (en) | 2015-04-17 | 2016-10-20 | Netherlands Translational Research Center B.V. | Prognostic biomarkers for ttk inhibitor chemotherapy |
| WO2019245590A1 (en) | 2018-06-18 | 2019-12-26 | Avista Pharma Solutions, Inc. | Chemical compounds |
| CA3128024A1 (en) | 2019-01-30 | 2020-08-06 | Avista Pharma Solutions, Inc. | Chemical compounds |
| WO2020160074A1 (en) | 2019-01-30 | 2020-08-06 | Avista Pharma Solutions, Inc. | Synthetic process and novel intermediates |
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| US5023252A (en) | 1985-12-04 | 1991-06-11 | Conrex Pharmaceutical Corporation | Transdermal and trans-membrane delivery of drugs |
| US5011472A (en) | 1988-09-06 | 1991-04-30 | Brown University Research Foundation | Implantable delivery system for biological factors |
| US7576085B2 (en) | 2002-09-23 | 2009-08-18 | Schering Corporation | Imidazopyrazines as cyclin dependent kinase inhibitors |
| ATE377600T1 (de) | 2002-09-23 | 2007-11-15 | Schering Corp | Imidazopyrazine als cdk-inhibitoren |
| US7186832B2 (en) | 2003-02-20 | 2007-03-06 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
| US7157460B2 (en) | 2003-02-20 | 2007-01-02 | Sugen Inc. | Use of 8-amino-aryl-substituted imidazopyrazines as kinase inhibitors |
| AR056785A1 (es) | 2005-11-10 | 2007-10-24 | Schering Corp | COMPUESTOS DE IMIDAZO[1,2-A]PIRAZINAS, uTILES COMO INHIBIDORES, REGULADORES O MODULADORES DE PROTEINQUINASAS |
| TW200803863A (en) | 2005-11-10 | 2008-01-16 | Schering Corp | Method for inhibiting protein kinases |
| US7893058B2 (en) | 2006-05-15 | 2011-02-22 | Janssen Pharmaceutica Nv | Imidazolopyrazine compounds useful for the treatment of degenerative and inflammatory diseases |
| US20090175852A1 (en) | 2006-06-06 | 2009-07-09 | Schering Corporation | Imidazopyrazines as protein kinase inhibitors |
| AR061229A1 (es) | 2006-06-06 | 2008-08-13 | Schering Corp | Imidazopirazinas como inhibidores de la proteina quinasa |
| WO2008030795A2 (en) | 2006-09-05 | 2008-03-13 | Boards Of Regents, The University Of Texas System | Compositions and methods for inhibition of tyrosine kinases |
| US8268809B2 (en) | 2006-09-05 | 2012-09-18 | Emory University | Kinase inhibitors for preventing or treating pathogen infection and method of use thereof |
| WO2008057512A2 (en) | 2006-11-08 | 2008-05-15 | Schering Corporation | Imidazopyrazines as protein kinase inhibitors |
| US20100298314A1 (en) | 2006-12-20 | 2010-11-25 | Schering Corporation | Novel jnk inhibitors |
| PE20090365A1 (es) * | 2007-06-14 | 2009-04-04 | Schering Corp | Imidazopirazinas como inhibidores de proteina quinasa |
| KR20100042287A (ko) | 2007-07-31 | 2010-04-23 | 쉐링 코포레이션 | 항암요법으로서의 항-유사분열제 및 아우로라 키나제 억제제 조합물 |
| GB0716292D0 (en) | 2007-08-21 | 2007-09-26 | Biofocus Dpi Ltd | Imidazopyrazine compounds |
| CA2710929A1 (en) | 2008-01-28 | 2009-08-06 | Schering Corporation | Imidazopyrazines as protein kinase inhibitors |
| JP2010111624A (ja) * | 2008-11-06 | 2010-05-20 | Shionogi & Co Ltd | Ttk阻害作用を有するインダゾール誘導体 |
| GB0822981D0 (en) * | 2008-12-17 | 2009-01-21 | Summit Corp Plc | Compounds for treatment of duchenne muscular dystrophy |
| CA2760077A1 (en) | 2009-04-29 | 2010-11-04 | Marcus Koppitz | Substituted imidazoquinoxalines |
| TW201107329A (en) * | 2009-07-30 | 2011-03-01 | Oncotherapy Science Inc | Fused imidazole derivative having ttk inhibitory action |
| CN102596932A (zh) | 2009-09-04 | 2012-07-18 | 拜耳医药股份有限公司 | 作为酪氨酸苏氨酸激酶抑制剂的取代氨基喹喔啉 |
| JP5802676B2 (ja) * | 2009-12-04 | 2015-10-28 | センワ バイオサイエンシズ インコーポレイテッド | Ck2阻害剤としてのピラゾロピリミジンおよび関連複素環化合物 |
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2011
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- 2011-05-27 EP EP11725886.3A patent/EP2576560B1/en active Active
- 2011-05-27 WO PCT/EP2011/058713 patent/WO2011151259A1/en not_active Ceased
- 2011-05-27 CN CN201180038047.1A patent/CN103038235B/zh not_active Expired - Fee Related
- 2011-05-27 US US13/700,956 patent/US9199999B2/en not_active Expired - Fee Related
- 2011-05-27 ES ES11725886.3T patent/ES2555261T3/es active Active
- 2011-05-27 CA CA2801031A patent/CA2801031A1/en not_active Abandoned
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