JP2014513138A5 - - Google Patents
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- Publication number
- JP2014513138A5 JP2014513138A5 JP2014509505A JP2014509505A JP2014513138A5 JP 2014513138 A5 JP2014513138 A5 JP 2014513138A5 JP 2014509505 A JP2014509505 A JP 2014509505A JP 2014509505 A JP2014509505 A JP 2014509505A JP 2014513138 A5 JP2014513138 A5 JP 2014513138A5
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- aryl
- mtor inhibitor
- item
- cancer
- 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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- 125000000217 alkyl group Chemical group 0.000 claims description 128
- RWRIWBAIICGTTQ-UHFFFAOYSA-N difluoromethane Chemical compound FCF RWRIWBAIICGTTQ-UHFFFAOYSA-N 0.000 claims description 127
- 125000003118 aryl group Chemical group 0.000 claims description 49
- 229940124302 mTOR inhibitor Drugs 0.000 claims description 41
- 239000003628 mammalian target of rapamycin inhibitor Substances 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 31
- 125000001072 heteroaryl group Chemical group 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 229940079593 drug Drugs 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 230000002062 proliferating effect Effects 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 7
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 6
- 230000001613 neoplastic effect Effects 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 3
- 208000026310 Breast neoplasm Diseases 0.000 claims description 3
- 206010009944 Colon cancer Diseases 0.000 claims description 3
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 3
- 206010014733 Endometrial cancer Diseases 0.000 claims description 3
- 206010014759 Endometrial neoplasm Diseases 0.000 claims description 3
- 206010033128 Ovarian cancer Diseases 0.000 claims description 3
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 3
- 229930012538 Paclitaxel Natural products 0.000 claims description 3
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 3
- 208000000102 Squamous Cell Carcinoma of Head and Neck Diseases 0.000 claims description 3
- 201000000459 head and neck squamous cell carcinoma Diseases 0.000 claims description 3
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 3
- 201000002120 neuroendocrine carcinoma Diseases 0.000 claims description 3
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 3
- 229960001592 paclitaxel Drugs 0.000 claims description 3
- 201000002528 pancreatic cancer Diseases 0.000 claims description 3
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 3
- 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 3
- 230000003442 weekly effect Effects 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 4
- 208000007766 Kaposi sarcoma Diseases 0.000 claims 1
- 101710088998 Response regulator inhibitor for tor operon Proteins 0.000 claims 1
- 208000015347 renal cell adenocarcinoma Diseases 0.000 claims 1
- 125000000304 alkynyl group Chemical group 0.000 description 56
- 125000005843 halogen group Chemical group 0.000 description 26
- 125000004093 cyano group Chemical group *C#N 0.000 description 17
- 125000004404 heteroalkyl group Chemical group 0.000 description 17
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 125000002877 alkyl aryl group Chemical group 0.000 description 12
- 125000000753 cycloalkyl group Chemical group 0.000 description 12
- 102000008135 Mechanistic Target of Rapamycin Complex 1 Human genes 0.000 description 10
- 108010035196 Mechanistic Target of Rapamycin Complex 1 Proteins 0.000 description 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 9
- 229910052736 halogen Inorganic materials 0.000 description 8
- 150000002367 halogens Chemical class 0.000 description 8
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 8
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 7
- 229960002930 sirolimus Drugs 0.000 description 7
- 102000009308 Mechanistic Target of Rapamycin Complex 2 Human genes 0.000 description 6
- 108010034057 Mechanistic Target of Rapamycin Complex 2 Proteins 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- 125000002950 monocyclic group Chemical group 0.000 description 6
- 239000003744 tubulin modulator Substances 0.000 description 6
- -1 C 2-10 Arkeni Ru Chemical group 0.000 description 5
- BUROJSBIWGDYCN-GAUTUEMISA-N AP 23573 Chemical compound C1C[C@@H](OP(C)(C)=O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 BUROJSBIWGDYCN-GAUTUEMISA-N 0.000 description 4
- 230000010190 G1 phase Effects 0.000 description 4
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 4
- 125000005024 alkenyl aryl group Chemical group 0.000 description 4
- 125000003545 alkoxy group Chemical group 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 230000018486 cell cycle phase Effects 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000004446 heteroarylalkyl group Chemical group 0.000 description 4
- 238000000021 kinase assay Methods 0.000 description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 description 4
- 229960001302 ridaforolimus Drugs 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 3
- 125000000392 cycloalkenyl group Chemical group 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 102000004243 Tubulin Human genes 0.000 description 2
- 108090000704 Tubulin Proteins 0.000 description 2
- 125000005025 alkynylaryl group Chemical group 0.000 description 2
- 125000003710 aryl alkyl group Chemical group 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 125000004043 oxo group Chemical group O=* 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 229960000235 temsirolimus Drugs 0.000 description 2
- QFJCIRLUMZQUOT-UHFFFAOYSA-N temsirolimus Natural products C1CC(O)C(OC)CC1CC(C)C1OC(=O)C2CCCCN2C(=O)C(=O)C(O)(O2)C(C)CCC2CC(OC)C(C)=CC=CC=CC(C)CC(C)C(=O)C(OC)C(O)C(C)=CC(C)C(=O)C1 QFJCIRLUMZQUOT-UHFFFAOYSA-N 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- YYSFXUWWPNHNAZ-PKJQJFMNSA-N umirolimus Chemical compound C1[C@@H](OC)[C@H](OCCOCC)CC[C@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 YYSFXUWWPNHNAZ-PKJQJFMNSA-N 0.000 description 2
- CGTADGCBEXYWNE-GTTQIJKGSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](\C(C)=C\C=C\C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-GTTQIJKGSA-N 0.000 description 2
- 241000257303 Hymenoptera Species 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical class O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910000077 silane Inorganic materials 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161482568P | 2011-05-04 | 2011-05-04 | |
| US61/482,568 | 2011-05-04 | ||
| PCT/US2012/036688 WO2012151562A1 (en) | 2011-05-04 | 2012-05-04 | Combination pharmaceutical compositions and uses thereof |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014513138A JP2014513138A (ja) | 2014-05-29 |
| JP2014513138A5 true JP2014513138A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 2015-06-25 |
| JP6047149B2 JP6047149B2 (ja) | 2016-12-21 |
Family
ID=47108075
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014509505A Active JP6047149B2 (ja) | 2011-05-04 | 2012-05-04 | 併用の医薬組成物およびその使用 |
Country Status (7)
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9512125B2 (en) | 2004-11-19 | 2016-12-06 | The Regents Of The University Of California | Substituted pyrazolo[3.4-D] pyrimidines as anti-inflammatory agents |
| US20110224223A1 (en) | 2008-07-08 | 2011-09-15 | The Regents Of The University Of California, A California Corporation | MTOR Modulators and Uses Thereof |
| CN103703174B (zh) | 2011-05-04 | 2017-05-10 | 因特利凯有限责任公司 | 联合药物组合物及其用途 |
| WO2012154695A2 (en) * | 2011-05-06 | 2012-11-15 | The Regents Of The University Of California | Treatment of polycystic disease |
| US9724354B2 (en) | 2013-03-22 | 2017-08-08 | Millennium Pharmaceuticals, Inc. | Combination of catalytic mTORC1/2 inhibitors and selective inhibitors of Aurora A kinase |
| WO2015002766A1 (en) * | 2013-07-02 | 2015-01-08 | Nikolai Khodarev | Anti-tumor therapy |
| WO2016004166A1 (en) * | 2014-07-02 | 2016-01-07 | Xavier University Of Louisiana | Boron-based prodrug strategy for increased bioavailability and lower-dosage requirements for drug molecules containing at least one phenol (or aromatic hydroxyl) group |
| EP3193902A4 (en) | 2014-09-11 | 2018-03-28 | The Regents of The University of California | mTORC1 INHIBITORS |
| US10118890B2 (en) | 2014-10-10 | 2018-11-06 | The Research Foundation For The State University Of New York | Trifluoromethoxylation of arenes via intramolecular trifluoromethoxy group migration |
| ES2749679T3 (es) | 2014-10-22 | 2020-03-23 | Bristol Myers Squibb Co | Compuestos de pirrolotriazina amina sustituidos como inhibidores de PI3k |
| EP3209664B1 (en) | 2014-10-22 | 2020-06-03 | Bristol-Myers Squibb Company | Bicyclic heteroaryl amine compounds as pi3k inhibitors |
| US10532226B2 (en) * | 2014-12-24 | 2020-01-14 | The University Of North Carolina At Chapel Hill | Combined local delivery of therapeutic agents using interventional devices and radiation |
| IL261957B (en) | 2016-03-28 | 2022-07-01 | Incyte Corp | Pyrrolotriazine compounds as tam inhibitors |
| MX387394B (es) | 2016-04-15 | 2025-03-18 | Cancer Research Tech Ltd | Compuestos heterociclicos como inhibidores de la cinasa ret. |
| HRP20221051T8 (hr) | 2016-04-15 | 2023-07-21 | Cancer Research Technology Limited | Heterociklički spojevi kao inhibitori ret kinaze |
| JP2019529520A (ja) * | 2016-10-07 | 2019-10-17 | アブラクシス バイオサイエンス， エルエルシー | 胆道がんを処置する方法 |
| GB201705971D0 (en) | 2017-04-13 | 2017-05-31 | Cancer Res Tech Ltd | Inhibitor compounds |
| FR3075794A1 (fr) | 2017-12-21 | 2019-06-28 | Galderma Research & Development | Nouveaux composes inhibiteurs de mtor |
| FR3075795A1 (fr) * | 2017-12-21 | 2019-06-28 | Galderma Research & Development | Nouveaux composes inhibiteurs de mtor |
| EP4234031A3 (en) | 2018-05-01 | 2024-02-28 | Revolution Medicines, Inc. | C40-, c28-, and c-32-linked rapamycin analogs as mtor inhibitors |
| EP3788050B1 (en) | 2018-05-01 | 2024-08-28 | Revolution Medicines, Inc. | C26-linked rapamycin analogs as mtor inhibitors |
| JP7668536B2 (ja) * | 2020-02-07 | 2025-04-25 | 範行 東 | 細胞周期のｇ１期初期制御剤 |
| US12014835B2 (en) | 2020-02-19 | 2024-06-18 | Vanderbilt University | Methods for evaluating therapeutic benefit of combination therapies |
| US20230084515A1 (en) * | 2020-02-19 | 2023-03-16 | Vanderbilt University | Therapeutic methods and compositions for treating cancer using braf and/or mek inhibitor combination therapy |
| AU2023275778A1 (en) | 2022-05-25 | 2024-12-12 | Revolution Medicines, Inc. | Methods of treating cancer with an mtor inhibitor |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001045676A2 (en) | 1999-12-20 | 2001-06-28 | Schering Corporation | Extended release oral dosage composition |
| WO2009008992A2 (en) | 2007-07-06 | 2009-01-15 | Osi Pharmaceuticals Inc. | Combination anti-cancer therapy comprising an inhibitor of both mtorc1 and mt0rc2 |
| US8993580B2 (en) * | 2008-03-14 | 2015-03-31 | Intellikine Llc | Benzothiazole kinase inhibitors and methods of use |
| NZ590258A (en) | 2008-07-08 | 2013-10-25 | Intellikine Llc | Kinase inhibitors and methods of use |
| CA2738429C (en) | 2008-09-26 | 2016-10-25 | Intellikine, Inc. | Heterocyclic kinase inhibitors |
| KR20110090911A (ko) * | 2008-10-31 | 2011-08-10 | 노파르티스 아게 | 포스파티딜이노시톨-3-키나아제 (ｐｉ3ｋ) 억제제 및 ｍｔｏｒ 억제제의 조합물 |
| US8476431B2 (en) * | 2008-11-03 | 2013-07-02 | Itellikine LLC | Benzoxazole kinase inhibitors and methods of use |
| CN103703174B (zh) | 2011-05-04 | 2017-05-10 | 因特利凯有限责任公司 | 联合药物组合物及其用途 |
-
2012
- 2012-05-04 CN CN201280033418.1A patent/CN103703174B/zh active Active
- 2012-05-04 CA CA2836769A patent/CA2836769C/en active Active
- 2012-05-04 JP JP2014509505A patent/JP6047149B2/ja active Active
- 2012-05-04 ES ES12779459.2T patent/ES2618489T3/es active Active
- 2012-05-04 WO PCT/US2012/036688 patent/WO2012151562A1/en active Application Filing
- 2012-05-04 US US14/113,982 patent/US20140357651A1/en not_active Abandoned
- 2012-05-04 EP EP12779459.2A patent/EP2705181B1/en active Active
-
2016
- 2016-04-07 US US15/092,713 patent/US10172858B2/en not_active Expired - Fee Related