JP2014525454A5 - - Google Patents
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- Publication number
- JP2014525454A5 JP2014525454A5 JP2014528568A JP2014528568A JP2014525454A5 JP 2014525454 A5 JP2014525454 A5 JP 2014525454A5 JP 2014528568 A JP2014528568 A JP 2014528568A JP 2014528568 A JP2014528568 A JP 2014528568A JP 2014525454 A5 JP2014525454 A5 JP 2014525454A5
- Authority
- JP
- Japan
- Prior art keywords
- fluoro
- methyl
- amide
- cancer
- pharmaceutically acceptable
- 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
- 150000001875 compounds Chemical class 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 21
- 201000010099 disease Diseases 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 20
- 230000002062 proliferating effect Effects 0.000 claims description 20
- -1 PD0325901 Chemical compound 0.000 claims description 19
- 229940124647 MEK inhibitor Drugs 0.000 claims description 14
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 claims description 14
- ACWZRVQXLIRSDF-UHFFFAOYSA-N binimetinib Chemical compound OCCONC(=O)C=1C=C2N(C)C=NC2=C(F)C=1NC1=CC=C(Br)C=C1F ACWZRVQXLIRSDF-UHFFFAOYSA-N 0.000 claims description 11
- BSMCAPRUBJMWDF-KRWDZBQOSA-N cobimetinib Chemical compound C1C(O)([C@H]2NCCCC2)CN1C(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1F BSMCAPRUBJMWDF-KRWDZBQOSA-N 0.000 claims description 11
- FIMYFEGKMOCQKT-UHFFFAOYSA-N 3,4-difluoro-2-(2-fluoro-4-iodoanilino)-n-(2-hydroxyethoxy)-5-[(3-oxooxazinan-2-yl)methyl]benzamide Chemical compound FC=1C(F)=C(NC=2C(=CC(I)=CC=2)F)C(C(=O)NOCCO)=CC=1CN1OCCCC1=O FIMYFEGKMOCQKT-UHFFFAOYSA-N 0.000 claims description 10
- UIYYKSUHRZUEQP-VIFPVBQESA-N 5-fluoro-2-(2-fluoro-4-methylsulfanylanilino)-n-[(2s)-2-hydroxypropoxy]-1-methyl-6-oxopyridine-3-carboxamide Chemical compound FC1=CC(SC)=CC=C1NC1=C(C(=O)NOC[C@H](C)O)C=C(F)C(=O)N1C UIYYKSUHRZUEQP-VIFPVBQESA-N 0.000 claims description 9
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 9
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 claims description 9
- 206010009944 Colon cancer Diseases 0.000 claims description 8
- 102000038030 PI3Ks Human genes 0.000 claims description 8
- 108091007960 PI3Ks Proteins 0.000 claims description 8
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 claims description 8
- 208000006265 Renal cell carcinoma Diseases 0.000 claims description 8
- LIRYPHYGHXZJBZ-UHFFFAOYSA-N trametinib Chemical compound CC(=O)NC1=CC=CC(N2C(N(C3CC3)C(=O)C3=C(NC=4C(=CC(I)=CC=4)F)N(C)C(=O)C(C)=C32)=O)=C1 LIRYPHYGHXZJBZ-UHFFFAOYSA-N 0.000 claims description 8
- OAWXZFGKDDFTGS-BYPYZUCNSA-N (2s)-pyrrolidine-1,2-dicarboxylic acid Chemical compound OC(=O)[C@@H]1CCCN1C(O)=O OAWXZFGKDDFTGS-BYPYZUCNSA-N 0.000 claims description 7
- 239000012828 PI3K inhibitor Substances 0.000 claims description 7
- 238000000034 method Methods 0.000 claims description 7
- 229940043441 phosphoinositide 3-kinase inhibitor Drugs 0.000 claims description 7
- MWUFVYLAWAXDHQ-HMNLTAHHSA-N (2e,5s,6s,8z,10r,11s)-17-(ethylamino)-5,6,15-trihydroxy-10,11-dimethyl-12-oxabicyclo[12.4.0]octadeca-1(18),2,8,14,16-pentaene-7,13-dione Chemical compound O([C@@H](C)[C@H](C)\C=C/C(=O)[C@@H](O)[C@@H](O)C/C=C/1)C(=O)C=2C\1=CC(NCC)=CC=2O MWUFVYLAWAXDHQ-HMNLTAHHSA-N 0.000 claims description 6
- GFMMXOIFOQCCGU-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-N-(cyclopropylmethoxy)-3,4-difluorobenzamide Chemical compound C=1C=C(I)C=C(Cl)C=1NC1=C(F)C(F)=CC=C1C(=O)NOCC1CC1 GFMMXOIFOQCCGU-UHFFFAOYSA-N 0.000 claims description 6
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 6
- 201000003793 Myelodysplastic syndrome Diseases 0.000 claims description 6
- 230000002401 inhibitory effect Effects 0.000 claims description 6
- RDSACQWTXKSHJT-NSHDSACASA-N n-[3,4-difluoro-2-(2-fluoro-4-iodoanilino)-6-methoxyphenyl]-1-[(2s)-2,3-dihydroxypropyl]cyclopropane-1-sulfonamide Chemical compound C1CC1(C[C@H](O)CO)S(=O)(=O)NC=1C(OC)=CC(F)=C(F)C=1NC1=CC=C(I)C=C1F RDSACQWTXKSHJT-NSHDSACASA-N 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims description 4
- 208000008839 Kidney Neoplasms Diseases 0.000 claims description 4
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims description 4
- 208000009905 Neurofibromatoses Diseases 0.000 claims description 4
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims description 4
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 4
- 206010038389 Renal cancer Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 201000004101 esophageal cancer Diseases 0.000 claims description 4
- 206010073071 hepatocellular carcinoma Diseases 0.000 claims description 4
- 231100000844 hepatocellular carcinoma Toxicity 0.000 claims description 4
- 201000010982 kidney cancer Diseases 0.000 claims description 4
- 201000007270 liver cancer Diseases 0.000 claims description 4
- 208000014018 liver neoplasm Diseases 0.000 claims description 4
- 201000005202 lung cancer Diseases 0.000 claims description 4
- 208000020816 lung neoplasm Diseases 0.000 claims description 4
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 4
- 201000001441 melanoma Diseases 0.000 claims description 4
- 201000004931 neurofibromatosis Diseases 0.000 claims description 4
- 201000002528 pancreatic cancer Diseases 0.000 claims description 4
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- 102000043136 MAP kinase family Human genes 0.000 claims description 2
- 108091054455 MAP kinase family Proteins 0.000 claims description 2
- 206010028980 Neoplasm Diseases 0.000 claims description 2
- 208000029742 colonic neoplasm Diseases 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- 229940124597 therapeutic agent Drugs 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims 2
- 208000011580 syndromic disease Diseases 0.000 claims 2
- 229960004066 trametinib Drugs 0.000 claims 2
- IHGVAVLSTPCCJP-UHFFFAOYSA-N 4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-amine Chemical compound N1=C(N)SC(C=2C=C(N=CC=2)C(C)(C)C(F)(F)F)=C1C IHGVAVLSTPCCJP-UHFFFAOYSA-N 0.000 claims 1
- 230000015572 biosynthetic process Effects 0.000 claims 1
- WWWTWPXKLJTKPM-UHFFFAOYSA-N 2-aminooxyethanol Chemical compound NOCCO WWWTWPXKLJTKPM-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 206010069755 K-ras gene mutation Diseases 0.000 description 1
- 102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201161529380P | 2011-08-31 | 2011-08-31 | |
| US61/529,380 | 2011-08-31 | ||
| US201161542463P | 2011-10-03 | 2011-10-03 | |
| US61/542,463 | 2011-10-03 | ||
| PCT/US2012/052955 WO2013066483A1 (en) | 2011-08-31 | 2012-08-30 | Synergistic combinations of pi3k- and mek-inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014525454A JP2014525454A (ja) | 2014-09-29 |
| JP2014525454A5 true JP2014525454A5 (https=) | 2015-10-15 |
| JP6058009B2 JP6058009B2 (ja) | 2017-01-11 |
Family
ID=47720713
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014528568A Active JP6058009B2 (ja) | 2011-08-31 | 2012-08-30 | Ｐｉ３ｋ−およびｍｅｋ−阻害剤の相乗的な組合せ |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US9675595B2 (https=) |
| EP (1) | EP2750675A1 (https=) |
| JP (1) | JP6058009B2 (https=) |
| KR (1) | KR20140072028A (https=) |
| CN (1) | CN103764144B (https=) |
| AU (1) | AU2012333092B2 (https=) |
| BR (1) | BR112014004587A2 (https=) |
| CA (1) | CA2846454A1 (https=) |
| MX (1) | MX2014002471A (https=) |
| RU (1) | RU2607944C2 (https=) |
| WO (1) | WO2013066483A1 (https=) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3613743B1 (en) | 2008-01-04 | 2022-03-16 | Intellikine, LLC | Processes for the preparation of 1h-pyrazolo[3,4-d]pyrimidin-4-amine derivatives |
| US8193182B2 (en) | 2008-01-04 | 2012-06-05 | Intellikine, Inc. | Substituted isoquinolin-1(2H)-ones, and methods of use thereof |
| TWI674262B (zh) | 2011-01-10 | 2019-10-11 | 美商英菲尼提製藥股份有限公司 | 製備異喹啉酮之方法及異喹啉酮之固體形式 |
| US8828998B2 (en) | 2012-06-25 | 2014-09-09 | Infinity Pharmaceuticals, Inc. | Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors |
| EP2914296B2 (en) | 2012-11-01 | 2021-09-29 | Infinity Pharmaceuticals, Inc. | Treatment of cancers using pi3 kinase isoform modulators |
| RU2015156221A (ru) * | 2013-06-11 | 2017-07-17 | Новартис Аг | Фармацевтические комбинация ингибитора pi3k и средства, дестабилизирующего микротрубочки |
| KR20160020502A (ko) * | 2013-06-18 | 2016-02-23 | 노파르티스 아게 | 제약 조합물 |
| BR112016012141A2 (pt) * | 2014-01-15 | 2017-08-08 | Novartis Ag | "combinações farmacêuticas, uso das mesmas, e embalagem comercial" |
| WO2015160975A2 (en) | 2014-04-16 | 2015-10-22 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| US20150320754A1 (en) * | 2014-04-16 | 2015-11-12 | Infinity Pharmaceuticals, Inc. | Combination therapies |
| AU2016349279A1 (en) * | 2015-11-03 | 2018-05-10 | Board Of Regents, The University Of Texas System | Combination of Bcl-2 inhibitor and MEK inhibitor for the treatment of cancer |
| RU2754507C2 (ru) | 2016-06-24 | 2021-09-02 | Инфинити Фармасьютикалз, Инк. | Комбинированная терапия |
| WO2020053125A1 (en) * | 2018-09-10 | 2020-03-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the treatment of neurofibromatosis |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DZ3401A1 (fr) | 2000-07-19 | 2002-01-24 | Warner Lambert Co | Esters oxygenes d'acides 4-iodophenylamino benzhydroxamiques |
| RU2192861C1 (ru) | 2001-06-29 | 2002-11-20 | Новосибирский институт биоорганической химии СО РАН | Композиция для антибластической терапии |
| SG2013013339A (en) * | 2002-03-13 | 2014-12-30 | Array Biopharma Inc | N3 alkylated benzimidazole derivatives as mek inhibitors |
| US7235537B2 (en) * | 2002-03-13 | 2007-06-26 | Array Biopharma, Inc. | N3 alkylated benzimidazole derivatives as MEK inhibitors |
| US7378423B2 (en) | 2004-06-11 | 2008-05-27 | Japan Tobacco Inc. | Pyrimidine compound and medical use thereof |
| AU2005252110B2 (en) | 2004-06-11 | 2008-09-04 | Shionogi & Co., Ltd. | 5-amino-2,4,7-trioxo-3,4,7,8-tetrahydro-2H-pyrido[2,3-D] pyrimidine derivatives and related compounds for the treatment of cancer |
| RU2368602C2 (ru) * | 2005-01-26 | 2009-09-27 | Айрм Ллк | Соединения и композиции в качестве ингибиторов протеинкиназ |
| SG177981A1 (en) | 2005-05-18 | 2012-02-28 | Array Biopharma Inc | 4-(phenylamino)-6-oxo-1, 6-dihydropyridazine-3-carboxamide derivatives as mek inhibitors for the treatment of hyperproliferative diseases |
| GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
| PE20070335A1 (es) | 2005-08-30 | 2007-04-21 | Novartis Ag | Benzimidazoles sustituidos y metodos para su preparacion |
| JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
| DK2074122T5 (da) | 2006-09-15 | 2014-03-17 | Pfizer Prod Inc | Pyrido (2, 3-d) pyrimidin0n-forbindelser og anvendelse deraf som pi3 inhibitorer |
| KR20110028651A (ko) * | 2008-07-11 | 2011-03-21 | 노파르티스 아게 | (ａ) 포스포이노시타이드 3-키나제 억제제 및 (ｂ) ｒａｓ/ｒａｆ/ｍｅｋ 경로의 조절제의 조합물 |
| UA104147C2 (uk) * | 2008-09-10 | 2014-01-10 | Новартис Аг | Похідна піролідиндикарбонової кислоти та її застосування у лікуванні проліферативних захворювань |
| KR101489045B1 (ko) * | 2009-10-12 | 2015-02-02 | 에프. 호프만-라 로슈 아게 | Ｐｉ3ｋ 억제자 및 ｍｅｋ 억제자의 조합 |
-
2012
- 2012-08-30 CN CN201280041783.7A patent/CN103764144B/zh not_active Expired - Fee Related
- 2012-08-30 US US14/240,499 patent/US9675595B2/en active Active
- 2012-08-30 KR KR1020147004859A patent/KR20140072028A/ko not_active Ceased
- 2012-08-30 RU RU2014112198A patent/RU2607944C2/ru not_active IP Right Cessation
- 2012-08-30 JP JP2014528568A patent/JP6058009B2/ja active Active
- 2012-08-30 CA CA2846454A patent/CA2846454A1/en not_active Abandoned
- 2012-08-30 BR BR112014004587A patent/BR112014004587A2/pt not_active IP Right Cessation
- 2012-08-30 MX MX2014002471A patent/MX2014002471A/es unknown
- 2012-08-30 EP EP12824789.7A patent/EP2750675A1/en not_active Withdrawn
- 2012-08-30 WO PCT/US2012/052955 patent/WO2013066483A1/en not_active Ceased
- 2012-08-30 AU AU2012333092A patent/AU2012333092B2/en not_active Ceased
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