ES2756748T3 - Uso de derivados de piridilo bicíclicos de anillo fusionado como inhibidores de fgfr4 - Google Patents
Uso de derivados de piridilo bicíclicos de anillo fusionado como inhibidores de fgfr4 Download PDFInfo
- Publication number
- ES2756748T3 ES2756748T3 ES15781518T ES15781518T ES2756748T3 ES 2756748 T3 ES2756748 T3 ES 2756748T3 ES 15781518 T ES15781518 T ES 15781518T ES 15781518 T ES15781518 T ES 15781518T ES 2756748 T3 ES2756748 T3 ES 2756748T3
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- Prior art keywords
- alkyl
- fgfr4
- ring
- dihydro
- carboxamide
- Prior art date
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- 101150082429 FGFR4 gene Proteins 0.000 title 1
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- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 42
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- 150000001860 citric acid derivatives Chemical class 0.000 claims description 3
- HXNZAVZZAPTZBP-UHFFFAOYSA-N N-(5-cyanopyridin-2-yl)-7-formyl-6-(hydroxymethyl)-3,4-dihydro-2H-1,8-naphthyridine-1-carboxamide Chemical compound OCc1cc2CCCN(C(=O)Nc3ccc(cn3)C#N)c2nc1C=O HXNZAVZZAPTZBP-UHFFFAOYSA-N 0.000 claims 1
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- BJEPYKJPYRNKOW-UHFFFAOYSA-L malate(2-) Chemical group [O-]C(=O)C(O)CC([O-])=O BJEPYKJPYRNKOW-UHFFFAOYSA-L 0.000 claims 1
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 abstract description 5
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- ZZBWJSLHFRIKGH-UHFFFAOYSA-N phenyl 7-(dimethoxymethyl)-3,4-dihydro-2H-1,8-naphthyridine-1-carboxylate Chemical compound COC(OC)c1ccc2CCCN(C(=O)Oc3ccccc3)c2n1 ZZBWJSLHFRIKGH-UHFFFAOYSA-N 0.000 description 1
- FNAPZFAKBBOCSZ-UHFFFAOYSA-N phenyl 7-(dimethoxymethyl)-6-iodo-3,4-dihydro-2H-1,8-naphthyridine-1-carboxylate Chemical compound COC(OC)c1nc2N(CCCc2cc1I)C(=O)Oc1ccccc1 FNAPZFAKBBOCSZ-UHFFFAOYSA-N 0.000 description 1
- BGVAIBDDJMMAML-UHFFFAOYSA-N phenyl n-(5-cyanopyridin-2-yl)carbamate Chemical compound C=1C=CC=CC=1OC(=O)NC1=CC=C(C#N)C=N1 BGVAIBDDJMMAML-UHFFFAOYSA-N 0.000 description 1
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- 125000004193 piperazinyl group Chemical group 0.000 description 1
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- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4375—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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| CN2014088094 | 2014-10-03 | ||
| PCT/US2015/053677 WO2016054483A1 (en) | 2014-10-03 | 2015-10-02 | Use of ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors |
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| PL (1) | PL3200786T3 (enExample) |
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| EP3200786B1 (en) * | 2014-10-03 | 2019-08-28 | Novartis AG | Use of ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors |
| CN113234072B (zh) * | 2016-05-20 | 2022-11-04 | 江苏豪森药业集团有限公司 | Fgfr4抑制剂、其制备方法和应用 |
| WO2018055503A1 (en) | 2016-09-20 | 2018-03-29 | Novartis Ag | Combination comprising a pd-1 antagonist and an fgfr4 inhibitor |
| JP7394623B2 (ja) * | 2016-11-02 | 2023-12-08 | ノバルティス アーゲー | Ｆｇｆｒ４インヒビターおよび胆汁酸捕捉薬の組合せ |
| TWI723480B (zh) * | 2018-07-27 | 2021-04-01 | 大陸商北京加科思新藥研發有限公司 | 用作fgfr4抑制劑的稠環衍生物 |
| AU2020242287A1 (en) | 2019-03-21 | 2021-09-02 | INSERM (Institut National de la Santé et de la Recherche Médicale) | A Dbait molecule in combination with kinase inhibitor for the treatment of cancer |
| KR20220098759A (ko) | 2019-11-08 | 2022-07-12 | 인쎄름 (엥스띠뛰 나씨오날 드 라 쌍떼 에 드 라 흐쉐르슈 메디깔) | 키나제 억제제에 대해 내성을 획득한 암의 치료 방법 |
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| BR112015000653A2 (pt) | 2012-07-11 | 2019-11-05 | Blueprint Medicines Corp | compostos inibidores do receptor de fator de crescimento de fibroblasto, sua composição farmacêutica e seus usos |
| WO2014059202A1 (en) | 2012-10-12 | 2014-04-17 | Bristol-Myers Squibb Company | Guanidine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| US9403774B2 (en) | 2012-10-12 | 2016-08-02 | Bristol-Myers Squibb Company | Guanidine and amine substituted tetrahydroisoquinoline compounds as factor xia inhibitors |
| WO2014079709A1 (en) | 2012-11-23 | 2014-05-30 | Ab Science | Use of small molecule inhibitors/activators in combination with (deoxy)nucleoside or (deoxy)nucleotide analogs for treatment of cancer and hematological malignancies or viral infections |
| AU2014228746B2 (en) | 2013-03-15 | 2018-08-30 | Celgene Car Llc | Heteroaryl compounds and uses thereof |
| US9321786B2 (en) | 2013-03-15 | 2016-04-26 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| KR102469849B1 (ko) | 2013-04-19 | 2022-11-23 | 인사이트 홀딩스 코포레이션 | Fgfr 저해제로서 이환식 헤테로사이클 |
| GB201307577D0 (en) | 2013-04-26 | 2013-06-12 | Astex Therapeutics Ltd | New compounds |
| EP3019491A4 (en) | 2013-07-09 | 2016-12-21 | Dana Farber Cancer Inst Inc | KINASEHEMMER FOR THE TREATMENT OF DISEASES |
| TW201605452A (zh) | 2013-08-28 | 2016-02-16 | 安斯泰來製藥股份有限公司 | 以嘧啶化合物作爲有效成分之醫藥組成物 |
| SG11201602069WA (en) | 2013-10-18 | 2016-04-28 | Eisai R&D Man Co Ltd | Pyrimidine fgfr4 inhibitors |
| DK3395814T3 (da) | 2013-10-25 | 2022-07-04 | Blueprint Medicines Corp | Hæmmere af fibroblastvækstfaktorreceptoren |
| AU2014338549B2 (en) * | 2013-10-25 | 2017-05-25 | Novartis Ag | Ring-fused bicyclic pyridyl derivatives as FGFR4 inhibitors |
| US10456449B2 (en) | 2014-06-16 | 2019-10-29 | Ngm Biopharmaceuticals, Inc. | Methods and uses for modulating bile acid homeostasis and treatment of bile acid disorders and diseases |
| EP3200786B1 (en) * | 2014-10-03 | 2019-08-28 | Novartis AG | Use of ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors |
| US9802917B2 (en) * | 2015-03-25 | 2017-10-31 | Novartis Ag | Particles of N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide |
| EP3273959A1 (en) * | 2015-03-25 | 2018-01-31 | Novartis Ag | Pharmaceutical combinations |
| JP7394623B2 (ja) | 2016-11-02 | 2023-12-08 | ノバルティス アーゲー | Ｆｇｆｒ４インヒビターおよび胆汁酸捕捉薬の組合せ |
-
2015
- 2015-10-02 EP EP15781518.4A patent/EP3200786B1/en active Active
- 2015-10-02 WO PCT/US2015/053677 patent/WO2016054483A1/en not_active Ceased
- 2015-10-02 PL PL15781518T patent/PL3200786T3/pl unknown
- 2015-10-02 US US15/516,443 patent/US20180185341A1/en not_active Abandoned
- 2015-10-02 JP JP2017517705A patent/JP6585167B2/ja active Active
- 2015-10-02 ES ES15781518T patent/ES2756748T3/es active Active
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2018
- 2018-11-13 US US16/190,087 patent/US10463653B2/en active Active
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2019
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- 2019-09-04 JP JP2019161051A patent/JP6794514B2/ja active Active
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| Publication number | Publication date |
|---|---|
| WO2016054483A1 (en) | 2016-04-07 |
| JP2019218398A (ja) | 2019-12-26 |
| US20190076412A1 (en) | 2019-03-14 |
| US10463653B2 (en) | 2019-11-05 |
| US10507201B2 (en) | 2019-12-17 |
| PL3200786T3 (pl) | 2020-03-31 |
| JP6585167B2 (ja) | 2019-10-02 |
| JP6794514B2 (ja) | 2020-12-02 |
| EP3200786B1 (en) | 2019-08-28 |
| EP3200786A1 (en) | 2017-08-09 |
| US20190231760A1 (en) | 2019-08-01 |
| US20180185341A1 (en) | 2018-07-05 |
| JP2017530154A (ja) | 2017-10-12 |
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