MA53759A - Formes cristallines de (s)-1-(4-fluorophényl)-1-(2-(4-(6-(1-méthyl-1h-pyrazol-4-yl))pyrrolo[2,1-f][1,2,4]triazin-4-yl)pipérazinyl)-pyrimidin-5-yl)éthan-1-amine et des procédés de fabrication - Google Patents

Formes cristallines de (s)-1-(4-fluorophényl)-1-(2-(4-(6-(1-méthyl-1h-pyrazol-4-yl))pyrrolo[2,1-f][1,2,4]triazin-4-yl)pipérazinyl)-pyrimidin-5-yl)éthan-1-amine et des procédés de fabrication

Info

Publication number
MA53759A
MA53759A MA053759A MA53759A MA53759A MA 53759 A MA53759 A MA 53759A MA 053759 A MA053759 A MA 053759A MA 53759 A MA53759 A MA 53759A MA 53759 A MA53759 A MA 53759A
Authority
MA
Morocco
Prior art keywords
ethan
triazin
pyrrolo
pyrazol
pyrimidin
Prior art date
Application number
MA053759A
Other languages
English (en)
Inventor
Brian Heinrich
Lauren Maceachern
Brenton Mar
Joshua D Waetzig
Gordon Wilkie
Original Assignee
Blueprint Medicines Corp
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=70476546&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=MA53759(A) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Blueprint Medicines Corp filed Critical Blueprint Medicines Corp
Publication of MA53759A publication Critical patent/MA53759A/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • 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
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A61P35/02—Antineoplastic agents specific for leukemia
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Hematology (AREA)
  • Oncology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
MA053759A 2019-04-12 2020-04-10 Formes cristallines de (s)-1-(4-fluorophényl)-1-(2-(4-(6-(1-méthyl-1h-pyrazol-4-yl))pyrrolo[2,1-f][1,2,4]triazin-4-yl)pipérazinyl)-pyrimidin-5-yl)éthan-1-amine et des procédés de fabrication MA53759A (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201962833527P 2019-04-12 2019-04-12
US201962844575P 2019-05-07 2019-05-07
US202062990269P 2020-03-16 2020-03-16

Publications (1)

Publication Number Publication Date
MA53759A true MA53759A (fr) 2021-08-04

Family

ID=70476546

Family Applications (1)

Application Number Title Priority Date Filing Date
MA053759A MA53759A (fr) 2019-04-12 2020-04-10 Formes cristallines de (s)-1-(4-fluorophényl)-1-(2-(4-(6-(1-méthyl-1h-pyrazol-4-yl))pyrrolo[2,1-f][1,2,4]triazin-4-yl)pipérazinyl)-pyrimidin-5-yl)éthan-1-amine et des procédés de fabrication

Country Status (20)

Country Link
US (5) US12060354B2 (fr)
EP (2) EP4302761A3 (fr)
JP (1) JP7728178B2 (fr)
CN (1) CN113966334B (fr)
CA (2) CA3296895A1 (fr)
DK (1) DK3856341T3 (fr)
ES (1) ES2966512T3 (fr)
FI (1) FI3856341T3 (fr)
HR (1) HRP20231533T1 (fr)
HU (1) HUE064283T2 (fr)
IL (2) IL287148A (fr)
LT (1) LT3856341T (fr)
MA (1) MA53759A (fr)
PL (1) PL3856341T3 (fr)
PT (1) PT3856341T (fr)
RS (1) RS64881B1 (fr)
SI (1) SI3856341T1 (fr)
SM (1) SMT202300447T1 (fr)
TW (1) TWI845657B (fr)
WO (1) WO2020210669A1 (fr)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LT3057969T (lt) 2013-10-17 2018-07-10 Blueprint Medicines Corporation Kompozicijos, naudojamos gydyti sutrikimams, susijusiems su kit
ES2966512T3 (es) 2019-04-12 2024-04-22 Blueprint Medicines Corp Formas cristalinas de (S)-1-(4-fluorofenil)-1-(2-(4-(6-(1-metil-1H-pirazol-4-il)pirrolo[2,1-f][1,2,4]triazin-4-il)piperazinil)-pirimidin-5-il)etan-1-amina y métodos de elaboración
CN114341138A (zh) * 2019-07-09 2022-04-12 桑多斯股份公司 口服可用的选择性kit和pdgfr激酶抑制剂的晶型
GB201915447D0 (en) * 2019-10-24 2019-12-11 Johnson Matthey Plc Polymorphs of avapritinib and methods of preparing the polymorphs
WO2021183709A1 (fr) 2020-03-11 2021-09-16 Teva Czech Industries S.R.O Formes à l'état solide d'avapritinib et leur procédé de préparation
EP4168119A1 (fr) 2020-06-17 2023-04-26 Teva Czech Industries s.r.o. Formes à l'état solide de sels d'avapritinib
HU231413B1 (hu) 2021-02-26 2023-08-28 Egis Gyógyszergyár Zrt. Eljárás avapritinib és intermedierek előállítására
IL305611A (en) 2021-03-03 2023-11-01 Blueprint Medicines Corp Synthetic methods and intermediates for the production of compounds for the treatment of PDGFRA-mediated diseases and kits
HU231755B1 (hu) * 2022-08-11 2026-02-28 Egis Gyógyszergyár Zrt. Új avapritinib sók és előállítási eljárásaik
US20240382493A1 (en) * 2023-05-18 2024-11-21 Blueprint Medicines Corporation Methods for treating systemic mastocytosis and gastrointestinal stromal tumors
WO2025170989A1 (fr) 2024-02-05 2025-08-14 Blueprint Medicines Corporation Traits de la mastocytose systémique indolente caractéristiques d'une maladie à haut risque et méthodes de traitement

Family Cites Families (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS61238784A (ja) 1985-04-17 1986-10-24 Sumitomo Seiyaku Kk コハク酸イミド誘導体及びその酸付加塩
US6982265B1 (en) 1999-05-21 2006-01-03 Bristol Myers Squibb Company Pyrrolotriazine inhibitors of kinases
CZ303660B6 (cs) 1999-05-21 2013-02-13 Bristol-Myers Squibb Company Pyrrolotriazin a farmaceutický prostredek s jeho obsahem
JP2003511378A (ja) 1999-10-07 2003-03-25 アムジエン・インコーポレーテツド トリアジン系キナーゼ阻害薬
SK9742002A3 (en) * 2000-01-07 2003-02-04 Transform Pharmaceuticals Inc High-throughput formation, identification, and analysis of diverse solid-forms
JP3481930B2 (ja) * 2000-03-30 2003-12-22 塩野義製薬株式会社 縮合イミダゾピリジン誘導体の新規製造法および新規結晶形
SE0102616D0 (sv) 2001-07-25 2001-07-25 Astrazeneca Ab Novel compounds
EP1497019B1 (fr) 2002-04-23 2015-05-20 Bristol-Myers Squibb Company Composes pyrrolo-triazine aniline utiles en tant qu'inhibiteurs de kinase
TW200508224A (en) 2003-02-12 2005-03-01 Bristol Myers Squibb Co Cyclic derivatives as modulators of chemokine receptor activity
NZ541836A (en) 2003-02-27 2008-12-24 Palau Pharma Sa Pyrazolopyridine derivatives
WO2005117909A2 (fr) 2004-04-23 2005-12-15 Exelixis, Inc. Modulateurs des proteines kinases et leurs methodes d'utilisation
EP1755607A2 (fr) 2004-04-29 2007-02-28 Pharmix Corporation Compositions et traitements pour l'inhibition de kinase et/ou de hmg-coa reductase
US20050288290A1 (en) 2004-06-28 2005-12-29 Borzilleri Robert M Fused heterocyclic kinase inhibitors
US7439246B2 (en) 2004-06-28 2008-10-21 Bristol-Myers Squibb Company Fused heterocyclic kinase inhibitors
JP5116687B2 (ja) 2005-11-02 2013-01-09 バイエル・ファルマ・アクチェンゲゼルシャフト がんおよび他の過剰増殖性疾患の処置のためのピロロ［２，１−ｆ］［１，２，４］トリアジン−４−イルアミンＩＧＦ−１Ｒキナーゼ阻害剤
US7348325B2 (en) 2005-11-30 2008-03-25 Bristol-Myers Squibb Company Pyrrolotriazine kinase inhibitors
PL1973910T3 (pl) 2006-01-27 2013-11-29 Shanghai hengrui pharmaceutical co ltd Pirolo[3,2-c]pirydyn-4-onowo-2-indolinonowe inhibitory kinazy białkowej
CN101511835B (zh) 2006-07-07 2013-11-27 布里斯托尔-迈尔斯斯奎布公司 吡咯并三嗪激酶抑制剂
CN101808693A (zh) 2007-07-25 2010-08-18 百时美施贵宝公司 三嗪激酶抑制剂
JP2011515401A (ja) 2008-03-20 2011-05-19 アムジエン・インコーポレーテツド オーロラキナーゼモジュレーターおよび使用方法
KR20100003912A (ko) 2008-07-02 2010-01-12 삼성전자주식회사 동일 포맷의 미디어 파일 간에 미디어 정보 호환이 가능한미디어 파일을 생성하는 방법 및 장치와 미디어 파일을실행하는 방법 및 장치
WO2010022055A2 (fr) 2008-08-20 2010-02-25 Amgen Inc. Inhibiteurs de canaux sodiques sensibles au potentiel
WO2010144345A1 (fr) 2009-06-08 2010-12-16 Abraxis Bioscience, Llc Dérivés de triazine et leurs applications thérapeutiques
US8486939B2 (en) 2009-07-07 2013-07-16 Pathway Therapeutics Inc. Pyrimidinyl and 1,3,5-triazinyl benzimidazoles and their use in cancer therapy
JP2013519732A (ja) 2010-02-17 2013-05-30 アムジエン・インコーポレーテツド 疼痛治療のためのナトリウムチャンネル阻害薬としてのアリールカルボキサミド誘導体
WO2012027495A1 (fr) 2010-08-27 2012-03-01 University Of The Pacific Analogues de pipérazinylpyrimidine en tant qu'inhibiteurs de protéine kinase
CN102040494A (zh) 2010-11-12 2011-05-04 西北师范大学 对氟苯甲醛的制备方法
NZ703495A (en) 2012-07-11 2018-02-23 Blueprint Medicines Corp Inhibitors of the fibroblast growth factor receptor
CN104981247A (zh) 2012-09-06 2015-10-14 普莱希科公司 用于激酶调节的化合物和方法及其适应症
SMT201800230T1 (it) 2012-12-21 2018-07-17 Plexxikon Inc Composti e metodi per la modulazione della chinasi e loro indicazioni
TWI629266B (zh) 2012-12-28 2018-07-11 藍印藥品公司 纖維母細胞生長因子受體之抑制劑
WO2014160521A1 (fr) 2013-03-15 2014-10-02 Blueprint Medicines Corporation Dérivés de pipérazine et leur utilisation comme modulateurs de kit
LT3057969T (lt) 2013-10-17 2018-07-10 Blueprint Medicines Corporation Kompozicijos, naudojamos gydyti sutrikimams, susijusiems su kit
US9334263B2 (en) 2013-10-17 2016-05-10 Blueprint Medicines Corporation Compositions useful for treating disorders related to kit
DK3395814T3 (da) 2013-10-25 2022-07-04 Blueprint Medicines Corp Hæmmere af fibroblastvækstfaktorreceptoren
WO2015108992A1 (fr) 2014-01-15 2015-07-23 Blueprint Medicines Corporation Composés hétérobicycliques et leur utilisation en tant qu'inhibiteurs du récepteur fgfr4
AR099789A1 (es) * 2014-03-24 2016-08-17 Actelion Pharmaceuticals Ltd Derivados de 8-(piperazin-1-il)-1,2,3,4-tetrahidro-isoquinolina
US9688680B2 (en) 2014-08-04 2017-06-27 Blueprint Medicines Corporation Compositions useful for treating disorders related to kit
WO2016127074A1 (fr) 2015-02-06 2016-08-11 Blueprint Medicines Corporation Utilisation de dérivés 2-(pyridine-3-yl)-pyrimidine en tant qu'inhibiteurs de ret
AU2016297754A1 (en) 2015-07-24 2018-02-15 Blueprint Medicines Corporation Compounds useful for treating disorders related to KIT and PDGFR
CA2995997A1 (fr) 2015-08-26 2017-03-02 Blueprint Medicines Corporation Composes et compositions utiles pour traiter des troubles associes au gene ntrk
US20170119760A1 (en) 2015-10-28 2017-05-04 Ab Science Use of masitinib for the treatment of progressive supranuclear palsy
NZ742351A (en) 2015-11-02 2023-03-31 Blueprint Medicines Corp Inhibitors of ret
MX2018006195A (es) 2015-11-19 2018-09-05 Blueprint Medicines Corp Compuestos y composiciones utiles para el tratamiento de trastornos relacionados con ntrk.
UY37155A (es) 2016-03-17 2017-10-31 Blueprint Medicines Corp Inhibidores de ret
FI3442977T3 (fi) 2016-04-15 2023-09-26 Blueprint Medicines Corp Aktiviinireseptorin kaltaisen kinaasin estäjät
IL263429B (en) * 2016-06-20 2022-08-01 Novartis Ag Crystalline forms of triazolopyrimidine compound
WO2018017983A1 (fr) 2016-07-22 2018-01-25 Blueprint Medicines Corporation Composés utiles pour traiter des troubles liés à ret
US10035789B2 (en) 2016-07-27 2018-07-31 Blueprint Medicines Corporation Compounds useful for treating disorders related to RET
WO2018049233A1 (fr) 2016-09-08 2018-03-15 Nicolas Stransky Inhibiteurs du récepteur du facteur de croissance des fibroblastes en combinaison avec des inhibiteurs de kinase dépendant de la cycline
US11040979B2 (en) 2017-03-31 2021-06-22 Blueprint Medicines Corporation Substituted pyrrolo[1,2-b]pyridazines for treating disorders related to KIT and PDGFR
CN109400610A (zh) 2017-08-18 2019-03-01 浙江海正药业股份有限公司 吡咯并三嗪类衍生物、其制备方法及其在医药上的用途
CN108191874B (zh) 2018-01-16 2019-11-29 成都施贝康生物医药科技有限公司 一种C-Kit抑制剂及其应用
AU2019216351B2 (en) * 2018-01-31 2024-07-25 Deciphera Pharmaceuticals, Llc Combination therapy for the treatment of mastocytosis
US20220010382A1 (en) 2018-11-12 2022-01-13 Blueprint Medicines Corporation Avapritinib resistance of kit mutants
ES2966512T3 (es) 2019-04-12 2024-04-22 Blueprint Medicines Corp Formas cristalinas de (S)-1-(4-fluorofenil)-1-(2-(4-(6-(1-metil-1H-pirazol-4-il)pirrolo[2,1-f][1,2,4]triazin-4-il)piperazinil)-pirimidin-5-il)etan-1-amina y métodos de elaboración
CN114341138A (zh) 2019-07-09 2022-04-12 桑多斯股份公司 口服可用的选择性kit和pdgfr激酶抑制剂的晶型
GB201915447D0 (en) 2019-10-24 2019-12-11 Johnson Matthey Plc Polymorphs of avapritinib and methods of preparing the polymorphs
US20220370465A1 (en) 2019-11-04 2022-11-24 Blueprint Medicines Corporation Treatment of mast cell diseases and eosinophilic disorders
CN110950872A (zh) 2019-12-25 2020-04-03 武汉九州钰民医药科技有限公司 制备靶向抗癌药avapritinib的方法
CN110938077B (zh) 2019-12-25 2021-04-27 武汉九州钰民医药科技有限公司 合成Avapritinib的方法

Also Published As

Publication number Publication date
JP2022526438A (ja) 2022-05-24
FI3856341T3 (fi) 2023-11-30
EP3856341A1 (fr) 2021-08-04
WO2020210669A1 (fr) 2020-10-15
TWI845657B (zh) 2024-06-21
IL287148A (en) 2021-12-01
JP7728178B2 (ja) 2025-08-22
SMT202300447T1 (it) 2024-01-10
CN113966334B (zh) 2025-01-21
CA3136707A1 (fr) 2020-10-15
CA3296895A1 (en) 2026-03-02
EP4302761A2 (fr) 2024-01-10
TW202104232A (zh) 2021-02-01
ES2966512T3 (es) 2024-04-22
PL3856341T3 (pl) 2024-03-04
SI3856341T1 (sl) 2024-02-29
EP4302761A3 (fr) 2024-03-27
CN113966334A (zh) 2022-01-21
US12060354B2 (en) 2024-08-13
US20240132510A1 (en) 2024-04-25
HRP20231533T1 (hr) 2024-03-01
PT3856341T (pt) 2023-12-12
RS64881B1 (sr) 2023-12-29
US11999744B2 (en) 2024-06-04
US12252494B2 (en) 2025-03-18
LT3856341T (lt) 2023-12-27
US20230271971A1 (en) 2023-08-31
US20230124801A1 (en) 2023-04-20
IL324301A (en) 2025-12-01
HUE064283T2 (hu) 2024-02-28
US20260116883A1 (en) 2026-04-30
US11964980B2 (en) 2024-04-23
DK3856341T3 (da) 2023-12-04
US20210147433A1 (en) 2021-05-20
EP3856341B1 (fr) 2023-09-06

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