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)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Dermatology (AREA)
  • Oncology (AREA)
  • Hematology (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
MX365614B (es) 2013-10-17 2019-06-07 Blueprint Medicines Corp Composiciones utiles para tratar trastornos relacionados con kit.
HUE064283T2 (hu) 2019-04-12 2024-02-28 Blueprint Medicines Corp Az (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)etán-1-amin kristályos formái és elõállítási eljárásai
US12590095B2 (en) * 2019-07-09 2026-03-31 Sandoz Ag Crystalline forms of an orally available, selective kit and PDGFR kinase inhibitor
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
US20230279009A1 (en) 2020-06-17 2023-09-07 Teva Czech Industries S.R.O Solid state forms of avapritinib salts
HU231413B1 (hu) * 2021-02-26 2023-08-28 Egis Gyógyszergyár Zrt. Eljárás avapritinib és intermedierek előállítására
JP7763848B2 (ja) 2021-03-03 2025-11-04 ブループリント メディシンズ コーポレイション Ｋｉｔ－およびｐｄｇｆｒａ－媒介性疾患を治療するための化合物を製造するための合成方法および中間生成物
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
IL144977A0 (en) 1999-05-21 2002-06-30 Bristol Myers Squibb Co Pyrrolotriazine derivatives and pharmaceutical compositions containing the same
MXPA02003436A (es) 1999-10-07 2002-08-20 Amgen Inc Inhibidores de triazina cinasa.
IL150524A0 (en) 2000-01-07 2003-02-12 Transform Pharmaceuticals Inc High-throughput formation, identification, and analysis of diverse solid-forms
WO2001074821A1 (fr) 2000-03-30 2001-10-11 Shionogi & Co., Ltd. Nouveau procede de production de derive d'imidazopyridine fondu et nouvelle forme cristalline
SE0102616D0 (sv) 2001-07-25 2001-07-25 Astrazeneca Ab Novel compounds
PL219736B1 (pl) 2002-04-23 2015-07-31 Bristol Myers Squibb Co Pochodna pirolotriazynoaniliny, kompozycja farmaceutyczna i jej zastosowanie
TW200508224A (en) 2003-02-12 2005-03-01 Bristol Myers Squibb Co Cyclic derivatives as modulators of chemokine receptor activity
UA81453C2 (en) 2003-02-27 2008-01-10 Pyrazolopyridine derivates
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
US7439246B2 (en) 2004-06-28 2008-10-21 Bristol-Myers Squibb Company Fused heterocyclic kinase inhibitors
US20050288290A1 (en) 2004-06-28 2005-12-29 Borzilleri Robert M Fused heterocyclic kinase inhibitors
EP1945222B1 (fr) 2005-11-02 2012-12-26 Bayer Pharma Aktiengesellschaft Derives pyrrolo[2,1-f] [1,2,4] triazin-4-ylamines comme inhibiteurs de la igf-1r kinase pour le traitement des cancers et d'autres maladies hyperproliferatives
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
SI2041138T1 (sl) 2006-07-07 2014-08-29 Bristol-Myers Squibb Company Pirolotriazin kinazni inhibitorji
US8415340B2 (en) 2007-07-25 2013-04-09 Bristol-Myers Squibb Company Triazine kinase inhibitors
AU2009226024B2 (en) 2008-03-20 2012-07-12 Amgen Inc. Aurora kinase modulators and method of use
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
CA2764818A1 (fr) 2009-06-08 2010-12-16 California Capital Equity, Llc Derives de triazine et leurs applications therapeutiques
CA2767008C (fr) 2009-07-07 2018-01-30 Pathway Therapeutics, Inc. Pyrimidinyl et 1,3,5-triazinyl benzimidazoles et leur utilisation dans le traitement du cancer
AU2011218167B2 (en) 2010-02-17 2014-07-10 Amgen Inc. Aryl carboxamide derivatives as sodium channel inhibitors for treatment of pain
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
JP6318156B2 (ja) 2012-09-06 2018-04-25 プレキシコン インコーポレーテッドＰｌｅｘｘｉｋｏｎ Ｉｎｃ． キナーゼをモジュレートするための化合物および方法、ならびにその指標
ME03000B (fr) 2012-12-21 2018-10-20 Plexxikon Inc Composés et procédés pour la modulation de kinase, et indications associées
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
US9334263B2 (en) 2013-10-17 2016-05-10 Blueprint Medicines Corporation Compositions useful for treating disorders related to kit
MX365614B (es) 2013-10-17 2019-06-07 Blueprint Medicines Corp Composiciones utiles para tratar trastornos relacionados con kit.
PT3395814T (pt) 2013-10-25 2022-07-27 Blueprint Medicines Corp Inibidores do recetor do fator de crescimento de fibroblastos
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
US10202365B2 (en) 2015-02-06 2019-02-12 Blueprint Medicines Corporation 2-(pyridin-3-yl)-pyrimidine derivatives as RET inhibitors
BR112018001190A2 (pt) 2015-07-24 2018-09-11 Blueprint Medicines Corp composições úteis para tratar distúrbios relacionados a kit e pdfgr
WO2017035354A1 (fr) 2015-08-26 2017-03-02 Blueprint Medicines Corporation Composés et compositions utiles pour traiter des troubles associés au gène ntrk
US20170119760A1 (en) 2015-10-28 2017-05-04 Ab Science Use of masitinib for the treatment of progressive supranuclear palsy
RS65069B1 (sr) 2015-11-02 2024-02-29 Blueprint Medicines Corp Inhibitori ret-a
SG10201912607SA (en) 2015-11-19 2020-02-27 Blueprint Medicines Corp Compounds and compositions useful for treating disorders related to ntrk
AR107912A1 (es) 2016-03-17 2018-06-28 Blueprint Medicines Corp Inhibidores de ret
FI3442977T3 (fi) 2016-04-15 2023-09-26 Blueprint Medicines Corp Aktiviinireseptorin kaltaisen kinaasin estäjät
JP7042812B2 (ja) 2016-06-20 2022-03-28 ノバルティス アーゲー トリアゾロピリミジン化合物の結晶形態
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
CN110022900A (zh) 2016-09-08 2019-07-16 蓝图药品公司 成纤维细胞生长因子受体4抑制剂与细胞周期蛋白依赖性激酶抑制剂的组合
WO2018183712A1 (fr) 2017-03-31 2018-10-04 Blueprint Medicines Corporation Composés de pyrrolo[1,2-b]pyridazine et compositions utiles pour traiter des troubles liés à kit et 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
CN118903436A (zh) * 2018-01-31 2024-11-08 德西费拉制药有限责任公司 治疗肥大细胞增多症的组合疗法
WO2020102095A1 (fr) 2018-11-12 2020-05-22 Blueprint Medicines Corporation Résistance à l'avapritinib de mutants de kit
HUE064283T2 (hu) 2019-04-12 2024-02-28 Blueprint Medicines Corp Az (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)etán-1-amin kristályos formái és elõállítási eljárásai
US12590095B2 (en) 2019-07-09 2026-03-31 Sandoz Ag Crystalline forms of an orally available, selective kit and PDGFR kinase inhibitor
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
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
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

Also Published As

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

Similar Documents

Publication Publication Date Title
SI3856341T1 (sl) Kristalinične oblike (s)-1-(4-fluorofenila)-1-(2-(4-(6-(1-metil-1h- pirazola-4-il)pirolo(2,1-f)(1,2,4)triazin-4-il)piperazinil)-pirimidin- 5-il)etan-1-amin in postopki izdelave
CR20210665A (es) Formas en estado sólido
UY38711A (es) Formas en estado sólido
IL319470A (en) History of 4-(8,3-diazabicyclo[1.2.3]octan-3-yl)-7-naphthalene-pyrido[3,4-D]pyrimidine as inhibitors of mutant KRAS(G12D) oncoprotein for cancer treatment
CY1123201T1 (el) Ενωσεις υποκατεστημενης πυραζολο[1,5-α]πυριδινης ως αναστολεις κινασης ret
DK1812440T3 (da) Pyrazolo[1,5-a]pyrimidiner, der kan anvendes som inhibistorer af proteinkinaser
ATE420883T1 (de) Pyrrolopyrimidine verwendbar als protein kinase inhibitoren
MX2020010675A (es) Derivados de pirazolo-triazina y/o pirazolo-pirimidina como inhibidor selectivo de cinasa dependiente de ciclina.
ATE508126T1 (de) Als kinaseinhibitoren geeignete aminopyrimidine
TW200607505A (en) Fused heterocyclic kinase inhibitors
CR9591A (es) Inhibidores de proteina cinasa derivados de pirrol (2,3-b) piridina
ATE316077T1 (de) Pyrimidin-essigsäure derivate geeignet zur behandlung von crth2-bedingten krankheiten
DE60336092D1 (de) Verfahren zur Herstellung substituierter Pyrimidine
ATE474835T1 (de) Als inhibitoren von proteinkinasen geeignete aminopyrimidine
MX2023000501A (es) Antagonistas del receptor del factor liberador de corticotropina.
WO2007015866A3 (fr) Inhibiteurs de la p38 kinase et procédés de traitement d’affections inflammatoires
DE602004032522D1 (de) Mit n-alkylhydroxamsäuren substituierte isoindolylverbindungen und deren pharmazeutische verwendung
PH12021551180A1 (en) Methods of treating myeloproliferative disorders
IL309359A (en) (R)-N-ethyl-5-fluoro-N-isopropyl-2-((5-(2-(6-((2-methoxyethyl)(methyl)amino)-2-methylhexane-3-yl)- salt 6,2-diazaspiro[4.3]octan-6-yl)-4,2,1-triazin-6-yl)oxy) benzamide besylate for the treatment of diseases such as cancer
EP4161522A4 (fr) Dérivés de pyrazolo [4,3-d]pyrimidine et leurs procédés d'utilisation pour le traitement de troubles prolifératifs cellulaires
DE602006017574D1 (de) Als protein-kinase-inhibitoren nutzbare benzimidazole
MX2021000432A (es) Formas solidas de compuestos de 5,6-dihidro-6-fenilbenzo[f]isoquin olin-2-amina sustituidos.
PH12022551451A1 (en) Solid forms of 2-[3-[4-amino-3-(2-fluoro-4-phenoxy-phenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile
PH12021551812A1 (en) The monohydrate of rogaratinib hydrochloride and solid states thereof
EA201990940A1 (ru) ЗАМЕЩЕННЫЕ ПИРАЗОЛО[1,5-a]ПИРИДИНОВЫЕ СОЕДИНЕНИЯ В КАЧЕСТВЕ ИНГИБИТОРОВ RET КИНАЗЫ