ES2686501T3 - Pirazolo[1,5-a]piridinas sustituidas como inhibidores de la quinasa del receptor de tropomiosina (Trk) - Google Patents

Pirazolo[1,5-a]piridinas sustituidas como inhibidores de la quinasa del receptor de tropomiosina (Trk) Download PDF

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ES2686501T3
ES2686501T3 ES12832784T ES12832784T ES2686501T3 ES 2686501 T3 ES2686501 T3 ES 2686501T3 ES 12832784 T ES12832784 T ES 12832784T ES 12832784 T ES12832784 T ES 12832784T ES 2686501 T3 ES2686501 T3 ES 2686501T3
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alkyl
halogen
optionally substituted
optional substituent
hydrogen
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Pradip Kumar Sasmal
Shahadat Ahmed
Ashok Tehim
Vidyadhar Paradkar
Prasanna M. Dattatreya
Nanjegowda Jagadeesh MAVINAHALLI
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Dr Reddys Laboratories Ltd
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Abstract

Un compuesto de fórmula (I),**Fórmula** sus sales farmacéuticamente aceptables, solvatos farmacéuticamente aceptables o estereoisómeros de los mismos, en donde A es**Fórmula** X1 es CH o N; R1 representa hidrógeno o -alquilo C1-C6; R2 se selecciona independientemente entre hidrógeno, halógeno, ciano, -alquilo C1-C6, haloalquilo C1-C6, haloalcoxi C1-C6, fenilo opcionalmente sustituido con 1 a 3 halógenos o un -O-heterociclilo opcionalmente sustituido en donde el sustituyente opcional se selecciona entre alquilo, -ORi o -C(O)N(Ri)2; cuando X1 es CH, opcionalmente dos R2 presentes en dos átomos de carbono adyacentes se combinan para formar un anillo heterocíclico de 5 a 7 miembros; R3 se selecciona independientemente entre halógeno, ciano, -ORi, -C(O)N(Ri)2 o dos R3 junto con el átomo de carbono al que están anclados forman un grupo espirocicloalquilo C3-C7 anclado a pirrolidina; o dos R3 cuando están unidos a átomos de carbono adyacentes forman un anillo de cicloalquilo C3-C7 fusionado a la pirrolidina; Ra se selecciona entre (i) un grupo seleccionado entre -alquilo C1-C6, hidroxialquilo C1-C6 o -alquil(C1-C6)alcoxi C1-C6 opcionalmente sustituidos en donde el sustituyente opcional se selecciona entre ciano, halógeno o -arilo C6-C12, (ii) un -cicloalquilo C3-C10 opcionalmente sustituido en donde el sustituyente opcional se selecciona entre ciano, -alquilo C1-C6, hidroxilo, halógeno o -Rs, (iii) un -arilo C6-C12 opcionalmente sustituido en donde el sustituyente opcional se selecciona entre ciano, hidroxilo, halógeno, -alquilo C1-C6 o -Rr (iv) un heterociclilo de 5 a 10 miembros opcionalmente sustituido en donde el sustituyente opcional se selecciona entre ciano, hidroxilo, halógeno o-alquilo C1-C6, (v) un heteroarilo de 5 a 10 miembros opcionalmente sustituido en donde el sustituyente opcional se selecciona entre ciano, oxo (>=O), hidroxilo, halógeno, -alquilo C1-C6, -alcoxi C1-C6, -NRcRd o -Rr, (vi)-NR4R5, (vii)-alquil(C1-C6)-arilo C6-C12; Rb representa hidrógeno o halógeno; R4 se selecciona entre hidrógeno, -alquilo C1-C6, -cicloalquilo C3-C10, -hidroxialquilo C1-C6, alcoxialquilo C1-C6, halogenoalquilo C1-C6 o -alquil(C1-C6)-cicloalquilo C3-C10; R5 se selecciona a partir de hidrógeno o -alquilo C1-C6 o -alquil(C1-C6)-cicloalquilo C3-C10; Alternativamente R4 y R5 junto con el átomo de nitrógeno al que están anclados pueden formar un anillo heterocíclico de 5 a 10 miembros opcionalmente sustituido que contiene opcionalmente 1-2 heteroátomos o grupos seleccionados entre -O-, -S-, -N-, -C(>=O)-, -S(>=O)- o -S(>=O)2- adicionales, en donde el sustituyente opcional se selecciona entre hidroxilo, -alquilo C1-C6, -C(>=O)-alquilo C1-C6, mesilo o COORe; Rc y Rd se seleccionan independientemente entre hidrógeno o -alquilo C1-C6; Re se selecciona entre hidrógeno o alquilo; Ri es hidrógeno, -alquilo C1-C6, -haloalquilo C1-C6, -alquil(C1-C6)alcoxi C1-C6, -cicloalquilo C3-C10, -alquil(C1- C6)-cicloalquilo C3-C10 opcionalmente sustituido en donde el sustituyente opcional es halógeno o -alquilo C1-C6 sustituido con 1 a 3 grupos hidroxi; Rr se selecciona independientemente entre un heterociclilo de 5 a 10 miembros o un heteroarilo de 5 a 10 miembros, en donde el sustituyente opcional se selecciona entre hidroxilo, halógeno, -alquilo C1-C6 o -alcoxi C1-C6; Rs es un -alquil(C1-C6)-arilo C6-C10 opcionalmente sustituido, en donde el sustituyente opcional es halógeno; m representa independientemente 0, 1, 2, 3 o 4; y n representa independientemente 0, 1, 2 o 3.
ES12832784T 2011-12-12 2012-12-12 Pirazolo[1,5-a]piridinas sustituidas como inhibidores de la quinasa del receptor de tropomiosina (Trk) Active ES2686501T3 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN4329CH2011 2011-12-12
PCT/IB2012/003012 WO2013088256A1 (en) 2011-12-12 2012-12-12 Substituted pyrazolo[1,5-a] pyridine as tropomyosin receptor kinase (trk) inhibitors

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US (7) US9045478B2 (es)
EP (2) EP2791139B1 (es)
JP (1) JP5990595B2 (es)
KR (2) KR20140105508A (es)
CN (1) CN104114553B (es)
AU (1) AU2012351748B2 (es)
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Families Citing this family (70)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102224153B (zh) 2008-09-22 2014-04-30 阵列生物制药公司 作为trk激酶抑制剂的取代的咪唑并[1，2-b]哒嗪化合物
KR102037619B1 (ko) 2008-10-22 2019-10-28 어레이 바이오파마 인크. ＴＲＫ 키나아제 억제제로서 치환된 피라졸로［１,５­ａ］ 피리미딘 화합물
AR077468A1 (es) 2009-07-09 2011-08-31 Array Biopharma Inc Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa
DK2918588T3 (en) 2010-05-20 2017-08-28 Array Biopharma Inc Macrocyclic compounds as TRK kinase inhibitors
WO2013088256A1 (en) * 2011-12-12 2013-06-20 Dr. Reddy's Laboratories Ltd. Substituted pyrazolo[1,5-a] pyridine as tropomyosin receptor kinase (trk) inhibitors
TWI663159B (zh) * 2013-12-10 2019-06-21 美商健臻公司 原肌球蛋白相關之激酶（ｔｒｋ）抑制劑
CA2934010A1 (en) 2013-12-20 2015-06-25 Pfizer Limited N-acylpiperidine ether tropomyosin-related kinase inhibitors
CN103819343B (zh) * 2014-02-17 2016-03-23 青岛农业大学 化合物2-烯丙基-4-氟-6-硝基苯酚的制备方法和农用生物活性
WO2015143652A1 (en) * 2014-03-26 2015-10-01 Merck Sharp & Dohme Corp. TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF
WO2015159175A1 (en) 2014-04-15 2015-10-22 Pfizer Inc. Tropomyosin-related kinase inhibitors containing both a 1h-pyrazole and a pyrimidine moiety
WO2015170218A1 (en) 2014-05-07 2015-11-12 Pfizer Inc. Tropomyosin-related kinase inhibitors
ES2667727T3 (es) * 2014-05-08 2018-05-14 Bayer Cropscience Aktiengesellschaft Pirazolopiridina sulfonamidas como nematicidas
EP3157921A1 (en) 2014-06-23 2017-04-26 Dr. Reddy's Laboratories Ltd. Substituted imidazo[1,2-a]pyridine compounds useful for the treatment of pain
WO2016009296A1 (en) 2014-07-16 2016-01-21 Pfizer Inc. N-acylpiperidine ether tropomyosin-related kinase inhibitors
WO2016020784A1 (en) 2014-08-05 2016-02-11 Pfizer Inc. N-acylpyrrolidine ether tropomyosin-related kinase inhibitors
EP3218380B1 (en) 2014-11-16 2021-03-17 Array Biopharma, Inc. Preparation of a crystalline form of (s)-n-(5-((r)-2-(2,5-difluorophenyl)-pyrrolidin-1-yl)-pyrazolo[1,5-a]pyrimidin-3-yl)-3-hydroxypyrrolidine-1-carboxamide hydrogen sulfate
WO2016100677A2 (en) 2014-12-18 2016-06-23 Genzyme Corporation Pharmaceutical formulations of tropomyosin related kinase (trk) inhibitors
CN104672121B (zh) * 2015-02-16 2017-10-24 上海华默西医药科技有限公司 2r‑(2,5‑二氟苯基)吡咯烷盐酸盐的制备方法
PL3305788T3 (pl) * 2015-05-29 2021-03-08 Wuxi Fortune Pharmaceutical Co., Ltd Inhibitor kinazy janusowej
TN2018000138A1 (en) 2015-10-26 2019-10-04 Array Biopharma Inc Point mutations in trk inhibitor-resistant cancer and methods relating to the same
US10045991B2 (en) 2016-04-04 2018-08-14 Loxo Oncology, Inc. Methods of treating pediatric cancers
PE20181888A1 (es) 2016-04-04 2018-12-11 Loxo Oncology Inc Formulaciones liquidas de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida
AU2017268371B2 (en) 2016-05-18 2020-11-19 Array Biopharma Inc. Preparation of (S)-N-(5-((R)-2-(2,5-difluorophenyl)pyrrolidin-1-yl)pyrazolo(1,5-A)pyrimidin-3-y l)-3-hydroxypyrrolidine-1-carboxamide
JOP20190092A1 (ar) 2016-10-26 2019-04-25 Array Biopharma Inc عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها
CN109890820B (zh) * 2016-10-28 2020-11-03 正大天晴药业集团股份有限公司 用作神经营养因子酪氨酸激酶受体抑制剂的氨基吡唑并嘧啶化合物
JOP20190213A1 (ar) 2017-03-16 2019-09-16 Array Biopharma Inc مركبات حلقية ضخمة كمثبطات لكيناز ros1
PL3621615T3 (pl) * 2017-05-12 2024-03-25 Enanta Pharmaceuticals, Inc. Inhibitory regulujące sygnał apoptozy kinazy 1 i sposoby ich stosowania
WO2018218051A1 (en) 2017-05-25 2018-11-29 Enanta Pharmaceuticals, Inc. Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
US10246439B2 (en) 2017-05-25 2019-04-02 Enanta Pharmaceuticals, Inc. Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
WO2018218042A1 (en) 2017-05-25 2018-11-29 Enanta Pharmaceuticals, Inc. Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
US10800760B2 (en) 2017-05-31 2020-10-13 Nantbio, Inc. Trk inhibition
US10738033B2 (en) 2017-05-31 2020-08-11 Nantbio, Inc. Trk inhibition
CN107286070B (zh) * 2017-07-19 2019-07-16 浙江师范大学 (r)-2-(2,5-二氟苯基)吡咯烷的合成方法及中间体
US10597382B2 (en) 2017-08-28 2020-03-24 Enanta Pharmaceuticals, Inc. Tetrazole containing apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
CA3080157A1 (en) 2017-10-26 2019-05-02 Array Biopharma Inc. Formulations of a macrocyclic trk kinase inhibitor
CN109867672B (zh) * 2017-12-02 2020-07-07 广东东阳光药业有限公司 吡唑[1,5-a]吡啶衍生物的盐及其用途
CN109867671B (zh) * 2017-12-02 2020-07-07 广东东阳光药业有限公司 一种吡唑[1,5-a]吡啶化合物的晶型及其药物组合物和用途
CN109867668B (zh) * 2017-12-02 2021-03-26 广东东阳光药业有限公司 一种吡唑[1,5-a]吡啶化合物的晶型及其药物组合物和用途
EP3727379A4 (en) * 2017-12-20 2021-12-15 Sunshine Lake Pharma Co., Ltd. PYRAZOLO [1,5-A] PYRIDINE DERIVATIVE SALTS AND THEIR USE
CN108218754B (zh) * 2018-01-23 2021-05-07 广东赛烽医药科技有限公司 一种2-(2,5-二氟苯基)吡咯烷的制备方法
MX2020008273A (es) 2018-02-06 2020-11-24 Univ Miami Inhibidores de la cinasa del complejo de activacion transcripcional notch ("nack") y metodos para el uso de los mismos.
MA52218A (fr) 2018-03-29 2021-02-17 Loxo Oncology Inc Traitement de cancers associés à trk
WO2019213239A1 (en) 2018-05-02 2019-11-07 Enanta Pharmaceuticals Inc. Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
KR20210005195A (ko) 2018-05-02 2021-01-13 이난타 파마슈티칼스, 인코포레이티드 아폽토시스 신호 조절 키나제 1 억제제를 포함하는 테트라졸 및 이의 사용 방법
GB201811825D0 (en) 2018-07-19 2018-09-05 Benevolentai Bio Ltd Organic compounds
CN108794370A (zh) * 2018-07-31 2018-11-13 上海弈柯莱生物医药科技有限公司 一种拉罗替尼中间体的制备方法
US10968199B2 (en) 2018-08-22 2021-04-06 Enanta Pharmaceuticals, Inc. Cycloalkyl-containing apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
GB201813791D0 (en) 2018-08-23 2018-10-10 Benevolental Bio Ltd Organic compounds
CN111171019A (zh) * 2018-11-13 2020-05-19 上海轶诺药业有限公司 一类五元并六元杂环化合物及其作为蛋白受体激酶抑制剂的用途
US11345699B2 (en) 2018-11-19 2022-05-31 Enanta Pharmaceuticals, Inc. Apoptosis signal-regulating kinase 1 inhibitors and methods of use thereof
CN109593802B (zh) * 2018-12-24 2021-10-01 上海健康医学院 一种(r)-2-(2,5-二氟苯基)吡咯烷或其盐的制备方法
EA202192575A1 (ru) 2019-03-21 2022-01-14 Онксео Соединения dbait в сочетании с ингибиторами киназ для лечения рака
US11466033B2 (en) 2019-03-25 2022-10-11 Enanta Pharmaceuticals, Inc. Substituted pyridines as apoptosis signal-regulating kinase 1 inhibitors
CN110015980A (zh) * 2019-05-14 2019-07-16 大连联化化学有限公司 一种合成叔丁基亚磺酰胺的方法
EP3981769A4 (en) * 2019-06-05 2023-07-19 Guangzhou Joyo Pharmatech Co., Ltd PYRROLOPYRIMIDINE COMPOUND AND USE
CN110751853B (zh) * 2019-10-25 2021-05-18 百度在线网络技术（北京）有限公司 停车位数据的有效性识别方法和装置
JP2023500906A (ja) 2019-11-08 2023-01-11 インサーム（インスティテュ ナシオナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシェ メディカル） キナーゼ阻害剤に対する獲得抵抗性を有するがんの処置方法
US20230399319A1 (en) * 2019-12-27 2023-12-14 Japan Tobacco Inc. Acylsulfamide Compound and Pharmaceutical Use Therefor
AU2021209418A1 (en) 2020-01-22 2022-07-21 Benevolentai Bio Limited Topical pharmaceutical compositions comprising imidazo[1,2-b]pyridazine compounds
WO2021148581A1 (en) 2020-01-22 2021-07-29 Onxeo Novel dbait molecule and its use
US20230112039A1 (en) 2020-01-22 2023-04-13 Benevolentai Bio Limited Pharmaceutical compositions and their uses
AU2021270672B2 (en) * 2020-05-15 2024-07-25 Cspc Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. Fused aza-heterocyclic amide compound and use thereof
US20230303510A1 (en) * 2020-07-29 2023-09-28 Ideaya Biosciences, Inc. Cyclized acetamido derivatives as dna polymerase theta inhibitors
CN112979646B (zh) * 2021-03-08 2022-01-14 北京富龙康泰生物技术有限公司 一种咪唑并吡啶类衍生物
WO2022234287A1 (en) 2021-05-06 2022-11-10 Benevolentai Bio Limited Imidazopyridazine derivatives useful as trk inhibitors
CN116120323A (zh) * 2021-11-15 2023-05-16 石药集团中奇制药技术（石家庄）有限公司 固体形式的氮杂稠环酰胺类化合物及其用途
CN116115618A (zh) * 2021-11-15 2023-05-16 石药集团中奇制药技术（石家庄）有限公司 一种治疗肿瘤的药物
CN115772170A (zh) * 2021-12-03 2023-03-10 徐诺药业(南京)有限公司 一种吡唑并[1,5-a]吡啶衍生物及其制备方法和应用
WO2024118887A1 (en) * 2022-11-30 2024-06-06 Blueprint Medicines Corporation N-phenyl-pyrazolo[1,5-a]pyridine-3-carboxamide derivatives as wild type c-kit kinase inhibitors for the treatment of urticaria
WO2024123966A1 (en) * 2022-12-07 2024-06-13 Third Harmonic Bio, Inc. Compounds and compositions as c-kit kinase inhibitors

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL336628A1 (en) * 1997-05-03 2000-07-03 Smithkline Beecham Plc Derivatives of tetrahydroisoquinoline as modulators of d3 dopamine receptors
JP2003231687A (ja) 2002-02-04 2003-08-19 Japan Tobacco Inc ピラゾリル縮合環化合物及びその医薬用途
ES2304511T3 (es) * 2002-06-04 2008-10-16 Schering Corporation Compuestos de pirazolo(1,5-a)pirimidina como agentes antivirales.
JP4511352B2 (ja) 2002-07-25 2010-07-28 ファイザー・インク 抗癌薬として有用なイソチアゾール誘導体
US7141568B2 (en) 2003-07-09 2006-11-28 Pfizer Italia S.R.L. Pyrrolo[3,4-c]pyrazole derivatives active as kinase inhibitors, process for their preparation and pharmaceutical compositions comprising them
CA2629743A1 (en) * 2005-12-08 2007-06-14 Novartis Ag Pyrazolo[1,5-a]pyridine-3-carboxylic acids as ephb and vegfr2 kinase inhibitors
US20100226881A1 (en) 2007-07-11 2010-09-09 Auckland Uniservices Limited PYRAZOLO[1,5-a]PYRIDINES AND THEIR USE IN CANCER THERAPY
ES2548135T3 (es) 2008-05-13 2015-10-14 Novartis Ag Heterociclos condensados que contienen nitrógeno y composiciones de los mismos como inhibidores de quinasa
KR102037619B1 (ko) * 2008-10-22 2019-10-28 어레이 바이오파마 인크. ＴＲＫ 키나아제 억제제로서 치환된 피라졸로［１,５­ａ］ 피리미딘 화합물
AP2013007103A0 (en) * 2011-02-25 2013-09-30 Irm Llc Compounds and compositions as TRK inhibitors
WO2013088256A1 (en) * 2011-12-12 2013-06-20 Dr. Reddy's Laboratories Ltd. Substituted pyrazolo[1,5-a] pyridine as tropomyosin receptor kinase (trk) inhibitors

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