TWI433849B - 作為ｔｒｋ激酶抑制劑之經取代之咪唑并〔１，２ｂ〕嗒化合物 - Google Patents
作為ｔｒｋ激酶抑制劑之經取代之咪唑并〔１，２ｂ〕嗒化合物 Download PDFInfo
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- TWI433849B TWI433849B TW98132033A TW98132033A TWI433849B TW I433849 B TWI433849 B TW I433849B TW 98132033 A TW98132033 A TW 98132033A TW 98132033 A TW98132033 A TW 98132033A TW I433849 B TWI433849 B TW I433849B
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- TW
- Taiwan
- Prior art keywords
- alkyl
- difluorophenyl
- imidazo
- pyrrolidin
- compound
- Prior art date
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims description 295
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title claims description 148
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title claims description 148
- -1 indole compound Chemical class 0.000 title claims description 52
- 229940096912 Trk tyrosine kinase inhibitor Drugs 0.000 title 1
- 125000000217 alkyl group Chemical group 0.000 claims description 186
- 150000001875 compounds Chemical class 0.000 claims description 133
- 125000001424 substituent group Chemical group 0.000 claims description 61
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- 238000000034 method Methods 0.000 claims description 36
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- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 31
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
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- 150000003839 salts Chemical class 0.000 claims description 24
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 21
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 14
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 claims description 14
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Families Citing this family (92)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ576234A (en) * | 2006-11-06 | 2011-06-30 | Supergen Inc | Imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine derivatives and their use as protein kinase inhibitors |
| AU2009246687B2 (en) | 2008-05-13 | 2012-08-09 | Irm Llc | Fused nitrogen containing heterocycles and compositions thereof as kinase inhibitors |
| SI2350075T1 (sl) * | 2008-09-22 | 2014-06-30 | Array Biopharma, Inc. | Substituirane imidazo (1,2b)piridazinske spojine kot Trk kinazni inhibitorji |
| BRPI0919873B8 (pt) | 2008-10-22 | 2021-05-25 | Array Biopharma Inc | compostos de pirazol[1,5-a]pirimidina substituídos como inibidores da trk quinase, seus processos de preparação e composições farmacêuticas |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| SMT201700372T1 (it) | 2010-05-20 | 2017-09-07 | Array Biopharma Inc | Composti macrociclici come inibitori di trk chinasi |
| US8637516B2 (en) | 2010-09-09 | 2014-01-28 | Irm Llc | Compounds and compositions as TRK inhibitors |
| RU2606131C2 (ru) | 2011-05-13 | 2017-01-10 | Эррэй Биофарма Инк. | СОЕДИНЕНИЯ ПИРРОЛИДИНИЛМОЧЕВИНЫ И ПИРРОЛИДИНИЛТИОМОЧЕВИНЫ КАК ИНГИБИТОРЫ КИНАЗЫ TrkA |
| WO2013009582A1 (en) | 2011-07-12 | 2013-01-17 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF |
| ES2671748T3 (es) | 2011-07-21 | 2018-06-08 | Tolero Pharmaceuticals, Inc. | Inhibidores heterocíclicos de proteína quinasas |
| EP2822559B1 (en) | 2012-03-09 | 2018-05-02 | Lexicon Pharmaceuticals, Inc. | Imidazo[1,2-b]pyridazine-based compounds, compositions comprising them, and uses thereof |
| WO2013176970A1 (en) | 2012-05-22 | 2013-11-28 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF |
| TWI585088B (zh) * | 2012-06-04 | 2017-06-01 | 第一三共股份有限公司 | 作爲激酶抑制劑之咪唑并［１，２－ｂ］嗒衍生物 |
| WO2014078331A1 (en) * | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-(arylalkyl)-n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| US9809578B2 (en) | 2012-11-13 | 2017-11-07 | Array Biopharma Inc. | Pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trkA kinase inhibitors |
| WO2014078378A1 (en) * | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078322A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Thiazolyl and oxazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078323A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-pyrrolidinyl, n'-pyrazolyl- urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| US9822118B2 (en) | 2012-11-13 | 2017-11-21 | Array Biopharma Inc. | Bicyclic heteroaryl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| US9790178B2 (en) | 2012-11-13 | 2017-10-17 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| SG11201503731SA (en) | 2012-11-13 | 2015-06-29 | Array Biopharma Inc | Bicyclic urea, thiourea, guanidine and cyanoguanidine compounds useful for the treatment of pain |
| WO2014078325A1 (en) * | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-(monocyclic aryl),n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078328A1 (en) * | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-bicyclic aryl,n'-pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2015039334A1 (en) | 2013-09-22 | 2015-03-26 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF |
| WO2015039333A1 (en) | 2013-09-22 | 2015-03-26 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF |
| RS59059B1 (sr) | 2014-01-24 | 2019-08-30 | Turning Point Therapeutics Inc | Diaril makrociklična jedinjenja kao modulatori protein kinaza |
| WO2015143654A1 (en) | 2014-03-26 | 2015-10-01 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF |
| WO2015143652A1 (en) * | 2014-03-26 | 2015-10-01 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF |
| WO2015143653A1 (en) | 2014-03-26 | 2015-10-01 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS,COMPOSITIONS AND METHODS THEREOF |
| MA40434B1 (fr) | 2014-05-15 | 2019-09-30 | Array Biopharma Inc | 1-((3s,4r)-4-(3-fluorophényl)-1-(2-méthoxyéthyl)pyrrolidin-3-yl)-3-(4-méthyl-3-(2-méthylpyrimidin-5-yl)-1-phényl-1h-pyrazol-5-yl)urée comme inhibiteur de la kinase trka |
| CA2967951C (en) | 2014-11-16 | 2023-11-07 | Array Biopharma, Inc. | 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 |
| 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 |
| WO2016161572A1 (en) | 2015-04-08 | 2016-10-13 | Merck Sharp & Dohme Corp. | TrkA KINASE INHIBITORS, COMPOSITIONS AND METHODS THEREOF |
| EP3722441A1 (en) | 2015-06-01 | 2020-10-14 | Loxo Oncology Inc. | Method of diagnosing a cancer for a treatment with a trk inhibitor |
| CN107735399B (zh) | 2015-07-02 | 2021-01-26 | 特普医药公司 | 作为蛋白质激酶的调节剂的手性二芳基大环 |
| PL3319969T3 (pl) | 2015-07-06 | 2024-06-24 | Turning Point Therapeutics, Inc. | Diarylowe polimorfy makrocykliczne |
| HRP20210177T1 (hr) | 2015-07-16 | 2021-03-19 | Array Biopharma, Inc. | Supstituirani spojevi pirazolo[1,5-a]piridina kao inhibitori ret kinaze |
| RU2020123800A (ru) | 2015-07-21 | 2020-10-02 | Тёрнинг Поинт Терапьютикс, Инк. | Хиральные диарильные макроциклы и их применение |
| EP3368039A1 (en) | 2015-10-26 | 2018-09-05 | The Regents of The University of Colorado, A Body Corporate | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| PT3439662T (pt) | 2016-04-04 | 2024-09-30 | Loxo Oncology Inc | Formulações líquidas de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| BR112018070017A2 (pt) | 2016-04-04 | 2019-02-05 | Loxo Oncology Inc | métodos de tratamento de cânceres pediátricos |
| PT3458456T (pt) | 2016-05-18 | 2020-12-07 | Array Biopharma Inc | Preparação de (s)-n-(5-((r)-2-(2,5-difluorofenil)pirrolidin-1-il)pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidino-1-carboxamida |
| AU2017302019A1 (en) | 2016-07-28 | 2019-02-07 | Turning Point Therapeutics, Inc. | Macrocycle kinase inhibitors |
| TWI704148B (zh) | 2016-10-10 | 2020-09-11 | 美商亞雷生物製藥股份有限公司 | 作為ｒｅｔ激酶抑制劑之經取代吡唑并[1,5-a]吡啶化合物 |
| JOP20190077A1 (ar) | 2016-10-10 | 2019-04-09 | Array Biopharma Inc | مركبات بيرازولو [1، 5-a]بيريدين بها استبدال كمثبطات كيناز ret |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| US10829492B2 (en) | 2016-10-28 | 2020-11-10 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Amino pyrazolopyrimidine compound used as neurotrophic factor tyrosine kinase receptor inhibitor |
| CN108003161B (zh) * | 2016-10-28 | 2020-10-09 | 正大天晴药业集团股份有限公司 | 神经营养因子酪氨酸激酶受体抑制剂 |
| CN106632353A (zh) * | 2016-11-18 | 2017-05-10 | 山东友帮生化科技有限公司 | 3‑硝基‑6‑氯咪唑并[1,2‑b]哒嗪的合成方法 |
| CN110267960B (zh) | 2017-01-18 | 2022-04-26 | 阿雷生物药品公司 | 作为RET激酶抑制剂的取代的吡唑并[1,5-a]吡嗪化合物 |
| WO2018136663A1 (en) | 2017-01-18 | 2018-07-26 | Array Biopharma, Inc. | Ret inhibitors |
| TWI808958B (zh) | 2017-01-25 | 2023-07-21 | 美商特普醫葯公司 | 涉及二芳基巨環化合物之組合療法 |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| CN109824566A (zh) * | 2017-07-19 | 2019-05-31 | 浙江师范大学 | 一种(r)-2-(2,5-二氟苯基)吡咯烷的合成方法 |
| KR102645316B1 (ko) | 2017-07-28 | 2024-03-07 | 터닝 포인트 테라퓨틱스, 인크. | 거대환형 화합물 및 이의 용도 |
| JP6916562B2 (ja) * | 2017-08-11 | 2021-08-11 | テリジーン リミテッドＴｅｌｉｇｅｎｅ Ｌｔｄ． | 化合物、その薬学的に許容される塩、溶媒和物、立体異性体及び互変異性体、並びに薬物組成物、過剰増殖性障害治療剤、過剰増殖性障害予防剤、薬物、癌治療剤、癌予防剤、及びキナーゼシグナル伝達調節剤 |
| PL3674307T3 (pl) | 2017-08-23 | 2023-11-27 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | Związek makrocykliczny zawierający ugrupowanie aminopirazolu i pirymidyny oraz kompozycja farmaceutyczna i i ch zastosowanie |
| TWI791053B (zh) | 2017-10-10 | 2023-02-01 | 美商亞雷生物製藥股份有限公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之結晶形式及其醫藥組合物 |
| TWI876442B (zh) | 2017-10-10 | 2025-03-11 | 美商絡速藥業公司 | 6-(2-羥基-2-甲基丙氧基)-4-(6-(6-((6-甲氧基吡啶-3-基)甲基)-3,6-二氮雜雙環[3.1.1]庚-3-基)吡啶-3-基)吡唑并[1,5-a]吡啶-3-甲腈之調配物 |
| CA3080157A1 (en) | 2017-10-26 | 2019-05-02 | Array Biopharma Inc. | Formulations of a macrocyclic trk kinase inhibitor |
| JP7194188B2 (ja) | 2017-12-19 | 2022-12-21 | ターニング・ポイント・セラピューティクス・インコーポレイテッド | 疾患を治療するための大環状化合物 |
| CN111630054B (zh) | 2018-01-18 | 2023-05-09 | 奥瑞生物药品公司 | 作为RET激酶抑制剂的取代的吡唑并[3,4-d]嘧啶化合物 |
| CA3087972C (en) | 2018-01-18 | 2023-01-10 | Array Biopharma Inc. | Substituted pyrazolyl[4,3-c]pyridinecompounds as ret kinase inhibitors |
| CN111971286B (zh) | 2018-01-18 | 2023-04-14 | 阿雷生物药品公司 | 作为RET激酶抑制剂的取代的吡咯并[2,3-d]嘧啶化合物 |
| 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 |
| MX2020009586A (es) * | 2018-03-14 | 2020-10-05 | Fochon Biosciences Ltd | Compuestos de (2-azabiciclo[3.1.0]hexan-2-il)pirazolo[1,5-a]pirimi dina e imidazo[1,2-b]piridazina sustituidos como inhibidores de cinasas trk. |
| WO2019191659A1 (en) | 2018-03-29 | 2019-10-03 | Loxo Oncology, Inc. | Treatment of trk-associated cancers |
| ES2989075T3 (es) | 2018-04-25 | 2024-11-25 | Primegene Beijing Co Ltd | Compuesto macrocíclico diarílico y composición farmacéutica y uso del mismo |
| GB201811825D0 (en) * | 2018-07-19 | 2018-09-05 | Benevolentai Bio Ltd | Organic compounds |
| KR102612513B1 (ko) | 2018-07-31 | 2023-12-12 | 록쏘 온콜로지, 인코포레이티드 | (s)-5-아미노-3-(4-((5-플루오로-2-메톡시벤즈아미도)메틸)페닐)-1-(1,1,1-트리플루오로프로판-2-일)-1h-피라졸-4-카르복스아미드의 분무-건조된 분산물 및 제제 |
| CN110857304B (zh) * | 2018-08-24 | 2021-05-18 | 北京富龙康泰生物技术有限公司 | Trk抑制剂、其制备方法和用途 |
| CA3111105A1 (en) | 2018-09-03 | 2020-03-12 | Tyligand Bioscience (Shanghai) Limited | Trk inhibitors useful as anticancer drugs |
| US11964988B2 (en) | 2018-09-10 | 2024-04-23 | Array Biopharma Inc. | Fused heterocyclic compounds as RET kinase inhibitors |
| CN111039947A (zh) * | 2018-10-15 | 2020-04-21 | 上海轶诺药业有限公司 | 一类蛋白受体激酶抑制剂的制备和应用 |
| 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 |
| CN111269233A (zh) * | 2018-12-05 | 2020-06-12 | 上海轶诺药业有限公司 | 一类咪唑并芳环类化合物的制备和应用 |
| CN109354578A (zh) * | 2018-12-06 | 2019-02-19 | 浙江师范大学 | 一种替尼中间体以及替尼的合成方法 |
| JP2022515198A (ja) | 2018-12-19 | 2022-02-17 | アレイ バイオファーマ インコーポレイテッド | ＦＧＦＲチロシンキナーゼの阻害剤としての置換ピラゾロ［１，５－ａ］ピリジン化合物 |
| WO2020131674A1 (en) | 2018-12-19 | 2020-06-25 | Array Biopharma Inc. | 7-((3,5-dimethoxyphenyl)amino)quinoxaline derivatives as fgfr inhibitors for treating cancer |
| JP7662528B2 (ja) | 2019-02-12 | 2025-04-15 | スミトモ ファーマ アメリカ， インコーポレイテッド | 複素環式タンパク質キナーゼ阻害剤を含む製剤 |
| JP7209415B2 (ja) | 2019-03-19 | 2023-01-20 | セントラル チャイナ ノーマル ユニバーシティ | ピラゾロピリミジン化合物、医薬組成物、及びその使用 |
| MX2021009863A (es) | 2019-03-21 | 2021-11-12 | Onxeo | Una molecula dbait en combinacion con inhibidor de quinasa para el tratamiento del cancer. |
| SG11202112381VA (en) | 2019-05-08 | 2021-12-30 | Tyk Medicines Inc | Compound used as kinase inhibitor and application thereof |
| WO2021047584A1 (en) * | 2019-09-11 | 2021-03-18 | Fochon Pharmaceuticals, Ltd. | SUBSTITUTED (2-AZABICYCLO [3.1.0] HEXAN-2-YL) PYRAZOLO [1, 5-a] PYRIMIDINE AND IMIDAZO [1, 2-b] PYRIDAZINE COMPOUNDS AS TRK KINASES INHIBITORS |
| WO2021089791A1 (en) | 2019-11-08 | 2021-05-14 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the treatment of cancers that have acquired resistance to kinase inhibitors |
| CN112812118A (zh) * | 2019-11-18 | 2021-05-18 | 上海轶诺药业有限公司 | 一类蛋白受体激酶抑制剂的制备和应用 |
| CN115297863A (zh) * | 2020-01-22 | 2022-11-04 | 博善人工智能生物科技有限公司 | 包含咪唑并[1,2-b]哒嗪化合物的表面药物组合物 |
| WO2021148581A1 (en) | 2020-01-22 | 2021-07-29 | Onxeo | Novel dbait molecule and its use |
| CN113563343B (zh) * | 2020-07-27 | 2022-05-24 | 杭州邦顺制药有限公司 | 取代的吡唑并[1,5-a]嘧啶化合物及其用途 |
| BR112023021215A2 (pt) * | 2021-04-13 | 2023-12-19 | Shenzhen Newdel Biotech Co Ltd | Compostos de alquinilfenilbenzamida, usos dos mesmos e composição farmacêutica compreendendo os referidos compostos |
| EP4363420A4 (en) * | 2021-07-01 | 2025-06-11 | Anheart Therapeutics (Hangzhou) Co., Ltd. | Crystalline forms of 3-{4-[(2r)-2-aminopropoxy]phenyl}-n-[(1r)- 1-(3-fluorophenyl) ethyl]imidazo[1,2-b]pyridazin-6-amine and salts thereof |
Family Cites Families (188)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100263817B1 (ko) | 1993-11-30 | 2000-08-16 | 윌리암스 로저 에이 | 염증치료용 치환 피라졸일벤젠술폰아미드 |
| US5844092A (en) | 1994-03-18 | 1998-12-01 | Genentech, Inc. | Human TRK receptors and neurotrophic factor inhibitors |
| US5877016A (en) | 1994-03-18 | 1999-03-02 | Genentech, Inc. | Human trk receptors and neurotrophic factor inhibitors |
| US5430021A (en) | 1994-03-18 | 1995-07-04 | Pharmavene, Inc. | Hydrophobic drug delivery systems |
| CA2206201A1 (en) | 1996-05-29 | 1997-11-29 | Yoshiaki Isobe | Pyrazole derivatives and their pharmaceutical use |
| WO1998049167A1 (en) | 1997-04-25 | 1998-11-05 | Takeda Chemical Industries, Ltd. | Condensed pyridazine derivatives, their production and use |
| US6534085B1 (en) | 1999-09-23 | 2003-03-18 | Bioresponse L.L.C. | Phytochemicals for promoting weight loss |
| BR0112272A (pt) | 2000-06-22 | 2003-05-06 | Genentech Inc | Anticorpo monoclonal anti-trkc agonista, cadeia pesada de anticorpo anti-trkc, cadeia leve de anticorpo anti-trkc, cadeia pesada de anticorpo anti-trkc murino, cadeia pesada de anticorpo anti-trkc humano, anticorpo agonista anti-trkc murino, anticorpo agonista anti-trkc humano, moléculas de ácido nucléico isolado, moléculas de ácido nucléico, vetor, linhagens de células hospedeiras, linhagens de células de hibridoma, célula hospedeira, polipeptìdeo, composição farmacêutica, método para o tratamento de neuropatia ou doença neurodegenerativa ou reparo de uma célula nervosa lesionada, método para aumentar a proliferação, manutenção ou regeneração de neurÈnios periféricos, método para o tratamento de doença ou condição que envolve a degeneração celular em um paciente mamìfero, método de indução de angiogênese, método de fabricação de um anticorpo anti-trkc, usos de um anticorpo |
| TWI312347B (en) | 2001-02-08 | 2009-07-21 | Eisai R&D Man Co Ltd | Bicyclic nitrogen-containing condensed ring compounds |
| KR20040049829A (ko) | 2001-05-30 | 2004-06-12 | 제넨테크, 인크. | 다양한 질환의 치료에 유용한 항-엔지에프 항체 |
| US20030199525A1 (en) | 2002-03-21 | 2003-10-23 | Hirst Gavin C. | Kinase inhibitors |
| US7449488B2 (en) | 2002-06-04 | 2008-11-11 | Schering Corporation | Pyrazolopyrimidines as protein kinase inhibitors |
| ITMI20021620A1 (it) | 2002-07-23 | 2004-01-23 | Novuspharma Spa | Composto ad ativita' antitumorale |
| JP4024624B2 (ja) | 2002-08-26 | 2007-12-19 | 富士通株式会社 | 半導体装置の製造方法及び製造装置 |
| US8580782B2 (en) | 2002-09-04 | 2013-11-12 | Merck Sharp & Dohme Corp. | Substituted pyrazolo[1,5-a]pyrimidines as cyclin dependent kinase inhibitors |
| US7196078B2 (en) | 2002-09-04 | 2007-03-27 | Schering Corpoartion | Trisubstituted and tetrasubstituted pyrazolopyrimidines as cyclin dependent kinase inhibitors |
| CA2497440C (en) | 2002-09-04 | 2011-03-22 | Schering Corporation | Pyrazolopyrimidines as cyclin-dependent kinase inhibitors |
| WO2004052315A2 (en) | 2002-12-11 | 2004-06-24 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| US7262199B2 (en) | 2002-12-11 | 2007-08-28 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| GB0303910D0 (en) | 2003-02-20 | 2003-03-26 | Merck Sharp & Dohme | Therapeutic agents |
| ES2325440T3 (es) | 2003-02-20 | 2009-09-04 | Smithkline Beecham Corporation | Compuestos de pirimidina. |
| WO2004082458A2 (en) | 2003-02-21 | 2004-09-30 | The Johns Hopkins University | Tyrosine kinome |
| JP2004277337A (ja) | 2003-03-14 | 2004-10-07 | Sumitomo Pharmaceut Co Ltd | ピラゾロ［１，５−ａ］ピリミジン誘導体 |
| EP1608652A1 (en) | 2003-03-31 | 2005-12-28 | Vernalis (Cambridge) Limited | Pyrazolopyrimidine compounds and their use in medicine |
| US20060094699A1 (en) | 2003-04-11 | 2006-05-04 | Kampen Gita Camilla T | Combination therapy using an 11beta-hydroxysteroid dehydrogenase type 1 inhibitor and a glucocorticoid receptor agonist to minimize the side effects associated with glucocorticoid receptor agonist therapy |
| EP1615667A2 (en) | 2003-04-11 | 2006-01-18 | Novo Nordisk A/S | Combinations of an 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor and a glucocorticoid receptor agonist |
| EP1615697A2 (en) | 2003-04-11 | 2006-01-18 | Novo Nordisk A/S | New pyrazolo[1,5-a] pyrimidine derivatives and pharmaceutical use thereof |
| US20070042941A1 (en) | 2003-04-28 | 2007-02-22 | Mitsuomi Hirashima | Galectin 9-inducing factors |
| PA8603801A1 (es) | 2003-05-27 | 2004-12-16 | Janssen Pharmaceutica Nv | Derivados de la quinazolina |
| JP2005008581A (ja) | 2003-06-20 | 2005-01-13 | Kissei Pharmaceut Co Ltd | 新規なピラゾロ［１，５−ａ］ピリミジン誘導体、それを含有する医薬組成物およびそれらの用途 |
| EA009517B1 (ru) | 2003-06-27 | 2008-02-28 | Байер Кропсайенс Аг | Пиразолопиримидины |
| EP1648509B8 (en) | 2003-07-15 | 2012-10-24 | Amgen Inc. | Human anti-ngf neutralizing antibodies as selective ngf pathway inhibitors |
| US7491794B2 (en) | 2003-10-14 | 2009-02-17 | Intermune, Inc. | Macrocyclic compounds as inhibitors of viral replication |
| MY141220A (en) | 2003-11-17 | 2010-03-31 | Astrazeneca Ab | Pyrazole derivatives as inhibitors of receptor tyrosine kinases |
| UA83881C2 (en) | 2003-12-18 | 2008-08-26 | Янссен Фармацевтика Н.В. | Pyrido- and pyrimidopyrimidine derivatives as anti-proliferative agents |
| WO2005062795A2 (en) | 2003-12-19 | 2005-07-14 | Plexxikon, Inc. | Compounds and methods for development of ret modulators |
| WO2005068424A1 (en) | 2004-01-20 | 2005-07-28 | Cell Therapeutics Europe S.R.L. | Indolinone derivatives as receptor tyrosine kinase ihibitors |
| US20050222171A1 (en) | 2004-01-22 | 2005-10-06 | Guido Bold | Organic compounds |
| WO2005099363A2 (en) | 2004-03-26 | 2005-10-27 | Whitehead Institute For Biomedical Research | Methods of diagnosing, preventing and treating cancer metastasis |
| CN1938311A (zh) | 2004-03-30 | 2007-03-28 | 因特蒙公司 | 作为病毒复制抑制剂的大环化合物 |
| GB0512324D0 (en) | 2005-06-16 | 2005-07-27 | Novartis Ag | Organic compounds |
| PE20060664A1 (es) | 2004-09-15 | 2006-08-04 | Novartis Ag | Amidas biciclicas como inhibidores de cinasa |
| KR20070090172A (ko) | 2004-11-04 | 2007-09-05 | 버텍스 파마슈티칼스 인코포레이티드 | 단백질 키나아제의 억제제로서 유용한피라졸로[1,5-ａ]피리미딘 |
| JO3088B1 (ar) | 2004-12-08 | 2017-03-15 | Janssen Pharmaceutica Nv | مشتقات كوينازولين كبيرة الحلقات و استعمالها بصفتها موانع كينيز متعددة الاهداف |
| DE102005003687A1 (de) | 2005-01-26 | 2006-07-27 | Sphingo Tec Gmbh | Immunoassay zur Bestimmung der Freisetzung von Neurotensin in die Zirkulation |
| CN101119996A (zh) | 2005-02-16 | 2008-02-06 | 阿斯利康(瑞典)有限公司 | 化学化合物 |
| HRP20100477T1 (hr) | 2005-02-16 | 2010-10-31 | Astrazeneca Ab | Kemijski spojevi |
| DK1869049T3 (da) | 2005-03-21 | 2009-05-18 | Lilly Co Eli | Imidazopyridazinforbindelser |
| US20090005396A1 (en) | 2005-04-27 | 2009-01-01 | Astrazeneca Ab | Use of Pyrazolyl-Pyrimidine Derivatives in the Treatment of Pain |
| US20080287437A1 (en) | 2005-05-16 | 2008-11-20 | Astrazeneca Ab | Pyrazolylaminopyrimidine Derivatives Useful as Tyrosine Kinase Inhibitors |
| CN100406650C (zh) | 2005-06-05 | 2008-07-30 | 徐斌 | 一种抗特大变位的模块式梳型桥梁伸缩缝装置 |
| ITRM20050290A1 (it) | 2005-06-07 | 2006-12-08 | Lay Line Genomics Spa | Uso di molecole in grado di inibire il legame tra ngf e il suo recettore trka come analgesici ad effetto prolungato. |
| US20070025540A1 (en) | 2005-07-07 | 2007-02-01 | Roger Travis | Call center routing based on talkativeness |
| EP2305696A3 (en) | 2005-07-25 | 2011-10-12 | Intermune, Inc. | Macrocyclic inhibitors of Hepatitis C virus replication |
| JP2009502734A (ja) * | 2005-07-29 | 2009-01-29 | アステラス製薬株式会社 | Ｌｃｋ阻害剤としての縮合複素環 |
| JP2009503071A (ja) | 2005-08-03 | 2009-01-29 | イーストマン ケミカル カンパニー | トコフェリルポリエチレングリコールスクシネート粉末及びその製造方法 |
| EP1926734A1 (en) | 2005-08-22 | 2008-06-04 | Amgen Inc. | Pyrazolopyridine and pyrazolopyrimidine compounds useful as kinase enzymes modulators |
| BRPI0615277A2 (pt) | 2005-08-25 | 2009-08-04 | Creabilis Therapeutics Spa | conjugado de polìmeros de k-252a, composição farmacêutica compreendendo o referido conjugado, bem como uso do mesmo |
| WO2007025090A2 (en) | 2005-08-25 | 2007-03-01 | Kalypsys, Inc. | Heterobicyclic and - tricyclic inhibitors of mapk/erk kinase |
| DE102005042742A1 (de) | 2005-09-02 | 2007-03-08 | Schering Ag | Substituierte Imidazo[1,2b]pyridazine als Kinase-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel |
| US20070078136A1 (en) | 2005-09-22 | 2007-04-05 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| JP5102212B2 (ja) | 2005-10-06 | 2012-12-19 | メルク・シャープ・アンド・ドーム・コーポレーション | プロテインキナーゼインヒビターとしてのピラゾロピリミジン |
| US20070082900A1 (en) | 2005-10-06 | 2007-04-12 | Schering Corporation | Methods for inhibiting protein kinases |
| EP1948633B1 (en) | 2005-10-11 | 2011-08-10 | Centre National De La Recherche Scientifique (Cnrs) | 3 -hydroxyflavone derivatives for the detection and the quantification of cell apoptosis |
| JP2009511595A (ja) | 2005-10-11 | 2009-03-19 | インターミューン・インコーポレーテッド | Ｃ型肝炎ウイルスの複製を阻害する化合物および方法 |
| CA2626789A1 (en) | 2005-10-21 | 2007-04-26 | Exelixis, Inc. | Pyrimidinones as casein kinase ii (ck2) modulators |
| GB0524436D0 (en) | 2005-11-30 | 2006-01-11 | Novartis Ag | Organic compounds |
| JP5474354B2 (ja) | 2005-12-30 | 2014-04-16 | アステックス、セラピューティックス、リミテッド | 医薬化合物 |
| US20080108611A1 (en) | 2006-01-19 | 2008-05-08 | Battista Kathleen A | Substituted thienopyrimidine kinase inhibitors |
| KR100846988B1 (ko) | 2006-03-06 | 2008-07-16 | 제일약품주식회사 | 신규한 티에노피리미딘 유도체 또는 이의 약학적으로허용가능한 염, 이의 제조방법 및 이를 함유하는 약학조성물 |
| CA2645137A1 (en) | 2006-03-07 | 2007-09-13 | James F. Blake | Heterobicyclic pyrazole compounds and methods of use |
| GB0606805D0 (en) | 2006-04-04 | 2006-05-17 | Novartis Ag | Organic compounds |
| DK2024372T3 (da) | 2006-04-26 | 2010-09-20 | Hoffmann La Roche | Thieno[3,2-d]pyrimidin-derivat, der er egnet som P13K inhibitor |
| US20090209580A1 (en) | 2006-05-18 | 2009-08-20 | Eisai R & D Management Co., Ltd. | Antitumor agent for thyroid cancer |
| US7389632B2 (en) | 2006-06-10 | 2008-06-24 | Uhlmann Pac-Systeme Gmbh & Co. Kg | Apparatus for distributing small objects in a fill station |
| EP1873157A1 (en) | 2006-06-21 | 2008-01-02 | Bayer Schering Pharma Aktiengesellschaft | Pyrazolopyrimidines and salts thereof, pharmaceutical compositions comprising same, methods of preparing same and uses of same |
| TWI419889B (zh) | 2006-07-05 | 2013-12-21 | Mitsubishi Tanabe Pharma Corp | 吡唑并〔１，５-ａ〕嘧啶化合物 |
| US20100029619A1 (en) * | 2006-08-04 | 2010-02-04 | Takeda Pharmaceutical Company Limted | Fused heterocyclic compound |
| US7531539B2 (en) | 2006-08-09 | 2009-05-12 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
| AU2007292924A1 (en) | 2006-09-07 | 2008-03-13 | Biogen Idec Ma Inc. | IRAK modulators for treating an inflammatory condition, cell proliferative disorder, immune disorder |
| KR20090073121A (ko) | 2006-09-29 | 2009-07-02 | 노파르티스 아게 | Ｐｉ3ｋ 지질 키나제 억제제로서의 피라졸로피리미딘 |
| AU2007315234A1 (en) * | 2006-10-30 | 2008-05-08 | Novartis Ag | Heterocyclic compounds as antiinflammatory agents |
| NZ576234A (en) | 2006-11-06 | 2011-06-30 | Supergen Inc | Imidazo[1,2-b]pyridazine and pyrazolo[1,5-a]pyrimidine derivatives and their use as protein kinase inhibitors |
| PE20121126A1 (es) | 2006-12-21 | 2012-08-24 | Plexxikon Inc | Compuestos pirrolo [2,3-b] piridinas como moduladores de quinasa |
| US20080234267A1 (en) | 2007-03-20 | 2008-09-25 | Karen Elizabeth Lackey | Compounds and Methods of Treatment |
| US20080234262A1 (en) | 2007-03-21 | 2008-09-25 | Wyeth | Pyrazolopyrimidine analogs and their use as mtor kinase and pi3 kinase inhibitors |
| WO2008116898A1 (en) | 2007-03-28 | 2008-10-02 | Biovitrum Ab (Publ) | Pyrazolo [1,5-a]pyrimidines as inhibitors of stearoyl-coa desaturase |
| MX2009010728A (es) | 2007-04-03 | 2009-10-26 | Array Biopharma Inc | Compuestos de imidazo[1,2-a]piridina como inhibidores de la tirosina-cinasa repectora. |
| WO2008137794A1 (en) | 2007-05-04 | 2008-11-13 | Irm Llc | Compounds and compositions as c-kit and pdgfr kinase inhibitors |
| DK2170827T3 (da) | 2007-06-21 | 2013-11-18 | Janssen Pharmaceutica Nv | Indolin-2-oner og aza-indolin-2-oner |
| PH12013501594A1 (en) | 2007-07-20 | 2014-05-12 | Nerviano Medical Sciences Srl | Substituted indazole derivatives active as kinase inhibitors |
| ES2517872T3 (es) | 2007-08-10 | 2014-11-04 | Regeneron Pharmaceuticals, Inc. | Anticuerpos humanos de alta afinidad para el factor de crecimiento nervioso humano |
| CA2702838A1 (en) | 2007-10-16 | 2009-04-23 | Wyeth Llc | Thienopyrimidine and pyrazolopyrimidine compounds and their use as mtor kinase and pi3 kinase inhibitors |
| CA2703329A1 (en) | 2007-10-23 | 2009-04-30 | Novartis Ag | Use of trkb antibodies for the treatment of respiratory disorders |
| WO2009060197A1 (en) | 2007-11-08 | 2009-05-14 | Centro Nacional De Investigaciones Oncologicas (Cnio) | Imidazopyridazines for use as protein kinase inhibitors |
| CL2009000090A1 (es) | 2008-01-17 | 2009-07-24 | Irm Llc | Anticuerpo que se une al receptor de tirosina quinasa b (trkb); composicion que comprende el anticuerpo; metodo para reducir los niveles de glucosa en la sangre y/o el peso corporal en un individuo. |
| JP2009203226A (ja) | 2008-01-31 | 2009-09-10 | Eisai R & D Management Co Ltd | ピリジン誘導体およびピリミジン誘導体を含有するレセプターチロシンキナーゼ阻害剤 |
| AU2009246687B2 (en) * | 2008-05-13 | 2012-08-09 | Irm Llc | Fused nitrogen containing heterocycles and compositions thereof as kinase inhibitors |
| WO2009143018A2 (en) | 2008-05-19 | 2009-11-26 | Plexxikon, Inc. | Compounds and methods for kinase modulation, and indications therefor |
| GEP20125502B (en) | 2008-05-23 | 2012-04-25 | Novartis Ag | Derivatives of quinolines and quinoxalines as protein tyrosine kinase inhibitors |
| CN102105151B (zh) | 2008-07-29 | 2013-12-18 | 内尔维阿诺医学科学有限公司 | Cdk抑制剂在治疗神经胶质瘤中的应用 |
| SI2350075T1 (sl) * | 2008-09-22 | 2014-06-30 | Array Biopharma, Inc. | Substituirane imidazo (1,2b)piridazinske spojine kot Trk kinazni inhibitorji |
| BRPI0919873B8 (pt) | 2008-10-22 | 2021-05-25 | Array Biopharma Inc | compostos de pirazol[1,5-a]pirimidina substituídos como inibidores da trk quinase, seus processos de preparação e composições farmacêuticas |
| MX2011004494A (es) | 2008-10-31 | 2011-05-24 | Genentech Inc | Compuestos de pirazolopirimidina inhibidores de jak y metodos. |
| WO2010058006A1 (en) | 2008-11-24 | 2010-05-27 | Nerviano Medical Sciences S.R.L. | Cdk inhibitor for the treatment of mesothelioma |
| JO3265B1 (ar) | 2008-12-09 | 2018-09-16 | Novartis Ag | مثبطات بيريديلوكسى اندولات vegf-r2 واستخدامها لعلاج المرض |
| JP5979877B2 (ja) | 2009-02-12 | 2016-08-31 | セル・シグナリング・テクノロジー・インコーポレイテツド | ヒト癌における変異ｒｏｓ発現 |
| AR077468A1 (es) | 2009-07-09 | 2011-08-31 | Array Biopharma Inc | Compuestos de pirazolo (1,5 -a) pirimidina sustituidos como inhibidores de trk- quinasa |
| JP2013519706A (ja) | 2010-02-18 | 2013-05-30 | アンスティチュ ナショナル ドゥ ラ サンテ エ ドゥ ラ ルシェルシュ メディカル | 癌転移を予防するための方法 |
| CA2795776A1 (en) | 2010-04-06 | 2011-10-13 | Caris Life Sciences Luxembourg Holdings, S.A.R.L. | Circulating biomarkers for disease |
| US8383793B2 (en) | 2010-04-15 | 2013-02-26 | St. Jude Children's Research Hospital | Methods and compositions for the diagnosis and treatment of cancer resistant to anaplastic lymphoma kinase (ALK) kinase inhibitors |
| TWI510487B (zh) | 2010-04-21 | 2015-12-01 | Plexxikon Inc | 用於激酶調節的化合物和方法及其適應症 |
| US8543395B2 (en) | 2010-05-18 | 2013-09-24 | Shazam Entertainment Ltd. | Methods and systems for performing synchronization of audio with corresponding textual transcriptions and determining confidence values of the synchronization |
| SMT201700372T1 (it) | 2010-05-20 | 2017-09-07 | Array Biopharma Inc | Composti macrociclici come inibitori di trk chinasi |
| WO2012024650A2 (en) | 2010-08-19 | 2012-02-23 | Abbott Laboratories | Anti-ngf antibodies and their use |
| US8637516B2 (en) | 2010-09-09 | 2014-01-28 | Irm Llc | Compounds and compositions as TRK inhibitors |
| WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
| JP6190723B2 (ja) | 2010-12-01 | 2017-08-30 | アルダーバイオ ホールディングス エルエルシー | 抗ｎｇｆ組成物およびその使用 |
| CN103492384B (zh) | 2011-02-25 | 2016-05-11 | 诺华股份有限公司 | 作为trk抑制剂的化合物和组合物 |
| RU2606131C2 (ru) | 2011-05-13 | 2017-01-10 | Эррэй Биофарма Инк. | СОЕДИНЕНИЯ ПИРРОЛИДИНИЛМОЧЕВИНЫ И ПИРРОЛИДИНИЛТИОМОЧЕВИНЫ КАК ИНГИБИТОРЫ КИНАЗЫ TrkA |
| WO2013059740A1 (en) | 2011-10-21 | 2013-04-25 | Foundation Medicine, Inc. | Novel alk and ntrk1 fusion molecules and uses thereof |
| AU2012339753A1 (en) | 2011-11-14 | 2014-06-19 | Tesaro, Inc. | Modulating certain tyrosine kinases |
| AU2012351748B2 (en) | 2011-12-12 | 2016-04-14 | Dr. Reddy's Laboratories Ltd. | Substituted pyrazolo[1,5-a] pyridine as tropomyosin receptor kinase (Trk) inhibitors |
| US8377946B1 (en) | 2011-12-30 | 2013-02-19 | Pharmacyclics, Inc. | Pyrazolo[3,4-d]pyrimidine and pyrrolo[2,3-d]pyrimidine compounds as kinase inhibitors |
| ES2605388T3 (es) | 2012-04-26 | 2017-03-14 | Ono Pharmaceutical Co., Ltd. | Compuesto inhibidor de Trk |
| JP6231556B2 (ja) | 2012-05-23 | 2017-11-15 | ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ | Ｎ−［５−（３，５−ジフルオロ−ベンジル）−１ｈ−インダゾール−３−イル］−４−（４−メチル−ピペラジン−１−イル）−２−（テトラヒドロ−ピラン−４−イルアミノ）−ベンズアミドの調製方法 |
| TWI585088B (zh) | 2012-06-04 | 2017-06-01 | 第一三共股份有限公司 | 作爲激酶抑制劑之咪唑并［１，２－ｂ］嗒衍生物 |
| WO2014036387A2 (en) | 2012-08-31 | 2014-03-06 | The Regents Of The University Of Colorado | Methods for diagnosis and treatment of cancer |
| CN114129566A (zh) | 2012-09-07 | 2022-03-04 | 埃克塞里艾克西斯公司 | 用于治疗肺腺癌的met、vegfr和ret的抑制剂 |
| US20140084039A1 (en) | 2012-09-24 | 2014-03-27 | Electro Scientific Industries, Inc. | Method and apparatus for separating workpieces |
| JP2014082984A (ja) | 2012-10-23 | 2014-05-12 | Astellas Pharma Inc | 新規ｎｔｒｋ２活性化変異の検出法 |
| CA2890207A1 (en) | 2012-11-05 | 2014-05-08 | Foundation Medicine, Inc. | Novel ntrk1 fusion molecules and uses thereof |
| HK1214831A1 (zh) | 2012-11-05 | 2016-08-05 | Foundation Medicine, Inc. | 新型融合分子及其应用 |
| WO2014078331A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-(arylalkyl)-n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078322A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | Thiazolyl and oxazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| US9822118B2 (en) | 2012-11-13 | 2017-11-21 | Array Biopharma Inc. | Bicyclic heteroaryl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| US9790178B2 (en) | 2012-11-13 | 2017-10-17 | Array Biopharma Inc. | Pyrrolidinyl urea, thiourea, guanidine and cyanoguanidine compounds as TrkA kinase inhibitors |
| WO2014078323A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-pyrrolidinyl, n'-pyrazolyl- urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| US9809578B2 (en) | 2012-11-13 | 2017-11-07 | Array Biopharma Inc. | Pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trkA kinase inhibitors |
| SG11201503731SA (en) | 2012-11-13 | 2015-06-29 | Array Biopharma Inc | Bicyclic urea, thiourea, guanidine and cyanoguanidine compounds useful for the treatment of pain |
| WO2014078328A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-bicyclic aryl,n'-pyrazolyl urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014078325A1 (en) | 2012-11-13 | 2014-05-22 | Array Biopharma Inc. | N-(monocyclic aryl),n'-pyrazolyl-urea, thiourea, guanidine and cyanoguanidine compounds as trka kinase inhibitors |
| WO2014083567A2 (en) | 2012-11-29 | 2014-06-05 | Yeda Research And Development Co. Ltd. | Methods of preventing tumor metastasis, treating and prognosing cancer and identifying agents which are putative metastasis inhibitors |
| US9447135B2 (en) | 2012-12-14 | 2016-09-20 | University Of Kentucky Research Foundation | Semi-synthetic mithramycin derivatives with anti-cancer activity |
| US9127055B2 (en) | 2013-02-08 | 2015-09-08 | Astellas Pharma Inc. | Method of treating pain with anti-human NGF antibody |
| ES2710556T3 (es) | 2013-02-19 | 2019-04-25 | Ono Pharmaceutical Co | Compuesto inhibidor de Trk |
| EP2981613A4 (en) | 2013-02-22 | 2016-11-02 | Boris C Bastian | FUSION POLYNUCLEOTIDES AND FUSION POLYPEPTIDES RELATED TO CANCER AND IN PARTICULAR TO MELANOMA AND USES THEREOF AS THERAPEUTIC AND DIAGNOSTIC OBJECTIVES |
| US20140243332A1 (en) | 2013-02-27 | 2014-08-28 | Oregon Health & Science University | Methods of treating cancers characterized by aberrent ros1 activity |
| US8937071B2 (en) | 2013-03-15 | 2015-01-20 | Glaxosmithkline Intellectual Property Development Limited | Compounds as rearranged during transfection (RET) inhibitors |
| EP3795696B1 (en) | 2013-03-15 | 2023-04-26 | The Board of Trustees of the Leland Stanford Junior University | Identification and use of circulating nucleic acid tumor markers |
| CA2907152A1 (en) | 2013-03-15 | 2014-09-25 | The Trustees Of Columbia University In The City Of New York | Fusion proteins and methods thereof |
| WO2014152777A2 (en) | 2013-03-15 | 2014-09-25 | Insight Genetics, Inc. | Methods and compositions for the diagnosis and treatment of cancers resistant to ros1 inhibitors |
| US10072298B2 (en) | 2013-04-17 | 2018-09-11 | Life Technologies Corporation | Gene fusions and gene variants associated with cancer |
| CN105378110B (zh) | 2013-04-17 | 2024-06-25 | 生命技术公司 | 与癌症相关的基因融合体和基因变异体 |
| EP3019489A4 (en) | 2013-07-11 | 2016-12-28 | Betta Pharmaceuticals Co Ltd | MODULATORS OF TYROSINE KINASE PROTEIN AND METHODS OF USE |
| JP6534930B2 (ja) | 2013-07-26 | 2019-06-26 | 公益財団法人がん研究会 | Ｎｔｒｋ３融合体の検出法 |
| EP3628749A1 (en) | 2013-07-30 | 2020-04-01 | Blueprint Medicines Corporation | Ntrk2 fusions |
| AU2014340398A1 (en) | 2013-10-24 | 2016-06-09 | Georgetown University | Methods and compositions for treating cancer |
| JPWO2015064621A1 (ja) | 2013-10-29 | 2017-03-09 | 公益財団法人がん研究会 | 新規融合体及びその検出法 |
| RS59059B1 (sr) | 2014-01-24 | 2019-08-30 | Turning Point Therapeutics Inc | Diaril makrociklična jedinjenja kao modulatori protein kinaza |
| CA2934043C (en) | 2014-02-05 | 2019-03-12 | VM Oncology LLC | Trka receptor tyrosine kinase antagonists and uses thereof |
| US10231965B2 (en) | 2014-02-20 | 2019-03-19 | Ignyta, Inc. | Molecules for administration to ROS1 mutant cancer cells |
| MA40434B1 (fr) | 2014-05-15 | 2019-09-30 | Array Biopharma Inc | 1-((3s,4r)-4-(3-fluorophényl)-1-(2-méthoxyéthyl)pyrrolidin-3-yl)-3-(4-méthyl-3-(2-méthylpyrimidin-5-yl)-1-phényl-1h-pyrazol-5-yl)urée comme inhibiteur de la kinase trka |
| WO2015183837A1 (en) | 2014-05-27 | 2015-12-03 | Brian Haynes | Compositions, methods, and uses related to ntrk2-tert fusions |
| US20170114415A1 (en) | 2014-05-30 | 2017-04-27 | The Regents Of The University Of Colorado, A Body Corporate | Activating ntrk1 gene fusions predictive of kinase inhibitor therapy |
| MX2017001302A (es) | 2014-08-01 | 2017-10-11 | Pharmacyclics Llc | Biomarcadores para predecir la respuesta del dlbcl al tratamiento con un inhibidor de la btk. |
| TWI560185B (en) | 2014-08-18 | 2016-12-01 | Ono Pharmaceutical Co | Acid addition salt of trk inhibitor compound |
| ES2952717T3 (es) | 2014-10-14 | 2023-11-03 | Novartis Ag | Moléculas de anticuerpos contra PD-L1 y usos de las mismas |
| CA2967951C (en) | 2014-11-16 | 2023-11-07 | Array Biopharma, Inc. | 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 |
| HUE067779T2 (hu) | 2014-12-15 | 2024-11-28 | Cmg Pharmaceutical Co Ltd | Kondenzált gyûrûs heteroaril vegyületek és azok felhasználása TRK inhibitorokként |
| HK1252267A1 (zh) | 2015-05-20 | 2019-05-24 | The Broad Institute Inc. | 共有的新抗原 |
| CA2987281A1 (en) | 2015-05-29 | 2016-12-08 | Ignyta, Inc. | Compositions and methods for treating patients with rtk mutant cells |
| EP3722441A1 (en) | 2015-06-01 | 2020-10-14 | Loxo Oncology Inc. | Method of diagnosing a cancer for a treatment with a trk inhibitor |
| US9782400B2 (en) | 2015-06-19 | 2017-10-10 | Macau University Of Science And Technology | Oncogenic ROS1 and ALK kinase inhibitor |
| AU2015101722A4 (en) | 2015-06-19 | 2016-05-19 | Macau University Of Science And Technology | Oncogenic ros1 and alk kinase inhibitor |
| GB201511546D0 (en) | 2015-07-01 | 2015-08-12 | Immatics Biotechnologies Gmbh | Novel peptides and combination of peptides for use in immunotherapy against ovarian cancer and other cancers |
| CN107735399B (zh) | 2015-07-02 | 2021-01-26 | 特普医药公司 | 作为蛋白质激酶的调节剂的手性二芳基大环 |
| EP3368039A1 (en) | 2015-10-26 | 2018-09-05 | The Regents of The University of Colorado, A Body Corporate | Point mutations in trk inhibitor-resistant cancer and methods relating to the same |
| US20170224662A1 (en) | 2016-01-22 | 2017-08-10 | The Medicines Company | Aqueous Formulations and Methods of Preparation and Use Thereof |
| WO2017155018A1 (ja) | 2016-03-11 | 2017-09-14 | 小野薬品工業株式会社 | Ｔｒｋ阻害剤抵抗性の癌治療剤 |
| PT3439662T (pt) | 2016-04-04 | 2024-09-30 | Loxo Oncology Inc | Formulações líquidas de (s)-n-(5-((r)-2-(2,5-difluorofenil)-pirrolidin-1-il)-pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidina-1-carboxamida |
| US10045991B2 (en) | 2016-04-04 | 2018-08-14 | Loxo Oncology, Inc. | Methods of treating pediatric cancers |
| US20210030737A1 (en) | 2016-04-19 | 2021-02-04 | Exelixis, Inc. | Triple Negative Breast Cancer Treatment Method |
| WO2017201156A1 (en) | 2016-05-18 | 2017-11-23 | Duke University | Method of treating kras wild-type metastatic colorectal cell carcinoma using cabozantinib plus panitumumab |
| PT3458456T (pt) | 2016-05-18 | 2020-12-07 | Array Biopharma Inc | Preparação de (s)-n-(5-((r)-2-(2,5-difluorofenil)pirrolidin-1-il)pirazolo[1,5-a]pirimidin-3-il)-3-hidroxipirrolidino-1-carboxamida |
| JOP20190092A1 (ar) | 2016-10-26 | 2019-04-25 | Array Biopharma Inc | عملية لتحضير مركبات بيرازولو[1، 5-a]بيريميدين وأملاح منها |
| JOP20190213A1 (ar) | 2017-03-16 | 2019-09-16 | Array Biopharma Inc | مركبات حلقية ضخمة كمثبطات لكيناز ros1 |
| CA3080157A1 (en) | 2017-10-26 | 2019-05-02 | Array Biopharma Inc. | Formulations of a macrocyclic trk kinase inhibitor |
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