EA201990904A1 - 1,3-дизамещенные производные циклобутана или азетидина в качестве ингибиторов гемопоэтической простагландин-d-синтазы - Google Patents

1,3-дизамещенные производные циклобутана или азетидина в качестве ингибиторов гемопоэтической простагландин-d-синтазы

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Publication number
EA201990904A1
EA201990904A1 EA201990904A EA201990904A EA201990904A1 EA 201990904 A1 EA201990904 A1 EA 201990904A1 EA 201990904 A EA201990904 A EA 201990904A EA 201990904 A EA201990904 A EA 201990904A EA 201990904 A1 EA201990904 A1 EA 201990904A1
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Eurasian Patent Office
Prior art keywords
prostaglandin
hemopoetic
cyclobutane
displaced
synthase inhibitors
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EA201990904A
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English (en)
Inventor
Дэвид Норман Дитон
Юй Го
Эшли Пол Хэнкок
Кристи Шульте
Бэрри Джордж Ширер
Эмили Деспаньет Смит
Юджин Л. Стюарт
Стивен Эндрю Томсон
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Глэксосмитклайн Интеллекчуал Проперти Дивелопмент Лимитед
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Publication of EA201990904A1 publication Critical patent/EA201990904A1/ru

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    • A61K31/397—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having four-membered rings, e.g. azetidine
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Abstract

Соединение формулы (I)где R, R, R, R, Y, Y, a, X и Z являются такими, как определено в настоящем документе. Соединения настоящего изобретения являются ингибиторами гемопоэтической простагландин-D-синтазы (H-PGDS) и могут применяться при лечении миодистрофии Дюшенна. Таким образом, изобретение также направлено на фармацевтические композиции, включающие соединение согласно изобретению. Изобретение также направлено на способы ингибирования активности H-PGDS и лечения связанных с ней нарушений с применением соединения согласно изобретению или фармацевтической композиции, включающей соединение согласно изобретению.
EA201990904A 2016-10-13 2017-10-12 1,3-дизамещенные производные циклобутана или азетидина в качестве ингибиторов гемопоэтической простагландин-d-синтазы EA201990904A1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201662407634P 2016-10-13 2016-10-13
PCT/IB2017/056320 WO2018069863A1 (en) 2016-10-13 2017-10-12 1,3 di-substituted cyclobutane or azetidine derivatives as hematopoietic prostaglandin d synthase inhibitors

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EA201990904A1 true EA201990904A1 (ru) 2019-08-30

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US (1) US11053234B2 (ru)
EP (1) EP3526206A1 (ru)
JP (1) JP6938628B2 (ru)
KR (1) KR20190072565A (ru)
CN (1) CN110072857A (ru)
AR (1) AR109931A1 (ru)
AU (1) AU2017342156B2 (ru)
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CO (1) CO2019003482A2 (ru)
CR (1) CR20190174A (ru)
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Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JOP20190072A1 (ar) 2016-10-13 2019-04-07 Glaxosmithkline Ip Dev Ltd مشتقات 1، 3 سيكلوبوتان ثنائي الاستبدال أو آزيتيدين كمثبطات للإنزيم المخلق للبروستاجلاندين d المكون للدم
UY37764A (es) * 2017-06-13 2019-01-02 Glaxosmithkline Ip Dev Ltd Nuevos compuestos inhibidores de la prostaglandina d sintasa hematopoyética (h-pgds)
IL301709A (en) 2017-08-09 2023-05-01 Denali Therapeutics Inc Compounds, preparations and methods
CR20210426A (es) 2019-02-13 2021-09-30 Denali Therapeutics Inc Compuestos, composiciones y métodos
WO2021152113A1 (en) 2020-01-31 2021-08-05 Bayer Aktiengesellschaft Substituted 2,3-benzodiazepines derivatives
WO2021207310A1 (en) 2020-04-08 2021-10-14 Agios Pharmaceuticals, Inc. Menin inhibitors and methods of use for treating cancer
CN113582880B (zh) * 2020-04-30 2023-11-17 南京药石科技股份有限公司 一种（3-氨基二环[1.1.1]戊烷-1-基）氨基甲酸叔丁酯的制备方法
CN111574473A (zh) * 2020-06-04 2020-08-25 宁夏农林科学院农业资源与环境研究所（宁夏土壤与植物营养重点实验室） 一种氨基噻唑类化合物的合成方法
CN111549000B (zh) * 2020-06-18 2022-07-29 中国医学科学院整形外科医院 一种过表达Hpgds的重组脂肪干细胞、制备方法及其应用
WO2021256569A1 (ja) 2020-06-19 2021-12-23 佐藤製薬株式会社 Ｈ－ｐｇｄｓを阻害する縮環化合物
CN114085167A (zh) * 2021-12-13 2022-02-25 华中药业股份有限公司 一种杂质ts-3a的制备方法
WO2023201014A1 (en) * 2022-04-15 2023-10-19 Vanderbilt University Benzothiazole-phenylsulfonyl-piperidine analogs as activators of n-acylphosphatidylethanolamine hydrolyzing phospholipase d

Family Cites Families (49)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4031221A (en) * 1974-06-17 1977-06-21 American Hoechst Corporation Method of treating pain and hypertension
US4956359A (en) 1985-02-28 1990-09-11 A. H. Robins Company, Inc. 3-aryloxy and 3-arylthioazetidinecarboxamides as anticonvulsants and antiepileptics
FI87559C (fi) 1985-02-28 1993-01-25 Robins Co Inc A H Foerfarande foer framstaellning av aktiva 3-fenyloxiazetidinkarboxamider
US6809088B2 (en) * 1997-03-24 2004-10-26 Societe De Conseils De Recherches Et D'applications Scientifiques (S.C.R.A.S.) Derivatives of 2-(iminomethyl)amino-phenyl, their preparation, their use as medicaments and the pharmaceutical compositions containing them
GB9801501D0 (en) 1998-01-23 1998-03-18 Cerebrus Ltd Chemical compounds - II
GB9917385D0 (en) 1999-07-23 1999-09-22 Cerebrus Ltd Chemical compounds-I
US6576265B1 (en) 1999-12-22 2003-06-10 Acell, Inc. Tissue regenerative composition, method of making, and method of use thereof
EP1217000A1 (en) 2000-12-23 2002-06-26 Aventis Pharma Deutschland GmbH Inhibitors of factor Xa and factor VIIa
CA2556239A1 (en) * 2004-02-11 2005-08-25 Amgen Inc. Vanilloid receptor ligands and their use in treatments
WO2005094805A1 (ja) 2004-04-01 2005-10-13 Institute Of Medicinal Molecular Design. Inc. イミン誘導体及びアミド誘導体
JP2007534740A (ja) * 2004-04-28 2007-11-29 ファイザー・インク バソプレッシンＶ１ａ受容体の阻害剤としての３−ヘテロシクリル−４−フェニル−トリアゾール誘導体
AP2007004047A0 (en) * 2005-01-20 2007-06-30 Pfizer Ltd Substituted triazole derivatives as oxtocin antagonists
US20090221644A1 (en) 2005-06-30 2009-09-03 Stuart Edward Bradley Gpcr Agonists
GB0514017D0 (en) * 2005-07-07 2005-08-17 Ionix Pharmaceuticals Ltd Chemical compounds
TW200720255A (en) 2005-07-13 2007-06-01 Taiho Pharmaceutical Co Ltd Benzoimidazole compound capable of inhibiting prostaglandin d synthetase
JP2007051121A (ja) 2005-07-22 2007-03-01 Taiho Yakuhin Kogyo Kk プロスタグランジンｄ合成酵素を阻害するピリミジン化合物
DOP2006000210A (es) * 2005-10-04 2007-06-15 Aventis Pharma Inc Compuestos de pirimidina amida como inhibidores de pgds
US20070208426A1 (en) * 2006-03-03 2007-09-06 Sdgi Holdings, Inc. Spinal implant with improved surface properties for delivery
WO2007106705A1 (en) * 2006-03-10 2007-09-20 Boehringer Ingelheim International Gmbh Soluble epoxide hydrolase inhibitors and methods of using same
US20110172230A1 (en) 2006-08-23 2011-07-14 Takahiro Ishii Urea compound or salt thereof
EP2129660A2 (en) 2006-12-19 2009-12-09 Pfizer Products Inc. Nicotinamide derivatives as inhibitors of h-pgds and their use for treating prostaglandin d2 mediated diseases
NZ579892A (en) 2007-03-30 2012-03-30 Sanofi Aventis Pyrimidine hydrazide compounds as prostaglandin D synthase inhibitors
GB0706793D0 (en) 2007-04-05 2007-05-16 Evotec Ag Compounds
EP2265578B1 (en) * 2008-03-04 2015-09-16 Vernalis (R&D) Ltd. Azetidine derivatives
US20110306597A1 (en) 2008-06-18 2011-12-15 James Michael Crawforth Nicotinamide Derivatives
JP2011524893A (ja) 2008-06-18 2011-09-08 ファイザー・リミテッド ニコチンアミド誘導体
WO2010024903A1 (en) * 2008-08-29 2010-03-04 Yangbo Feng BENZO[d]OXAZOLES AND BENZO[d]THIAZOLES AS KINASE INHIBITORS
MY154000A (en) 2008-09-22 2015-04-30 Cayman Chem Co Multiheteroaryl compounds as inhibitors of h-pgds and their use for treating prostaglandin d2 mediated diseases
CA2754613C (en) * 2009-03-09 2016-07-12 Taiho Pharmaceutical Co., Ltd. Piperazine compound capable of inhibiting prostaglandin d synthase
JPWO2011043359A1 (ja) 2009-10-06 2013-03-04 協和発酵キリン株式会社 芳香族複素環化合物を含有する医薬
CA2776242C (en) 2009-10-08 2014-09-02 Sanofi Phenyloxadiazole derivatives as pgds inhibitors
MY161134A (en) 2010-01-22 2017-04-14 Taiho Pharmaceutical Co Ltd Piperazine compound having a pgds inhibitory effect
AU2011253003B2 (en) 2010-05-13 2014-05-01 Amgen Inc. Heteroaryloxyheterocyclyl compounds as PDE10 inhibitors
AU2011253058A1 (en) * 2010-05-13 2012-12-06 Amgen Inc. Heteroaryloxycarbocyclyl compounds as PDE10 inhibitors
US9050334B2 (en) * 2010-07-16 2015-06-09 Innov88 Llc MIF inhibitors and their uses
JP2013537180A (ja) * 2010-09-13 2013-09-30 ノバルティス アーゲー トリアジン−オキサジアゾール類
KR101400192B1 (ko) 2010-12-31 2014-05-27 제일모직 주식회사 포지티브형 감광성 수지 조성물, 이를 사용하여 제조된 감광성 수지막 및 상기 감광성 수지막을 포함하는 반도체 소자
WO2012142498A2 (en) 2011-04-13 2012-10-18 Innovimmune Biotherapeutics, Inc. Mif inhibitors and their uses
KR20140030267A (ko) 2011-05-23 2014-03-11 사노피 Ｎ­알킬 그룹을 함유하는 중수소화된 화합물의 제조방법
WO2013074387A1 (en) * 2011-11-14 2013-05-23 Merck Sharp & Dohme Corp. Imidazole derivatives
JPWO2013146754A1 (ja) * 2012-03-27 2015-12-14 塩野義製薬株式会社 Ｔｒｐｖ４阻害活性を有する芳香族複素５員環誘導体
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
JP2016513112A (ja) 2013-02-18 2016-05-12 ザ スクリプス リサーチ インスティテュート 治療的潜在能力を有するバソプレッシン受容体のモジュレーター
WO2014179144A1 (en) 2013-04-29 2014-11-06 E. I. Du Pont De Nemours And Company Fungicidal heterocyclic compounds
CA2949511A1 (en) 2014-05-19 2015-11-26 Merial, Inc. Anthelmintic compounds
TWI695831B (zh) * 2014-09-13 2020-06-11 香港商南北兄弟藥業投資有限公司 Ｃｒｔｈ２拮抗劑化合物及其用途
NZ736450A (en) 2015-03-30 2022-04-29 Mission Therapeutics Ltd 1-cyano-pyrrolidine compounds as usp30 inhibitors
BR112018012469B1 (pt) 2015-12-17 2020-11-24 Astex Therapeutics Limited compostos quinolina-3-carboxamidas como inibidores da h-pgds, composição farmacêutica compreendendo os ditos compostos e uso terapêutico dos mesmos.
JOP20190072A1 (ar) 2016-10-13 2019-04-07 Glaxosmithkline Ip Dev Ltd مشتقات 1، 3 سيكلوبوتان ثنائي الاستبدال أو آزيتيدين كمثبطات للإنزيم المخلق للبروستاجلاندين d المكون للدم

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