NO329136B1 - Kinazoliner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom - Google Patents

Kinazoliner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom Download PDF

Info

Publication number: NO329136B1
Authority: NO; Norway
Prior art keywords: quinazolin; methyl; ylmethyl; aminopurin; tolyl
Prior art date: 2000-04-25

Application number

NO20025104A

Other languages

English (en)

Norwegian (no)

Other versions

NO20025104D0 (no

NO20025104L (no

Inventor

C Gregory Sowell

Edward A Kesicki

Chanchal Sadhu

Ken Dick

Jennifer Treiberg

Amy Oliver

Original Assignee

Icos 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.)

2000-04-25

Filing date

2002-10-24

Publication date

2010-08-30

2002-10-24 Application filed by Icos Corp filed Critical Icos Corp

2002-10-24 Publication of NO20025104D0 publication Critical patent/NO20025104D0/no

2002-12-10 Publication of NO20025104L publication Critical patent/NO20025104L/no

2010-08-30 Publication of NO329136B1 publication Critical patent/NO329136B1/no

Links

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NO20025104A 2000-04-25 2002-10-24 Kinazoliner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom NO329136B1 (no)

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NO20100777A NO20100777L (no)	2000-04-25	2010-05-28	Kinazolinoner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom

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Families Citing this family (217)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6545004B1 (en) *	1999-10-27	2003-04-08	Cytokinetics, Inc.	Methods and compositions utilizing quinazolinones
US7230000B1 (en)	1999-10-27	2007-06-12	Cytokinetics, Incorporated	Methods and compositions utilizing quinazolinones
US7671200B2 (en) *	1999-10-27	2010-03-02	Cytokinetics, Inc.	Quinazolinone KSP inhibitors
US6667300B2 (en)	2000-04-25	2003-12-23	Icos Corporation	Inhibitors of human phosphatidylinositol 3-kinase delta
US6403588B1 (en)	2000-04-27	2002-06-11	Yamanouchi Pharmaceutical Co., Ltd.	Imidazopyridine derivatives
US6608053B2 (en)	2000-04-27	2003-08-19	Yamanouchi Pharmaceutical Co., Ltd.	Fused heteroaryl derivatives
US7829084B2 (en) *	2001-01-17	2010-11-09	Trubion Pharmaceuticals, Inc.	Binding constructs and methods for use thereof
US20030133939A1 (en)	2001-01-17	2003-07-17	Genecraft, Inc.	Binding domain-immunoglobulin fusion proteins
US7754208B2 (en)	2001-01-17	2010-07-13	Trubion Pharmaceuticals, Inc.	Binding domain-immunoglobulin fusion proteins
IL149462A0 (en) *	2001-05-09	2002-11-10	Warner Lambert Co	Method of treating or inhibiting neutrophil chemotaxis by administering a mek inhibitor
US6689782B2 (en)	2001-07-16	2004-02-10	Essential Therapeutics, Inc.	Fungal efflux pump inhibitors
AU2002364889A1 (en) *	2001-09-24	2003-06-10	University Of Aarhus	Methods for diagnosis and treatment of diseases associated with altered expression of nrf2
EP1442132A2 (en) *	2001-10-26	2004-08-04	Novartis AG	Methods for the treatment of osteoarthritis and compositions thereof
CA2465491A1 (en) *	2001-11-07	2003-05-15	Merck & Co., Inc.	Mitotic kinesin inhibitors
WO2003070701A2 (en)	2002-02-15	2003-08-28	Cytokinetics, Inc.	Syntheses of quinazolinones
TWI314928B (en)	2002-02-28	2009-09-21	Novartis A	5-phenylthiazole derivatives and use as pi3 kinase inhibitors
US7381730B2 (en) *	2002-03-15	2008-06-03	Bristol-Myers Squibb Company	3-arylquinazoline derivatives as selective estrogen receptor beta modulators
US6900219B2 (en)	2002-04-04	2005-05-31	Cv Therapeutics, Inc.	ABCA-1 elevating compounds
US7214800B2 (en) *	2002-05-09	2007-05-08	Cytokinetics, Inc.	Compounds, compositions, and methods
CA2485148A1 (en)	2002-05-09	2003-11-20	Cytokinetics, Inc.	Pyrimidinone compounds, compositions and methods
EP1513820A4 (en) *	2002-05-23	2006-09-13	Cytokinetics Inc	COMPOUNDS, COMPOSITIONS AND METHODS
WO2003106426A1 (en)	2002-06-14	2003-12-24	Cytokinetics, Inc.	Compounds, compositions, and methods
WO2004005532A2 (en) *	2002-07-10	2004-01-15	Massachusetts Institute Of Technology	Solid-phase and solution-phase synthesis of glycosylphosphatidylinositol glycans
AU2003256805A1 (en) *	2002-07-23	2004-02-09	Cytokinetics, Inc.	Compounds compositions and methods
US20040048853A1 (en) *	2002-08-21	2004-03-11	Gustave Bergnes	Compounds, compositions, and methods
WO2004034972A2 (en)	2002-09-30	2004-04-29	Cytokinetics, Inc.	Compounds, compositions, and methods
UA82205C2 (en)	2002-09-30	2008-03-25	Байер Фармасьютикалз Корпорейшн	Fused azole-pyrimidine derivatives
US20040132732A1 (en) *	2002-10-21	2004-07-08	Wei Han	Quinazolinones and derivatives thereof as factor Xa inhibitors
CA2508601A1 (en) *	2002-12-06	2004-06-24	Warner-Lambert Company Llc	Benzoxazin-3-ones and derivatives thereof as inhibitors of pi3k
AU2003303231A1 (en) *	2002-12-20	2004-07-14	Warner-Lambert Company Llc	Benzoxazines and derivatives thereof as inhibitors of pi3ks
US7550590B2 (en)	2003-03-25	2009-06-23	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
US7429596B2 (en) *	2003-06-20	2008-09-30	The Regents Of The University Of California	1H-pyrrolo [2,3-D] pyrimidine derivatives and methods of use thereof
EP1660486A4 (en)	2003-08-08	2006-12-13	Ulysses Pharmaceutical Product	HALOGENATED CHINAZOLINYL NITROFURANES AS ANTIBACTERIAL AGENTS
KR20060041309A (ko) *	2003-08-13	2006-05-11	다케다 야쿠힌 고교 가부시키가이샤	４-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도
WO2005016348A1 (en) *	2003-08-14	2005-02-24	Icos Corporation	Method of inhibiting immune responses stimulated by an endogenous factor
US20050054614A1 (en) *	2003-08-14	2005-03-10	Diacovo Thomas G.	Methods of inhibiting leukocyte accumulation
US7790734B2 (en) *	2003-09-08	2010-09-07	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
WO2005030751A2 (en) *	2003-09-08	2005-04-07	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
KR20060070572A (ko)	2003-09-18	2006-06-23	콘포마 세러퓨틱스 코포레이션	Ｈｓｐ90-저해제로서의 신규 헤테로시클릭 화합물
JP2007510652A (ja) *	2003-11-03	2007-04-26	サイトキネティクス・インコーポレーテッド	ピリミジン−４−オン化合物、組成物、および方法
EP1692112A4 (en)	2003-12-08	2008-09-24	Cytokinetics Inc	COMPOUNDS, COMPOSITIONS, AND METHODS
US20050239809A1 (en) *	2004-01-08	2005-10-27	Watts Stephanie W	Methods for treating and preventing hypertension and hypertension-related disorders
UA83416C2 (en) *	2004-02-13	2008-07-10	Баниу Фармасьютикал Ко., Лтд.	Fused ring 4-oxopyrimidine derivative
WO2005082904A1 (ja) *	2004-02-26	2005-09-09	Kyowa Hakko Kogyo Co., Ltd.	好中球性炎症疾患の予防及び／または治療剤
CN102127057A (zh) *	2004-03-15	2011-07-20	武田药品工业株式会社	二肽基肽酶抑制剂
NZ551004A (en)	2004-04-02	2010-07-30	Prana Biotechnology Ltd	Neurologically-active compounds
JP2007536363A (ja) *	2004-05-06	2007-12-13	キャンサーリサーチテクノロジーリミテッド	癌の処置のための化合物および組成物
CA2730540A1 (en) *	2004-05-13	2005-12-01	Vanderbilt University	Phosphoinositide 3-kinase delta selective inhibitors for inhibiting angiogenesis
SI2612862T1 (sl)	2004-05-13	2017-04-26	Icos Corporation	Kinazolini kot inhibitorji humane fosfatidilinozitol 3-kinaze delta
JP2008500338A (ja) *	2004-05-25	2008-01-10	イコス・コーポレイション	造血細胞の異常増殖を治療及び／又は予防する方法
CA2569406A1 (en) *	2004-06-04	2005-12-22	Icos Corporation	Methods for treating mast cell disorders
KR20130103580A (ko) *	2004-08-24	2013-09-23	추가이 세이야쿠 가부시키가이샤	항 글리피칸 3 항체를 이용한 어쥬번트 요법
US20060079573A1 (en) *	2004-10-10	2006-04-13	Jakob Vinten-Johansen	Methods and compositions for preventing vasospasm
US9512125B2 (en) *	2004-11-19	2016-12-06	The Regents Of The University Of California	Substituted pyrazolo[3.4-D] pyrimidines as anti-inflammatory agents
WO2006068978A2 (en)	2004-12-21	2006-06-29	Takeda Pharmaceutial Company Limited	Dipeptidyl peptidase inhibitors
WO2006089106A2 (en) *	2005-02-17	2006-08-24	Icos Corporation	Phosphoinositide 3-kinase inhibitors for inhibiting leukocyte accumulation
CA2602257A1 (en)	2005-03-30	2006-10-05	Conforma Therapeutics Corporation	Alkynyl pyrrolopyrimidines and related analogs as hsp90-inhibitors
EP1903040A4 (en) *	2005-07-05	2010-08-04	Banyu Pharma Co Ltd	PROCESS FOR THE PREPARATION OF A 4 (3H) -CHINAZOLINONE DERIVATIVE
HRP20140338T1 (hr)	2005-07-25	2014-06-20	Emergent Product Development Seattle, Llc	Smanjenje broja b-stanica upotrebom molekula koje se specifiäśno vežu na cd37 i cd20
AU2006283846B2 (en) *	2005-08-26	2012-04-05	Merck Serono Sa	Pyrazine derivatives and use as PI3K inhibitors
GEP20135838B (en)	2005-09-14	2013-06-10	Takeda Pharmaceutical	Dipeptidyl peptidase inhibitors usage at diabetes treatment
EP2073810B1 (en) *	2006-09-13	2011-08-31	Takeda Pharmaceutical Company Limited	Use of 2-6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2h-pyrimidin-1-ylmethyl-4-fluoro-benzonitrile for treating diabetes, cancer, autoimmune disorders and hiv infection
PE20070622A1 (es) *	2005-09-14	2007-08-22	Takeda Pharmaceutical	Administracion de inhibidores de dipeptidil peptidasa
CN101360723A (zh) *	2005-09-16	2009-02-04	武田药品工业株式会社	制备嘧啶二酮衍生物的方法
US20070087005A1 (en)	2005-10-14	2007-04-19	Lazar Gregory A	Anti-glypican-3 antibody
EP1790342A1 (de)	2005-11-11	2007-05-30	Zentaris GmbH	Pyridopyrazin-Derivate und deren Verwendung als Modulatoren der Signaltransduktionswege
AU2006313701B2 (en)	2005-11-11	2012-05-31	Aeterna Zentaris Gmbh	Novel pyridopyrazines and their use as modulators of kinases
US8217042B2 (en)	2005-11-11	2012-07-10	Zentaris Gmbh	Pyridopyrazines and their use as modulators of kinases
EP2455382B1 (en)	2005-12-13	2016-10-26	Incyte Holdings Corporation	Heteroaryl substituted pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrimidines as Janus kinase inhibitors
EP1999108A1 (en) *	2006-03-28	2008-12-10	Takeda Pharmaceutical Company Limited	Preparation of (r)-3-aminopiperidine dihydrochloride
WO2007114926A2 (en) *	2006-04-04	2007-10-11	The Regents Of The University Of California	Kinase antagonists
GB0610242D0 (en) *	2006-05-23	2006-07-05	Novartis Ag	Organic compounds
WO2007146968A2 (en) *	2006-06-12	2007-12-21	Trubion Pharmaceuticals, Inc.	Single-chain multivalent binding proteins with effector function
AU2007282678B2 (en) *	2006-08-08	2012-09-27	Aska Pharmaceutical Co., Ltd.	Quinazoline derivative
US8324383B2 (en)	2006-09-13	2012-12-04	Takeda Pharmaceutical Company Limited	Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
WO2008041118A2 (en) *	2006-10-04	2008-04-10	Pfizer Products Inc.	Pyrido[4,3-d]pyrimidin-4(3h)-one derivatives as calcium receptor antagonists
CN101522682A (zh)	2006-10-30	2009-09-02	诺瓦提斯公司	作为抗炎剂的杂环化合物
KR20090087027A (ko)	2006-11-13	2009-08-14	일라이 릴리 앤드 캄파니	염증 질환 및 암의 치료를 위한 티에노피리미디논
TW200838536A (en) *	2006-11-29	2008-10-01	Takeda Pharmaceutical	Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
US8093236B2 (en)	2007-03-13	2012-01-10	Takeda Pharmaceuticals Company Limited	Weekly administration of dipeptidyl peptidase inhibitors
EP3070090B1 (en)	2007-06-13	2018-12-12	Incyte Holdings Corporation	Use of salts of the janus kinase inhibitor (r)-3-(4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h- pyrazol-1-yl)-3- cyclopentylpropanenitrile
UY31137A1 (es) *	2007-06-14	2009-01-05	Smithkline Beecham Corp	Derivados de quinazolina como inhibidores de la pi3 quinasa
GB2467670B (en)	2007-10-04	2012-08-01	Intellikine Inc	Chemical entities and therapeutic uses thereof
WO2009058361A1 (en) *	2007-10-31	2009-05-07	Dynavax Technologies Corp.	Inhibition of type i ifn production
CA2716334A1 (en) *	2007-11-13	2009-05-22	Icos Corporation	Inhibitors of human phosphatidyl-inositol 3-kinase delta
EP3613743B1 (en)	2008-01-04	2022-03-16	Intellikine, LLC	Processes for the preparation of 1h-pyrazolo[3,4-d]pyrimidin-4-amine derivatives
US8193182B2 (en)	2008-01-04	2012-06-05	Intellikine, Inc.	Substituted isoquinolin-1(2H)-ones, and methods of use thereof
RU2537549C2 (ru) *	2008-01-04	2015-01-10	Интелликайн ЭлЭлСи	Некоторые химические структуры, композиции и способы
US8637542B2 (en)	2008-03-14	2014-01-28	Intellikine, Inc.	Kinase inhibitors and methods of use
US8993580B2 (en) *	2008-03-14	2015-03-31	Intellikine Llc	Benzothiazole kinase inhibitors and methods of use
EP2365003A1 (en)	2008-04-11	2011-09-14	Emergent Product Development Seattle, LLC	CD37 immunotherapeutic and combination with bifunctional chemotherapeutic thereof
US10517839B2 (en) *	2008-06-09	2019-12-31	Cornell University	Mast cell inhibition in diseases of the retina and vitreous
US20110224223A1 (en) *	2008-07-08	2011-09-15	The Regents Of The University Of California, A California Corporation	MTOR Modulators and Uses Thereof
JP5788316B2 (ja)	2008-07-08	2015-09-30	インテリカイン，エルエルシー	キナーゼインヒビターおよび使用方法
US8703778B2 (en)	2008-09-26	2014-04-22	Intellikine Llc	Heterocyclic kinase inhibitors
WO2010045542A2 (en)	2008-10-16	2010-04-22	The Regents Of The University Of California	Fused ring heteroaryl kinase inhibitors
US8476431B2 (en)	2008-11-03	2013-07-02	Itellikine LLC	Benzoxazole kinase inhibitors and methods of use
US9492449B2 (en)	2008-11-13	2016-11-15	Gilead Calistoga Llc	Therapies for hematologic malignancies
CN102271683B (zh)	2008-11-13	2014-07-09	吉里德卡利斯托加公司	恶性血液病的治疗
RU2526156C2 (ru) *	2008-11-13	2014-08-20	ЭМЕРДЖЕНТ ПРОДАКТ ДИВЕЛОПМЕНТ СИЭТЛ, ЭлЭлСи	Cd37-иммунотерапевтическая комбинированная терапия и ее применения
AU2009322187B2 (en) *	2008-12-04	2015-02-19	The United States Of America, As Represented By The Secretary, Department Of Health And Human Services	Phosphatidylinositol-3-kinase p110 delta-targeted drugs in the treatment of CNS disorders
US20120165309A1 (en)	2009-02-12	2012-06-28	Astellas Pharma Inc.	Hetero ring derivative
CA2756347A1 (en)	2009-03-24	2010-09-30	Gilead Calistoga Llc	Atropisomers of 2-purinyl-3-tolyl-quinazolinone derivatives and methods of use
WO2010110686A1 (en)	2009-03-27	2010-09-30	Pathway Therapeutics Limited	Pyrimidinyl and 1,3,5 triazinyl benzimidazoles and their use in cancer therapy
SG174527A1 (en)	2009-03-27	2011-11-28	Pathway Therapeutics Inc	Pyrimidinyl and 1,3,5-triazinyl benzimidazole sulfonamides and their use in cancer therapy
CN102458410A (zh) *	2009-04-20	2012-05-16	吉联亚·卡利斯托加有限责任公司	治疗实体瘤的方法
EP2427195B1 (en)	2009-05-07	2019-05-01	Intellikine, LLC	Heterocyclic compounds and uses thereof
WO2010151735A2 (en) *	2009-06-25	2010-12-29	Amgen Inc.	Heterocyclic compounds and their uses
US8486939B2 (en)	2009-07-07	2013-07-16	Pathway Therapeutics Inc.	Pyrimidinyl and 1,3,5-triazinyl benzimidazoles and their use in cancer therapy
EA201270184A1 (ru) *	2009-07-21	2012-08-30	ГИЛИЭД КАЛИСТОГА ЭлЭлСи	Лечение расстройств печени ингибиторами pi3k
PE20121148A1 (es)	2009-08-17	2012-09-07	Intellikine Llc	Compuestos heterociclicos y usos de los mismos
US8980899B2 (en)	2009-10-16	2015-03-17	The Regents Of The University Of California	Methods of inhibiting Ire1
GB0918249D0 (en)	2009-10-19	2009-12-02	Respivert Ltd	Compounds
WO2011049625A1 (en)	2009-10-20	2011-04-28	Mansour Samadpour	Method for aflatoxin screening of products
PH12012500901A1 (en)	2009-11-05	2016-08-05	Rhizen Pharmaceuticals Sa	Novel benzopyran kinase modulators
PT3354652T (pt)	2010-03-10	2020-07-20	Incyte Holdings Corp	Derivados de piperidin-4-ilazetidina como inibidores de jak1
RS54824B1 (sr)	2010-05-21	2016-10-31	Incyte Holdings Corp	Topikalna formulacija za inhibiciju jak-a
CA2799579A1 (en)	2010-05-21	2011-11-24	Intellikine, Inc.	Chemical compounds, compositions and methods for kinase modulation
EP3399026B1 (en)	2010-06-14	2024-06-26	The Scripps Research Institute	Reprogramming of cells to a new fate
KR101759762B1 (ko)	2010-08-10	2017-07-19	아스텔라스세이야쿠 가부시키가이샤	헤테로환 화합물
CN103228141B (zh)	2010-09-03	2016-04-20	拜耳知识产权有限责任公司	取代的稠合的嘧啶酮和二氢嘧啶酮
EP2619209A1 (en)	2010-09-24	2013-07-31	Gilead Calistoga LLC	Atropisomers of pi3k-inhibiting compounds
WO2012044641A1 (en)	2010-09-29	2012-04-05	Pathway Therapeutics Inc.	1,3,5-triazinyl benzimidazole sulfonamides and their use in cancer therapy
UY33337A (es)	2010-10-18	2011-10-31	Respivert Ltd	DERIVADOS SUSTITUIDOS DE 1H-PIRAZOL[ 3,4-d]PIRIMIDINA COMO INHIBIDORES DE LAS FOSFOINOSITIDA 3-QUINASAS
JP2013545749A (ja)	2010-11-10	2013-12-26	インフィニティーファーマシューティカルズ，インコーポレイテッド	複素環化合物及びその使用
CA2818542A1 (en)	2010-11-19	2012-05-24	Incyte Corporation	Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
TWI674262B (zh)	2011-01-10	2019-10-11	美商英菲尼提製藥股份有限公司	製備異喹啉酮之方法及異喹啉酮之固體形式
WO2012116237A2 (en)	2011-02-23	2012-08-30	Intellikine, Llc	Heterocyclic compounds and uses thereof
US9295673B2 (en)	2011-02-23	2016-03-29	Intellikine Llc	Combination of mTOR inhibitors and P13-kinase inhibitors, and uses thereof
US20140213630A1 (en)	2011-03-08	2014-07-31	Thomas Diacovo	Methods and pharmaceutical compositions for treating lymphoid malignancy
ES2608967T3 (es)	2011-03-28	2017-04-17	Mei Pharma, Inc.	(Aralquilamino sustituido en alfa y heteroarilalquilamino)pirimidinil y 1,3,5-triazinil benzimidazoles, composiciones farmacéuticas que los contienen, y estos compuestos para usar en el tratamiento de enfermedades proliferativas
CN102731525A (zh) *	2011-04-08	2012-10-17	上海艾力斯医药科技有限公司	苯并吗啉衍生物
EP2518070A1 (en)	2011-04-29	2012-10-31	Almirall, S.A.	Pyrrolotriazinone derivatives as PI3K inhibitors
HRP20190128T1 (hr)	2011-05-04	2019-03-08	Rhizen Pharmaceuticals S.A.	Novi spojevi kao modulatori protein kinaza
MY165963A (en)	2011-06-20	2018-05-18	Incyte Holdings Corp	Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as jak inhibitors
WO2013012915A1 (en)	2011-07-19	2013-01-24	Infinity Pharmaceuticals Inc.	Heterocyclic compounds and uses thereof
MX2014000648A (es)	2011-07-19	2014-09-25	Infinity Pharmaceuticals Inc	Compuestos heterociclicos y sus usos.
KR20140075693A (ko)	2011-08-29	2014-06-19	인피니티 파마슈티칼스, 인코포레이티드	헤테로사이클릭 화합물 및 그의 용도
MX370814B (es)	2011-09-02	2020-01-08	Univ California	Pirazolo[3,4-d]pirimidinas sustituidas y usos de las mismas.
SI2834241T1 (sl)	2012-03-05	2021-06-30	Gilead Calistoga Llc	Polimorfne oblike (S)-2-(1-(9H-purin-6-ilamino)propil)-5-fluoro-3-fenilkinazolin-4(3H)-ONA
US8940742B2 (en)	2012-04-10	2015-01-27	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
US8828998B2 (en)	2012-06-25	2014-09-09	Infinity Pharmaceuticals, Inc.	Treatment of lupus, fibrotic conditions, and inflammatory myopathies and other disorders using PI3 kinase inhibitors
CN109970742A (zh)	2012-07-04	2019-07-05	理森制药股份公司	选择性PI3Kδ抑制剂
TW201414734A (zh)	2012-07-10	2014-04-16	Takeda Pharmaceutical	氮雜吲哚衍生物
CN104768952B (zh) *	2012-08-08	2016-10-19	山东亨利医药科技有限责任公司	PI3Kδ抑制剂
MX2015003874A (es)	2012-09-26	2015-12-16	Univ California	Modulacion de ire1.
AU2013333938A1 (en)	2012-10-16	2015-04-09	Almirall, S.A.	Pyrrolotriazinone derivatives as PI3K inhibitors
EP2914296B2 (en)	2012-11-01	2021-09-29	Infinity Pharmaceuticals, Inc.	Treatment of cancers using pi3 kinase isoform modulators
US9737521B2 (en)	2012-11-08	2017-08-22	Rhizen Pharmaceuticals Sa	Pharmaceutical compositions containing a PDE4 inhibitor and a PI3 delta or dual PI3 delta-gamma kinase inhibitor
CN113384546A (zh)	2012-11-15	2021-09-14	因赛特公司	鲁索利替尼的缓释剂型
WO2014075392A1 (en) *	2012-11-16	2014-05-22	Merck Sharp & Dohme Corp.	Purine inhibitors of human phosphatidylinositol 3-kinase delta
NZ708864A (en)	2012-12-21	2016-09-30	Gilead Calistoga Llc	Substituted pyrimidine aminoalkyl-quinazolones as phosphatidylinositol 3-kinase inhibitors
JP6207100B2 (ja)	2012-12-21	2017-10-04	ギリアードカリストガエルエルシー	イソキノリノンまたはキナゾリノンホスファチジルイノシトール３−キナーゼ阻害剤
WO2014138168A1 (en)	2013-03-06	2014-09-12	Incyte Corporation	Processes and intermediates for making a jak inhibitor
US9481667B2 (en)	2013-03-15	2016-11-01	Infinity Pharmaceuticals, Inc.	Salts and solid forms of isoquinolinones and composition comprising and methods of using the same
US20160024051A1 (en)	2013-03-15	2016-01-28	Infinity Pharmaceuticals, Inc.	Salts and solid forms of isoquinolinones and composition comprising and methods of using the same
JO3279B1 (ar)	2013-03-15	2018-09-16	Respivert Ltd	مشتقات 2-((4- امينو -3- (3- فلورو-5- هيدروكسي فينيل)-h1- بيرازولو [d-3,4] بيرمدين-1-يل )ميثيل )- 3- (2- تراي فلورو ميثيل ) بينزيل ) كوينازولين -4 (h3)- واحد واستخدامها كمثبطات فوسفواينوسيتايد 3- كاينيز
US9227977B2 (en)	2013-03-15	2016-01-05	Respivert Ltd.	Phosphoinositide 3-kinase inhibitors
ES2667173T3 (es) *	2013-06-14	2018-05-09	Gilead Calistoga Llc	Inhibidores de fosfatidilinositol 3-quinasa
CN105431437B (zh)	2013-07-02	2020-03-10	理森制药股份公司	PI3K蛋白激酶抑制剂，特别是δ抑制剂和/或γ抑制剂
UY35675A (es)	2013-07-24	2015-02-27	Novartis Ag	Derivados sustituidos de quinazolin-4-ona
SG10201801069QA (en)	2013-08-07	2018-03-28	Incyte Corp	Sustained release dosage forms for a jak1 inhibitor
US9657007B2 (en)	2013-09-22	2017-05-23	Calitor Sciences, Llc	Substituted aminopyrimidine compounds and methods of use
WO2015051241A1 (en)	2013-10-04	2015-04-09	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
MX2021012208A (es)	2013-10-04	2023-01-19	Infinity Pharmaceuticals Inc	Compuestos heterocíclicos y usos de los mismos.
US20150105383A1 (en)	2013-10-10	2015-04-16	Acetylon Pharmaceuticals, Inc.	HDAC Inhibitors, Alone Or In Combination With PI3K Inhibitors, For Treating Non-Hodgkin's Lymphoma
WO2015061204A1 (en)	2013-10-21	2015-04-30	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
WO2015095601A1 (en)	2013-12-20	2015-06-25	Gilead Calistoga Llc	Process methods for phosphatidylinositol 3-kinase inhibitors
US9708327B2 (en)	2013-12-20	2017-07-18	Gilead Calistoga Llc	Polymorphic forms of a hydrochloride salt of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one
WO2015106014A1 (en)	2014-01-09	2015-07-16	Takeda Pharmaceutical Company Limited	Azaindole derivatives
AR099052A1 (es)	2014-01-09	2016-06-29	Takeda Pharmaceuticals Co	Derivados de azaindol
NZ724368A (en)	2014-03-19	2023-07-28	Infinity Pharmaceuticals Inc	Heterocyclic compounds for use in the treatment of pi3k-gamma mediated disorders
WO2015160975A2 (en)	2014-04-16	2015-10-22	Infinity Pharmaceuticals, Inc.	Combination therapies
WO2015168079A1 (en)	2014-04-29	2015-11-05	Infinity Pharmaceuticals, Inc.	Pyrimidine or pyridine derivatives useful as pi3k inhibitors
ES2880999T3 (es)	2014-05-27	2021-11-26	Rhizen Pharmaceuticals S A	Sal de tosilato cristalina de un inhibidor selectivo de PI3K delta para uso en formulaciones farmacéuticas
KR20170012558A (ko)	2014-06-13	2017-02-02	길리애드 사이언시즈, 인코포레이티드	포스파티딜이노시톨 3-키나제 억제제
EP3154960A1 (en) *	2014-06-13	2017-04-19	Gilead Sciences, Inc.	Phosphatidylinositol 3-kinase inhibitors
HK1231477A1 (zh)	2014-06-13	2017-12-22	吉利德科学公司	磷脂酰肌醇3-激酶抑制剂
WO2015191745A1 (en)	2014-06-13	2015-12-17	Gilead Sciences, Inc.	Phosphatidylinositol 3-kinase inhibitors
CA2952018A1 (en)	2014-06-13	2015-12-17	Gilead Sciences, Inc.	Quinazolinone derivatives as phosphatidylinositol 3-kinase inhibitors
EP3160960B1 (en)	2014-06-24	2021-10-13	Gilead Sciences, Inc.	Phosphatidylinositol 3-kinase inhibitors
MX2017000208A (es)	2014-07-04	2017-05-01	Lupin Ltd	Derivados de quinolizinona como inhibidores de pi3k.
WO2016054491A1 (en)	2014-10-03	2016-04-07	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
US11376326B2 (en)	2015-07-01	2022-07-05	Chugai Seiyaku Kabushiki Kaisha	GPC3-targeting therapeutic agent which is administered to patient for whom the GPC3-targeting therapeutic agent is effective
WO2017003723A1 (en)	2015-07-01	2017-01-05	Crinetics Pharmaceuticals, Inc.	Somatostatin modulators and uses thereof
EP4212536B1 (en)	2015-07-02	2025-02-19	F. Hoffmann-La Roche AG	Benzoxazepin oxazolidinone compounds and methods of use
WO2017001658A1 (en)	2015-07-02	2017-01-05	F. Hoffmann-La Roche Ag	Benzoxazepin oxazolidinone compounds and methods of use
SMT202100541T1 (it)	2015-08-21	2021-11-12	Morphosys Ag	Combinazioni e loro usi
EP4585268A3 (en)	2015-09-14	2025-10-15	Twelve Therapeutics, Inc.	Solid forms of isoquinolinone derivatives, process of making, compositions comprising, and methods of using the same
EP3352760B1 (en)	2015-09-21	2026-03-11	Aptevo Research and Development LLC	Cd3 binding polypeptides
WO2017103825A1 (en)	2015-12-18	2017-06-22	Lupin Limited	Quinolizinone derivatives as pi3k inhibitors
US10759806B2 (en)	2016-03-17	2020-09-01	Infinity Pharmaceuticals, Inc.	Isotopologues of isoquinolinone and quinazolinone compounds and uses thereof as PI3K kinase inhibitors
WO2017214269A1 (en)	2016-06-08	2017-12-14	Infinity Pharmaceuticals, Inc.	Heterocyclic compounds and uses thereof
RU2754507C2 (ru)	2016-06-24	2021-09-02	Инфинити Фармасьютикалз, Инк.	Комбинированная терапия
EP3272348A1 (en)	2016-07-21	2018-01-24	LEK Pharmaceuticals d.d.	Pharmaceutical composition comprising idelalisib
TW201813963A (zh)	2016-09-23	2018-04-16	美商基利科學股份有限公司	磷脂醯肌醇3-激酶抑制劑
TW201825465A (zh)	2016-09-23	2018-07-16	美商基利科學股份有限公司	磷脂醯肌醇3-激酶抑制劑
TW201815787A (zh)	2016-09-23	2018-05-01	美商基利科學股份有限公司	磷脂醯肌醇3-激酶抑制劑
WO2018057808A1 (en)	2016-09-23	2018-03-29	Gilead Sciences, Inc.	Benzimidazole derivatives and their use as phosphatidylinositol 3-kinase inhibitors
CN108239074B (zh) *	2016-12-26	2021-07-06	中国医学科学院药物研究所	喹唑啉类化合物及其制备方法、用途和药物组合物
US11534443B2 (en)	2016-12-26	2022-12-27	Institute Of Materia Medica, Chinese Academy Of Medical Sciences	Quinazoline compounds, preparation method, use, and pharmaceutical composition thereof
EP3573619A4 (en)	2017-01-27	2020-10-28	SignalRX Pharmaceuticals, Inc.	THIENOPYRANONES AND FURANOPYRANONES AS KINASE, BROMODOMAIN AND CHECKPOINT INHIBITORS
US11028068B2 (en)	2017-07-25	2021-06-08	Crinetics Pharmaceuticals, Inc.	Somatostatin modulators and uses thereof
CN111386264A (zh) *	2017-07-31	2020-07-07	纽约市哥伦比亚大学理事会	用于治疗t-细胞急性淋巴细胞白血病的化合物、组合物和方法
KR20200041358A (ko)	2017-08-14	2020-04-21	메이 파마, 아이엔씨.	병용 요법
AR113922A1 (es)	2017-12-08	2020-07-01	Incyte Corp	Terapia de combinación de dosis baja para el tratamiento de neoplasias mieloproliferativas
EA202091830A1 (ru)	2018-01-30	2020-12-29	Инсайт Корпорейшн	Способы и промежуточные соединения для получения ингибитора jak
WO2019178596A1 (en)	2018-03-16	2019-09-19	Johnson Matthey Public Limited Company	Pyridine or n,n-dimethyl acetamide solvated solid state forms of solvated idelalisib, their use and preparation
MD3773593T2 (ro)	2018-03-30	2024-10-31	Incyte Corp	Tratament hidradenitei supurative utilizând inhibitori ai JAK
WO2020038394A1 (zh) *	2018-08-21	2020-02-27	南京明德新药研发有限公司	吡唑并嘧啶衍生物及其作为pi3k抑制剂的应用
EP3870173A4 (en)	2018-10-24	2022-06-22	Vanderbilt University	WDR5 INHIBITORS AND MODULATORS
CA3118493A1 (en)	2018-11-05	2020-05-14	Iovance Biotherapeutics, Inc.	Expansion of tils utilizing akt pathway inhibitors
CN111269231B (zh) *	2018-12-04	2023-06-09	安徽中科拓苒药物科学研究有限公司	一种选择性PI3Kδ抑制剂及其用途
WO2020201073A1 (en) *	2019-03-29	2020-10-08	INSERM (Institut National de la Santé et de la Recherche Médicale)	Methods for the treatment of keloid, hypertrophic scars and/or hyperpigmentation disorders
US12577227B2 (en)	2019-06-04	2026-03-17	Vanderbilt University	WDR5 inhibitors and modulators
US11833155B2 (en)	2020-06-03	2023-12-05	Incyte Corporation	Combination therapy for treatment of myeloproliferative neoplasms
CN112830927A (zh) *	2021-03-04	2021-05-25	山西科灜科技有限公司	一种嘌呤喹唑啉酮衍生物及其制备方法

Family Cites Families (30)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1053063A (sr) *	1963-05-18
DE2027645A1 (de)	1970-06-05	1971-12-09	Byk Gulden Lomberg Chemische Fa bnk GmbH, 7750 Konstanz	Piperazinylalkyl chinazolon (4) den vate, Verfahren zu deren Herstellung und sie enthaltende Arzneimittel
DE2644265C2 (de) *	1976-09-30	1983-02-10	Bayer Ag, 5090 Leverkusen	Chinazoline
US4183931A (en) *	1977-09-08	1980-01-15	Research Corporation	2-Ketoalkyl-4(3H)-quinazolinones
JPS55118917A (en) *	1979-03-06	1980-09-12	Mitsubishi Electric Corp	Production of quinazolone ring-containing epoxy resin
JPS55118918A (en) *	1979-03-06	1980-09-12	Mitsubishi Electric Corp	Production of quinazolone ring-containing epoxy resin
JPS6017375B2 (ja) *	1979-06-20	1985-05-02	三菱電機株式会社	ポリアミド樹脂の製造方法
US4782137A (en)	1984-01-24	1988-11-01	Immunex Corporation	Synthesis of protein with an identification peptide, and hybrid polypeptide incorporating same
US4703004A (en)	1984-01-24	1987-10-27	Immunex Corporation	Synthesis of protein with an identification peptide
US4851341A (en)	1986-12-19	1989-07-25	Immunex Corporation	Immunoaffinity purification system
US5011912A (en)	1986-12-19	1991-04-30	Immunex Corporation	Hybridoma and monoclonal antibody for use in an immunoaffinity purification system
GB9301000D0 (en) *	1993-01-20	1993-03-10	Glaxo Group Ltd	Chemical compounds
GB9404485D0 (en) *	1994-03-09	1994-04-20	Cancer Res Campaign Tech	Benzamide analogues
FI951367A7 (fi) *	1994-03-28	1995-09-29	Japan Energy Corp	Puriinijohdannaiset ja tulehdustautien tukahduttajat (suppressantit)
US5480906A (en)	1994-07-01	1996-01-02	Eli Lilly And Company	Stereochemical Wortmannin derivatives
AU712835B2 (en) *	1994-08-12	1999-11-18	Pro-Neuron, Inc.	Methods for treating sepsis or inflammatory diseases with oxypurine nucleosides
US6043062A (en)	1995-02-17	2000-03-28	The Regents Of The University Of California	Constitutively active phosphatidylinositol 3-kinase and uses thereof
GB9611460D0 (en) *	1996-06-01	1996-08-07	Ludwig Inst Cancer Res	Novel lipid kinase
US5858753A (en)	1996-11-25	1999-01-12	Icos Corporation	Lipid kinase
IL127296A (en) *	1996-12-31	2003-01-12	Reddy Research Foundation	Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them
GB9702701D0 (en) *	1997-02-01	1997-04-02	Univ Newcastle Ventures Ltd	Quinazolinone compounds
SK113299A3 (en) *	1997-02-28	2001-05-10	Pfizer Prod Inc	Atropisomers of 3-aryl-4(3h)-quinazolinones and their use as ampa-receptor antagonists
IL125950A0 (en) *	1997-09-05	1999-04-11	Pfizer Prod Inc	Methods of administering ampa receptor antagonists to treat dyskinesias associated with dopamine agonist therapy
US5822910A (en)	1997-10-02	1998-10-20	Shewmake; I. W.	Fishing line tensioning device
JP2002500188A (ja) *	1998-01-08	2002-01-08	ザ・ユニバーシティ・オブ・バージニア・パテント・ファウンデーション	Ａ２ａアデノシンレセプター作動因子
ATE286032T1 (de) *	1998-04-23	2005-01-15	Reddys Lab Ltd Dr	Heterozyklische verbindungen,und deren verwendung in arzneimittel,verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammenstellungen
US6100090A (en)	1999-06-25	2000-08-08	Isis Pharmaceuticals Inc.	Antisense inhibition of PI3K p85 expression
US6046049A (en)	1999-07-19	2000-04-04	Isis Pharmaceuticals Inc.	Antisense modulation of PI3 kinase p110 delta expression
EP1857443B1 (en)	2000-01-24	2012-03-28	AstraZeneca AB	Therapeutic morpholino-substituted compounds
DK1268472T3 (da)	2000-02-07	2004-12-06	Bristol Myers Squibb Co	3-aminopyrazolinhibitorer af cyclinafhængige kinaser

2001
- 2001-04-24 ES ES15200992T patent/ES2788383T3/es not_active Expired - Lifetime
- 2001-04-24 DK DK01928855.4T patent/DK1278748T3/da active
- 2001-04-24 PT PT80064579T patent/PT1939203E/pt unknown
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- 2001-04-24 AT AT01928855T patent/ATE502941T1/de active
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- 2001-04-24 PT PT01928855T patent/PT1278748E/pt unknown
- 2001-04-24 RS YUP-804/02A patent/RS51458B/sr unknown
- 2001-04-24 US US09/841,341 patent/US6518277B1/en not_active Expired - Lifetime
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- 2001-04-24 DK DK10163434.3T patent/DK2223922T3/en active
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- 2001-04-24 DK DK08006457.9T patent/DK1939203T3/en active
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- 2001-04-24 AU AU5566701A patent/AU5566701A/xx active Pending
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Also Published As

Publication number	Publication date
CN1440408B (zh)	2012-07-18
NO20100777L (no)	2002-12-10
EA200200990A1 (ru)	2003-06-26
AU2001255667C1 (en)	2016-06-09
US6800620B2 (en)	2004-10-05
HRP20020838B1 (sr)	2012-12-31
AU5566701A (en)	2001-11-07
YU80402A (sh)	2005-09-19
CA2406278A1 (en)	2001-11-01
CY1117672T1 (el)	2017-05-17
US20030195211A1 (en)	2003-10-16
IL231360A0 (en)	2014-04-30
US6518277B1 (en)	2003-02-11
WO2001081346A3 (en)	2002-03-21
NO20025104D0 (no)	2002-10-24
SI2223922T1 (sl)	2016-04-29
EA008241B1 (ru)	2007-04-27
PT3029041T (pt)	2020-05-13
BRPI0110371B1 (pt)	2016-09-27
WO2001081346A2 (en)	2001-11-01
GEP20084317B (en)	2008-02-25
DE60144277D1 (de)	2011-05-05
EP2223922B1 (en)	2016-03-02
IL152275A0 (en)	2003-05-29
HRP20020838A2 (en)	2004-12-31
EP1278748A2 (en)	2003-01-29
MXPA02010618A (es)	2004-05-05
ES2788383T3 (es)	2020-10-21
CA2406278C (en)	2012-06-05
JP2003531209A (ja)	2003-10-21
NO20025104L (no)	2002-12-10
EP3029041B1 (en)	2020-03-04
ATE502941T1 (de)	2011-04-15
NZ522076A (en)	2005-08-26
HU230554B1 (hu)	2016-12-28
HUP0300497A2 (hu)	2003-06-28
EP2223922A2 (en)	2010-09-01
EP3029041A1 (en)	2016-06-08
DK1278748T3 (da)	2011-04-18
SI3029041T1 (sl)	2020-08-31
HUP0300497A3 (en)	2004-10-28
EP2223922A3 (en)	2011-04-27
HK1053308A1 (en)	2003-10-17
PT1939203E (pt)	2015-02-04
AU2001255667B2 (en)	2006-03-02
DK2223922T3 (en)	2016-06-06
ES2527754T3 (es)	2015-01-29
IS6585A (is)	2002-10-21
BR0110371A (pt)	2003-06-17
IL245146A0 (en)	2016-06-30
ES2567260T3 (es)	2016-04-21
IL231360A (en)	2016-04-21
RS51458B (sr)	2011-04-30
JP4642309B2 (ja)	2011-03-02
BRPI0110371B8 (pt)	2021-05-25
IS2822B (is)	2013-02-15
DK1939203T3 (en)	2015-02-23
CN1440408A (zh)	2003-09-03
KR20020093077A (ko)	2002-12-12
KR100785363B1 (ko)	2007-12-18
PT1278748E (pt)	2011-03-31
EP1278748B1 (en)	2011-03-23

Legal Events

Date	Code	Title	Description
2021-05-10	MK1K	Patent expired

Publication	Publication Date	Title
NO329136B1 (no)	2010-08-30	Kinazoliner, slike forbindelser for anvendelse som medikament, farmasoytiske preparater inneholdende slike samt anvendelse av slike for fremstilling av medikament for behandling av sykdom
US10695349B2 (en)	2020-06-30	Inhibitors of human phosphatidylinositol 3-kinase delta
AU2002323426A1 (en)	2003-07-03	Inhibitors of human phosphatidyl-inositol 3-kinase delta
AU2001255667A1 (en)	2002-01-24	Inhibitors of human phosphatidyl-inositol 3-kinase delta
EP1939203B1 (en)	2014-11-19	Inhibitors of human phosphatidyl-inositol 3-kinase delta isoform
HK1224674B (en)	2021-01-29	Inhibitors of human phosphatidyl-inositol 3-kinase delta
HK1224674A1 (en)	2017-08-25	Inhibitors of human phosphatidyl-inositol 3-kinase delta
PL213200B1 (pl)	2013-01-31	Selektywne inhibitory PI3Kδ, kompozycje je zawierajace oraz ich zastosowania medyczne
HK1053308B (en)	2011-08-05	Inhibitors of human phosphatidyl-inositol 3-kinase delta