CA2744498C - Mlk inhibitors and methods of use - Google Patents

Mlk inhibitors and methods of use Download PDF

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Publication number
CA2744498C
CA2744498C CA2744498A CA2744498A CA2744498C CA 2744498 C CA2744498 C CA 2744498C CA 2744498 A CA2744498 A CA 2744498A CA 2744498 A CA2744498 A CA 2744498A CA 2744498 C CA2744498 C CA 2744498C
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Prior art keywords
recited
compound
disease
mmol
disorder
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French (fr)
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CA2744498A1 (en
Inventor
Harris A. Gelbard
Stephen Dewhurst
Val S. Goodfellow
Torsten Wiemann
Colin Loweth
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University of Rochester
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University of Rochester
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/438The ring being spiro-condensed with carbocyclic or heterocyclic ring systems
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    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
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    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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    • A61K31/535Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
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    • C07D471/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
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CA2744498A 2008-11-25 2009-11-25 Mlk inhibitors and methods of use Active CA2744498C (en)

Applications Claiming Priority (7)

Application Number Priority Date Filing Date Title
US11795008P 2008-11-25 2008-11-25
US61/117,950 2008-11-25
US14877809P 2009-01-30 2009-01-30
US14875509P 2009-01-30 2009-01-30
US61/148,755 2009-01-30
US61/148,778 2009-01-30
PCT/US2009/065878 WO2010068483A2 (en) 2008-11-25 2009-11-25 Mlk inhibitors and methods of use

Publications (2)

Publication Number Publication Date
CA2744498A1 CA2744498A1 (en) 2010-06-17
CA2744498C true CA2744498C (en) 2017-10-24

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CA2744498A Active CA2744498C (en) 2008-11-25 2009-11-25 Mlk inhibitors and methods of use

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US (4) US8877772B2 (enExample)
EP (2) EP3037421A3 (enExample)
JP (2) JP5930278B2 (enExample)
CN (1) CN102264743B (enExample)
AU (1) AU2009324894B2 (enExample)
CA (1) CA2744498C (enExample)
ES (1) ES2554375T3 (enExample)
WO (1) WO2010068483A2 (enExample)

Families Citing this family (113)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8227603B2 (en) 2006-08-01 2012-07-24 Cytokinetics, Inc. Modulating skeletal muscle
EP2583970B1 (en) 2006-08-02 2015-10-14 Cytokinetics, Inc. Certain chemical entities, compositions and methods comprising imidazopyrimidines
US8299248B2 (en) 2006-08-02 2012-10-30 Cytokinetics, Incorporated Certain 1H-imidazo[4,5-b]pyrazin-2(3H)-ones and 1H-imidazo[4,5-b]pyrazin-2-ols and methods for their use
ES2631003T3 (es) 2006-10-19 2017-08-25 Signal Pharmaceuticals, Llc Compuestos heteroarilo, sus composiciones y métodos de tratamiento con ellos
US7998976B2 (en) 2008-02-04 2011-08-16 Cytokinetics, Inc. Certain chemical entities, compositions and methods
CN101983061A (zh) 2008-02-04 2011-03-02 赛特凯恩蒂克公司 某种化学物质、组合物和方法
AU2009278442B2 (en) 2008-08-05 2013-09-26 Daiichi Sankyo Company, Limited Imidazopyridin-2-one Derivatives
CN102264721B (zh) 2008-11-10 2015-12-09 沃泰克斯药物股份有限公司 用作atr激酶抑制剂的化合物
AU2009324894B2 (en) * 2008-11-25 2015-04-09 University Of Rochester MLK inhibitors and methods of use
CN106518856B (zh) 2008-12-19 2020-04-28 沃泰克斯药物股份有限公司 用作atr激酶抑制剂的化合物
KR20120091240A (ko) 2009-10-26 2012-08-17 시그날 파마소티칼 엘엘씨 헤테로아릴 화합물의 합성 및 정제 방법
US8962631B2 (en) 2010-05-12 2015-02-24 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
JP2013526540A (ja) 2010-05-12 2013-06-24 バーテックス ファーマシューティカルズ インコーポレイテッド Atrキナーゼ阻害剤として有用な化合物
US8969356B2 (en) 2010-05-12 2015-03-03 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
US9062008B2 (en) 2010-05-12 2015-06-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
MX2012013082A (es) 2010-05-12 2013-05-09 Vertex Pharma Derivados de 2-aminopiridina utiles como iinhibidores de cinasa atr.
SG185524A1 (en) 2010-05-12 2012-12-28 Vertex Pharma Compounds useful as inhibitors of atr kinase
WO2011149950A2 (en) * 2010-05-24 2011-12-01 University Of Rochester Bicyclic heteroaryl kinase inhibitors and methods of use
US8623869B2 (en) 2010-06-23 2014-01-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
DE102010049877A1 (de) 2010-11-01 2012-05-03 Merck Patent Gmbh 7-((1,2,3)Triazol-4-yl)-pyrrolo(2,3) pyrazinderivate
EP2487159A1 (en) 2011-02-11 2012-08-15 MSD Oss B.V. RorgammaT inhibitors
CA2832100A1 (en) 2011-04-05 2012-10-11 Vertex Pharmaceuticals Incorporated Aminopyrazine compounds useful as inhibitors of tra kinase
JP2014520161A (ja) 2011-06-22 2014-08-21 バーテックス ファーマシューティカルズ インコーポレイテッド Atrキナーゼ阻害剤として有用な化合物
US9309250B2 (en) 2011-06-22 2016-04-12 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-b]pyrazines as ATR kinase inhibitors
US9096602B2 (en) 2011-06-22 2015-08-04 Vertex Pharmaceuticals Incorporated Substituted pyrrolo[2,3-B]pyrazines as ATR kinase inhibitors
EP2731611B1 (en) 2011-07-13 2019-09-18 Cytokinetics, Inc. Combination therapie for als
WO2013049720A1 (en) 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
CN103958507A (zh) 2011-09-30 2014-07-30 沃泰克斯药物股份有限公司 可用作atr激酶抑制剂的化合物
CA2850566C (en) 2011-09-30 2022-05-03 Vertex Pharmaceuticals Incorporated Process for making 4-[chloro-n-hydroxycarbonimidoyl]phenyl derivative
EP3733185B1 (en) 2011-09-30 2022-12-07 Vertex Pharmaceuticals Incorporated Treating non-small cell lung cancer with atr inhibitors
WO2013049719A1 (en) 2011-09-30 2013-04-04 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
KR101978537B1 (ko) 2011-10-19 2019-05-14 시그날 파마소티칼 엘엘씨 Tor 키나제 억제제를 사용한 암의 치료
WO2013071088A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
US8846918B2 (en) 2011-11-09 2014-09-30 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2013071093A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Pyrazine compounds useful as inhibitors of atr kinase
US8841449B2 (en) 2011-11-09 2014-09-23 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
WO2013071090A1 (en) 2011-11-09 2013-05-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase
SG10201604558SA (en) 2011-12-02 2016-07-28 Signal Pharm Llc Pharmaceutical compositions of 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4 methoxycyclohexyl)-3,4-dihydropyrazino [2,3-b]pyrazin-2(1h)-one, a solid form thereof and methods of their use
JP6114317B2 (ja) 2012-02-24 2017-04-12 シグナル ファーマシューティカルズ,エルエルシー Torキナーゼ阻害剤の組合せ療法を用いて、非小細胞肺がんを処置する方法
CN102627646A (zh) * 2012-03-19 2012-08-08 苏州四同医药科技有限公司 一种3-碘-5-溴-4,7-二氮杂吲哚的制备方法
EP2833973B1 (en) 2012-04-05 2017-09-13 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of atr kinase and combination therapies thereof
WO2014026327A1 (en) 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. 4-heteroaryl substituted benzoic acid compounds as rorgammat inhibitors and uses thereof
WO2014026330A1 (en) 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. 3-AMINOCYCLOALKYL COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
WO2014026329A1 (en) 2012-08-15 2014-02-20 Merck Sharp & Dohme Corp. N-alkylated indole and indazole compounds as rorgammat inhibitors and uses thereof
US8999632B2 (en) 2012-10-04 2015-04-07 Vertex Pharmaceuticals Incorporated Method for measuring ATR inhibition mediated increases in DNA damage
US8912198B2 (en) 2012-10-16 2014-12-16 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of ATR kinase
AU2013203714B2 (en) 2012-10-18 2015-12-03 Signal Pharmaceuticals, Llc Inhibition of phosphorylation of PRAS40, GSK3-beta or P70S6K1 as a marker for TOR kinase inhibitory activity
US9765039B2 (en) 2012-11-21 2017-09-19 Zenith Epigenetics Ltd. Biaryl derivatives as bromodomain inhibitors
US9073878B2 (en) 2012-11-21 2015-07-07 Zenith Epigenetics Corp. Cyclic amines as bromodomain inhibitors
EP2925319B1 (en) * 2012-11-30 2019-01-09 University Of Rochester Mixed lineage kinase inhibitors for hiv/aids therapies
DK3418281T3 (da) 2012-12-07 2020-12-07 Vertex Pharma Pyrazolo[1,5-a]pyrimidiner, der er anvendelige som inhibitorer af atr-kinase til behandling af cancersygdomme
US9260426B2 (en) 2012-12-14 2016-02-16 Arrien Pharmaceuticals Llc Substituted 1H-pyrrolo [2, 3-b] pyridine and 1H-pyrazolo [3, 4-b] pyridine derivatives as salt inducible kinase 2 (SIK2) inhibitors
CN105073744B (zh) 2012-12-21 2019-11-08 齐尼思表观遗传学有限公司 作为溴结构域抑制剂的新型杂环化合物
EA201591327A1 (ru) 2013-01-16 2015-12-30 СИГНАЛ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи Замещенные пирролопиримидиновые соединения, их композиции и способы лечения с использованием таких соединений
CN105431148A (zh) * 2013-03-07 2016-03-23 加利菲亚生物公司 混合谱系激酶抑制剂及治疗方法
JP2016512815A (ja) 2013-03-15 2016-05-09 バーテックス ファーマシューティカルズ インコーポレイテッドVertex Pharmaceuticals Incorporated Atrキナーゼの阻害剤として有用な縮合ピラゾロピリミジン誘導体
TWI631949B (zh) 2013-04-17 2018-08-11 標誌製藥公司 使用tor激酶抑制劑組合療法以治療癌症之方法
MX377267B (es) 2013-04-17 2025-03-07 Signal Pharm Llc Tratamiento de cáncer con dihidropirazino-pirazinas.
SG10201708111YA (en) 2013-04-17 2017-11-29 Signal Pharm Llc Combination therapy comprising a dihydropyrazino-pyrazine compound and an androgen receptor antagonist for treating prostate cancer
CA2909629C (en) 2013-04-17 2022-12-13 Signal Pharmaceuticals, Llc Pharmaceutical formulations, processes, solid forms and methods of use relating to 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one
TW201521725A (zh) 2013-04-17 2015-06-16 Signal Pharm Llc 使用tor激酶抑制劑組合療法以治療癌症之方法
JP6382946B2 (ja) 2013-04-17 2018-08-29 シグナル ファーマシューティカルズ,エルエルシー ジヒドロピラジノ−ピラジンによる癌治療
WO2014172436A1 (en) 2013-04-17 2014-10-23 Signal Pharmaceuticals, Llc Combination therapy comprising a tor kinase inhibitor and a 5-substituted quinazolinone compound for treating cancer
WO2014181813A1 (ja) * 2013-05-10 2014-11-13 武田薬品工業株式会社 複素環化合物
CA3143529A1 (en) 2013-05-29 2014-12-04 Signal Pharmaceuticals, Llc Pharmaceutical compositions 0f 7-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1-((trans)-4-methoxycyclohexyl)-3,4-dihydropyrazino [2,3-b]pyrazin-2(1h)-one, a solid form thereof and methods of their use
US9636328B2 (en) 2013-06-21 2017-05-02 Zenith Epigenetics Ltd. Substituted bicyclic compounds as bromodomain inhibitors
CA2915838C (en) 2013-06-21 2023-04-18 Zenith Epigenetics Corp. Bicyclic bromodomain inhibitors
CN105593224B (zh) 2013-07-31 2021-05-25 恒元生物医药科技(苏州)有限公司 作为溴结构域抑制剂的新型喹唑啉酮类化合物
PT3077397T (pt) 2013-12-06 2020-01-22 Vertex Pharma Composto de 2-amino-6-fluoro-n-[5-fluoro-piridin-3-il]pirazolo[1,5-a]pirimidin-3-carboxamida útil como inibidor da atr quinase, a sua preparação, diferentes formas sólidas e derivados radiomarcados do mesmo
EP3131551A4 (en) 2014-04-16 2017-09-20 Signal Pharmaceuticals, LLC SOLID FORMS COMPRISING 1-ETHYL-7-(2-METHYL-6-(1H-1,2,4-TRIAZOL-3-YL) PYRIDIN-3-YL)-3,4-DIHYDROPYRAZINO(2,3-b)PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF
NZ714742A (en) 2014-04-16 2017-04-28 Signal Pharm Llc Solid forms of 1-ethyl-7-(2-methyl-6-(1h-1,2,4-triazol-3-yl)pyridin-3-yl)-3,4-dihydropyrazino[2,3-b]pyrazin-2(1h)-one, compositions thereof and methods of their use
WO2015160882A1 (en) 2014-04-16 2015-10-22 Signal Pharmaceuticals, Llc SOLID FORMS COMPRISING 7-(6-(2-HYDROXYPROPAN-2YL) PYRIDIN-3-YL)-1-(TRANS)-4-METHOXYCYCLOHEXYL)-3, 4-DIHYDROPYRAZINO[2,3-b] PYRAZIN-2(1H)-ONE, AND A COFORMER, COMPOSITIONS AND METHODS OF USE THEREOF
EP3131552B1 (en) 2014-04-16 2020-07-15 Signal Pharmaceuticals, LLC Methods for treating cancer using tor kinase inhibitor combination therapy
KR102575125B1 (ko) 2014-06-05 2023-09-07 버텍스 파마슈티칼스 인코포레이티드 Atr 키나제의 저해제로서 유용한 2-아미노-6-플루오로-n-[5-플루오로-피리딘-3-일]-피라졸로[1,5-a]피리미딘-3-카복스아미드 화합물의 방사성표지된 유도체, 상기 화합물의 제조 및 이의 다양한 고체 형태
DK3157566T3 (da) 2014-06-17 2019-07-22 Vertex Pharma Fremgangsmåde til behandling af cancer under anvendelse af en kombination chk1- og atr-inhibitorer
AU2015289929A1 (en) 2014-07-14 2017-03-02 Signal Pharmaceuticals, Llc Methods of treating a cancer using substituted pyrrolopyrimidine compounds, compositions thereof
NZ629796A (en) 2014-07-14 2015-12-24 Signal Pharm Llc Amorphous form of 4-((4-(cyclopentyloxy)-5-(2-methylbenzo[d]oxazol-6-yl)-7h-pyrrolo[2,3-d]pyrimidin-2-yl)amino)-3-methoxy-n-methylbenzamide, compositions thereof and methods of their use
HUE049277T2 (hu) 2014-08-15 2020-09-28 Janssen Pharmaceuticals Inc Triazolok mint NR2B receptor inhibitorok
DK3180315T3 (da) 2014-08-15 2020-04-06 Janssen Pharmaceuticals Inc Pyrazoler
EP3227280B1 (en) 2014-12-01 2019-04-24 Zenith Epigenetics Ltd. Substituted pyridines as bromodomain inhibitors
EP3227281A4 (en) 2014-12-01 2018-05-30 Zenith Epigenetics Ltd. Substituted pyridinones as bromodomain inhibitors
US10292968B2 (en) 2014-12-11 2019-05-21 Zenith Epigenetics Ltd. Substituted heterocycles as bromodomain inhibitors
HK1245247A1 (zh) 2014-12-17 2018-08-24 恒翼生物医药科技(上海)有限公司 溴结构域的抑制剂
WO2016130818A1 (en) 2015-02-11 2016-08-18 Merck Sharp & Dohme Corp. SUBSTITUTED PYRAZOLE COMPOUNDS AS RORgammaT INHIBITORS AND USES THEREOF
US10160755B2 (en) * 2015-04-08 2018-12-25 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
LT3319963T (lt) 2015-07-09 2020-03-25 Janssen Pharmaceutica Nv Pakeistieji 4-azaindolai ir jų, kaip glun2b receptoriaus moduliatorių, panaudojimas
MX395066B (es) 2015-09-30 2025-03-24 Vertex Pharma Método para tratar cáncer usando una combinación de agentes que dañan el adn e inhibidores de proteína relacionada con ataxia telangiectasia y rad3 (atr).
CA3002846A1 (en) 2015-10-27 2017-05-04 Merck Sharp & Dohme Corp. Substituted bicyclic pyrazole compounds as rorgammat inhibitors and uses thereof
AU2016344118A1 (en) 2015-10-27 2018-05-10 Merck Sharp & Dohme Corp. Heteroaryl substituted benzoic acids as rorgammat inhibitors and uses thereof
KR20180070697A (ko) 2015-10-27 2018-06-26 머크 샤프 앤드 돔 코포레이션 Ror감마t 저해제로서의 치환된 인다졸 화합물 및 이의 용도
JP6923543B2 (ja) 2016-02-10 2021-08-18 ヤンセン ファーマシューティカ エヌ.ベー. Nr2b選択的nmda調節因子としての置換1,2,3−トリアゾール
TW201819376A (zh) 2016-10-06 2018-06-01 比利時商健生藥品公司 經取代之1H-咪唑並[4,5-b]吡啶-2(3H)-酮及其作為GLUN2B受體調節劑之用途
BR112019027402A2 (pt) 2017-06-22 2020-07-07 Celgene Corporation tratamento de carcinoma hepatocelular caracterizado por infecção pelo vírus da hepatite b
WO2019169306A1 (en) 2018-03-01 2019-09-06 The Trustees Of Columbia University In The City Of New York Compounds, compositions, and methods for suppressing toxic endoplasmic reticulum stress
US11008302B2 (en) 2018-04-04 2021-05-18 Janssen Pharmaceutica Nv Substituted pyridine and pyrimidines and their use as GluN2B receptor modulators
WO2020061377A1 (en) * 2018-09-19 2020-03-26 Genentech, Inc. Spirocyclic 2,3-dihydro-7-azaindole compounds and uses thereof
US20220220206A1 (en) * 2019-05-20 2022-07-14 Mayo Foundation For Medical Education And Research Treating chronic liver disease
PH12021552839A1 (en) 2019-06-14 2022-10-03 Janssen Pharmaceutica Nv Substituted pyrazolo-pyridine amides and their use as glun2b receptor modulators
WO2020249791A1 (en) 2019-06-14 2020-12-17 Janssen Pharmaceutica Nv SUBSTITUTED PYRAZOLO[4,3-b]PYRIDINES AND THEIR USE AS GLUN2B RECEPTOR MODULATORS
PE20220386A1 (es) 2019-06-14 2022-03-18 Janssen Pharmaceutica Nv Amidas de pirazolo-piridina sustituidas y su uso como moduladores del receptor glun2b
AU2020293584A1 (en) 2019-06-14 2022-01-20 Janssen Pharmaceutica Nv Pyridine carbamates and their use as GluN2B receptor modulators
US11993587B2 (en) 2019-06-14 2024-05-28 Janssen Pharmaceutica Nv Substituted pyrazolo-pyrazines and their use as GluN2B receptor modulators
BR112021025141A2 (pt) 2019-06-14 2022-01-25 Janssen Pharmaceutica Nv Pirazolo-piridinas heteroaromáticas substituídas e seu uso como moduladores do receptor glun2b
MX2021015511A (es) 2019-06-14 2022-01-31 Janssen Pharmaceutica Nv Carbamatos de pirazina y sus usos como moduladores del receptor glun2b.
US20220396575A1 (en) * 2019-08-30 2022-12-15 Tsd Life Sciences Co., Ltd. Imidazopyridine derivative and pharmaceutical composition comprising same as active ingredient
US12509430B2 (en) 2020-02-14 2025-12-30 President And Fellows Of Harvard College Inhibitors of nicotinamide N-methyltransferase, compositions and uses thereof
WO2021237111A1 (en) * 2020-05-21 2021-11-25 Stemsynergy Therapeutics, Inc. Notch inhibitors and uses thereof
WO2023050323A1 (en) * 2021-09-30 2023-04-06 Citrix Systems, Inc. Automated transfer of peripheral device operations
US11661409B1 (en) 2022-01-31 2023-05-30 Pioneura Corporation Acid addition salts, compositions, and methods of treating
US11479541B1 (en) 2022-01-31 2022-10-25 Pioneura Corporation Acid addition salts, compositions, and methods of treating thereof
WO2023207911A1 (zh) * 2022-04-24 2023-11-02 上海医药集团股份有限公司 一种双环杂环化合物、药物组合物和应用
CN117050075A (zh) * 2022-05-05 2023-11-14 中国药科大学 一类联芳环类bet抑制剂及合成方法与用途
CN117447392B (zh) * 2023-09-13 2024-11-26 广州大学 一种荧光材料及其制备方法和应用

Family Cites Families (78)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4933438A (en) 1984-02-29 1990-06-12 University Of Florida Brain-specific analogues of centrally acting amines
US6150354A (en) 1987-01-15 2000-11-21 Bonnie Davis Compounds for the treatment of Alzheimer's disease
US5133974A (en) 1989-05-05 1992-07-28 Kv Pharmaceutical Company Extended release pharmaceutical formulations
NZ242744A (en) 1991-05-14 1997-02-24 Ernir Snorrason Use of a cholinesterase inhibitor (eg a galanthamine derivative) for treating fatigue
IT1250421B (it) 1991-05-30 1995-04-07 Recordati Chem Pharm Composizione farmaceutica a rilascio controllato con proprieta' bio-adesive.
US6537579B1 (en) 1993-02-22 2003-03-25 American Bioscience, Inc. Compositions and methods for administration of pharmacologically active compounds
FR2710265B1 (fr) 1993-09-22 1995-10-20 Adir Composition pharmaceutique bioadhésive pour la libération contrôlée de principes actifs.
US5618819A (en) 1994-07-07 1997-04-08 Adir Et Compagnie 1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one and oxazolo[4,5-b]pyridin-2-(3H)-one compounds
US6548084B2 (en) 1995-07-20 2003-04-15 Smithkline Beecham Plc Controlled release compositions
US6245347B1 (en) 1995-07-28 2001-06-12 Zars, Inc. Methods and apparatus for improved administration of pharmaceutically active compounds
DE19541260A1 (de) 1995-11-06 1997-05-07 Lohmann Therapie Syst Lts Therapeutische Zubereitung zur transdermalen Applikation von Wirkstoffen durch die Haut
US6512010B1 (en) 1996-07-15 2003-01-28 Alza Corporation Formulations for the administration of fluoxetine
CN1277550A (zh) 1997-09-11 2000-12-20 尼科梅德丹麦有限公司 非甾体抗炎药物(NSAIDs)的改进释放的复合型组合物
US6624200B2 (en) 1998-08-25 2003-09-23 Columbia Laboratories, Inc. Bioadhesive progressive hydration tablets
GB9721437D0 (en) 1997-10-10 1997-12-10 Glaxo Group Ltd Heteroaromatic compounds and their use in medicine
US6607751B1 (en) 1997-10-10 2003-08-19 Intellipharamaceutics Corp. Controlled release delivery device for pharmaceutical agents incorporating microbial polysaccharide gum
US6403597B1 (en) 1997-10-28 2002-06-11 Vivus, Inc. Administration of phosphodiesterase inhibitors for the treatment of premature ejaculation
US6248864B1 (en) 1997-12-31 2001-06-19 Adherex Technologies, Inc. Compounds and methods and modulating tissue permeability
US6613358B2 (en) 1998-03-18 2003-09-02 Theodore W. Randolph Sustained-release composition including amorphous polymer
US6312717B1 (en) 1998-07-07 2001-11-06 Bristol-Myers Squibb Company Method for treatment of anxiety and depression
US20020009478A1 (en) 1998-08-24 2002-01-24 Douglas Joseph Dobrozsi Oral liquid mucoadhesive compositions
SE9802864D0 (sv) 1998-08-27 1998-08-27 Pharmacia & Upjohn Ab Transdermally administered tolterodine as antimuscarinic agent for the treatment of overactive bladder
ATE286725T1 (de) 1998-10-01 2005-01-15 Novartis Pharma Gmbh Neue oral anzuwendende arzneizubereitungen für rivastigmine mit kontrollierter wirkstoffabgabe
US6248363B1 (en) 1999-11-23 2001-06-19 Lipocine, Inc. Solid carriers for improved delivery of active ingredients in pharmaceutical compositions
GB9904933D0 (en) 1999-03-04 1999-04-28 Glaxo Group Ltd Compounds
US6624171B1 (en) 1999-03-04 2003-09-23 Smithkline Beecham Corporation Substituted aza-oxindole derivatives
GB9904995D0 (en) 1999-03-04 1999-04-28 Glaxo Group Ltd Substituted aza-oxindole derivatives
US6498176B1 (en) 1999-03-04 2002-12-24 Smithklinebeecham Corporation 3-(anilinomethylene) oxindoles as protein tyrosine kinase and protein serine/threonine kinase inhibitors
FR2792527B1 (fr) 1999-04-22 2004-08-13 Ethypharm Lab Prod Ethiques Microgranules de ketoprofene, procede de preparation et compositions pharmaceutiques
US6541020B1 (en) 1999-07-09 2003-04-01 Trimeris, Inc. Methods and compositions for administration of therapeutic reagents
ATE264330T1 (de) 1999-07-21 2004-04-15 Astrazeneca Ab Verbindungen
US6562375B1 (en) 1999-08-04 2003-05-13 Yamanouchi Pharmaceuticals, Co., Ltd. Stable pharmaceutical composition for oral use
ES2295062T3 (es) 1999-09-02 2008-04-16 Nostrum Pharmaceuticals, Inc. Formulacion granulada de liberacion sostenida.
US6544548B1 (en) 1999-09-13 2003-04-08 Keraplast Technologies, Ltd. Keratin-based powders and hydrogel for pharmaceutical applications
US6080736A (en) 1999-10-27 2000-06-27 Janus Pharmaceuticals, Inc. Methods and compositions for treating and preventing anxiety and anxiety disorders using optically pure (R) tofisopam
US6461631B1 (en) 1999-11-16 2002-10-08 Atrix Laboratories, Inc. Biodegradable polymer composition
AU2463701A (en) 1999-12-29 2001-07-09 Nanodelivery, Inc. Drug delivery system exhibiting permeability control
US6589549B2 (en) 2000-04-27 2003-07-08 Macromed, Incorporated Bioactive agent delivering system comprised of microparticles within a biodegradable to improve release profiles
US6524621B2 (en) 2000-05-01 2003-02-25 Aeropharm Technology Inc. Core formulation
US6482440B2 (en) 2000-09-21 2002-11-19 Phase 2 Discovery, Inc. Long acting antidepressant microparticles
US6524615B2 (en) 2001-02-21 2003-02-25 Kos Pharmaceuticals, Incorporated Controlled release pharmaceutical composition
WO2002070662A2 (en) 2001-03-02 2002-09-12 Gpc Biotech Ag Three hybrid assay system
US20030187026A1 (en) 2001-12-13 2003-10-02 Qun Li Kinase inhibitors
EP1599475A2 (en) * 2003-03-06 2005-11-30 Eisai Co., Ltd. Jnk inhibitors
GB2400101A (en) * 2003-03-28 2004-10-06 Biofocus Discovery Ltd Compounds capable of binding to the active site of protein kinases
MXPA06000091A (es) * 2003-07-02 2006-04-07 Sugen Inc Arilmetiltriazolo e imidazopirazinas como inhibidores de c-met.
TWI339206B (en) 2003-09-04 2011-03-21 Vertex Pharma Compositions useful as inhibitors of protein kinases
KR101216372B1 (ko) * 2004-03-30 2013-01-04 버텍스 파마슈티칼스 인코포레이티드 Jak 및 기타 단백질 키나제의 억제제로서 유용한 아자인돌
US20060011139A1 (en) 2004-07-16 2006-01-19 Applied Materials, Inc. Heated substrate support for chemical vapor deposition
CN101027302B (zh) * 2004-07-27 2011-05-11 Sgx药物公司 吡咯并吡啶激酶调节剂
US7709645B2 (en) * 2004-07-27 2010-05-04 Sgx Pharmaceuticals, Inc. Pyrrolo-pyridine kinase modulators
US7626021B2 (en) 2004-07-27 2009-12-01 Sgx Pharmaceuticals, Inc. Fused ring heterocycle kinase modulators
EP1781654A1 (en) 2004-07-27 2007-05-09 SGX Pharmaceuticals, Inc. Pyrrolo-pyridine kinase modulators
US7361764B2 (en) 2004-07-27 2008-04-22 Sgx Pharmaceuticals, Inc. Pyrrolo-pyridine kinase modulators
AU2005289644A1 (en) * 2004-09-24 2006-04-06 Janssen Pharmaceutica, N.V. Imidazo{4,5-b}pyrazinone inhibitors of protein kinases
AU2005302707A1 (en) 2004-10-27 2006-05-11 Janssen Pharmaceutica N.V. Pyridine imidazoles and aza-indoles as progesterone receptor modulators
JP4954086B2 (ja) * 2004-12-08 2012-06-13 グラクソスミスクライン・リミテッド・ライアビリティ・カンパニー 1h−ピロロ[2,3−b]ピリジン
JP2008530212A (ja) 2005-02-16 2008-08-07 シェーリング コーポレイション Cxcr3アンタゴニスト活性を有するピペラジン−ピペリジン
MY153898A (en) * 2005-06-22 2015-04-15 Plexxikon Inc Compounds and methods for kinase modulation, and indications therefor
JP2007108926A (ja) 2005-10-12 2007-04-26 Denso Corp 運転支援装置及びプログラム
KR20080080984A (ko) 2005-12-08 2008-09-05 아이알엠 엘엘씨 Hiv 감염을 억제하기 위한 방법 및 조성물
WO2007130523A2 (en) 2006-05-05 2007-11-15 George Mason Intellectual Properties, Inc. Compositions and methods for detecting and treating hiv infection
EP2029593A1 (en) * 2006-05-22 2009-03-04 AstraZeneca AB Indole derivatives
US7732447B2 (en) * 2006-06-22 2010-06-08 Cephalon, Inc. Fused [d]pyridazin-7-ones
EP2583970B1 (en) 2006-08-02 2015-10-14 Cytokinetics, Inc. Certain chemical entities, compositions and methods comprising imidazopyrimidines
ES2631003T3 (es) * 2006-10-19 2017-08-25 Signal Pharmaceuticals, Llc Compuestos heteroarilo, sus composiciones y métodos de tratamiento con ellos
GB0706168D0 (en) 2007-03-29 2007-05-09 Glaxo Group Ltd Compounds
JP2010524858A (ja) 2007-04-10 2010-07-22 エスジーエックス ファーマシューティカルズ、インコーポレイテッド 縮合環複素環キナーゼ調節因子
KR101524817B1 (ko) 2007-04-18 2015-06-01 깃세이 야쿠힌 고교 가부시키가이샤 질소 함유 축합환 유도체, 그것을 함유하는 의약 조성물 및 그 의약 용도
JP2011500806A (ja) 2007-10-25 2011-01-06 メルク・シャープ・エンド・ドーム・コーポレイション 治療用化合物
CA2713710A1 (en) 2008-02-25 2009-09-03 F. Hoffmann-La Roche Ag Pyrrolopyrazine kinase inhibitors
AU2009278442B2 (en) * 2008-08-05 2013-09-26 Daiichi Sankyo Company, Limited Imidazopyridin-2-one Derivatives
JP2012509342A (ja) * 2008-11-20 2012-04-19 オーエスアイ・フアーマスーテイカルズ・インコーポレーテツド 置換ピロロ[2,3−b]−ピリジンおよび−ピラジン
AU2009324894B2 (en) * 2008-11-25 2015-04-09 University Of Rochester MLK inhibitors and methods of use
WO2010068899A1 (en) 2008-12-12 2010-06-17 Creighton University Nanoparticles comprising combinations of antiretroviral agents and use thereof
WO2011149950A2 (en) 2010-05-24 2011-12-01 University Of Rochester Bicyclic heteroaryl kinase inhibitors and methods of use
MX2013004981A (es) 2010-11-02 2013-11-04 Univ Nebraska Composiciones y metodos para la administracion de agentes terapeuticos.
EP2925319B1 (en) 2012-11-30 2019-01-09 University Of Rochester Mixed lineage kinase inhibitors for hiv/aids therapies

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