CN1057296C - 吗啉速激肽受体拮抗剂及其制备方法和用途 - Google Patents

吗啉速激肽受体拮抗剂及其制备方法和用途 Download PDF

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Publication number
CN1057296C
CN1057296C CN94195008A CN94195008A CN1057296C CN 1057296 C CN1057296 C CN 1057296C CN 94195008 A CN94195008 A CN 94195008A CN 94195008 A CN94195008 A CN 94195008A CN 1057296 C CN1057296 C CN 1057296C
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China
Prior art keywords
phenyl
morpholine
methyl
oxo
trifluoromethyl
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Expired - Lifetime
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CN94195008A
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English (en)
Chinese (zh)
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CN1142819A (zh
Inventor
C·P·多恩
P·E·芬克
J·J·哈勒
M·麦科斯
S·G·米尔斯
S·K·沙
M·S·钱伯斯
T·哈里森
T·拉杜瓦赫蒂
B·J·威廉斯
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Merck Sharp and Dohme LLC
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Merck and Co Inc
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Publication of CN1142819A publication Critical patent/CN1142819A/zh
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
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    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
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    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/30—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings
    • C07D265/32—1,4-Oxazines; Hydrogenated 1,4-oxazines not condensed with other rings with oxygen atoms directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/12—1,4-Thiazines; Hydrogenated 1,4-thiazines not condensed with other rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings

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  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Pain & Pain Management (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pulmonology (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychiatry (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
  • Rheumatology (AREA)
  • Vascular Medicine (AREA)
  • Otolaryngology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Peptides Or Proteins (AREA)
CN94195008A 1993-12-17 1994-12-13 吗啉速激肽受体拮抗剂及其制备方法和用途 Expired - Lifetime CN1057296C (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US16988993A 1993-12-17 1993-12-17
US08/169,889 1993-12-17

Publications (2)

Publication Number Publication Date
CN1142819A CN1142819A (zh) 1997-02-12
CN1057296C true CN1057296C (zh) 2000-10-11

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EP (1) EP0734381B1 (enExample)
JP (1) JP3245424B2 (enExample)
KR (1) KR100335704B1 (enExample)
CN (1) CN1057296C (enExample)
AT (1) ATE194336T1 (enExample)
AU (1) AU701862B2 (enExample)
BG (1) BG64775B1 (enExample)
BR (1) BR9408351A (enExample)
CA (1) CA2178949C (enExample)
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CZ (1) CZ295381B6 (enExample)
DE (2) DE122004000019I1 (enExample)
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Families Citing this family (109)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU221139B1 (en) * 1993-12-29 2002-08-28 Merck Sharp & Dohme Tachykinin antagonist substituted morpholine derivatives, preparation and use thereof
IL112778A0 (en) * 1994-03-04 1995-05-26 Merck & Co Inc Substituted heterocycles, their preparation and pharmaceutical compositions containing them
US5747491A (en) * 1994-05-05 1998-05-05 Merck Sharp & Dohme Ltd. Morpholine derivatives and their use as antagonists of tachikinins
DK0777659T3 (da) * 1994-08-15 2001-09-03 Merck Sharp & Dohme Morpholinderivater og deres anvendelse som terapeutiske midler
GB9417956D0 (en) * 1994-09-02 1994-10-26 Merck Sharp & Dohme Therapeutic agents
GB9505491D0 (en) * 1995-03-18 1995-05-03 Merck Sharp & Dohme Therapeutic agents
GB9511031D0 (en) * 1995-06-01 1995-07-26 Merck Sharp & Dohme Chemical process
GB9513118D0 (en) * 1995-06-28 1995-08-30 Merck Sharp & Dohme Therapeutic agents
GB9523244D0 (en) * 1995-11-14 1996-01-17 Merck Sharp & Dohme Therapeutic agents
US5750549A (en) * 1996-10-15 1998-05-12 Merck & Co., Inc. Cycloalkyl tachykinin receptor antagonists
ZA985765B (en) 1997-07-02 1999-08-04 Merck & Co Inc Polymorphic form of a tachykinin receptor antagonist.
DE69838421D1 (en) * 1997-07-02 2007-10-25 Merck & Co Inc Polymorphe form des tachykininrezeptorantagonisten 2-(r)-(1-(r)-(3,5-bis(trifluormethyl)phenyl)ethoxy)-3-(s)-(4-fluor)phenyl-4-(3-5-oxo-1h,4h-1,2,4-triazolo)methylmorpholin
GB9813025D0 (en) * 1998-06-16 1998-08-12 Merck Sharp & Dohme Chemical synthesis
ES2359235T3 (es) 1999-02-24 2011-05-19 F. Hoffmann-La Roche Ag Derivados de 4-fenilpiridina y su empleo como antagonistas del receptor nk-1.
IL144717A0 (en) 1999-02-24 2002-06-30 Hoffmann La Roche Phenyl-and pyridinyl derivatives
CA2364662C (en) 1999-02-24 2009-10-20 F. Hoffmann-La Roche Ag 3-phenylpyridine derivatives and their use as nk-1 receptor antagonists
US6291465B1 (en) 1999-03-09 2001-09-18 Hoffmann-La Roche Inc. Biphenyl derivatives
PT1246806E (pt) 1999-11-03 2008-04-03 Amr Technology Inc Tetra-hidroisoquinolinas aril- e heteroaril-substituídas e sua utilização no bloqueio da recaptação de norepinefrina, dopamina e serotonina.
US7163949B1 (en) 1999-11-03 2007-01-16 Amr Technology, Inc. 4-phenyl substituted tetrahydroisoquinolines and use thereof
EP1103545B1 (en) * 1999-11-29 2003-11-05 F. Hoffmann-La Roche Ag 2-(3,5-Bis-trifluoromethyl-phenyl)-N-methyl-N-(6-morpholin-4-yl-4-o-tolyl-pyridin-3-yl)-isobutyramide
US6452001B2 (en) 2000-05-25 2002-09-17 Hoffmann-La Roche Inc. Diazapane derivatives useful as antagonists of neurokinin 1 receptor and methods for their formation
AR030284A1 (es) 2000-06-08 2003-08-20 Merck & Co Inc Proceso para la sintesis de (2r, 2-alfa-r,3a) -2-[1-(3,5-bis(trifluorometil) fenil) etoxi]-3-(4-fluorofenil)-1,4-oxazina; dicho compuesto y sus formas polimorficas
US6482829B2 (en) 2000-06-08 2002-11-19 Hoffmann-La Roche Inc. Substituted heterocyclic siprodecane compound active as an antagonist of neurokinin 1 receptor
JP5132864B2 (ja) 2000-07-11 2013-01-30 アルバニー モレキュラー リサーチ， インコーポレイテッド ４−フェニル置換テトラヒドロイソキノリンおよびその使用方法
ME01311B (me) 2000-07-14 2013-12-20 Hoffmann La Roche N-oksidi kao proljekovi 4-fenil-piridinskih derivata koji su antagonisti nki receptora
TWI287003B (en) 2000-07-24 2007-09-21 Hoffmann La Roche 4-phenyl-pyridine derivatives
TWI259180B (en) 2000-08-08 2006-08-01 Hoffmann La Roche 4-Phenyl-pyridine derivatives
YU39503A (sh) 2000-11-22 2006-05-25 F. Hoffmann-La Roche Ag. Derivati pirimidina
US6642226B2 (en) 2001-02-06 2003-11-04 Hoffman-La Roche Inc. Substituted phenyl-piperidine methanone compounds
MXPA03010321A (es) * 2001-05-14 2004-02-17 Hoffmann La Roche Derivados de 1-oxa-3,9-diaza-spiro-5,5-undecan-2-onas y su uso como antagonista del receptor de neurocinina.
US6849624B2 (en) 2001-07-31 2005-02-01 Hoffmann-La Roche Inc. Aromatic and heteroaromatic substituted amides
US6638981B2 (en) 2001-08-17 2003-10-28 Epicept Corporation Topical compositions and methods for treating pain
IL162096A0 (en) * 2001-12-07 2005-11-20 Pfizer Prod Inc Citric acid salt of a therapeutic compound and pharmaceutical compositions thereof
UA76810C2 (uk) * 2001-12-10 2006-09-15 Мерк Енд Ко., Інк. Фармацевтична композиція антагоніста рецептора тахікініну у формі наночастинок
AR039625A1 (es) * 2002-04-18 2005-03-02 Merck & Co Inc Proceso para la preparacion de 5-((2(r)--(1(r)- (3,5-bis (trifluormetil) fenil)etoxi-3 (s) - (4-fluorfenil) -4-morfolinil) metil) -1,2-dihidro-3h-1,2,4-triazol-3-ona
CA2514037C (en) * 2003-01-31 2012-03-13 F. Hoffmann-La Roche Ag Crystalline modification of 2-(3,5-bis-trifluoromethyl-phenyl)-n-[6-(1,1-dioxo-1.lambda.6-thiomorpholin-4-yl)-4(4-fluoro-2-methyl-phenyl)-pyridin-3-yl]-n-methyl-isobutyramide
GB0310881D0 (en) * 2003-05-12 2003-06-18 Merck Sharp & Dohme Pharmaceutical formulation
JP4490421B2 (ja) 2003-07-03 2010-06-23 エフ．ホフマン−ラ ロシュ アーゲー 統合失調症を処置するデュアルｎｋ１／ｎｋ３アンタゴニスト
TWI280239B (en) 2003-07-15 2007-05-01 Hoffmann La Roche Process for preparation of pyridine derivatives
ES2246687B2 (es) 2004-02-11 2006-11-16 Miguel Muñoz Saez Utilizacion de antagonistas no peptidicos de receptores nk1 para la produccion de apoptosis en celulas tumorales.
AU2005274927B2 (en) 2004-07-15 2011-11-03 Albany Molecular Research, Inc. Aryl-and heteroaryl-substituted tetrahydroisoquinolines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
BRPI0606843A2 (pt) 2005-02-22 2009-07-21 Hoffmann La Roche antagonistas de nk 1
JP4768010B2 (ja) 2005-03-23 2011-09-07 エフ．ホフマン−ラ ロシュ アーゲー 嘔吐のためのｎｋ−１アンタゴニストの代謝物
US8362075B2 (en) 2005-05-17 2013-01-29 Merck Sharp & Dohme Corp. Cyclohexyl sulphones for treatment of cancer
EP1904069B1 (en) 2005-07-15 2018-06-13 Albany Molecular Research, Inc. Aryl-and heteroaryl-substituted tetrahydrobenzazepines and use thereof to block reuptake of norepinephrine, dopamine, and serotonin
WO2007039420A1 (en) 2005-09-23 2007-04-12 F. Hoffmann-La Roche Ag Novel dosage formulation
KR20080048502A (ko) 2005-09-29 2008-06-02 머크 앤드 캄파니 인코포레이티드 멜라노코르틴-4 수용체 조절제로서의 아실화스피로피페리딘 유도체
WO2007044829A2 (en) 2005-10-06 2007-04-19 Dr. Reddy's Laboratories Ltd. Preparation of aprepitant
KR20080089659A (ko) * 2006-02-03 2008-10-07 그렌마크 파머수티칼스 엘티디. 아프레피탄트의 비정질 및 결정 형태 및 그것의 제조 방법
GB0603041D0 (en) 2006-02-15 2006-03-29 Angeletti P Ist Richerche Bio Therapeutic compounds
WO2008026216A2 (en) * 2006-08-28 2008-03-06 Hetero Drugs Limited Process for purification of aprepitant
EP2698157B1 (en) 2006-09-22 2015-05-20 Merck Sharp & Dohme Corp. Method of treatment using fatty acid synthesis inhibitors
US20110218176A1 (en) 2006-11-01 2011-09-08 Barbara Brooke Jennings-Spring Compounds, methods, and treatments for abnormal signaling pathways for prenatal and postnatal development
CN101190330A (zh) 2006-11-30 2008-06-04 深圳市鼎兴生物医药技术开发有限公司 胆碱酯酶在拮抗速激肽药物中的应用
AU2008204380B2 (en) 2007-01-10 2013-08-15 Msd Italia S.R.L. Amide substituted indazoles as poly(ADP-ribose)polymerase (PARP) inhibitors
WO2008090117A1 (en) 2007-01-24 2008-07-31 Glaxo Group Limited Pharmaceutical compositions comprising 3, 5-diamin0-6- (2, 3-dichl0phenyl) -l, 2, 4-triazine or r (-) -2, 4-diamino-5- (2, 3-dichlorophenyl) -6-fluoromethyl pyrimidine and an nk1
CA2682727C (en) 2007-04-02 2016-03-22 Banyu Pharmaceutical Co., Ltd. Indoledione derivative
ATE475645T1 (de) 2007-04-20 2010-08-15 Hoffmann La Roche Pyrrolidinderivate als doppelte nk1/nk3- rezeptorenantagonisten
AU2008269154B2 (en) 2007-06-27 2014-06-12 Merck Sharp & Dohme Llc 4-carboxybenzylamino derivatives as histone deacetylase inhibitors
AU2008285718A1 (en) 2007-08-07 2009-02-12 F. Hoffmann-La Roche Ag Pyrrolidine aryl-ether as NK3 receptor antagonists
EP2254420A4 (en) 2008-02-20 2012-02-15 Targia Pharmaceuticals CNS PHARMACEUTICALS AND METHOD FOR THEIR USE
JP2011515343A (ja) 2008-03-03 2011-05-19 タイガー ファーマテック チロシンキナーゼ阻害薬
US9156812B2 (en) 2008-06-04 2015-10-13 Bristol-Myers Squibb Company Crystalline form of 6-[(4S)-2-methyl-4-(2-naphthyl)-1,2,3,4-tetrahydroisoquinolin-7-yl]pyridazin-3-amine
SG172363A1 (en) 2008-12-23 2011-07-28 Pharmasset Inc Synthesis of purine nucleosides
CN102753563A (zh) 2008-12-23 2012-10-24 吉利德制药有限责任公司 核苷类似物
AR074897A1 (es) 2008-12-23 2011-02-23 Pharmasset Inc Fosforamidatos de nucleosidos
WO2010114780A1 (en) 2009-04-01 2010-10-07 Merck Sharp & Dohme Corp. Inhibitors of akt activity
WO2010132437A1 (en) 2009-05-12 2010-11-18 Albany Molecular Research, Inc. Aryl, heteroaryl, and heterocycle substituted tetrahydroisoquinolines and use thereof
EP2429296B1 (en) 2009-05-12 2017-12-27 Albany Molecular Research, Inc. 7-([1,2,4,]triazolo[1,5,-a]pyridin-6-yl)-4-(3,4-dichlorophenyl)-1,2,3,4- tetrahydroisoquinoline and use thereof
ES2528404T3 (es) 2009-05-12 2015-02-10 Bristol-Myers Squibb Company Formas cristalinas de (S)-7-([1,2,4]triazol[1,5-a]piridin-6-il)-4-(3,4-diclorofenil)-1,2,3,4-tetrahidroisoquinolina y sus usos
CN104945382B (zh) 2009-10-14 2020-02-07 默沙东公司 提高p53活性的取代的哌啶和其用途
WO2011123668A2 (en) 2010-03-31 2011-10-06 Pharmasset, Inc. Stereoselective synthesis of phosphorus containing actives
US8487102B2 (en) 2010-04-20 2013-07-16 Hoffmann-La Roche Inc. Pyrrazolopyridine compounds as dual NK1/NK3 receptor antagonists
WO2011163330A1 (en) 2010-06-24 2011-12-29 Merck Sharp & Dohme Corp. Novel heterocyclic compounds as erk inhibitors
AU2011285909B2 (en) 2010-08-02 2016-11-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (CTNNB1) gene expression using short interfering nucleic acid (siNA)
ES2376564B1 (es) 2010-08-12 2013-01-24 Manuel Vicente Salinas Martín Utilización de anticuerpos contra los receptores nk1, nk2 y/o nk3, para producir apoptosis en las células tumorales y modificar el estroma, la inmunidad y la vascularización intra y peritumorales, como tratamiento del cáncer.
EP3587574B1 (en) 2010-08-17 2022-03-16 Sirna Therapeutics, Inc. Rna interference mediated inhibition of hepatitis b virus (hbv) gene expression using short interfering nucleic acid (sina)
EP2608669B1 (en) 2010-08-23 2016-06-22 Merck Sharp & Dohme Corp. NOVEL PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES AS mTOR INHIBITORS
WO2012030685A2 (en) 2010-09-01 2012-03-08 Schering Corporation Indazole derivatives useful as erk inhibitors
US9242981B2 (en) 2010-09-16 2016-01-26 Merck Sharp & Dohme Corp. Fused pyrazole derivatives as novel ERK inhibitors
KR101833578B1 (ko) 2010-09-23 2018-02-28 누포믹스 리미티드 아프레피탄트 l-프롤린 조성물 및 공결정
DK2632472T3 (en) 2010-10-29 2018-03-19 Sirna Therapeutics Inc RNA INTERFERENCE-MEDIATED INHIBITION OF GENE EXPRESSION USING SHORT INTERFERRING NUCLEIC ACIDS (SINA)
EP2654748B1 (en) 2010-12-21 2016-07-27 Merck Sharp & Dohme Corp. Indazole derivatives useful as erk inhibitors
EP2699568A1 (en) 2011-04-21 2014-02-26 Piramal Enterprises Limited A crystalline form of a salt of a morpholino sulfonyl indole derivative and a process for its preparation
WO2012146692A1 (en) 2011-04-29 2012-11-01 Sandoz Ag Novel intermediates for the preparation of highly pure aprepitant or fosaprepitant
EP2770987B1 (en) 2011-10-27 2018-04-04 Merck Sharp & Dohme Corp. Novel compounds that are erk inhibitors
US9532993B2 (en) 2011-11-25 2017-01-03 Nuformix Limited Aprepitant L-proline solvates—compositions and cocrystals
EP2837381A4 (en) 2011-12-13 2015-12-09 Servicio Andaluz De Salud USE OF MEDICAMENTS FOR THE TREATMENT OF CANCER THAT CHANGE THE PERITUMORAL ENVIRONMENT
CZ304770B6 (cs) 2012-03-13 2014-10-08 Zentiva, K.S. Způsob výroby 3-(((2R,3S)-2-((R)-1-(3,5-bis(trifluormethyl)fenyl)ethoxy)-3-(4-fluorfenyl)morfolino)methyl)-1H-1,2,4-triazol-5(4H)-onu (Aprepitantu) v polymorfní formě II
EP3453762B1 (en) 2012-05-02 2021-04-21 Sirna Therapeutics, Inc. Short interfering nucleic acid (sina) compositions
KR20150060724A (ko) 2012-09-28 2015-06-03 머크 샤프 앤드 돔 코포레이션 Erk 억제제인 신규 화합물
RS56680B1 (sr) 2012-11-28 2018-03-30 Merck Sharp & Dohme Kompozicije i postupci za lečenje kancera
MX373639B (es) 2012-12-20 2020-05-04 Merck Sharp & Dohme Imidazopiridinas sustituidas como inhibidores de doble minuto 2 humana.
EP2951180B1 (en) 2013-01-30 2018-05-02 Merck Sharp & Dohme Corp. 2,6,7,8 substituted purines as hdm2 inhibitors
ES2493693B1 (es) 2013-02-11 2015-07-07 Servicio Andaluz De Salud Método para predecir o pronosticar la respuesta de un sujeto humano que padece un cáncer al tratamiento con un antagonista del receptor NK1
WO2015034925A1 (en) 2013-09-03 2015-03-12 Moderna Therapeutics, Inc. Circular polynucleotides
CN103694146B (zh) * 2013-12-04 2015-10-28 深圳万乐药业有限公司 2-(2-氯-1-亚乙基)酰肼甲酸甲酯的制备方法
ES2541870B1 (es) 2013-12-27 2016-05-12 Servicio Andaluz De Salud Uso de antagonistas no peptídicos de NK1 en una determinada dosis para el tratamiento del cáncer
TW201613888A (en) 2014-09-26 2016-04-16 Helsinn Healthcare Sa Crystalline forms of an NK-1 antagonist
US10005803B2 (en) 2015-10-06 2018-06-26 Helsinn Healthcare Sa Crystalline forms of fosnetupitant
AU2017276588B2 (en) 2016-06-06 2022-06-02 Helsinn Healthcare Sa Physiologically balanced injectable formulations of fosnetupitant
US10975084B2 (en) 2016-10-12 2021-04-13 Merck Sharp & Dohme Corp. KDM5 inhibitors
WO2019094312A1 (en) 2017-11-08 2019-05-16 Merck Sharp & Dohme Corp. Prmt5 inhibitors
EP3706742B1 (en) 2017-11-08 2023-03-15 Merck Sharp & Dohme LLC Prmt5 inhibitors
US11993602B2 (en) 2018-08-07 2024-05-28 Merck Sharp & Dohme Llc PRMT5 inhibitors
KR20210046009A (ko) 2018-08-07 2021-04-27 머크 샤프 앤드 돔 코포레이션 Prmt5 억제제
WO2020033284A1 (en) 2018-08-07 2020-02-13 Merck Sharp & Dohme Corp. Prmt5 inhibitors
WO2021198255A1 (en) 2020-04-03 2021-10-07 Nerre Therapeutics Limited An nk-1 receptor antagonist for treating a disease selecting from sepsis, septic shock,, acute respiratory distress syndrome (ards) or multiple organ dysfunction syndrome (mods)
BR112022024208A2 (pt) 2020-06-02 2022-12-20 Nerre Therapeutics Ltd Antagonistas do receptor de neurocinina (nk)-1 para uso no tratamento de condições de fibrose pulmonar promovidas por lesão mecânica aos pulmões

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0528495A1 (en) * 1991-08-20 1993-02-24 Merck Sharp & Dohme Ltd. Azacyclic compounds, processes for their preparation and pharmaceutical compositions containing them

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2534915B1 (fr) * 1982-10-26 1985-10-25 Lafon Labor Nouveaux derives de 2-(phenoxymethyl)-morpholine, utilisation en therapeutique et procede de preparation
IL106142A (en) * 1992-06-29 1997-03-18 Merck & Co Inc Morpholine and thiomorpholine tachykinin receptor antagonists, their preparation and pharmaceutical compositions containing them
US5633266A (en) * 1993-02-18 1997-05-27 Merck Sharp & Dohme Ltd. Azacyclic compounds compositions containing them and their use as tachykinin antagonists

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0528495A1 (en) * 1991-08-20 1993-02-24 Merck Sharp & Dohme Ltd. Azacyclic compounds, processes for their preparation and pharmaceutical compositions containing them

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