CN103269592B - 环胺取代的噁唑烷酮cetp抑制剂 - Google Patents

环胺取代的噁唑烷酮cetp抑制剂 Download PDF

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Publication number
CN103269592B
CN103269592B CN201180062829.9A CN201180062829A CN103269592B CN 103269592 B CN103269592 B CN 103269592B CN 201180062829 A CN201180062829 A CN 201180062829A CN 103269592 B CN103269592 B CN 103269592B
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China
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mmol
methyl
reaction
methoxyphenyl
mixture
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Expired - Fee Related
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CN201180062829.9A
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English (en)
Chinese (zh)
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CN103269592A (zh
Inventor
Z.卢
Y-H.陈
C.史密斯
H.李
C.F.汤普森
R.斯维斯
P.辛克莱尔
F.卡拉施
J.亨特
S.E.亚当森
G.董
D.L.安迪卡
X.钱
W.孙
P.瓦查尔
K.赵
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Merck Sharp & Dohme LLC
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Merck Sharp & Dohme LLC
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/08—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic 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
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/535—Heterocyclic 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
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P5/00—Drugs for disorders of the endocrine 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
    • 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
    • A61P9/10—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
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Cardiology (AREA)
  • Hematology (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Endocrinology (AREA)
  • Obesity (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN201180062829.9A 2010-10-29 2011-10-25 环胺取代的噁唑烷酮cetp抑制剂 Expired - Fee Related CN103269592B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US40830810P 2010-10-29 2010-10-29
US61/408308 2010-10-29
PCT/US2011/057584 WO2012058187A1 (en) 2010-10-29 2011-10-25 Cyclic amine substituted oxazolidinone cetp inhibitor

Publications (2)

Publication Number Publication Date
CN103269592A CN103269592A (zh) 2013-08-28
CN103269592B true CN103269592B (zh) 2016-05-11

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US (1) US9221834B2 (enExample)
EP (1) EP2632269B1 (enExample)
JP (1) JP5852662B2 (enExample)
CN (1) CN103269592B (enExample)
AR (1) AR083579A1 (enExample)
AU (1) AU2011320665B2 (enExample)
CA (1) CA2814846A1 (enExample)
ES (1) ES2623759T3 (enExample)
TW (1) TW201305146A (enExample)
WO (1) WO2012058187A1 (enExample)

Families Citing this family (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JO3210B1 (ar) 2011-10-28 2018-03-08 Merck Sharp & Dohme مثبط منصهر لبروتين نقل الكوليسترليستير اوكسازوليدينون ثمائي الحلقة
WO2013165854A1 (en) * 2012-05-02 2013-11-07 Merck Sharp & Dohme Corp. Cyclic amine substituted heterocyclic cetp inhibitors
CN103958484B (zh) * 2012-07-19 2015-11-25 上海恒瑞医药有限公司 噁唑烷酮类衍生物、其制备方法及其在医药上的应用
CN102977044A (zh) * 2012-11-26 2013-03-20 盛世泰科生物医药技术(苏州)有限公司 一种3-(4-甲氧基苯基)-异噁唑-5-羧酸的制备方法
EP2934518B1 (en) 2012-12-19 2020-02-19 Merck Sharp & Dohme Corp. Spirocyclic cetp inhibitors
WO2014099834A1 (en) 2012-12-20 2014-06-26 Merck Sharp & Dohme Corp. Therapeutic thiazolidinone compounds
AU2014213125B2 (en) * 2013-01-31 2016-06-02 Chong Kun Dang Pharmaceutical Corp. Biaryl- or heterocyclic biaryl-substituted cyclohexene derivative compounds as CETP inhibitors
EP3027619B1 (en) 2013-07-30 2019-01-02 Merck Sharp & Dohme Corp. Bicyclic ureas and thiadiazolidine-1,1-dioxides as cetp inhibitors
US9688630B2 (en) 2013-10-10 2017-06-27 Merck Sharp & Dohme Corp. 3,3′-disubstituted indolines as inhibitors of cholesterol ester transfer protein
US9663534B2 (en) 2013-12-17 2017-05-30 Merck Sharp & Dohme Corp. Fused bicyclic isoxazolines as inhibitors of cholesterol ester transfer protein
EP3174537B1 (en) * 2014-07-29 2021-06-23 Merck Sharp & Dohme Corp. Monocyclic isoxazolines as inhibitors of cholesterol ester transfer protein
EP3191445B1 (en) * 2014-09-09 2019-06-12 Bristol-Myers Squibb Company Cyclobutane containing carboxylic acid gpr120 modulators
WO2017011279A1 (en) 2015-07-13 2017-01-19 Merck Sharp & Dohme Corp. Bicyclic heterocycles as inhibitors of cholesterol ester transfer protein
KR20200091395A (ko) * 2017-09-27 2020-07-30 페도라 파마슈티칼스 인코포레이티드 디아자비시클로옥탄 유도체의 결정형 및 그의 제조 방법

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1980904A (zh) * 2004-07-02 2007-06-13 默克公司 Cetp抑制剂
WO2007081569A2 (en) * 2005-12-30 2007-07-19 Merck & Co., Inc. Cetp inhibitors

Family Cites Families (7)

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AU1856997A (en) 1996-02-02 1997-08-22 Merck & Co., Inc. Method for raising hdl cholesterol levels
DOP2005000123A (es) 2004-07-02 2011-07-15 Merck Sharp & Dohme Inhibidores de cetp
JP5040036B2 (ja) 2005-12-30 2012-10-03 メルク・シャープ・エンド・ドーム・コーポレイション Ｃｅｔｐ阻害剤として有用な１，３−オキサゾリジン−２−オン誘導体
US7781426B2 (en) 2005-12-30 2010-08-24 Merck Sharp & Dohme Corp. CETP inhibitors
WO2011028395A1 (en) * 2009-08-24 2011-03-10 Merck Sharp & Dohme Corp. Pyridyl oxazolidinone cetp inhibitor
JO3210B1 (ar) 2011-10-28 2018-03-08 Merck Sharp & Dohme مثبط منصهر لبروتين نقل الكوليسترليستير اوكسازوليدينون ثمائي الحلقة
WO2013165854A1 (en) 2012-05-02 2013-11-07 Merck Sharp & Dohme Corp. Cyclic amine substituted heterocyclic cetp inhibitors

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1980904A (zh) * 2004-07-02 2007-06-13 默克公司 Cetp抑制剂
WO2007081569A2 (en) * 2005-12-30 2007-07-19 Merck & Co., Inc. Cetp inhibitors

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
"Discovery of new cholesteryl ester transfer protein inhibitors via ligand-based pharmacophore modeling and QSAR analysis followed by synthetic exploration";Reema Abu Khalaf et al.;《European Journal of Medicinal Chemistry》;20100430;第45卷;第1598–1617页 *

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ES2623759T3 (es) 2017-07-12
JP5852662B2 (ja) 2016-02-03
AU2011320665A1 (en) 2013-05-09
AU2011320665B2 (en) 2015-09-03
EP2632269B1 (en) 2017-03-15
JP2013544805A (ja) 2013-12-19
TW201305146A (zh) 2013-02-01
US9221834B2 (en) 2015-12-29
EP2632269A4 (en) 2015-01-21
AR083579A1 (es) 2013-03-06
EP2632269A1 (en) 2013-09-04
US20130331372A1 (en) 2013-12-12
CN103269592A (zh) 2013-08-28
CA2814846A1 (en) 2012-05-03
WO2012058187A1 (en) 2012-05-03

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