CN109195963B - 作为apj激动剂的6-羟基-4-氧代-1，4-二氢嘧啶-5-甲酰胺 - Google Patents

作为apj激动剂的6-羟基-4-氧代-1，4-二氢嘧啶-5-甲酰胺 Download PDF

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CN109195963B
CN109195963B CN201780031787.XA CN201780031787A CN109195963B CN 109195963 B CN109195963 B CN 109195963B CN 201780031787 A CN201780031787 A CN 201780031787A CN 109195963 B CN109195963 B CN 109195963B
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carbonyl
hydroxy
dihydropyrimidin
pyrrolidine
dimethoxyphenyl
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CN109195963A (zh
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皮祖兰
D·M·比尔德
R·P·布里加斯
H·芬莱
W·江
J·A·约翰逊
R·M·劳伦斯
孟巍
M·C·迈尔斯
M·菲利普斯
G·O·托拉
张晓军
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Bristol Myers Squibb Co
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero 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
    • 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
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • 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
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • 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
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic 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
    • C07D471/02—Heterocyclic 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
    • C07D471/04—Ortho-condensed systems

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  • General Health & Medical Sciences (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
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  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Hospice & Palliative Care (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
CN201780031787.XA 2016-03-24 2017-03-23 作为apj激动剂的6-羟基-4-氧代-1，4-二氢嘧啶-5-甲酰胺 Active CN109195963B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201662312780P 2016-03-24 2016-03-24
US62/312,780 2016-03-24
PCT/US2017/023801 WO2017165640A1 (en) 2016-03-24 2017-03-23 6-hydroxy-4-oxo-1,4-dihydropyrimidine-5-carboxamides as apj agonists

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Publication Number Publication Date
CN109195963A CN109195963A (zh) 2019-01-11
CN109195963B true CN109195963B (zh) 2021-04-23

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US (2) US10106528B2 (enExample)
EP (1) EP3433247B1 (enExample)
JP (1) JP6716711B2 (enExample)
KR (1) KR102433280B1 (enExample)
CN (1) CN109195963B (enExample)
AR (1) AR107973A1 (enExample)
AU (1) AU2017238504B2 (enExample)
BR (1) BR112018068341A2 (enExample)
CA (1) CA3018346A1 (enExample)
CL (1) CL2018002671A1 (enExample)
CO (1) CO2018011105A2 (enExample)
EA (1) EA037162B1 (enExample)
ES (1) ES2895124T3 (enExample)
IL (1) IL261904B (enExample)
MA (1) MA43761A (enExample)
MX (1) MX379088B (enExample)
MY (1) MY189454A (enExample)
SG (1) SG11201808163WA (enExample)
TW (1) TWI744301B (enExample)
UY (1) UY37169A (enExample)
WO (1) WO2017165640A1 (enExample)
ZA (1) ZA201806356B (enExample)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PH12017502158B1 (en) 2015-06-03 2022-04-27 Bristol Meyers Squibb Co 4-hydroxy-3-(heteroaryl)pyridine-2-one apj agonists for use in the treatment of cardiovascular disorders
WO2017066402A1 (en) 2015-10-14 2017-04-20 Bristol-Myers Squibb Company 2,4-dihydroxy-nicotinamides as apj agonists
PE20181269A1 (es) 2015-12-04 2018-08-03 Bristol Myers Squibb Co Agonistas del receptor de apelina y metodos de uso
SG11201804674UA (en) 2015-12-16 2018-06-28 Bristol Myers Squibb Co Heteroarylhydroxypyrimidinones as agonists of the apj receptor
CN109195963B (zh) * 2016-03-24 2021-04-23 百时美施贵宝公司 作为apj激动剂的6-羟基-4-氧代-1，4-二氢嘧啶-5-甲酰胺
WO2017192485A1 (en) 2016-05-03 2017-11-09 Amgen Inc. Heterocyclic triazole compounds as agonists of the apj receptor
WO2017218633A1 (en) 2016-06-14 2017-12-21 Bristol-Myers Squibb Company 6-hydroxy-5-(phenyl/heteroarylsulfonyl)pyrimidin-4(1h)-one as apj agonists
WO2017218617A1 (en) 2016-06-14 2017-12-21 Bristol-Myers Squibb Company 4-hydroxy-3-sulfonylpyridin-2(1h)-ones as apj receptor agonists
JP7037558B2 (ja) 2016-10-14 2022-03-16 ブリストル－マイヤーズ スクイブ カンパニー ３－スルホニル－５－アミノピリジン－２，４－ジオール ａｐｊアゴニスト
US11046680B1 (en) 2016-11-16 2021-06-29 Amgen Inc. Heteroaryl-substituted triazoles as APJ receptor agonists
US10736883B2 (en) 2016-11-16 2020-08-11 Amgen Inc. Triazole furan compounds as agonists of the APJ receptor
EP3541803B1 (en) 2016-11-16 2020-12-23 Amgen Inc. Triazole pyridyl compounds as agonists of the apj receptor
EP3541810B1 (en) 2016-11-16 2020-12-23 Amgen Inc. Triazole phenyl compounds as agonists of the apj receptor
MA46827A (fr) 2016-11-16 2019-09-25 Amgen Inc Composés de triazole à substitution cycloalkyle en tant qu'agonistes du récepteur apj
MA46824A (fr) 2016-11-16 2019-09-25 Amgen Inc Composés de triazole substitués par alkyle en tant qu'agonistes du récepteur apj
US11149040B2 (en) 2017-11-03 2021-10-19 Amgen Inc. Fused triazole agonists of the APJ receptor
WO2019213006A1 (en) 2018-05-01 2019-11-07 Amgen Inc. Substituted pyrimidinones as agonists of the apj receptor

Family Cites Families (45)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CH602664A5 (en) * 1973-06-14 1978-07-31 Sandoz Ag 2-Tert. amino-alkylamino-pyrimidine derivs.
GB2263639A (en) 1992-01-28 1993-08-04 Merck & Co Inc Substituted pyrimidinones as neurotensin antagonists
CZ298812B6 (cs) 1996-07-01 2008-02-13 Dr. Reddy's Laboratories Limited Azolidindionové deriváty, způsob jejich přípravy, farmaceutické kompozice s jejich obsahem a jejich použití v léčbě diabetu a příbuzných nemocí
JP2004504302A (ja) 2000-07-18 2004-02-12 ニューロジェン・コーポレーション ５−置換２−アリール−４−ピリミジノン
TW200300349A (en) 2001-11-19 2003-06-01 Sankyo Co A 4-oxoqinoline derivative
KR20050036911A (ko) 2002-05-09 2005-04-20 싸이토키네틱스, 인코포레이티드 화합물들, 방법 및 조성물
JP2005530806A (ja) 2002-05-23 2005-10-13 メルク　エンド　カムパニー　インコーポレーテッド 有糸分裂キネシン阻害薬
JP2004339159A (ja) 2003-05-16 2004-12-02 Sankyo Co Ltd ４−オキソキノリン誘導体を含有する医薬組成物
US7790734B2 (en) 2003-09-08 2010-09-07 Takeda Pharmaceutical Company Limited Dipeptidyl peptidase inhibitors
EP1682534A2 (en) 2003-11-03 2006-07-26 Cytokinetics, Inc. Pyrimidin-4-one compounds, compositions, and methods
AU2004305069C1 (en) 2003-12-19 2010-07-29 Merck Sharp & Dohme Corp. Mitotic kinesin inhibitors
WO2007033196A1 (en) 2005-09-14 2007-03-22 Bristol-Myers Squibb Company Met kinase inhibitors
WO2007037543A1 (ja) 2005-09-29 2007-04-05 Banyu Pharmaceutical Co., Ltd. ビアリールアミド誘導体
MX2008007049A (es) 2005-11-30 2008-10-23 Vertex Pharma Inhibidores de c-met y usos de los mismos.
WO2007124397A2 (en) 2006-04-21 2007-11-01 Trustees Of Boston University Ionic viscoelastics and viscoelastic salts
WO2008052863A2 (de) 2006-10-10 2008-05-08 Proionic Production Of Ionic Substances Gmbh & Co Keg Verfahren zur umsetzung von 1,3-hetero-aromatischen 2-carboxylaten mit wasser
WO2008052861A2 (de) 2006-10-10 2008-05-08 Proionic Production Of Ionic Substances Gmbh & Co Keg Verfahren zur herstellung von 1,3 -hetero-aromatischen carbonaten
CL2008000065A1 (es) * 2007-01-12 2008-09-22 Smithkline Beecham Corp Compuestos derivados de glicina n-sustituida, inhibidores de hif prolil hidroxilasas; su proceso de preparacion; composicion farmaceutica que comprende a dichos compuestos; y su uso en el tratamiento de la anemia.
MX2009008531A (es) 2007-02-16 2009-08-26 Amgen Inc Cetonas de heterociclilo que contienen nitrogeno y su uso como inhibidores de c-met.
US8415321B2 (en) 2008-04-15 2013-04-09 Raymond F. Schinazi Nucleoside derivatives for treatment of Caliciviridae infections, including Norovirus infections
WO2010072696A2 (de) 2008-12-22 2010-07-01 Basf Se Mischungen hydrophober und hydrophiler ionischer flüssigkeiten und ihre verwendung in flüssigkeitsringverdichtern
AR076601A1 (es) 2009-05-21 2011-06-22 Chlorion Pharma Inc Pirimidinas como agentes terapeuticos
US9212130B2 (en) 2010-08-10 2015-12-15 Shionogi & Co., Ltd. Heterocyclic derivative and pharmaceutical composition comprising the same
JP2014522570A (ja) 2011-05-31 2014-09-04 メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツング 電解質配合物
US9518068B2 (en) 2011-05-31 2016-12-13 Merck Patent Gmbh Compounds containing hydrido-tricyano-borate anions
WO2014004676A1 (en) 2012-06-26 2014-01-03 Ironwood Pharmaceuticals, Inc. Use of faah inhibitors as neuroprotective agents in the cns
DE102012021452A1 (de) 2012-10-31 2014-04-30 Merck Patent Gmbh Salze mit Trihydroperfluoralkoxybutansulfonat- oder Trihydroperfluoralkoxypropansulfonat-Anion
CN105358531B (zh) 2013-03-14 2017-11-14 利兰-斯坦福大学初级学院的董事会 线粒体醛脱氢酶‑2调节剂和其使用方法
FI3421462T3 (fi) 2013-06-27 2023-06-26 Pfizer Heteroaromaattisia yhdisteitä ja niiden käyttö dopamiini-d1-ligandeina
WO2014207100A1 (en) 2013-06-27 2014-12-31 Basf Se A process for coating paper with cellulose using a solution containing cellulose
WO2015079028A1 (de) 2013-11-29 2015-06-04 Vtu Holding Gmbh Verrfahren zum aushärten eines klebstoffs mittels mikrowellenbestrahlung
US10570128B2 (en) * 2014-05-28 2020-02-25 Sanford Burnham Prebys Medical Discovery Institute Agonists of the apelin receptor and methods of use thereof
MA39999A (fr) * 2014-06-06 2015-12-10 Res Triangle Inst Agonistes du récepteur de l'apeline (apj) et leurs utilisations
WO2016074757A1 (de) 2014-11-11 2016-05-19 Merck Patent Gmbh Verfahren zur herstellung von mono- und bis(perfluoralkyl)fluorophosphatsalzen und deren säuren
ES2905399T3 (es) 2015-04-24 2022-04-08 Shionogi & Co Derivados heterocíclicos de seis miembros y composición farmacéutica que los comprende
JP6356364B1 (ja) 2015-05-20 2018-07-11 アムジエン・インコーポレーテツド Ａｐｊ受容体のトリアゾールアゴニスト
PH12017502158B1 (en) * 2015-06-03 2022-04-27 Bristol Meyers Squibb Co 4-hydroxy-3-(heteroaryl)pyridine-2-one apj agonists for use in the treatment of cardiovascular disorders
KR101711744B1 (ko) 2015-07-16 2017-03-02 경희대학교 산학협력단 옥사디아졸 유도체, 이의 제조방법 및 이를 포함하는 전자수송층
WO2017066402A1 (en) 2015-10-14 2017-04-20 Bristol-Myers Squibb Company 2,4-dihydroxy-nicotinamides as apj agonists
US10626096B2 (en) 2015-11-24 2020-04-21 Sanford Burnham Prebys Medical Discovery Institute Azole derivatives as apelin receptor agonist
PE20181269A1 (es) 2015-12-04 2018-08-03 Bristol Myers Squibb Co Agonistas del receptor de apelina y metodos de uso
SG11201804674UA (en) 2015-12-16 2018-06-28 Bristol Myers Squibb Co Heteroarylhydroxypyrimidinones as agonists of the apj receptor
CN109195963B (zh) * 2016-03-24 2021-04-23 百时美施贵宝公司 作为apj激动剂的6-羟基-4-氧代-1，4-二氢嘧啶-5-甲酰胺
WO2017218617A1 (en) 2016-06-14 2017-12-21 Bristol-Myers Squibb Company 4-hydroxy-3-sulfonylpyridin-2(1h)-ones as apj receptor agonists
WO2017218633A1 (en) 2016-06-14 2017-12-21 Bristol-Myers Squibb Company 6-hydroxy-5-(phenyl/heteroarylsulfonyl)pyrimidin-4(1h)-one as apj agonists

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Discovery of 4-oxo-6-((pyrimidin-2-ylthio)methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221) as a functional antagonist of the apelin (APJ) receptor;Patrick R. Maloney等;《Bioorganic & Medicinal Chemistry Letters》;20120907;第22卷;第6656-6660页 *

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