TWI744301B - 做為apj促效劑之6-羥基-4-側氧-1,4-二氫嘧啶-5-甲醯胺 - Google Patents
做為apj促效劑之6-羥基-4-側氧-1,4-二氫嘧啶-5-甲醯胺 Download PDFInfo
- Publication number
- TWI744301B TWI744301B TW106109801A TW106109801A TWI744301B TW I744301 B TWI744301 B TW I744301B TW 106109801 A TW106109801 A TW 106109801A TW 106109801 A TW106109801 A TW 106109801A TW I744301 B TWI744301 B TW I744301B
- Authority
- TW
- Taiwan
- Prior art keywords
- carbonyl
- hydroxy
- dihydropyrimidin
- pyrrolidine
- dimethoxyphenyl
- Prior art date
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- ZDOSOKQNSNIJBY-UHFFFAOYSA-N CC(N(C)C(O)=C1C(N(CC2)CC2[Re])=O)=NC1=O Chemical compound CC(N(C)C(O)=C1C(N(CC2)CC2[Re])=O)=NC1=O ZDOSOKQNSNIJBY-UHFFFAOYSA-N 0.000 description 1
- XJINZNWPEQMMBV-UHFFFAOYSA-N CCCCCCNC Chemical compound CCCCCCNC XJINZNWPEQMMBV-UHFFFAOYSA-N 0.000 description 1
- BFXUALMCVABIFZ-UHFFFAOYSA-N CCc1cccc(CC)c1N(C(c1n[n](C)cc1)=N1)C(O)=C(C(N(CC2)CC2c(ncc(Cl)c2)c2F)=O)C1=O Chemical compound CCc1cccc(CC)c1N(C(c1n[n](C)cc1)=N1)C(O)=C(C(N(CC2)CC2c(ncc(Cl)c2)c2F)=O)C1=O BFXUALMCVABIFZ-UHFFFAOYSA-N 0.000 description 1
Classifications
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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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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Cardiology (AREA)
- Diabetes (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201662312780P | 2016-03-24 | 2016-03-24 | |
| US62/312,780 | 2016-03-24 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201736362A TW201736362A (zh) | 2017-10-16 |
| TWI744301B true TWI744301B (zh) | 2021-11-01 |
Family
ID=58464691
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW106109801A TWI744301B (zh) | 2016-03-24 | 2017-03-23 | 做為apj促效劑之6-羥基-4-側氧-1,4-二氫嘧啶-5-甲醯胺 |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US10106528B2 (https=) |
| EP (1) | EP3433247B1 (https=) |
| JP (1) | JP6716711B2 (https=) |
| KR (1) | KR102433280B1 (https=) |
| CN (1) | CN109195963B (https=) |
| AR (1) | AR107973A1 (https=) |
| AU (1) | AU2017238504B2 (https=) |
| BR (1) | BR112018068341A2 (https=) |
| CA (1) | CA3018346A1 (https=) |
| CL (1) | CL2018002671A1 (https=) |
| CO (1) | CO2018011105A2 (https=) |
| EA (1) | EA037162B1 (https=) |
| ES (1) | ES2895124T3 (https=) |
| IL (1) | IL261904B (https=) |
| MA (1) | MA43761A (https=) |
| MX (1) | MX379088B (https=) |
| MY (1) | MY189454A (https=) |
| SG (1) | SG11201808163WA (https=) |
| TW (1) | TWI744301B (https=) |
| UY (1) | UY37169A (https=) |
| WO (1) | WO2017165640A1 (https=) |
| ZA (1) | ZA201806356B (https=) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL3303330T3 (pl) | 2015-06-03 | 2019-10-31 | Bristol Myers Squibb Co | Agoniści 4 - hydroksy - 3 - ( heteroarylo ) pirydyno - 2 - onowi receptora apj do stosowania w leczeniu zaburzeń sercowo-naczyniowych |
| CA3001974A1 (en) | 2015-10-14 | 2017-04-20 | Bristol-Myers Squibb Company | 2,4-dihydroxy-nicotinamides as apj agonists |
| EP3383860B1 (en) | 2015-12-04 | 2021-01-20 | Bristol-Myers Squibb Company | Apelin receptor agonists and methods of use |
| TW201725203A (zh) | 2015-12-16 | 2017-07-16 | 必治妥美雅史谷比公司 | 作為ａｐｊ受體促效劑之雜芳基羥基嘧啶酮 |
| SG11201808163WA (en) * | 2016-03-24 | 2018-10-30 | Bristol Myers Squibb Co | 6-hydroxy-4-oxo-1,4-dihydropyrimidine-5-carboxamides as apj agonists |
| US9988369B2 (en) | 2016-05-03 | 2018-06-05 | Amgen Inc. | Heterocyclic triazole compounds as agonists of the APJ receptor |
| ES2844184T3 (es) | 2016-06-14 | 2021-07-21 | Bristol Myers Squibb Co | 4-hidroxi-3-sulfonilpiridin-2(1H)-onas como agonistas del receptor de APJ |
| US10508104B2 (en) | 2016-06-14 | 2019-12-17 | Bristol-Myers Squibb Company | 6-hydroxy-5-(phenyl/heteroarylsulfonyl)pyrimidin-4(1H)-one as APJ agonists |
| CN110072850B (zh) | 2016-10-14 | 2023-07-21 | 百时美施贵宝公司 | 3-磺酰基-5-氨基吡啶-2,4-二醇apj激动剂 |
| WO2018093579A1 (en) | 2016-11-16 | 2018-05-24 | Amgen Inc. | Triazole phenyl compounds as agonists of the apj receptor |
| US11046680B1 (en) | 2016-11-16 | 2021-06-29 | Amgen Inc. | Heteroaryl-substituted triazoles as APJ receptor agonists |
| WO2018093576A1 (en) | 2016-11-16 | 2018-05-24 | Amgen Inc. | Alkyl substituted triazole compounds as agonists of the apj receptor |
| US10736883B2 (en) | 2016-11-16 | 2020-08-11 | Amgen Inc. | Triazole furan compounds as agonists of the APJ receptor |
| WO2018093577A1 (en) | 2016-11-16 | 2018-05-24 | Amgen Inc. | Cycloalkyl substituted triazole 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 |
| MA50509A (fr) | 2017-11-03 | 2021-06-02 | Amgen Inc | Agonistes de triazole fusionnés du récepteur apj |
| US11807624B2 (en) | 2018-05-01 | 2023-11-07 | Amgen Inc. | Substituted pyrimidinones as agonists of the APJ receptor |
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| WO2015184011A2 (en) * | 2014-05-28 | 2015-12-03 | Sanford-Burnham Medical Research Institute | Agonists of the apelin receptor and methods of use thereof |
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| PL3303330T3 (pl) * | 2015-06-03 | 2019-10-31 | Bristol Myers Squibb Co | Agoniści 4 - hydroksy - 3 - ( heteroarylo ) pirydyno - 2 - onowi receptora apj do stosowania w leczeniu zaburzeń sercowo-naczyniowych |
| KR101711744B1 (ko) | 2015-07-16 | 2017-03-02 | 경희대학교 산학협력단 | 옥사디아졸 유도체, 이의 제조방법 및 이를 포함하는 전자수송층 |
| CA3001974A1 (en) | 2015-10-14 | 2017-04-20 | Bristol-Myers Squibb Company | 2,4-dihydroxy-nicotinamides as apj agonists |
| EP3380970B1 (en) | 2015-11-24 | 2023-01-04 | Sanford Burnham Prebys Medical Discovery Institute | Novel azole derivatives as apelin receptor agonist |
| EP3383860B1 (en) | 2015-12-04 | 2021-01-20 | Bristol-Myers Squibb Company | Apelin receptor agonists and methods of use |
| TW201725203A (zh) | 2015-12-16 | 2017-07-16 | 必治妥美雅史谷比公司 | 作為ａｐｊ受體促效劑之雜芳基羥基嘧啶酮 |
| SG11201808163WA (en) * | 2016-03-24 | 2018-10-30 | Bristol Myers Squibb Co | 6-hydroxy-4-oxo-1,4-dihydropyrimidine-5-carboxamides as apj agonists |
| ES2844184T3 (es) | 2016-06-14 | 2021-07-21 | Bristol Myers Squibb Co | 4-hidroxi-3-sulfonilpiridin-2(1H)-onas como agonistas del receptor de APJ |
| US10508104B2 (en) | 2016-06-14 | 2019-12-17 | Bristol-Myers Squibb Company | 6-hydroxy-5-(phenyl/heteroarylsulfonyl)pyrimidin-4(1H)-one as APJ agonists |
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| EP3433247B1 (en) | 2021-09-08 |
| IL261904A (en) | 2018-10-31 |
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| WO2017165640A1 (en) | 2017-09-28 |
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| SG11201808163WA (en) | 2018-10-30 |
| US10106528B2 (en) | 2018-10-23 |
| US20170275272A1 (en) | 2017-09-28 |
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| CA3018346A1 (en) | 2017-09-28 |
| EA037162B1 (ru) | 2021-02-12 |
| MX2018011194A (es) | 2019-01-10 |
| BR112018068341A2 (pt) | 2019-01-15 |
| KR102433280B1 (ko) | 2022-08-17 |
| CN109195963B (zh) | 2021-04-23 |
| IL261904B (en) | 2020-09-30 |
| ES2895124T3 (es) | 2022-02-17 |
| CO2018011105A2 (es) | 2018-10-22 |
| AU2017238504B2 (en) | 2021-05-27 |
| ZA201806356B (en) | 2021-05-26 |
| US20190002441A1 (en) | 2019-01-03 |
| MX379088B (es) | 2025-03-10 |
| CL2018002671A1 (es) | 2019-01-25 |
| KR20180129836A (ko) | 2018-12-05 |
| JP6716711B2 (ja) | 2020-07-01 |
| CN109195963A (zh) | 2019-01-11 |
| EP3433247A1 (en) | 2019-01-30 |
| EA201892123A1 (ru) | 2019-02-28 |
| AR107973A1 (es) | 2018-07-04 |
| TW201736362A (zh) | 2017-10-16 |
| AU2017238504A1 (en) | 2018-11-15 |
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