ES2863903T3 - 6-hidroxi-5-(fenil/heteroarilsulfonil)pirimidin-4(1H)-ona como agonistas de APJ - Google Patents
6-hidroxi-5-(fenil/heteroarilsulfonil)pirimidin-4(1H)-ona como agonistas de APJ Download PDFInfo
- Publication number
- ES2863903T3 ES2863903T3 ES17732693T ES17732693T ES2863903T3 ES 2863903 T3 ES2863903 T3 ES 2863903T3 ES 17732693 T ES17732693 T ES 17732693T ES 17732693 T ES17732693 T ES 17732693T ES 2863903 T3 ES2863903 T3 ES 2863903T3
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- ES
- Spain
- Prior art keywords
- hydroxy
- dihydropyrimidin
- butyl
- benzenesulfonyl
- methylpyridin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title claims abstract description 34
- 239000000556 agonist Substances 0.000 title description 10
- 125000005143 heteroarylsulfonyl group Chemical group 0.000 title description 4
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 title description 2
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 225
- 150000001875 compounds Chemical class 0.000 claims abstract description 208
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 141
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 120
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 116
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 116
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 98
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 94
- 150000003839 salts Chemical class 0.000 claims abstract description 58
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 45
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 43
- 125000004452 carbocyclyl group Chemical group 0.000 claims abstract description 42
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 35
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 32
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 28
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 27
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 24
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 24
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 12
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 10
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims abstract description 8
- 125000000714 pyrimidinyl group Chemical group 0.000 claims abstract description 8
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 7
- 125000006706 (C3-C6) carbocyclyl group Chemical group 0.000 claims abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
- -1 2-butyl-1- (2,6-dimethoxyphenyl) -5 - ({4'-fluoro- [1,1'-biphenyl] -4-yl} sulfonyl) -6-hydroxy-1,4-dihydropyridine-4 -one Chemical compound 0.000 claims description 221
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 69
- 229910052702 rhenium Inorganic materials 0.000 claims description 58
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 47
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 43
- 206010019280 Heart failures Diseases 0.000 claims description 40
- 239000000203 mixture Substances 0.000 claims description 31
- 238000011282 treatment Methods 0.000 claims description 25
- 229910004013 NO 2 Inorganic materials 0.000 claims description 23
- 239000008194 pharmaceutical composition Substances 0.000 claims description 22
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 21
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 18
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 13
- 206010012601 diabetes mellitus Diseases 0.000 claims description 12
- 239000003937 drug carrier Substances 0.000 claims description 12
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 11
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- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
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- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 5
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- ZFCVZKCELQGSOD-UHFFFAOYSA-N COc1cccc(OC)c1-n1c(O)c(c(=O)nc1-c1ccc(F)cc1)S(=O)(=O)c1ccc(Br)cc1 Chemical compound COc1cccc(OC)c1-n1c(O)c(c(=O)nc1-c1ccc(F)cc1)S(=O)(=O)c1ccc(Br)cc1 ZFCVZKCELQGSOD-UHFFFAOYSA-N 0.000 claims description 3
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- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 3
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 230000002107 myocardial effect Effects 0.000 claims description 3
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
- 238000007634 remodeling Methods 0.000 claims description 3
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- GQSDDWJYAMNCBY-UHFFFAOYSA-N C(CCC)C=1N(C(=C(C(N=1)=O)S(=O)(=O)C1=CC=C(C=C1)C=1N(C=CN=1)C)O)C1=C(C=CC=C1OC)OC Chemical compound C(CCC)C=1N(C(=C(C(N=1)=O)S(=O)(=O)C1=CC=C(C=C1)C=1N(C=CN=1)C)O)C1=C(C=CC=C1OC)OC GQSDDWJYAMNCBY-UHFFFAOYSA-N 0.000 claims description 2
- NIZSVEUKAIVESW-UHFFFAOYSA-N C(CCC)C=1N(C(=C(C(N=1)=O)S(=O)(=O)C1CCN(CC1)C)O)C1=C(C=CC=C1OC)OC Chemical compound C(CCC)C=1N(C(=C(C(N=1)=O)S(=O)(=O)C1CCN(CC1)C)O)C1=C(C=CC=C1OC)OC NIZSVEUKAIVESW-UHFFFAOYSA-N 0.000 claims description 2
- QBBPFWGSCXSRPQ-UHFFFAOYSA-N CCCCc1nc(=O)c(c(O)n1-c1c(OC)cccc1OC)S(=O)(=O)C1CCNCC1 Chemical compound CCCCc1nc(=O)c(c(O)n1-c1c(OC)cccc1OC)S(=O)(=O)C1CCNCC1 QBBPFWGSCXSRPQ-UHFFFAOYSA-N 0.000 claims description 2
- 101100516563 Caenorhabditis elegans nhr-6 gene Proteins 0.000 claims description 2
- 208000031229 Cardiomyopathies Diseases 0.000 claims description 2
- OTIBTHYYHYCRQH-VWLOTQADSA-N FC1=NC=CC(=C1C)C1=CC=C(C=C1)S(=O)(=O)C=1C(N=C(N(C=1O)[C@@H](COC)C1=CC=CC=C1)CCC(C)C)=O Chemical compound FC1=NC=CC(=C1C)C1=CC=C(C=C1)S(=O)(=O)C=1C(N=C(N(C=1O)[C@@H](COC)C1=CC=CC=C1)CCC(C)C)=O OTIBTHYYHYCRQH-VWLOTQADSA-N 0.000 claims description 2
- 206010061216 Infarction Diseases 0.000 claims description 2
- 230000007574 infarction Effects 0.000 claims description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 2
- 235000005152 nicotinamide Nutrition 0.000 claims description 2
- 239000011570 nicotinamide Substances 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 90
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 claims 4
- 125000004211 3,5-difluorophenyl group Chemical group [H]C1=C(F)C([H])=C(*)C([H])=C1F 0.000 claims 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims 3
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 3
- LIHFGAZTVOUBRD-UHFFFAOYSA-N C(C)OCC=1N(C(=C(C(N=1)=O)S(=O)(=O)C1=CC(=C(C=C1)C1=C(C(=NC=C1)F)C)F)O)C(COC)C1=CC(=CC=C1)F Chemical compound C(C)OCC=1N(C(=C(C(N=1)=O)S(=O)(=O)C1=CC(=C(C=C1)C1=C(C(=NC=C1)F)C)F)O)C(COC)C1=CC(=CC=C1)F LIHFGAZTVOUBRD-UHFFFAOYSA-N 0.000 claims 3
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- HRHSFIMIWKXBJU-UXMRNZNESA-N COC[C@@H](c1ccccc1)n1c(nc(O)c(c1=O)S(=O)(=O)c1ccc(cc1)-c1ccc(F)nc1C)C1CCCO1 Chemical compound COC[C@@H](c1ccccc1)n1c(nc(O)c(c1=O)S(=O)(=O)c1ccc(cc1)-c1ccc(F)nc1C)C1CCCO1 HRHSFIMIWKXBJU-UXMRNZNESA-N 0.000 claims 3
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Classifications
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- 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
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- 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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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- 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
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- 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
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- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
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- 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
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- 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
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- 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
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- 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
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- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
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- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
- C07D413/12—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 chain containing hetero atoms as chain links
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- 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
- C07D417/02—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 two hetero rings
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- C—CHEMISTRY; METALLURGY
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- 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
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Landscapes
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- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (2)
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| US201662349692P | 2016-06-14 | 2016-06-14 | |
| PCT/US2017/037405 WO2017218633A1 (en) | 2016-06-14 | 2017-06-14 | 6-hydroxy-5-(phenyl/heteroarylsulfonyl)pyrimidin-4(1h)-one as apj agonists |
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| MY189453A (en) | 2015-06-03 | 2022-02-14 | Bristol Myers Squibb Co | 4-hydroxy-3-(heteroaryl)pyridine-2-one apj agonists for use in the treatment of cardiovascular disorders |
| CA3001974A1 (en) | 2015-10-14 | 2017-04-20 | Bristol-Myers Squibb Company | 2,4-dihydroxy-nicotinamides as apj agonists |
| WO2017096130A1 (en) | 2015-12-04 | 2017-06-08 | 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 |
| MA43761A (fr) | 2016-03-24 | 2021-05-05 | Bristol Myers Squibb Co | 6-hydroxy-4-oxo-1,4-dihydropyrimidine-5-carboxamides comme inhibiteurs de la apj |
| WO2017192485A1 (en) | 2016-05-03 | 2017-11-09 | Amgen Inc. | Heterocyclic triazole compounds as agonists of the apj receptor |
| KR102521955B1 (ko) | 2016-06-14 | 2023-04-13 | 브리스톨-마이어스 스큅 컴퍼니 | Apj 수용체 효능제로서의 4-히드록시-3-술포닐피리딘-2(1h)-온 |
| EP3526198B1 (en) | 2016-10-14 | 2020-08-12 | Bristol-Myers Squibb Company | 3-sulfonyl-5-aminopyridine-2,4-diol apj agonists |
| MA46827A (fr) | 2016-11-16 | 2019-09-25 | Amgen Inc | Composés de triazole à substitution cycloalkyle en tant qu'agonistes du récepteur apj |
| US10906890B2 (en) | 2016-11-16 | 2021-02-02 | Amgen Inc. | Triazole phenyl compounds as agonists of the APJ receptor |
| EP3541792B1 (en) | 2016-11-16 | 2020-12-23 | Amgen Inc. | Triazole furan compounds as agonists of the apj receptor |
| WO2018097945A1 (en) | 2016-11-16 | 2018-05-31 | Amgen Inc. | Heteroaryl-substituted triazoles as apj receptor agonists |
| WO2018093580A1 (en) | 2016-11-16 | 2018-05-24 | Amgen Inc. | Triazole pyridyl compounds as agonists of the apj receptor |
| US11191762B2 (en) | 2016-11-16 | 2021-12-07 | Amgen Inc. | Alkyl substituted triazole compounds as agonists of the APJ Receptor |
| WO2019089335A1 (en) | 2017-11-03 | 2019-05-09 | Amgen Inc. | Fused triazole agonists of the apj receptor |
| US20210009711A1 (en) * | 2018-03-14 | 2021-01-14 | Elstar Therapeutics, Inc. | Multifunctional molecules and uses thereof |
| WO2019213006A1 (en) | 2018-05-01 | 2019-11-07 | Amgen Inc. | Substituted pyrimidinones as agonists of the apj receptor |
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| WO1995014014A2 (en) * | 1993-11-19 | 1995-05-26 | Parke, Davis & Company | Pyrone derivatives as protease inhibitors and antiviral agents |
| US5691335A (en) * | 1994-07-29 | 1997-11-25 | Suntory Limited | Imidazolidine derivative and use thereof |
| JP3537231B2 (ja) * | 1995-07-24 | 2004-06-14 | 第一サントリーファーマ株式会社 | ヒダントイン誘導体およびその用途 |
| US10570128B2 (en) * | 2014-05-28 | 2020-02-25 | Sanford Burnham Prebys Medical Discovery Institute | Agonists of the apelin receptor and methods of use thereof |
| MY189453A (en) | 2015-06-03 | 2022-02-14 | Bristol Myers Squibb Co | 4-hydroxy-3-(heteroaryl)pyridine-2-one apj agonists for use in the treatment of cardiovascular disorders |
| CA3001974A1 (en) | 2015-10-14 | 2017-04-20 | Bristol-Myers Squibb Company | 2,4-dihydroxy-nicotinamides as apj agonists |
| WO2017096130A1 (en) | 2015-12-04 | 2017-06-08 | 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 |
| MA43761A (fr) | 2016-03-24 | 2021-05-05 | Bristol Myers Squibb Co | 6-hydroxy-4-oxo-1,4-dihydropyrimidine-5-carboxamides comme inhibiteurs de la apj |
| KR102521955B1 (ko) | 2016-06-14 | 2023-04-13 | 브리스톨-마이어스 스큅 컴퍼니 | Apj 수용체 효능제로서의 4-히드록시-3-술포닐피리딘-2(1h)-온 |
| EP3526198B1 (en) | 2016-10-14 | 2020-08-12 | Bristol-Myers Squibb Company | 3-sulfonyl-5-aminopyridine-2,4-diol apj agonists |
-
2017
- 2017-06-14 US US16/309,161 patent/US10508104B2/en active Active
- 2017-06-14 CN CN201780036877.8A patent/CN109311821B/zh active Active
- 2017-06-14 EP EP17732693.1A patent/EP3468956B1/en active Active
- 2017-06-14 JP JP2018565285A patent/JP6993357B2/ja active Active
- 2017-06-14 KR KR1020197000800A patent/KR102384668B1/ko active Active
- 2017-06-14 WO PCT/US2017/037405 patent/WO2017218633A1/en not_active Ceased
- 2017-06-14 ES ES17732693T patent/ES2863903T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| WO2017218633A1 (en) | 2017-12-21 |
| CN109311821A (zh) | 2019-02-05 |
| JP2019518036A (ja) | 2019-06-27 |
| KR102384668B1 (ko) | 2022-04-07 |
| JP6993357B2 (ja) | 2022-01-13 |
| CN109311821B (zh) | 2022-10-14 |
| KR20190018161A (ko) | 2019-02-21 |
| US20190194173A1 (en) | 2019-06-27 |
| EP3468956B1 (en) | 2021-03-03 |
| EP3468956A1 (en) | 2019-04-17 |
| US10508104B2 (en) | 2019-12-17 |
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