CA2859992A1 - Novel morpholinyl derivatives useful as mogat-2 inhibitors - Google Patents
Novel morpholinyl derivatives useful as mogat-2 inhibitors Download PDFInfo
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- CA2859992A1 CA2859992A1 CA2859992A CA2859992A CA2859992A1 CA 2859992 A1 CA2859992 A1 CA 2859992A1 CA 2859992 A CA2859992 A CA 2859992A CA 2859992 A CA2859992 A CA 2859992A CA 2859992 A1 CA2859992 A1 CA 2859992A1
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- 239000003112 inhibitor Substances 0.000 title description 3
- 125000002757 morpholinyl group Chemical group 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 98
- 150000003839 salts Chemical class 0.000 claims abstract description 30
- 208000006575 hypertriglyceridemia Diseases 0.000 claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 31
- 229910052731 fluorine Inorganic materials 0.000 claims description 22
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
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- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 3
- 150000003841 chloride salts Chemical class 0.000 claims description 2
- 150000002688 maleic acid derivatives Chemical class 0.000 claims description 2
- LQAMWHULUZTCMH-GFMGDHOUSA-N (z)-but-2-enedioic acid;n-[(1r)-1-[4-[[(2s)-2-(4-fluorophenyl)morpholin-4-yl]methyl]phenyl]ethyl]methanesulfonamide Chemical compound OC(=O)\C=C/C(O)=O.C1=CC([C@H](NS(C)(=O)=O)C)=CC=C1CN1C[C@H](C=2C=CC(F)=CC=2)OCC1 LQAMWHULUZTCMH-GFMGDHOUSA-N 0.000 claims 1
- COPNNBDLRZEYRB-FOWJKZASSA-N n-[(1r)-1-[4-[[(2s)-2-(4-fluorophenyl)morpholin-4-yl]methyl]phenyl]ethyl]methanesulfonamide;hydrochloride Chemical compound Cl.C1=CC([C@H](NS(C)(=O)=O)C)=CC=C1CN1C[C@H](C=2C=CC(F)=CC=2)OCC1 COPNNBDLRZEYRB-FOWJKZASSA-N 0.000 claims 1
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- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 8
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- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical class O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 238000010791 quenching Methods 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Natural products C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 5
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- 150000002632 lipids Chemical class 0.000 description 5
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- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
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- OVIHXYHYVKMHCN-HNCPQSOCSA-N (2s)-2-(4-fluorophenyl)morpholine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1[C@@H]1OCCNC1 OVIHXYHYVKMHCN-HNCPQSOCSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 3
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Classifications
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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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/12—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms
- C07D295/135—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly or doubly bound nitrogen atoms with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- 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
-
- 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
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/02—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms with only carbon-to-carbon double bonds as unsaturation
- C07C57/13—Dicarboxylic acids
- C07C57/145—Maleic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/02—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements
- C07D295/027—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring
- C07D295/03—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms containing only hydrogen and carbon atoms in addition to the ring hetero elements containing only one hetero ring with the ring nitrogen atoms directly attached to acyclic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Obesity (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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP12382037.5 | 2012-01-31 | ||
| EP12382037 | 2012-01-31 | ||
| US201261617093P | 2012-03-29 | 2012-03-29 | |
| US61/617,093 | 2012-03-29 | ||
| EP12382433.6 | 2012-11-06 | ||
| EP12382433 | 2012-11-06 | ||
| PCT/US2013/022828 WO2013116065A1 (en) | 2012-01-31 | 2013-01-24 | Novel morpholinyl derivatives useful as mogat-2 inhibitors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2859992A1 true CA2859992A1 (en) | 2013-08-08 |
Family
ID=48905712
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2859992A Abandoned CA2859992A1 (en) | 2012-01-31 | 2013-01-24 | Novel morpholinyl derivatives useful as mogat-2 inhibitors |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US8993568B2 (enExample) |
| EP (1) | EP2809661B1 (enExample) |
| JP (1) | JP5852269B2 (enExample) |
| KR (1) | KR20140107641A (enExample) |
| CN (1) | CN104080777B (enExample) |
| AP (1) | AP2014007793A0 (enExample) |
| AU (1) | AU2013215549B2 (enExample) |
| BR (1) | BR112014018712A8 (enExample) |
| CA (1) | CA2859992A1 (enExample) |
| CL (1) | CL2014001862A1 (enExample) |
| CO (1) | CO7020914A2 (enExample) |
| CR (1) | CR20140325A (enExample) |
| DO (1) | DOP2014000177A (enExample) |
| EA (1) | EA024182B1 (enExample) |
| ES (1) | ES2571577T3 (enExample) |
| GT (1) | GT201400169A (enExample) |
| IL (1) | IL233542A0 (enExample) |
| MX (1) | MX2014008604A (enExample) |
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| EP2807147A1 (en) | 2012-01-23 | 2014-12-03 | Eli Lilly and Company | Phenyl methanesulfonamide derivatives useful as mgat - 2 inhibitors |
| SG11201404508XA (en) | 2012-01-31 | 2014-10-30 | Lilly Co Eli | Novel morpholinyl derivatives useful as mogat-2 inhibitors |
| AR089771A1 (es) | 2012-01-31 | 2014-09-17 | Lilly Co Eli | Derivados de bencil sulfonamida utiles como inhibidores de mogat-2 |
| EP2917194B1 (en) | 2012-11-06 | 2017-09-27 | Eli Lilly and Company | Novel benzyl sulfonamide compounds useful as mogat-2 inhibitors |
| US10335401B2 (en) | 2015-12-21 | 2019-07-02 | Shionogi & Co., Ltd. | Non-aromatic heterocyclic derivative having MGAT2 inhibitory activity |
| TWI782056B (zh) | 2017-07-14 | 2022-11-01 | 日商鹽野義製藥股份有限公司 | 具有ｍｇａｔ２抑制活性的縮合環衍生物 |
| KR20210114001A (ko) | 2019-01-11 | 2021-09-17 | 시오노기 앤드 컴파니, 리미티드 | Mgat2 저해 활성을 갖는 다이하이드로피라졸로피라지논 유도체 |
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| US5889006A (en) | 1995-02-23 | 1999-03-30 | Schering Corporation | Muscarinic antagonists |
| GB9702194D0 (en) | 1997-02-04 | 1997-03-26 | Lilly Co Eli | Sulphonide derivatives |
| WO2000006083A2 (en) | 1998-07-31 | 2000-02-10 | Eli Lilly And Company | Sulfonamide derivatives |
| CA2338862A1 (en) | 1998-07-31 | 2000-02-10 | Dennis Michael Zimmerman | Alkenyl sulphonamide derivatives |
| GB0408777D0 (en) | 2004-04-20 | 2004-05-26 | Glaxo Group Ltd | Compounds |
| EP1655283A1 (en) | 2004-11-08 | 2006-05-10 | Evotec OAI AG | 11beta-HSD1 Inhibitors |
| EP1659113A1 (en) | 2004-11-08 | 2006-05-24 | Evotec AG | Inhibitors of 11beta-hydroxy steroid dehydrogenase type 1 (11beta-HSD1) |
| US8232282B2 (en) | 2006-09-28 | 2012-07-31 | Dainippon Sumitomo Pharma Co., Ltd. | Compound having bicyclic pyrimidine structure and pharmaceutical composition comprising the same |
| TW200831092A (en) * | 2006-12-21 | 2008-08-01 | Astrazeneca Ab | Therapeutic agents |
| CN102026976A (zh) * | 2007-12-05 | 2011-04-20 | 阿斯利康(瑞典)有限公司 | 作为抗肥胖药物的吗啉衍生物 |
| AU2008345225A1 (en) | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| US20110015198A1 (en) | 2008-03-28 | 2011-01-20 | Banyu Pharmaceutical Co., Inc. | Diarylmethylamide derivative having melanin-concentrating hormone receptor antagonism |
| AU2009254547A1 (en) * | 2008-06-04 | 2009-12-10 | Astrazeneca Ab (Publ) | New compounds V |
| CA2751244A1 (en) | 2009-02-23 | 2010-08-26 | Msd K.K. | Pyrimidin-4(3h)-one derivatives |
| JP2014051434A (ja) | 2010-12-28 | 2014-03-20 | Dainippon Sumitomo Pharma Co Ltd | 二環性ピリミジン誘導体 |
| EP2807147A1 (en) | 2012-01-23 | 2014-12-03 | Eli Lilly and Company | Phenyl methanesulfonamide derivatives useful as mgat - 2 inhibitors |
| AR089771A1 (es) | 2012-01-31 | 2014-09-17 | Lilly Co Eli | Derivados de bencil sulfonamida utiles como inhibidores de mogat-2 |
| SG11201404508XA (en) | 2012-01-31 | 2014-10-30 | Lilly Co Eli | Novel morpholinyl derivatives useful as mogat-2 inhibitors |
| EP2917194B1 (en) | 2012-11-06 | 2017-09-27 | Eli Lilly and Company | Novel benzyl sulfonamide compounds useful as mogat-2 inhibitors |
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- 2013-01-24 CN CN201380007113.8A patent/CN104080777B/zh not_active Expired - Fee Related
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- 2014-07-30 PH PH12014501712A patent/PH12014501712B1/en unknown
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| BR112014018712A2 (enExample) | 2017-06-20 |
| AU2013215549A1 (en) | 2014-07-17 |
| US20150005305A1 (en) | 2015-01-01 |
| JP2015504917A (ja) | 2015-02-16 |
| HK1199024A1 (zh) | 2015-06-19 |
| PH12014501712A1 (en) | 2014-10-13 |
| ZA201405227B (en) | 2016-05-25 |
| CR20140325A (es) | 2014-08-25 |
| DOP2014000177A (es) | 2014-08-31 |
| AU2013215549B2 (en) | 2015-09-03 |
| IL233542A0 (en) | 2014-08-31 |
| JP5852269B2 (ja) | 2016-02-03 |
| EA201491227A1 (ru) | 2015-01-30 |
| PH12014501712B1 (en) | 2014-10-13 |
| CL2014001862A1 (es) | 2014-11-14 |
| ES2571577T3 (es) | 2016-05-26 |
| US8993568B2 (en) | 2015-03-31 |
| GT201400169A (es) | 2015-08-27 |
| KR20140107641A (ko) | 2014-09-04 |
| EP2809661A1 (en) | 2014-12-10 |
| WO2013116065A1 (en) | 2013-08-08 |
| BR112014018712A8 (pt) | 2017-07-11 |
| EA024182B1 (ru) | 2016-08-31 |
| AP2014007793A0 (en) | 2014-07-31 |
| CO7020914A2 (es) | 2014-08-11 |
| SG11201404508XA (en) | 2014-10-30 |
| EP2809661B1 (en) | 2016-04-06 |
| PE20141789A1 (es) | 2014-11-19 |
| CN104080777A (zh) | 2014-10-01 |
| MX2014008604A (es) | 2014-08-22 |
| CN104080777B (zh) | 2015-12-09 |
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