RU2662157C2 - 2-пиридоновое соединение - Google Patents
2-пиридоновое соединение Download PDFInfo
- Publication number
- RU2662157C2 RU2662157C2 RU2015122717A RU2015122717A RU2662157C2 RU 2662157 C2 RU2662157 C2 RU 2662157C2 RU 2015122717 A RU2015122717 A RU 2015122717A RU 2015122717 A RU2015122717 A RU 2015122717A RU 2662157 C2 RU2662157 C2 RU 2662157C2
- Authority
- RU
- Russia
- Prior art keywords
- compound
- cyclopropyl
- difluoroethyl
- compounds
- phenyl
- Prior art date
Links
- -1 2-pyridone compound Chemical class 0.000 title claims abstract description 48
- 150000001875 compounds Chemical class 0.000 claims abstract description 189
- 239000003814 drug Substances 0.000 claims abstract description 36
- ABERLDAQFUZISG-SJLPKXTDSA-N 3-cyclopropyl-6-[(1r)-1-[4-(1,1-difluoroethyl)phenyl]-2-[(2r)-5-oxopyrrolidin-2-yl]ethyl]-1h-pyridin-2-one Chemical compound C1=CC(C(F)(F)C)=CC=C1[C@H](C=1NC(=O)C(C2CC2)=CC=1)C[C@@H]1NC(=O)CC1 ABERLDAQFUZISG-SJLPKXTDSA-N 0.000 claims abstract description 23
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 23
- 230000000694 effects Effects 0.000 claims abstract description 23
- 230000004913 activation Effects 0.000 claims abstract description 17
- 150000003839 salts Chemical class 0.000 claims abstract description 16
- 238000011282 treatment Methods 0.000 claims abstract description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 11
- 201000010099 disease Diseases 0.000 claims abstract description 10
- 230000002265 prevention Effects 0.000 claims abstract description 8
- 108010021582 Glucokinase Proteins 0.000 claims abstract description 6
- 102000030595 Glucokinase Human genes 0.000 claims abstract description 3
- 238000000034 method Methods 0.000 claims description 68
- 239000002904 solvent Substances 0.000 claims description 45
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 37
- 229940079593 drug Drugs 0.000 claims description 24
- 239000013078 crystal Substances 0.000 claims description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 238000010521 absorption reaction Methods 0.000 claims description 10
- 230000001747 exhibiting effect Effects 0.000 claims description 10
- 238000000862 absorption spectrum Methods 0.000 claims description 9
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- 238000002844 melting Methods 0.000 claims description 8
- 230000008018 melting Effects 0.000 claims description 8
- 230000000704 physical effect Effects 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 6
- 125000006002 1,1-difluoroethyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000000843 powder Substances 0.000 claims description 4
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- 239000000126 substance Substances 0.000 abstract description 19
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- 229940124828 glucokinase activator Drugs 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 55
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- 238000006243 chemical reaction Methods 0.000 description 29
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000003112 inhibitor Substances 0.000 description 21
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 16
- 125000006239 protecting group Chemical group 0.000 description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 239000012442 inert solvent Substances 0.000 description 13
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
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- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
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- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
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- 238000005859 coupling reaction Methods 0.000 description 10
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 9
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- 238000001914 filtration Methods 0.000 description 9
- 229910052763 palladium Inorganic materials 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 9
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical class OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- 230000015572 biosynthetic process Effects 0.000 description 7
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- 210000004369 blood Anatomy 0.000 description 7
- 201000001421 hyperglycemia Diseases 0.000 description 7
- 230000002218 hypoglycaemic effect Effects 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 239000000018 receptor agonist Substances 0.000 description 7
- 229940044601 receptor agonist Drugs 0.000 description 7
- 239000012453 solvate Substances 0.000 description 7
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
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- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
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- 210000002237 B-cell of pancreatic islet Anatomy 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- 102000004877 Insulin Human genes 0.000 description 5
- 108090001061 Insulin Proteins 0.000 description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
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- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
- 229940126062 Compound A Drugs 0.000 description 4
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- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 4
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- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 4
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- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 4
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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
-
- 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
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Ophthalmology & Optometry (AREA)
- Child & Adolescent Psychology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2012-249792 | 2012-11-13 | ||
| JP2012249792 | 2012-11-13 | ||
| PCT/JP2013/080517 WO2014077235A1 (ja) | 2012-11-13 | 2013-11-12 | ２－ピリドン化合物 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2015122717A RU2015122717A (ru) | 2017-01-10 |
| RU2662157C2 true RU2662157C2 (ru) | 2018-07-24 |
Family
ID=50731146
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2015122717A RU2662157C2 (ru) | 2012-11-13 | 2013-11-12 | 2-пиридоновое соединение |
Country Status (25)
| Country | Link |
|---|---|
| US (1) | US9695148B2 (Direct) |
| EP (1) | EP2921489B1 (Direct) |
| JP (1) | JP5963025B2 (Direct) |
| KR (1) | KR102160841B1 (Direct) |
| CN (1) | CN104768944B (Direct) |
| AU (1) | AU2013345930B2 (Direct) |
| BR (1) | BR112015010823A2 (Direct) |
| CA (1) | CA2891406C (Direct) |
| DK (1) | DK2921489T3 (Direct) |
| ES (1) | ES2641469T3 (Direct) |
| HU (1) | HUE034557T2 (Direct) |
| IL (1) | IL238701B (Direct) |
| IN (1) | IN2015DN03869A (Direct) |
| MX (1) | MX361479B (Direct) |
| MY (1) | MY173812A (Direct) |
| NO (1) | NO2921489T3 (Direct) |
| NZ (1) | NZ707832A (Direct) |
| PH (1) | PH12015501056B1 (Direct) |
| PL (1) | PL2921489T3 (Direct) |
| PT (1) | PT2921489T (Direct) |
| RU (1) | RU2662157C2 (Direct) |
| SG (1) | SG11201503716RA (Direct) |
| TW (1) | TWI591064B (Direct) |
| WO (1) | WO2014077235A1 (Direct) |
| ZA (1) | ZA201503323B (Direct) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6048533B2 (ja) * | 2014-05-12 | 2016-12-21 | 日産化学工業株式会社 | ２−ピリドン化合物を含有する医薬 |
| EP3144305A4 (en) * | 2014-05-13 | 2017-12-27 | Nissan Chemical Industries, Ltd. | Method for producing 2-pyridone compound |
| LT3804714T (lt) * | 2018-05-31 | 2025-03-10 | Hua Medicine (Shanghai) Ltd. | Farmacinis derinys ir kompozicija, ir derinio preparatas, kurio sudėtyje yra gliukokinazės aktyvatorius ir biguanido hipoglikeminis vaistas, taip pat jų gamybos būdas ir panaudojimas |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA016595B1 (ru) * | 2007-07-17 | 2012-06-29 | Бристол-Маерс Сквибб Компани | Способ модулирования рецептора gpr119, сопряженного с g-белком, и используемые при этом соединения |
| EP2508513A1 (en) * | 2009-12-04 | 2012-10-10 | Taisho Pharmaceutical Co., Ltd. | 2-pyridone compounds |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4275069A (en) | 1979-01-22 | 1981-06-23 | The Upjohn Company | Anti-diabetic 1,2-dihydro-2-oxo-6-alkyl-nicotinic acids |
| CZ301366B6 (cs) | 1999-03-29 | 2010-02-03 | F. Hoffmann-La Roche Ag | 2-Fenyl-3-cykloalkylpropionamidová sloucenina, zpusob její prípravy a farmaceutický prostredek s jejím obsahem |
| US6353111B1 (en) | 1999-12-15 | 2002-03-05 | Hoffmann-La Roche Inc. | Trans olefinic glucokinase activators |
| EP2076502B1 (en) | 2006-06-08 | 2011-05-18 | Eli Lilly And Company | Substituted carboxamides as group i metabotropic receptor antagonists |
| JP5419706B2 (ja) | 2006-12-20 | 2014-02-19 | タケダ カリフォルニア インコーポレイテッド | グルコキナーゼアクチベーター |
| EP2318370A1 (en) | 2008-07-29 | 2011-05-11 | Pfizer Inc. | Fluorinated heteroaryls |
| JP2013010750A (ja) * | 2011-06-02 | 2013-01-17 | Taisho Pharmaceutical Co Ltd | ２−ピリドン化合物を含有する医薬 |
-
2013
- 2013-11-12 EP EP13855534.7A patent/EP2921489B1/en active Active
- 2013-11-12 RU RU2015122717A patent/RU2662157C2/ru active
- 2013-11-12 BR BR112015010823A patent/BR112015010823A2/pt not_active Application Discontinuation
- 2013-11-12 SG SG11201503716RA patent/SG11201503716RA/en unknown
- 2013-11-12 DK DK13855534.7T patent/DK2921489T3/en active
- 2013-11-12 MY MYPI2015701491A patent/MY173812A/en unknown
- 2013-11-12 AU AU2013345930A patent/AU2013345930B2/en not_active Ceased
- 2013-11-12 PL PL13855534T patent/PL2921489T3/pl unknown
- 2013-11-12 MX MX2015005884A patent/MX361479B/es active IP Right Grant
- 2013-11-12 NO NO13855534A patent/NO2921489T3/no unknown
- 2013-11-12 NZ NZ707832A patent/NZ707832A/en not_active IP Right Cessation
- 2013-11-12 ES ES13855534.7T patent/ES2641469T3/es active Active
- 2013-11-12 WO PCT/JP2013/080517 patent/WO2014077235A1/ja not_active Ceased
- 2013-11-12 CA CA2891406A patent/CA2891406C/en not_active Expired - Fee Related
- 2013-11-12 IN IN3869DEN2015 patent/IN2015DN03869A/en unknown
- 2013-11-12 CN CN201380059272.2A patent/CN104768944B/zh not_active Expired - Fee Related
- 2013-11-12 US US14/442,157 patent/US9695148B2/en not_active Expired - Fee Related
- 2013-11-12 PT PT138555347T patent/PT2921489T/pt unknown
- 2013-11-12 JP JP2014546982A patent/JP5963025B2/ja not_active Expired - Fee Related
- 2013-11-12 KR KR1020157012117A patent/KR102160841B1/ko not_active Expired - Fee Related
- 2013-11-12 HU HUE13855534A patent/HUE034557T2/en unknown
- 2013-11-13 TW TW102141288A patent/TWI591064B/zh not_active IP Right Cessation
-
2015
- 2015-05-07 IL IL238701A patent/IL238701B/en active IP Right Grant
- 2015-05-12 PH PH12015501056A patent/PH12015501056B1/en unknown
- 2015-05-13 ZA ZA2015/03323A patent/ZA201503323B/en unknown
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EA016595B1 (ru) * | 2007-07-17 | 2012-06-29 | Бристол-Маерс Сквибб Компани | Способ модулирования рецептора gpr119, сопряженного с g-белком, и используемые при этом соединения |
| EP2508513A1 (en) * | 2009-12-04 | 2012-10-10 | Taisho Pharmaceutical Co., Ltd. | 2-pyridone compounds |
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