JP5715127B2 - Ｇｐｒ１１９アゴニスト - Google Patents
Ｇｐｒ１１９アゴニスト Download PDFInfo
- Publication number
- JP5715127B2 JP5715127B2 JP2012520691A JP2012520691A JP5715127B2 JP 5715127 B2 JP5715127 B2 JP 5715127B2 JP 2012520691 A JP2012520691 A JP 2012520691A JP 2012520691 A JP2012520691 A JP 2012520691A JP 5715127 B2 JP5715127 B2 JP 5715127B2
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- JP
- Japan
- Prior art keywords
- mmol
- methanesulfonyl
- tetrahydro
- mixture
- give
- 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.)
- Expired - Fee Related
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- 229940100607 GPR119 agonist Drugs 0.000 title description 8
- AJJISMLYIMQAKP-OAHLLOKOSA-N 5-[4-[(2r)-4-(3-fluoro-4-methylsulfonylphenoxy)butan-2-yl]piperidin-1-yl]-3-propan-2-yl-1,2,4-oxadiazole Chemical compound CC(C)C1=NOC(N2CCC(CC2)[C@H](C)CCOC=2C=C(F)C(=CC=2)S(C)(=O)=O)=N1 AJJISMLYIMQAKP-OAHLLOKOSA-N 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 128
- 150000003839 salts Chemical class 0.000 claims description 27
- -1 2-Fluoro-2-methyl-propyl Chemical group 0.000 claims description 25
- 238000011282 treatment Methods 0.000 claims description 16
- 206010012601 diabetes mellitus Diseases 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 208000008589 Obesity Diseases 0.000 claims description 12
- 235000020824 obesity Nutrition 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 229960004034 sitagliptin Drugs 0.000 claims description 7
- MFFMDFFZMYYVKS-SECBINFHSA-N sitagliptin Chemical compound C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F MFFMDFFZMYYVKS-SECBINFHSA-N 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- RDTBTUCYZYOHAM-UHFFFAOYSA-N 1-methylsulfonyl-4-[4-[[1-[[1-(trifluoromethyl)cyclopropyl]methyl]piperidin-4-yl]methoxy]phenyl]-3,6-dihydro-2h-pyridine Chemical compound C1N(S(=O)(=O)C)CCC(C=2C=CC(OCC3CCN(CC4(CC4)C(F)(F)F)CC3)=CC=2)=C1 RDTBTUCYZYOHAM-UHFFFAOYSA-N 0.000 claims description 4
- 239000004615 ingredient Substances 0.000 claims description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 150
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- 239000000203 mixture Substances 0.000 description 71
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 58
- 239000007787 solid Substances 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 53
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 239000000243 solution Substances 0.000 description 46
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 33
- 239000012044 organic layer Substances 0.000 description 33
- 238000002360 preparation method Methods 0.000 description 31
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 30
- 238000006243 chemical reaction Methods 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 22
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- 239000012267 brine Substances 0.000 description 19
- 239000008103 glucose Substances 0.000 description 19
- 238000000034 method Methods 0.000 description 19
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 19
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 17
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- 235000019341 magnesium sulphate Nutrition 0.000 description 16
- 239000010410 layer Substances 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- 101000996752 Homo sapiens Glucose-dependent insulinotropic receptor Proteins 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 description 10
- 102100039994 Gastric inhibitory polypeptide Human genes 0.000 description 10
- 102100033839 Glucose-dependent insulinotropic receptor Human genes 0.000 description 10
- 241001465754 Metazoa Species 0.000 description 10
- 239000000556 agonist Substances 0.000 description 10
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- 239000012141 concentrate Substances 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 8
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 8
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 description 8
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 8
- 102100040918 Pro-glucagon Human genes 0.000 description 8
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 8
- 241000699670 Mus sp. Species 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
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- 239000013058 crude material Substances 0.000 description 7
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- 229910052757 nitrogen Inorganic materials 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
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- 238000005481 NMR spectroscopy Methods 0.000 description 6
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- 125000006239 protecting group Chemical group 0.000 description 6
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 description 5
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 5
- 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 5
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- GELKGHVAFRCJNA-UHFFFAOYSA-N 2,2-Dimethyloxirane Chemical compound CC1(C)CO1 GELKGHVAFRCJNA-UHFFFAOYSA-N 0.000 description 4
- 101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
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- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
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- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Hydrogenated Pyridines (AREA)
Applications Claiming Priority (5)
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|---|---|---|---|
| EP09382114.8 | 2009-07-15 | ||
| EP09382114 | 2009-07-15 | ||
| US24544509P | 2009-09-24 | 2009-09-24 | |
| US61/245,445 | 2009-09-24 | ||
| PCT/US2010/041645 WO2011008663A1 (en) | 2009-07-15 | 2010-07-12 | Gpr119 agonists |
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| JP2012533546A JP2012533546A (ja) | 2012-12-27 |
| JP2012533546A5 JP2012533546A5 (enExample) | 2013-08-08 |
| JP5715127B2 true JP5715127B2 (ja) | 2015-05-07 |
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| JP2012520691A Expired - Fee Related JP5715127B2 (ja) | 2009-07-15 | 2010-07-12 | Ｇｐｒ１１９アゴニスト |
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| JP (1) | JP5715127B2 (enExample) |
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| AR (1) | AR077638A1 (enExample) |
| AU (1) | AU2010273642B2 (enExample) |
| BR (1) | BRPI1015921A2 (enExample) |
| CA (1) | CA2764906C (enExample) |
| CO (1) | CO6480977A2 (enExample) |
| CR (1) | CR20120012A (enExample) |
| DO (1) | DOP2012000006A (enExample) |
| EA (1) | EA020540B1 (enExample) |
| EC (1) | ECSP12011606A (enExample) |
| IL (1) | IL216776A0 (enExample) |
| MA (1) | MA33428B1 (enExample) |
| MX (1) | MX2012000704A (enExample) |
| NZ (1) | NZ597125A (enExample) |
| PE (1) | PE20121045A1 (enExample) |
| SG (1) | SG177646A1 (enExample) |
| TN (1) | TN2012000002A1 (enExample) |
| TW (1) | TWI429634B (enExample) |
| WO (1) | WO2011008663A1 (enExample) |
| ZA (1) | ZA201200227B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL377847A1 (pl) | 2003-01-14 | 2006-02-20 | Arena Pharmaceuticals Inc. | 1,2,3-Tripodstawione pochodne arylowe i heteroarylowe jako modulatory metabolizmu oraz profilaktyka i leczenie związanych z nim zaburzeń takich jak cukrzyca i hiperglikemia |
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| US11007175B2 (en) | 2015-01-06 | 2021-05-18 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the S1P1 receptor |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL377847A1 (pl) * | 2003-01-14 | 2006-02-20 | Arena Pharmaceuticals Inc. | 1,2,3-Tripodstawione pochodne arylowe i heteroarylowe jako modulatory metabolizmu oraz profilaktyka i leczenie związanych z nim zaburzeń takich jak cukrzyca i hiperglikemia |
| CA2661371A1 (en) | 2006-08-30 | 2008-03-06 | Biovitrum Ab (Publ) | Pyrimidine compounds for treating gpr119 related disorders |
| US7638541B2 (en) * | 2006-12-28 | 2009-12-29 | Metabolex Inc. | 5-ethyl-2-{4-[4-(4-tetrazol-1-yl-phenoxymethyl)-thiazol-2-yl]-piperidin-1-yl}-pyrimidine |
| CA2697551C (en) | 2007-09-20 | 2013-03-12 | Irm Llc | Piperidine derivatives as modulators of gpr119 activity |
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| CN102471313B (zh) | 2014-06-04 |
| KR101365854B1 (ko) | 2014-02-21 |
| AU2010273642B2 (en) | 2014-03-13 |
| ECSP12011606A (es) | 2012-02-29 |
| EP2454251A1 (en) | 2012-05-23 |
| CO6480977A2 (es) | 2012-07-16 |
| WO2011008663A1 (en) | 2011-01-20 |
| ZA201200227B (en) | 2013-06-26 |
| US8207344B2 (en) | 2012-06-26 |
| CA2764906A1 (en) | 2011-01-20 |
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| TN2012000002A1 (en) | 2013-09-19 |
| JP2012533546A (ja) | 2012-12-27 |
| NZ597125A (en) | 2013-08-30 |
| BRPI1015921A2 (pt) | 2016-04-26 |
| CN102471313A (zh) | 2012-05-23 |
| MX2012000704A (es) | 2012-03-07 |
| AU2010273642A1 (en) | 2012-01-19 |
| DOP2012000006A (es) | 2012-01-31 |
| KR20120024964A (ko) | 2012-03-14 |
| IL216776A0 (en) | 2012-03-01 |
| MA33428B1 (fr) | 2012-07-03 |
| CA2764906C (en) | 2014-06-10 |
| EA020540B1 (ru) | 2014-11-28 |
| CR20120012A (es) | 2012-03-28 |
| TWI429634B (zh) | 2014-03-11 |
| SG177646A1 (en) | 2012-02-28 |
| US20110015199A1 (en) | 2011-01-20 |
| EA201270169A1 (ru) | 2012-06-29 |
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