ES2428492T3 - Moduladores del receptor 88 acoplado a proteína G - Google Patents
Moduladores del receptor 88 acoplado a proteína G Download PDFInfo
- Publication number
- ES2428492T3 ES2428492T3 ES10765715T ES10765715T ES2428492T3 ES 2428492 T3 ES2428492 T3 ES 2428492T3 ES 10765715 T ES10765715 T ES 10765715T ES 10765715 T ES10765715 T ES 10765715T ES 2428492 T3 ES2428492 T3 ES 2428492T3
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- Prior art keywords
- alkyl
- compound
- mmol
- phenyl
- pharmaceutically acceptable
- Prior art date
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- 102000004169 proteins and genes Human genes 0.000 title description 2
- 108090000623 proteins and genes Proteins 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 126
- 150000003839 salts Chemical class 0.000 claims abstract description 45
- 239000001257 hydrogen Substances 0.000 claims abstract description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 26
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 25
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 22
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 21
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 18
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 14
- 125000005843 halogen group Chemical group 0.000 claims abstract description 14
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 14
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 13
- 229910052701 rubidium Inorganic materials 0.000 claims abstract description 12
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 9
- 125000006699 (C1-C3) hydroxyalkyl group Chemical group 0.000 claims abstract description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 5
- 125000003386 piperidinyl group Chemical group 0.000 claims abstract description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims abstract description 4
- 125000002071 phenylalkoxy group Chemical group 0.000 claims abstract description 4
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 88
- 238000000034 method Methods 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 241000124008 Mammalia Species 0.000 claims description 8
- 208000012902 Nervous system disease Diseases 0.000 claims description 7
- 208000030159 metabolic disease Diseases 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 6
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- 201000000980 schizophrenia Diseases 0.000 claims description 6
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- 208000028017 Psychotic disease Diseases 0.000 claims description 4
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- 208000011117 substance-related disease Diseases 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 3
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 3
- 125000000304 alkynyl group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 198
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 166
- -1 7-azabicyclo [2,2,1] hept-7-yl Chemical group 0.000 description 110
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 74
- 235000019439 ethyl acetate Nutrition 0.000 description 71
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- 239000000243 solution Substances 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 44
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 37
- 235000019341 magnesium sulphate Nutrition 0.000 description 37
- 239000011541 reaction mixture Substances 0.000 description 37
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- 239000012267 brine Substances 0.000 description 25
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 25
- OOQRPGJTEUOBHT-WDSKDSINSA-N (1s,2s)-2-thiophen-2-ylcyclopropane-1-carboxylic acid Chemical compound OC(=O)[C@H]1C[C@@H]1C1=CC=CS1 OOQRPGJTEUOBHT-WDSKDSINSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- 101001033058 Homo sapiens Probable G-protein coupled receptor 88 Proteins 0.000 description 17
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- OKKJLVBELUTLKV-VMNATFBRSA-N methanol-d1 Chemical compound [2H]OC OKKJLVBELUTLKV-VMNATFBRSA-N 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 14
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 13
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- 239000000725 suspension Substances 0.000 description 13
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 12
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- 239000000843 powder Substances 0.000 description 12
- 239000007821 HATU Substances 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 239000012317 TBTU Substances 0.000 description 11
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 11
- 238000004440 column chromatography Methods 0.000 description 11
- 238000009472 formulation Methods 0.000 description 11
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 150000001263 acyl chlorides Chemical class 0.000 description 10
- 150000001412 amines Chemical class 0.000 description 10
- 239000000376 reactant Substances 0.000 description 10
- XOFLBQFBSOEHOG-UUOKFMHZSA-N γS-GTP Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=S)[C@@H](O)[C@H]1O XOFLBQFBSOEHOG-UUOKFMHZSA-N 0.000 description 10
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
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- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 7
- 125000003858 2-ethylbutoxy group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])O*)C([H])([H])C([H])([H])[H] 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
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- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/36—Opioid-abuse
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- A—HUMAN NECESSITIES
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- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- 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
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/57—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C233/60—Carboxylic acid amides having carbon atoms of carboxamide groups bound to carbon atoms of rings other than six-membered aromatic rings having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Addiction (AREA)
- Obesity (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Child & Adolescent Psychology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Compounds Containing Sulfur Atoms (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US24946509P | 2009-10-07 | 2009-10-07 | |
| US249465P | 2009-10-07 | ||
| PCT/US2010/051572 WO2011044195A1 (en) | 2009-10-07 | 2010-10-06 | Modulators of g protein-coupled receptor 88 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2428492T3 true ES2428492T3 (es) | 2013-11-08 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES10765715T Active ES2428492T3 (es) | 2009-10-07 | 2010-10-06 | Moduladores del receptor 88 acoplado a proteína G |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US8497271B2 (enExample) |
| EP (1) | EP2486030B1 (enExample) |
| JP (1) | JP2013507369A (enExample) |
| CN (1) | CN102686575A (enExample) |
| ES (1) | ES2428492T3 (enExample) |
| IN (1) | IN2012DN02876A (enExample) |
| WO (1) | WO2011044195A1 (enExample) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8426414B2 (en) | 2009-10-09 | 2013-04-23 | Bristol-Myers Squibb Company | Modulators of G protein-coupled receptor 88 |
| US8304577B2 (en) | 2009-10-09 | 2012-11-06 | Bristol-Myers Squibb Company | Modulators of G protein-coupled receptor 88 |
| US8598213B2 (en) | 2011-07-08 | 2013-12-03 | H. Lundbeck A/S | Positive allosteric modulators of nicotinic acetylcholine receptor |
| UA111746C2 (uk) * | 2011-07-08 | 2016-06-10 | Х. Луннбек А/С | Позитивні алостеричні модулятори нікотинового рецептора ацетилхоліну |
| US8703953B2 (en) | 2012-03-09 | 2014-04-22 | Bristol-Myers Squibb Company | Aryl ether-base kinase inhibitors |
| WO2014006117A1 (en) * | 2012-07-06 | 2014-01-09 | H. Lundbeck A/S | New positive allosteric modulators of nicotinic acetylcholine receptor |
| HK1216095A1 (zh) * | 2012-12-10 | 2016-10-14 | H. Lundbeck A/S | 烟碱乙酰胆碱受体的新的正向别构调节剂 |
| US10253027B2 (en) | 2013-07-08 | 2019-04-09 | Bristol-Myers Squibb Company | Aryl lactam kinase inhibitors |
| WO2015054358A1 (en) | 2013-10-11 | 2015-04-16 | Bristol-Myers Squibb Company | Pyrrolotriazine kinase inhibitors |
| CN113005089A (zh) * | 2019-12-20 | 2021-06-22 | 泰州医药城国科化物生物医药科技有限公司 | 一种无标记细胞膜受体gpr88的细胞筛选模型及应用 |
| CN111592531B (zh) * | 2020-06-23 | 2023-08-15 | 上海鲲博玖瑞医药科技发展有限公司 | 福瑞塞替的制备方法 |
| GB202209195D0 (en) | 2022-06-22 | 2022-08-10 | Pandeia Therapeutics Ltd | Modulators of g protein-coupled receptor 88 |
| GB202209193D0 (en) | 2022-06-22 | 2022-08-10 | Pandeia Therapeutics Ltd | Modulators of g protein-coupled receptor 88 |
| WO2026055419A1 (en) | 2024-09-05 | 2026-03-12 | Acadia Pharmaceuticals Inc. | Modulators of g protein-coupled receptor 88 |
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| CN100494167C (zh) | 2005-08-02 | 2009-06-03 | 天津大学 | 抗乙肝病毒的叔胺氧化物及制备方法和制备药物的应用 |
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