JP2018522034A5 - - Google Patents
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- Publication number
- JP2018522034A5 JP2018522034A5 JP2018504993A JP2018504993A JP2018522034A5 JP 2018522034 A5 JP2018522034 A5 JP 2018522034A5 JP 2018504993 A JP2018504993 A JP 2018504993A JP 2018504993 A JP2018504993 A JP 2018504993A JP 2018522034 A5 JP2018522034 A5 JP 2018522034A5
- Authority
- JP
- Japan
- Prior art keywords
- salt
- azaspiro
- piperidin
- compound
- hydrogen
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims 24
- 150000003839 salts Chemical class 0.000 claims 24
- 229910052739 hydrogen Inorganic materials 0.000 claims 21
- 239000001257 hydrogen Substances 0.000 claims 21
- 150000002431 hydrogen Chemical class 0.000 claims 13
- 125000001183 hydrocarbyl group Chemical group 0.000 claims 12
- -1 cyano, hydroxy, methoxy Chemical group 0.000 claims 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 10
- 125000003118 aryl group Chemical group 0.000 claims 10
- 229910052731 fluorine Inorganic materials 0.000 claims 10
- 239000011737 fluorine Substances 0.000 claims 10
- 125000001153 fluoro group Chemical group F* 0.000 claims 10
- 125000005842 heteroatom Chemical group 0.000 claims 10
- 229910052760 oxygen Inorganic materials 0.000 claims 10
- 229910052717 sulfur Inorganic materials 0.000 claims 10
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 claims 9
- 229910052757 nitrogen Inorganic materials 0.000 claims 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 6
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims 6
- 229910052794 bromium Inorganic materials 0.000 claims 6
- 229910052801 chlorine Inorganic materials 0.000 claims 6
- 239000000460 chlorine Substances 0.000 claims 6
- 229910052799 carbon Inorganic materials 0.000 claims 4
- 125000004432 carbon atom Chemical group C* 0.000 claims 4
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims 4
- 125000000217 alkyl group Chemical group 0.000 claims 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 3
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims 2
- 150000001721 carbon Chemical group 0.000 claims 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 2
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims 2
- 125000004043 oxo group Chemical group O=* 0.000 claims 2
- 208000020016 psychiatric disease Diseases 0.000 claims 2
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
- AQTFKGDWFRRIHR-UHFFFAOYSA-L 3-[18-(2-carboxylatoethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,24-diid-2-yl]propanoate;cobalt(2+);hydron Chemical compound [Co+2].[N-]1C(C=C2C(=C(C)C(C=C3C(=C(C)C(=C4)[N-]3)C=C)=N2)C=C)=C(C)C(CCC(O)=O)=C1C=C1C(CCC(O)=O)=C(C)C4=N1 AQTFKGDWFRRIHR-UHFFFAOYSA-L 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 claims 1
- 206010065390 Inflammatory pain Diseases 0.000 claims 1
- 201000002832 Lewy body dementia Diseases 0.000 claims 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims 1
- 230000001154 acute effect Effects 0.000 claims 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000001684 chronic effect Effects 0.000 claims 1
- 208000010877 cognitive disease Diseases 0.000 claims 1
- 230000001149 cognitive effect Effects 0.000 claims 1
- 230000000694 effects Effects 0.000 claims 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims 1
- GKODYOLWAJKWOR-OAHLLOKOSA-N ethyl 6-[4-[(2R)-2-ethyl-5-oxopyrrolidin-1-yl]piperidin-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate Chemical compound C(C)[C@H]1N(C(CC1)=O)C1CCN(CC1)C1CC2(CN(C2)C(=O)OCC)C1 GKODYOLWAJKWOR-OAHLLOKOSA-N 0.000 claims 1
- PIAGNFVSQQDWNF-MRXNPFEDSA-N ethyl 6-[4-[(2R)-4,4-difluoro-2-(hydroxymethyl)pyrrolidin-1-yl]piperidin-1-yl]-2-azaspiro[3.3]heptane-2-carboxylate Chemical compound FC1(C[C@@H](N(C1)C1CCN(CC1)C1CC2(CN(C2)C(=O)OCC)C1)CO)F PIAGNFVSQQDWNF-MRXNPFEDSA-N 0.000 claims 1
- ZVYGUQXJVNRSMW-ATNAJCNCSA-N ethyl 6-[4-[(2S)-2-ethyl-5-oxopyrrolidin-1-yl]piperidin-1-yl]-2-azaspiro[3.4]octane-2-carboxylate Chemical compound C(C)[C@@H]1N(C(CC1)=O)C1CCN(CC1)C1CC2(CN(C2)C(=O)OCC)CC1 ZVYGUQXJVNRSMW-ATNAJCNCSA-N 0.000 claims 1
- FNPNRGQANRLYMU-MYJWUSKBSA-N ethyl 6-[4-[(2S)-2-methyl-5-oxopyrrolidin-1-yl]piperidin-1-yl]-2-azaspiro[3.4]octane-2-carboxylate Chemical compound C[C@@H]1N(C(CC1)=O)C1CCN(CC1)C1CC2(CN(C2)C(=O)OCC)CC1 FNPNRGQANRLYMU-MYJWUSKBSA-N 0.000 claims 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 1
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 claims 1
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims 1
- 125000002883 imidazolyl group Chemical group 0.000 claims 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims 1
- DVZYRUCGRJANBZ-QRWMCTBCSA-N methyl 6-[4-[(2R)-2-(1,3-oxazol-5-yl)pyrrolidin-1-yl]piperidin-1-yl]-2-azaspiro[3.4]octane-2-carboxylate Chemical compound O1C=NC=C1[C@@H]1N(CCC1)C1CCN(CC1)C1CC2(CN(C2)C(=O)OC)CC1 DVZYRUCGRJANBZ-QRWMCTBCSA-N 0.000 claims 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims 1
- 230000003551 muscarinic effect Effects 0.000 claims 1
- 230000000926 neurological effect Effects 0.000 claims 1
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 125000003226 pyrazolyl group Chemical group 0.000 claims 1
- 239000000018 receptor agonist Substances 0.000 claims 1
- 229940044601 receptor agonist Drugs 0.000 claims 1
- 229920006395 saturated elastomer Polymers 0.000 claims 1
- 201000000980 schizophrenia Diseases 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1513740.9A GB201513740D0 (en) | 2015-08-03 | 2015-08-03 | Muscarinic agonist |
| GB1513740.9 | 2015-08-03 | ||
| PCT/GB2016/052384 WO2017021728A1 (en) | 2015-08-03 | 2016-08-03 | Muscarinic agonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2018522034A JP2018522034A (ja) | 2018-08-09 |
| JP2018522034A5 true JP2018522034A5 (https=) | 2019-09-12 |
| JP6847093B2 JP6847093B2 (ja) | 2021-03-24 |
Family
ID=54063147
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2018504993A Active JP6847093B2 (ja) | 2015-08-03 | 2016-08-03 | ムスカリン様アゴニスト |
Country Status (10)
| Country | Link |
|---|---|
| US (2) | US10548884B2 (https=) |
| EP (1) | EP3331528B1 (https=) |
| JP (1) | JP6847093B2 (https=) |
| CN (1) | CN107949384B (https=) |
| AU (1) | AU2016302047B2 (https=) |
| CA (1) | CA2994143C (https=) |
| DK (1) | DK3331528T3 (https=) |
| ES (1) | ES2894855T3 (https=) |
| GB (1) | GB201513740D0 (https=) |
| WO (1) | WO2017021728A1 (https=) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2012338581B2 (en) | 2011-11-18 | 2016-12-08 | Nxera Pharma Uk Limited | Muscarinic M1 receptor agonists |
| GB201404922D0 (en) | 2014-03-19 | 2014-04-30 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201513740D0 (en) * | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonist |
| GB201513743D0 (en) | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonists |
| GB201519352D0 (en) | 2015-11-02 | 2015-12-16 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| WO2017107089A1 (en) | 2015-12-23 | 2017-06-29 | Merck Sharp & Dohme Corp. | 3- (1h-pyrazol-4-yl) pyridineallosteric modulators of the m4 muscarinic acetylcholine receptor |
| US10329289B2 (en) | 2015-12-23 | 2019-06-25 | Merck Sharp & Dohme Corp. | 6,7-dihydro-5H-pyrrolo[3,4-B]pyridin-5-one allosteric modulators of the M4 muscarinic acetylcholine receptor |
| GB201617454D0 (en) | 2016-10-14 | 2016-11-30 | Heptares Therapeutics Limited | Pharmaceutical compounds |
| WO2018112843A1 (en) | 2016-12-22 | 2018-06-28 | Merck Sharp & Dohme Corp. | Heteroaryl piperidine ether allosteric modulators of the m4 muscarinic acetylcholine receptor |
| WO2018112842A1 (en) | 2016-12-22 | 2018-06-28 | Merck Sharp & Dohme Corp. | 6,6-fused heteroaryl piperidine ether allosteric modulators of m4 muscarinic acetylcholine receptor |
| US12600726B2 (en) | 2017-07-12 | 2026-04-14 | Vanderbilt University | Antagonists of the muscarinic acetylcholine receptor M4 |
| IL310346A (en) | 2017-10-20 | 2024-03-01 | Univ Vanderbilt | Muscarinic acetylcholine M4 receptor antagonists |
| EP3732163A4 (en) * | 2017-12-20 | 2021-07-14 | Vanderbilt University | MUSCARIN M4 ACETYLCHOLIN RECEPTOR ANTAGONISTS |
| EP4219464A1 (en) | 2018-03-23 | 2023-08-02 | Pfizer Inc. | Piperazine azaspiro derivaves |
| GB201810239D0 (en) | 2018-06-22 | 2018-08-08 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201819960D0 (en) | 2018-12-07 | 2019-01-23 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201819961D0 (en) | 2018-12-07 | 2019-01-23 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB202020191D0 (en) | 2020-12-18 | 2021-02-03 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| IL291569B2 (en) * | 2019-09-25 | 2025-04-01 | Oncoarendi Therapeutics Sa | Process for the production of 5-(4-((2S,5S)-5-(4-chlorobenzyl)-2-methylmorpholino)piperidin-1-yl)-1H-4,2,1-triazol-3-amine |
| KR20220079921A (ko) * | 2019-10-09 | 2022-06-14 | 노파르티스 아게 | M4 작용제로서의 2-아자스피로[3.4]옥탄 유도체 |
| PE20221454A1 (es) * | 2019-10-09 | 2022-09-21 | Novartis Ag | Derivados de 2-azaespiro[3.4]octano como agonistas de m4 |
| EP4069367B1 (en) | 2019-12-06 | 2024-05-15 | Neurocrine Biosciences, Inc. | Muscarinic receptor 4 antagonists and methods of use |
| EP4100410B1 (en) * | 2020-02-05 | 2026-04-22 | Neurocrine Biosciences, Inc. | Muscarinic receptor 4 antagonists and methods of use |
| WO2023114224A1 (en) | 2021-12-13 | 2023-06-22 | Sage Therapeutics, Inc. | Combination of muscarinic receptor positive modulators and nmda positive allosteric modulators |
| WO2025030095A1 (en) * | 2023-08-03 | 2025-02-06 | Neurocrine Biosciences, Inc. | Methods of synthesis |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101426499A (zh) | 2006-02-22 | 2009-05-06 | 弗特克斯药品有限公司 | 毒蕈碱受体调节剂 |
| NZ570497A (en) * | 2006-02-22 | 2011-09-30 | Vertex Pharma | Spiro condensed 4,4'-quinilino-piperidines derivatives as modulators of muscarinic receptors |
| JP2012506883A (ja) | 2008-10-29 | 2012-03-22 | グリュネンタール・ゲゼルシャフト・ミト・ベシュレンクテル・ハフツング | 置換されたスピロアミン |
| FR2945531A1 (fr) | 2009-05-12 | 2010-11-19 | Sanofi Aventis | Derives de 7-aza-spiro°3,5!nonane-7-carboxylates, leur preparation et leur application en therapeutique |
| AU2012338581B2 (en) * | 2011-11-18 | 2016-12-08 | Nxera Pharma Uk Limited | Muscarinic M1 receptor agonists |
| BR112015006029B1 (pt) * | 2012-09-18 | 2022-01-25 | Heptares Therapeutics Limited | Compostos aza bicíclicos como agonistas de receptor m1 muscarínicos, composição farmacêutica compreendendo ditos compostos e uso dos mesmos para tratar um distúrbio cognitivo ou distúrbio psicótico ou para tratar ou reduzir a gravidade de dores agudas, crônicas, neuropáticas ou inflamatórias |
| WO2014122474A1 (en) * | 2013-02-07 | 2014-08-14 | Takeda Pharmaceutical Company Limited | Piperidin-1 -yl and azepin-1 -yl carboxylates as muscarinic m4 receptor agonists |
| KR102352388B1 (ko) * | 2014-02-06 | 2022-01-17 | 헵테얼즈 테라퓨틱스 리미티드 | 무스카린성 m1 수용체 및/또는 m4 수용체 작용제로서 바이사이클릭 아자 화합물 |
| GB201504675D0 (en) * | 2015-03-19 | 2015-05-06 | Heptares Therapeutics Ltd | Pharmaceutical compounds |
| GB201513743D0 (en) | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonists |
| GB201513740D0 (en) * | 2015-08-03 | 2015-09-16 | Heptares Therapeutics Ltd | Muscarinic agonist |
-
2015
- 2015-08-03 GB GBGB1513740.9A patent/GB201513740D0/en not_active Ceased
-
2016
- 2016-08-03 WO PCT/GB2016/052384 patent/WO2017021728A1/en not_active Ceased
- 2016-08-03 EP EP16750221.0A patent/EP3331528B1/en active Active
- 2016-08-03 CA CA2994143A patent/CA2994143C/en active Active
- 2016-08-03 CN CN201680045225.6A patent/CN107949384B/zh active Active
- 2016-08-03 ES ES16750221T patent/ES2894855T3/es active Active
- 2016-08-03 DK DK16750221.0T patent/DK3331528T3/da active
- 2016-08-03 AU AU2016302047A patent/AU2016302047B2/en active Active
- 2016-08-03 JP JP2018504993A patent/JP6847093B2/ja active Active
- 2016-08-03 US US15/749,743 patent/US10548884B2/en active Active
-
2019
- 2019-12-27 US US16/728,762 patent/US11324738B2/en active Active
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