EA038368B1 - N-[4-фтор-5-[[(2s,4s)-2-метил-4-[(5-метил-1,2,4-оксадиазол-3-ил)метокси]-1-пиперидил]метил]тиазол-2-ил]ацетамид в качестве ингибитора oga - Google Patents
N-[4-фтор-5-[[(2s,4s)-2-метил-4-[(5-метил-1,2,4-оксадиазол-3-ил)метокси]-1-пиперидил]метил]тиазол-2-ил]ацетамид в качестве ингибитора oga Download PDFInfo
- Publication number
- EA038368B1 EA038368B1 EA201991515A EA201991515A EA038368B1 EA 038368 B1 EA038368 B1 EA 038368B1 EA 201991515 A EA201991515 A EA 201991515A EA 201991515 A EA201991515 A EA 201991515A EA 038368 B1 EA038368 B1 EA 038368B1
- Authority
- EA
- Eurasian Patent Office
- Prior art keywords
- methyl
- compound
- pharmaceutically acceptable
- mixture
- acceptable salt
- Prior art date
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- FRVXHWNHGWUTQO-CABZTGNLSA-N N-[4-fluoro-5-[[(2S,4S)-2-methyl-4-[(5-methyl-1,2,4-oxadiazol-3-yl)methoxy]piperidin-1-yl]methyl]-1,3-thiazol-2-yl]acetamide Chemical compound FC=1N=C(SC=1CN1[C@H](C[C@H](CC1)OCC1=NOC(=N1)C)C)NC(C)=O FRVXHWNHGWUTQO-CABZTGNLSA-N 0.000 title claims description 11
- 229940126137 O-GlcNAcase inhibitor Drugs 0.000 title description 2
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- 208000027061 mild cognitive impairment Diseases 0.000 claims description 8
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 2
- 238000001228 spectrum Methods 0.000 claims description 2
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims 1
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- 239000010410 layer Substances 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 24
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 23
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- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 18
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- MDUZWICIRWGKLU-UHFFFAOYSA-N N-(4-fluoro-5-formyl-1,3-thiazol-2-yl)acetamide Chemical compound FC=1N=C(SC=1C=O)NC(C)=O MDUZWICIRWGKLU-UHFFFAOYSA-N 0.000 description 6
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- 239000007983 Tris buffer Substances 0.000 description 6
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 6
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- MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 6
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- VVHYBDXTTJTWRO-JQWIXIFHSA-N tert-butyl (2S,4S)-2-methyl-4-[(5-methyl-1,2,4-oxadiazol-3-yl)methoxy]piperidine-1-carboxylate Chemical compound C[C@@H]1N(CC[C@@H](C1)OCC1=NOC(=N1)C)C(=O)OC(C)(C)C VVHYBDXTTJTWRO-JQWIXIFHSA-N 0.000 description 5
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Classifications
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- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- A—HUMAN NECESSITIES
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- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
-
- 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
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/09—Geometrical isomers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201762451137P | 2017-01-27 | 2017-01-27 | |
| PCT/US2018/014331 WO2018140299A1 (en) | 2017-01-27 | 2018-01-19 | N-[4-fluoro-5-[[(2s,4s)-2-methyl-4-[(5-methyl-1,2,4-oxadiazol-3-yl)methoxy]-1-piperidyl]methyl]thiazol-2-yl]acetamide as oga inhibitor |
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| EA201991515A1 EA201991515A1 (ru) | 2020-01-16 |
| EA038368B1 true EA038368B1 (ru) | 2021-08-17 |
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| EA201991515A EA038368B1 (ru) | 2017-01-27 | 2018-01-19 | N-[4-фтор-5-[[(2s,4s)-2-метил-4-[(5-метил-1,2,4-оксадиазол-3-ил)метокси]-1-пиперидил]метил]тиазол-2-ил]ацетамид в качестве ингибитора oga |
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| JP6563017B2 (ja) | 2014-08-28 | 2019-08-21 | エースニューロン・ソシエテ・アノニム | グリコシダーゼ阻害剤 |
| EP3419976B1 (en) | 2016-02-25 | 2021-04-07 | Asceneuron SA | Acid addition salts of piperazine derivatives |
| CA3012624A1 (en) | 2016-02-25 | 2017-08-31 | Asceneuron S.A. | Glycosidase inhibitors |
| CA3012560A1 (en) | 2016-02-25 | 2017-08-31 | Asceneuron S.A. | Glycosidase inhibitors |
| US11261183B2 (en) | 2016-02-25 | 2022-03-01 | Asceneuron Sa | Sulfoximine glycosidase inhibitors |
| TWI669302B (zh) | 2017-05-25 | 2019-08-21 | 美商美國禮來大藥廠 | 5-甲基-1,3,4-<img align="absmiddle" height="18px" width="27px" file="d10999.TIF" alt="其他非圖式 ed10999.png" img-content="tif" orientation="portrait" inline="yes" giffile="ed10999.png"></img>二唑-2-基化合物 |
| WO2019037860A1 (en) | 2017-08-24 | 2019-02-28 | Asceneuron S.A. | LINEAR INHIBITORS OF GLYCOSIDASE |
| TWI726329B (zh) | 2018-06-22 | 2021-05-01 | 美商美國禮來大藥廠 | 2,3-二氫呋喃并[2,3-b]吡啶化合物 |
| JP2021530552A (ja) * | 2018-07-31 | 2021-11-11 | イーライ リリー アンド カンパニー | 併用療法 |
| CN112469476B (zh) * | 2018-07-31 | 2024-07-16 | 伊莱利利公司 | 5-甲基-4-氟-噻唑-2-基化合物 |
| US12016852B2 (en) | 2018-08-22 | 2024-06-25 | Asceneuron Sa | Pyrrolidine glycosidase inhibitors |
| WO2020039028A1 (en) | 2018-08-22 | 2020-02-27 | Asceneuron S. A. | Tetrahydro-benzoazepine glycosidase inhibitors |
| KR102839500B1 (ko) | 2018-08-22 | 2025-07-28 | 아셰뉴론 에스아 | 글리코시다제 억제제로서 유용한 피페라진 유도체의 숙시네이트 및 푸마레이트 산 부가염 |
| US11731972B2 (en) | 2018-08-22 | 2023-08-22 | Asceneuron Sa | Spiro compounds as glycosidase inhibitors |
| AU2019344922B2 (en) * | 2018-09-19 | 2025-02-06 | Biogen Ma Inc. | O-glycoprotein-2-acetamido-2-deoxy-3-d-glucopyranosidase inhibitors |
| TWI716107B (zh) | 2018-09-26 | 2021-01-11 | 美商美國禮來大藥廠 | 6-氟-2-甲基苯并[d]噻唑-5-基化合物 |
| TW202039482A (zh) | 2018-12-05 | 2020-11-01 | 美商百健Ｍａ公司 | 嗎啉基、哌嗪基、氧氮雜環庚烷基及二氮雜環庚烷基o-醣蛋白-2-乙醯胺基-2-去氧-3-d-葡萄哌喃醣苷酶抑制劑 |
| US20220106305A1 (en) * | 2019-02-04 | 2022-04-07 | Biogen Ma Inc. | Bicyclic ether o-glycoprotein-2-acetamido-2-deoxy-3-d-glucopyranosidase inhibitors |
| WO2021094312A1 (en) | 2019-11-11 | 2021-05-20 | Janssen Pharmaceutica Nv | Pyrrolidine and bicycloheteroaryl containing oga inhibitor compounds |
| WO2021110656A1 (en) | 2019-12-02 | 2021-06-10 | Janssen Pharmaceutica Nv | Oga inhibitor compounds |
| KR20220118483A (ko) | 2019-12-18 | 2022-08-25 | 얀센 파마슈티카 엔.브이. | Oga 억제제 화합물 |
| WO2021123297A1 (en) | 2019-12-18 | 2021-06-24 | Janssen Pharmaceutica Nv | Oga inhibitor compounds |
| WO2021123291A1 (en) | 2019-12-18 | 2021-06-24 | Janssen Pharmaceutica Nv | Oga inhibitor compounds |
| AR123031A1 (es) * | 2020-07-23 | 2022-10-26 | Lilly Co Eli | Régimen de dosis baja y formulación de un compuesto 5-metil-1,2,4-oxadiazol-3-ilo |
| PE20231168A1 (es) * | 2020-08-03 | 2023-07-26 | Biogen Ma Inc | Formas cristalinas de un inhibidor de la o-glucoproteina-2-acetamido-2-desoxi-3-d-glucopiranosidasa |
| MX2024004514A (es) * | 2021-10-22 | 2024-05-07 | Lilly Co Eli | Terapia de combinacion con el inhibidor de o-glcnacasa (oga). |
| WO2023150483A1 (en) | 2022-02-03 | 2023-08-10 | Eli Lilly And Company | Regional tau imaging for diagnosing and treating alzheimer's disease |
| WO2024083820A1 (en) | 2022-10-18 | 2024-04-25 | Institut National de la Santé et de la Recherche Médicale | Method and composition for determining the level of o-glcnacylation in horses |
| WO2025184490A1 (en) * | 2024-03-01 | 2025-09-04 | Biogen Ma Inc. | N-[4-fluor-5-[[(2s, 4 r)-4-[(6-methoxy-4-pyrimidinyl)oxy]- 2-methyl-1-pyrrolidinyl] methyl ]-2-thiazolyl]acetamid for use in the treatment of alzheimer disease |
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| WO2014159234A1 (en) * | 2013-03-14 | 2014-10-02 | Merck Patent Gmbh | Glycosidase inhibitors |
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|---|---|---|---|---|
| GB8726763D0 (en) | 1987-11-16 | 1987-12-23 | Fujisawa Pharmaceutical Co | Thiazole compounds |
| AU2004232799A1 (en) | 2003-04-18 | 2004-11-04 | Eli Lilly And Company | (Piperidinyloxy)phenyl, (piperidinyloxy)pyridinyl, (piperidinylsulfanyl)phenyl and (piperidinylsulfanyl)pyridinyl compounds as 5-HT1F agonists |
| SE0302116D0 (sv) | 2003-07-21 | 2003-07-21 | Astrazeneca Ab | Novel compounds |
| JP2009521448A (ja) * | 2005-12-21 | 2009-06-04 | シェーリング コーポレイション | ヒスタミンｈ３アンタゴニストとして有用なフェノキシピペリジンおよびそのアナログ |
| EP2139332A4 (en) * | 2007-03-28 | 2010-04-21 | Merck Sharp & Dohme | SUBSTITUTED PYRIDO [2,3-D] PYRIMIDIN DERIVATIVES AS CANNABINOID-1 RECEPTOR MODULATORS |
| TWI431004B (zh) * | 2008-05-02 | 2014-03-21 | Lilly Co Eli | Ｂａｃｅ抑制劑 |
| US9120781B2 (en) | 2010-05-11 | 2015-09-01 | Simon Fraser University | Selective glycosidase inhibitors and uses thereof |
| WO2014192868A1 (ja) * | 2013-05-30 | 2014-12-04 | 大日本住友製薬株式会社 | 環状アミノメチルピリミジン誘導体 |
| JP6563017B2 (ja) | 2014-08-28 | 2019-08-21 | エースニューロン・ソシエテ・アノニム | グリコシダーゼ阻害剤 |
| US10913733B2 (en) | 2015-12-18 | 2021-02-09 | Alectos Therapeutics Inc. | Substituted piperidines thiazolyl acetamides as glycosidase inhibitors and uses thereof |
| US20200079766A1 (en) * | 2016-12-16 | 2020-03-12 | Janssen Pharmaceutica Nv | Monocyclic oga inhibitor compounds |
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- 2018-01-19 WO PCT/US2018/014331 patent/WO2018140299A1/en not_active Ceased
- 2018-01-19 HU HUE18703154A patent/HUE054990T2/hu unknown
- 2018-01-19 SI SI201830274T patent/SI3573983T1/sl unknown
- 2018-01-19 PE PE2019001459A patent/PE20191406A1/es unknown
- 2018-01-19 EP EP18703154.7A patent/EP3573983B1/en active Active
- 2018-01-19 HR HRP20211011TT patent/HRP20211011T1/hr unknown
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2019
- 2019-06-26 ZA ZA2019/04171A patent/ZA201904171B/en unknown
- 2019-06-27 IL IL267693A patent/IL267693B/en unknown
- 2019-07-12 CL CL2019001978A patent/CL2019001978A1/es unknown
- 2019-07-18 CO CONC2019/0007711A patent/CO2019007711A2/es unknown
- 2019-07-18 DO DO2019000187A patent/DOP2019000187A/es unknown
- 2019-07-25 PH PH12019501707A patent/PH12019501707A1/en unknown
- 2019-07-26 EC ECSENADI201953616A patent/ECSP19053616A/es unknown
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2021
- 2021-06-10 CY CY20211100516T patent/CY1124257T1/el unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014159234A1 (en) * | 2013-03-14 | 2014-10-02 | Merck Patent Gmbh | Glycosidase inhibitors |
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