JP7311583B2 - Ｇａｂａ受容体モジュレーターとしてのジフルオロメチル－フェニルトリアゾール - Google Patents
Ｇａｂａ受容体モジュレーターとしてのジフルオロメチル－フェニルトリアゾール Download PDFInfo
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- JP7311583B2 JP7311583B2 JP2021503007A JP2021503007A JP7311583B2 JP 7311583 B2 JP7311583 B2 JP 7311583B2 JP 2021503007 A JP2021503007 A JP 2021503007A JP 2021503007 A JP2021503007 A JP 2021503007A JP 7311583 B2 JP7311583 B2 JP 7311583B2
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- DQMZLTXERSFNPB-UHFFFAOYSA-N primidone Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NCNC1=O DQMZLTXERSFNPB-UHFFFAOYSA-N 0.000 description 1
- 229960002393 primidone Drugs 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 229960004431 quetiapine Drugs 0.000 description 1
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960001534 risperidone Drugs 0.000 description 1
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 description 1
- 238000010079 rubber tapping Methods 0.000 description 1
- POGQSBRIGCQNEG-UHFFFAOYSA-N rufinamide Chemical compound N1=NC(C(=O)N)=CN1CC1=C(F)C=CC=C1F POGQSBRIGCQNEG-UHFFFAOYSA-N 0.000 description 1
- 229960003014 rufinamide Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- MFBOGIVSZKQAPD-UHFFFAOYSA-M sodium butyrate Chemical compound [Na+].CCCC([O-])=O MFBOGIVSZKQAPD-UHFFFAOYSA-M 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- CGRKYEALWSRNJS-UHFFFAOYSA-N sodium;2-methylbutan-2-olate Chemical compound [Na+].CCC(C)(C)[O-] CGRKYEALWSRNJS-UHFFFAOYSA-N 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229960001897 stiripentol Drugs 0.000 description 1
- IBLNKMRFIPWSOY-FNORWQNLSA-N stiripentol Chemical compound CC(C)(C)C(O)\C=C\C1=CC=C2OCOC2=C1 IBLNKMRFIPWSOY-FNORWQNLSA-N 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- GNLNGVZPEKSDAR-UHFFFAOYSA-N tert-butyl 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazole-1-carboxylate Chemical compound CC1=NN(C(=O)OC(C)(C)C)C(C)=C1B1OC(C)(C)C(C)(C)O1 GNLNGVZPEKSDAR-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 229960002784 thioridazine Drugs 0.000 description 1
- 229960001918 tiagabine Drugs 0.000 description 1
- PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 description 1
- 229960005013 tiotixene Drugs 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 229960004394 topiramate Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229960002324 trifluoperazine Drugs 0.000 description 1
- ZEWQUBUPAILYHI-UHFFFAOYSA-N trifluoperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 ZEWQUBUPAILYHI-UHFFFAOYSA-N 0.000 description 1
- GETQZCLCWQTVFV-UHFFFAOYSA-O trimethylammonium Chemical compound C[NH+](C)C GETQZCLCWQTVFV-UHFFFAOYSA-O 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 229960005318 vigabatrin Drugs 0.000 description 1
- PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 description 1
- 229960000607 ziprasidone Drugs 0.000 description 1
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 description 1
- 229960001475 zolpidem Drugs 0.000 description 1
- ZAFYATHCZYHLPB-UHFFFAOYSA-N zolpidem Chemical compound N1=C2C=CC(C)=CN2C(CC(=O)N(C)C)=C1C1=CC=C(C)C=C1 ZAFYATHCZYHLPB-UHFFFAOYSA-N 0.000 description 1
- 229960002911 zonisamide Drugs 0.000 description 1
- UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP18184716.1 | 2018-07-20 | ||
| EP18184716 | 2018-07-20 | ||
| PCT/EP2019/069593 WO2020016443A1 (en) | 2018-07-20 | 2019-07-19 | Difluoromethyl-phenyl triazoles as gaba receptor modulators |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| JP2021531291A JP2021531291A (ja) | 2021-11-18 |
| JP2021531291A5 JP2021531291A5 (https=) | 2022-07-27 |
| JPWO2020016443A5 JPWO2020016443A5 (https=) | 2022-07-27 |
| JP7311583B2 true JP7311583B2 (ja) | 2023-07-19 |
Family
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| Application Number | Title | Priority Date | Filing Date |
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| JP2021503007A Active JP7311583B2 (ja) | 2018-07-20 | 2019-07-19 | Ｇａｂａ受容体モジュレーターとしてのジフルオロメチル－フェニルトリアゾール |
Country Status (8)
| Country | Link |
|---|---|
| US (2) | US10941137B2 (https=) |
| EP (1) | EP3823967B1 (https=) |
| JP (1) | JP7311583B2 (https=) |
| CN (1) | CN112424197B (https=) |
| AR (1) | AR117615A1 (https=) |
| BR (1) | BR102019014802A2 (https=) |
| TW (1) | TW202019915A (https=) |
| WO (1) | WO2020016443A1 (https=) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI901650B (zh) * | 2020-03-26 | 2025-10-21 | 匈牙利商羅特格登公司 | 啶及吡啶并〔３，４－ｃ〕嗒衍生物 |
| EP4149933B1 (en) * | 2020-05-13 | 2024-06-12 | F. Hoffmann-La Roche AG | New triazolyl derivatives as gaba a alpha5 pam |
| EP3950683A1 (en) * | 2020-08-05 | 2022-02-09 | Boehringer Ingelheim International GmbH | Difluoromethyl-pyridin-2-yl triazoles |
| ES3061465T3 (en) * | 2020-08-05 | 2026-04-06 | Saniona As | Difluoromethyl-pyridin-2-yl triazoles |
| EP3971179A1 (en) * | 2020-09-22 | 2022-03-23 | Boehringer Ingelheim International GmbH | Difluoromethyl-pyridin-2-yl triazoles |
| EP3992188A1 (en) * | 2020-10-29 | 2022-05-04 | Boehringer Ingelheim International GmbH | Difluoromethyl-pyridin-2-yl triazoles |
| AU2022327398A1 (en) * | 2021-08-12 | 2024-03-21 | Shanghai SIMR Biotechnology Co., Ltd | Substituted triazole derivative, preparation method therefor, pharmaceutical composition thereof, and use thereof |
| HU231691B1 (hu) | 2021-09-29 | 2025-10-28 | Richter Gedeon Nyrt | GABAA ALFA5 receptor modulátor hatású biciklusos aminszármazékok |
| CN116462664B (zh) * | 2022-03-08 | 2025-07-01 | 上海赛默罗生物科技有限公司 | 吡唑环类化合物、其制备方法、组合物及应用 |
| CN116854680A (zh) * | 2022-03-28 | 2023-10-10 | 上海赛默罗生物科技有限公司 | 异噁唑-杂环类衍生物、药物组合物和用途 |
| CN119080754A (zh) * | 2023-06-05 | 2024-12-06 | 武汉人福创新药物研发中心有限公司 | 作为α5-GABAA受体调节剂的杂环化合物及其用途 |
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| JP2013543852A (ja) | 2010-11-09 | 2013-12-09 | エフ．ホフマン−ラ ロシュ アーゲー | トリアゾール誘導体及びその神経障害に対する使用 |
| WO2014001280A1 (en) | 2012-06-26 | 2014-01-03 | Aniona Aps | A phenyl triazole derivative and its use for modulating the gabaa receptor complex |
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| JP2015521643A (ja) | 2012-06-26 | 2015-07-30 | サニオナ・エイピイエス | フェニルトリアゾール誘導体及びｇａｂａａ受容体複合体を調節するための該フェニルトリアゾール誘導体の使用 |
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| CN101263139A (zh) | 2005-09-19 | 2008-09-10 | 弗·哈夫曼-拉罗切有限公司 | 作为GABA Aα5逆激动剂的异唑衍生物 |
| AU2006301376A1 (en) | 2005-10-11 | 2007-04-19 | F. Hoffmann-La Roche Ag | Isoxazole derivatives |
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| JP5015172B2 (ja) | 2005-12-23 | 2012-08-29 | エフ．ホフマン−ラ ロシュ アーゲー | アリール−イソオキサゾロ−４−イル−オキサジアゾール誘導体 |
| WO2007074089A1 (en) | 2005-12-27 | 2007-07-05 | F. Hoffmann-La Roche Ag | Aryl-isoxazol-4-yl-imidazo[1, 5-a]pyridine derivatives |
| ATE527255T1 (de) | 2005-12-27 | 2011-10-15 | Hoffmann La Roche | Aryl-isoxazol-4-yl-imidazol-derivate |
| TW200812982A (en) | 2006-05-24 | 2008-03-16 | Lilly Co Eli | Compounds and methods for modulating FXR |
| AU2007267183B2 (en) | 2006-05-31 | 2011-10-20 | F. Hoffmann-La Roche Ag | Aryl-4-ethynyl-isoxazole derivatives |
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| KR101237576B1 (ko) | 2007-12-04 | 2013-03-04 | 에프. 호프만-라 로슈 아게 | 아이속사졸로-피리딘 유도체 |
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-
2019
- 2019-07-18 BR BR102019014802A patent/BR102019014802A2/pt not_active Application Discontinuation
- 2019-07-19 EP EP19742592.9A patent/EP3823967B1/en active Active
- 2019-07-19 CN CN201980047952.XA patent/CN112424197B/zh active Active
- 2019-07-19 US US16/516,398 patent/US10941137B2/en active Active
- 2019-07-19 JP JP2021503007A patent/JP7311583B2/ja active Active
- 2019-07-19 WO PCT/EP2019/069593 patent/WO2020016443A1/en not_active Ceased
- 2019-07-19 AR ARP190102039A patent/AR117615A1/es not_active Application Discontinuation
- 2019-07-19 TW TW108125527A patent/TW202019915A/zh unknown
-
2021
- 2021-01-27 US US17/160,285 patent/US20210147393A1/en not_active Abandoned
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|---|---|---|---|---|
| JP2011505402A (ja) | 2007-12-04 | 2011-02-24 | エフ．ホフマン−ラ ロシュ アーゲー | イソオキサゾロ−ピリダジン誘導体 |
| JP2013543852A (ja) | 2010-11-09 | 2013-12-09 | エフ．ホフマン−ラ ロシュ アーゲー | トリアゾール誘導体及びその神経障害に対する使用 |
| WO2014001280A1 (en) | 2012-06-26 | 2014-01-03 | Aniona Aps | A phenyl triazole derivative and its use for modulating the gabaa receptor complex |
| WO2014001278A1 (en) | 2012-06-26 | 2014-01-03 | Aniona Aps | A phenyl triazole derivative and its use for modulating the gabaa receptor complex |
| JP2015521643A (ja) | 2012-06-26 | 2015-07-30 | サニオナ・エイピイエス | フェニルトリアゾール誘導体及びｇａｂａａ受容体複合体を調節するための該フェニルトリアゾール誘導体の使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| US10941137B2 (en) | 2021-03-09 |
| US20200024261A1 (en) | 2020-01-23 |
| EP3823967B1 (en) | 2022-08-31 |
| WO2020016443A1 (en) | 2020-01-23 |
| AR117615A1 (es) | 2021-08-18 |
| TW202019915A (zh) | 2020-06-01 |
| EP3823967A1 (en) | 2021-05-26 |
| CN112424197A (zh) | 2021-02-26 |
| US20210147393A1 (en) | 2021-05-20 |
| CN112424197B (zh) | 2025-04-22 |
| JP2021531291A (ja) | 2021-11-18 |
| BR102019014802A2 (pt) | 2020-02-04 |
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