TWI716446B - 橋聯哌啶衍生物 - Google Patents
橋聯哌啶衍生物 Download PDFInfo
- Publication number
- TWI716446B TWI716446B TW105129076A TW105129076A TWI716446B TW I716446 B TWI716446 B TW I716446B TW 105129076 A TW105129076 A TW 105129076A TW 105129076 A TW105129076 A TW 105129076A TW I716446 B TWI716446 B TW I716446B
- Authority
- TW
- Taiwan
- Prior art keywords
- triazolo
- amine
- azabicyclo
- tetrahydro
- trifluoromethyl
- Prior art date
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- OVTXWZSJDIFYMP-UHFFFAOYSA-N ethyl 2-[3,5-bis(trifluoromethyl)phenyl]-5-(oxan-2-yloxy)pentanoate Chemical compound FC(C=1C=C(C=C(C=1)C(F)(F)F)C(C(=O)OCC)CCCOC1OCCCC1)(F)F OVTXWZSJDIFYMP-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000005284 excitation Effects 0.000 description 1
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- 239000008187 granular material Substances 0.000 description 1
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- GRRNUXAQVGOGFE-NZSRVPFOSA-N hygromycin B Chemical compound O[C@@H]1[C@@H](NC)C[C@@H](N)[C@H](O)[C@H]1O[C@H]1[C@H]2O[C@@]3([C@@H]([C@@H](O)[C@@H](O)[C@@H](C(N)CO)O3)O)O[C@H]2[C@@H](O)[C@@H](CO)O1 GRRNUXAQVGOGFE-NZSRVPFOSA-N 0.000 description 1
- 229940097277 hygromycin b Drugs 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- GDQYFKGLAUOXST-UHFFFAOYSA-N indolizin-2-amine Chemical compound C1=CC=CN2C=C(N)C=C21 GDQYFKGLAUOXST-UHFFFAOYSA-N 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
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- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002605 large molecules Chemical group 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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- 230000000873 masking effect Effects 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
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- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- DFTYYBRLWCAUHP-UHFFFAOYSA-N methyl 2-(2-chloro-4-fluorophenyl)acetate Chemical compound COC(=O)CC1=CC=C(F)C=C1Cl DFTYYBRLWCAUHP-UHFFFAOYSA-N 0.000 description 1
- BXNYZIJXGIVTJL-UHFFFAOYSA-N methyl 5-chloro-2-(2-chloro-4-fluorophenyl)pentanoate Chemical compound COC(C(CCCCl)C1=C(C=C(C=C1)F)Cl)=O BXNYZIJXGIVTJL-UHFFFAOYSA-N 0.000 description 1
- SDDKIZNHOCEXTF-UHFFFAOYSA-N methyl carbamimidothioate Chemical compound CSC(N)=N SDDKIZNHOCEXTF-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- HNBDRPTVWVGKBR-UHFFFAOYSA-N n-pentanoic acid methyl ester Natural products CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 231100000618 neurotoxin Toxicity 0.000 description 1
- 102000046701 nicastrin Human genes 0.000 description 1
- 108700022821 nicastrin Proteins 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- NOGORYGYLODPPL-UHFFFAOYSA-N o-methyl methanethioate Chemical compound COC=S NOGORYGYLODPPL-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
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- 238000007254 oxidation reaction Methods 0.000 description 1
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- 239000002245 particle Substances 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
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- 235000011056 potassium acetate Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 229940024999 proteolytic enzymes for treatment of wounds and ulcers Drugs 0.000 description 1
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- 238000004007 reversed phase HPLC Methods 0.000 description 1
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- 238000007142 ring opening reaction Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- SYXYWTXQFUUWLP-UHFFFAOYSA-N sodium;butan-1-olate Chemical compound [Na+].CCCC[O-] SYXYWTXQFUUWLP-UHFFFAOYSA-N 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- FQFILJKFZCVHNH-UHFFFAOYSA-N tert-butyl n-[3-[(5-bromo-2-chloropyrimidin-4-yl)amino]propyl]carbamate Chemical compound CC(C)(C)OC(=O)NCCCNC1=NC(Cl)=NC=C1Br FQFILJKFZCVHNH-UHFFFAOYSA-N 0.000 description 1
- DKACXUFSLUYRFU-UHFFFAOYSA-N tert-butyl n-aminocarbamate Chemical compound CC(C)(C)OC(=O)NN DKACXUFSLUYRFU-UHFFFAOYSA-N 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000011277 treatment modality Methods 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical compound C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 0.000 description 1
- 125000004360 trifluorophenyl group Chemical group 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- 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
- 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
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
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)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Psychiatry (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15184480 | 2015-09-09 | ||
| EP15184480.0 | 2015-09-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| TW201718601A TW201718601A (zh) | 2017-06-01 |
| TWI716446B true TWI716446B (zh) | 2021-01-21 |
Family
ID=54072754
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| TW105129076A TWI716446B (zh) | 2015-09-09 | 2016-09-08 | 橋聯哌啶衍生物 |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US10604517B2 (OSRAM) |
| EP (1) | EP3347363B1 (OSRAM) |
| JP (1) | JP6831372B2 (OSRAM) |
| CN (1) | CN107922437B (OSRAM) |
| AR (1) | AR105965A1 (OSRAM) |
| TW (1) | TWI716446B (OSRAM) |
| WO (1) | WO2017042114A1 (OSRAM) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI753009B (zh) * | 2016-09-09 | 2022-01-21 | 瑞士商赫孚孟拉羅股份公司 | 2-(6-硝基吡啶-3-基)-9H-二吡啶并[2,3-b;3',4'-d]吡咯之製備方法 |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3347363B1 (en) | 2015-09-09 | 2020-01-01 | H. Hoffnabb-La Roche Ag | N-(3-azabicyclo[3.2.1]octan-8-yl)-8-(4-phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[l,5-a]pyridin-2-amine derivatives as gamma-secretase modulators for treating alzheimer's disease |
| CN109311878B (zh) * | 2016-06-27 | 2022-05-24 | 豪夫迈·罗氏有限公司 | 作为γ-分泌酶调节剂的三唑并吡啶类化合物 |
| AR109829A1 (es) * | 2016-09-29 | 2019-01-30 | Hoffmann La Roche | Derivados de piperidina puenteados |
| JP6956175B2 (ja) | 2016-10-04 | 2021-11-02 | エフ．ホフマン−ラ ロシュ アーゲーＦ． Ｈｏｆｆｍａｎｎ−Ｌａ Ｒｏｃｈｅ Ａｋｔｉｅｎｇｅｓｅｌｌｓｃｈａｆｔ | 二環式ヘテロアリール誘導体 |
| US10941147B2 (en) * | 2016-11-01 | 2021-03-09 | Hoffmann-La Roche Inc. | Bicyclic heteroaryl derivatives |
| CN111315745B (zh) * | 2017-12-18 | 2023-07-14 | 豪夫迈·罗氏有限公司 | 三唑并-氮杂䓬衍生物 |
| WO2019141832A1 (en) * | 2018-01-22 | 2019-07-25 | F. Hoffmann-La Roche Ag | Triazolo-azepine derivatives |
| KR102829709B1 (ko) | 2018-09-03 | 2025-07-04 | 에프. 호프만-라 로슈 아게 | 바이사이클릭 헤테로아릴 유도체 |
| EP3894411B1 (en) * | 2018-12-13 | 2024-06-19 | F. Hoffmann-La Roche AG | 7-phenoxy-n-(3-azabicyclo[3.2.1]octan-8-yl)-6,7-dihydro-5h-pyrrolo[1,2-b][1,2,4]triazol-2-amine derivatives and related compounds as gamma-secretase modulators for the treatment of alzheimer's disease |
| US12275709B2 (en) | 2018-12-27 | 2025-04-15 | Hoffmann-La Roche Inc. | Process for the preparation of exo-tert-butyl N-(3-azabicyclo[3.2.1]octan-8-yl)carbamate |
| WO2020215094A1 (en) | 2019-04-18 | 2020-10-22 | The Johns Hopkins University | Substituted 2-amino-pyrazolyl-[1,2,4]triazolo[1,5a] pyridine derivatives and use thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011101304A2 (en) * | 2010-02-17 | 2011-08-25 | F. Hoffmann-La Roche Ag | Piperidine derivatives |
| WO2012116965A1 (en) * | 2011-03-02 | 2012-09-07 | F. Hoffmann-La Roche Ag | Bridged piperidine derivatives |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003211993A1 (en) * | 2002-02-15 | 2003-09-04 | Kyowa Hakko Kogyo Co., Ltd. | (1,2,4)TRIAZOLO(1,5-c)PYRIMIDINE DERIVATIVES |
| CN101952275B (zh) * | 2008-02-22 | 2014-06-18 | 弗·哈夫曼-拉罗切有限公司 | β-淀粉样蛋白的调节剂 |
| WO2009128669A2 (ko) * | 2008-04-16 | 2009-10-22 | 엘지이노텍주식회사 | 발광 소자 및 그 제조방법 |
| JP5378532B2 (ja) * | 2008-11-10 | 2013-12-25 | エフ．ホフマン−ラ ロシュ アーゲー | 複素環γ−セクレターゼモジュレーター |
| TWI461425B (zh) * | 2009-02-19 | 2014-11-21 | Janssen Pharmaceuticals Inc | 作為伽瑪分泌酶調節劑之新穎經取代的苯并唑、苯并咪唑、唑并吡啶及咪唑并吡啶衍生物類 |
| MX2011011753A (es) * | 2009-05-07 | 2011-11-29 | Janssen Pharmaceuticals Inc | Nuevos derivados sustitutos de indazol y aza-indazol como moduladores de la gamma secretasa. |
| WO2010138901A1 (en) * | 2009-05-29 | 2010-12-02 | Biogen Idec Ma Inc | Carboxylic acid-containing compounds, derivatives thereof, and related methods of use |
| US20110117966A1 (en) * | 2009-10-23 | 2011-05-19 | Appsware Wireless, Llc | System and Device for Consolidating SIM, Personal Token, and Associated Applications |
| US20110190269A1 (en) * | 2010-02-01 | 2011-08-04 | Karlheinz Baumann | Gamma secretase modulators |
| EP2687528A1 (en) * | 2012-07-17 | 2014-01-22 | Ares Trading S.A. | Fused triazole derivatives as gamma secretase modulators |
| EP3347363B1 (en) | 2015-09-09 | 2020-01-01 | H. Hoffnabb-La Roche Ag | N-(3-azabicyclo[3.2.1]octan-8-yl)-8-(4-phenyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[l,5-a]pyridin-2-amine derivatives as gamma-secretase modulators for treating alzheimer's disease |
-
2016
- 2016-09-05 EP EP16763491.4A patent/EP3347363B1/en active Active
- 2016-09-05 WO PCT/EP2016/070800 patent/WO2017042114A1/en not_active Ceased
- 2016-09-05 CN CN201680051165.9A patent/CN107922437B/zh active Active
- 2016-09-05 JP JP2018512604A patent/JP6831372B2/ja active Active
- 2016-09-08 AR ARP160102743A patent/AR105965A1/es unknown
- 2016-09-08 TW TW105129076A patent/TWI716446B/zh not_active IP Right Cessation
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2018
- 2018-03-06 US US15/913,087 patent/US10604517B2/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011101304A2 (en) * | 2010-02-17 | 2011-08-25 | F. Hoffmann-La Roche Ag | Piperidine derivatives |
| WO2012116965A1 (en) * | 2011-03-02 | 2012-09-07 | F. Hoffmann-La Roche Ag | Bridged piperidine derivatives |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI753009B (zh) * | 2016-09-09 | 2022-01-21 | 瑞士商赫孚孟拉羅股份公司 | 2-(6-硝基吡啶-3-基)-9H-二吡啶并[2,3-b;3',4'-d]吡咯之製備方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| TW201718601A (zh) | 2017-06-01 |
| CN107922437A (zh) | 2018-04-17 |
| US10604517B2 (en) | 2020-03-31 |
| EP3347363B1 (en) | 2020-01-01 |
| EP3347363A1 (en) | 2018-07-18 |
| HK1251902A1 (zh) | 2019-04-26 |
| AR105965A1 (es) | 2017-11-29 |
| US20180237432A1 (en) | 2018-08-23 |
| JP6831372B2 (ja) | 2021-02-17 |
| JP2018526410A (ja) | 2018-09-13 |
| CN107922437B (zh) | 2021-12-10 |
| WO2017042114A1 (en) | 2017-03-16 |
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