KR20180053357A - 2,3,4,5-테트라히드로피리딘-6-아민 유도체 - Google Patents
2,3,4,5-테트라히드로피리딘-6-아민 유도체 Download PDFInfo
- Publication number
- KR20180053357A KR20180053357A KR1020187010344A KR20187010344A KR20180053357A KR 20180053357 A KR20180053357 A KR 20180053357A KR 1020187010344 A KR1020187010344 A KR 1020187010344A KR 20187010344 A KR20187010344 A KR 20187010344A KR 20180053357 A KR20180053357 A KR 20180053357A
- Authority
- KR
- South Korea
- Prior art keywords
- cyclopropyl
- alkyl
- alkyloxy
- mmol
- oxy
- 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.)
- Withdrawn
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- DHGUMNJVFYRSIG-UHFFFAOYSA-N 2,3,4,5-tetrahydropyridin-6-amine Chemical class NC1=NCCCC1 DHGUMNJVFYRSIG-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 164
- 238000000034 method Methods 0.000 claims abstract description 84
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 53
- 206010012289 Dementia Diseases 0.000 claims abstract description 50
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 25
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
- 208000010877 cognitive disease Diseases 0.000 claims abstract description 13
- 208000027061 mild cognitive impairment Diseases 0.000 claims abstract description 13
- 206010039966 Senile dementia Diseases 0.000 claims abstract description 12
- 108010090849 Amyloid beta-Peptides Proteins 0.000 claims abstract description 11
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- 206010044688 Trisomy 21 Diseases 0.000 claims abstract description 8
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- 230000002265 prevention Effects 0.000 claims abstract description 7
- 206010067889 Dementia with Lewy bodies Diseases 0.000 claims abstract description 3
- 201000002832 Lewy body dementia Diseases 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 100
- 125000003545 alkoxy group Chemical group 0.000 claims description 77
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 51
- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 claims description 36
- 125000005843 halogen group Chemical group 0.000 claims description 36
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 32
- 125000001424 substituent group Chemical group 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 125000001153 fluoro group Chemical group F* 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 125000004104 aryloxy group Chemical group 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000002883 imidazolyl group Chemical group 0.000 claims description 6
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 5
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 claims description 3
- 208000027089 Parkinsonian disease Diseases 0.000 claims description 2
- 206010034010 Parkinsonism Diseases 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
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- -1 Tetrahydropyridine-6-amine compound Chemical class 0.000 abstract description 31
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- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 78
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- 229910052757 nitrogen Inorganic materials 0.000 description 21
- 229920006395 saturated elastomer Polymers 0.000 description 21
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- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 13
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 13
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Classifications
-
- 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
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/81—Amides; Imides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/84—Nitriles
- C07D213/85—Nitriles in position 3
-
- 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
- C07D401/02—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 two hetero rings
- C07D401/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP15186394 | 2015-09-23 | ||
| EP15186394.1 | 2015-09-23 | ||
| EP16172005 | 2016-05-30 | ||
| EP16172005.7 | 2016-05-30 | ||
| PCT/EP2016/072710 WO2017050978A1 (en) | 2015-09-23 | 2016-09-23 | 2,3,4,5-tetrahydropyridin-6-amine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20180053357A true KR20180053357A (ko) | 2018-05-21 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| KR1020187010344A Withdrawn KR20180053357A (ko) | 2015-09-23 | 2016-09-23 | 2,3,4,5-테트라히드로피리딘-6-아민 유도체 |
Country Status (14)
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| US (1) | US20180334447A1 (https=) |
| EP (1) | EP3353163B1 (https=) |
| JP (1) | JP2018527387A (https=) |
| KR (1) | KR20180053357A (https=) |
| CN (1) | CN108026069A (https=) |
| AU (1) | AU2016328589A1 (https=) |
| BR (1) | BR112018005591A2 (https=) |
| CA (1) | CA2995161A1 (https=) |
| EA (1) | EA035026B1 (https=) |
| HK (1) | HK1254800A1 (https=) |
| IL (1) | IL258217A (https=) |
| MX (1) | MX2018003565A (https=) |
| TW (1) | TW201726651A (https=) |
| WO (1) | WO2017050978A1 (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2019208509A1 (en) * | 2018-04-23 | 2019-10-31 | Shionogi & Co., Ltd. | Bicyclic heterocycle derivatives having selective bace1 inhibitory activity |
| TW202014191A (zh) | 2018-04-27 | 2020-04-16 | 日商鹽野義製藥股份有限公司 | 具有選擇性ｂａｃｅ１抑制活性的四氫哌喃并衍生物 |
| CN114380736B (zh) * | 2020-10-21 | 2023-10-03 | 复旦大学 | 一种2,3,4,5-四氢吡啶类化合物的合成方法 |
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| UY32799A (es) * | 2009-07-24 | 2011-02-28 | Novartis Ag | Derivados de oxazina y su uso en el tratamiento de trastornos neurológicos |
| US20120258961A1 (en) * | 2009-12-24 | 2012-10-11 | Shionogi & Co., Ltd. | 4-amino-1,3-thiazine or oxazine derivative |
| US8673894B2 (en) | 2010-05-07 | 2014-03-18 | Hoffmann-La Roche Inc. | 2,5,6,7-tetrahydro-[1,4]oxazepin-3-ylamine or 2,3,6,7-tetrahydro-[1,4]oxazepin-5-ylamine compounds |
| KR101730937B1 (ko) * | 2010-06-09 | 2017-04-27 | 얀센 파마슈티카 엔.브이. | 베타-세크레타아제(ｂａｃｅ) 저해제로 유용한 5,6-디하이드로-2ｈ-[1,4]옥사진-3-일-아민 유도체 |
| JP5766198B2 (ja) | 2010-10-29 | 2015-08-19 | 塩野義製薬株式会社 | 縮合アミノジヒドロピリミジン誘導体 |
| US8815841B2 (en) | 2011-02-18 | 2014-08-26 | Hoffmann-La Roche Inc. | 1,4-Oxazepines as BACE1 and/or BACE2 inhibitors |
| US8785436B2 (en) | 2011-05-16 | 2014-07-22 | Hoffmann-La Roche Inc. | 1,3-oxazines as BACE 1 and/or BACE2 inhibitors |
| WO2014059185A1 (en) * | 2012-10-12 | 2014-04-17 | Amgen Inc. | Amino - dihydrothiazine and amino - dioxido dihydrothiazine compounds as beta-secretase antagonists and methods of use |
| CA2902212C (en) | 2013-03-01 | 2020-10-13 | Amgen Inc. | Perfluorinated 5,6-dihydro-4h-1,3-oxazin-2-amine compounds as beta-secretase inhibitors and methods of use |
| CN106029639B (zh) * | 2014-02-19 | 2019-01-08 | H.隆德贝克有限公司 | 治疗阿尔茨海默病的bace1抑制剂的2-氨基-3，5，5-三氟-3，4，5，6-四氢吡啶 |
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2016
- 2016-09-21 TW TW105130403A patent/TW201726651A/zh unknown
- 2016-09-23 KR KR1020187010344A patent/KR20180053357A/ko not_active Withdrawn
- 2016-09-23 CN CN201680055231.XA patent/CN108026069A/zh active Pending
- 2016-09-23 AU AU2016328589A patent/AU2016328589A1/en not_active Abandoned
- 2016-09-23 WO PCT/EP2016/072710 patent/WO2017050978A1/en not_active Ceased
- 2016-09-23 HK HK18113885.1A patent/HK1254800A1/zh unknown
- 2016-09-23 JP JP2018514794A patent/JP2018527387A/ja active Pending
- 2016-09-23 BR BR112018005591A patent/BR112018005591A2/pt not_active Application Discontinuation
- 2016-09-23 EP EP16770283.6A patent/EP3353163B1/en active Active
- 2016-09-23 EA EA201890769A patent/EA035026B1/ru not_active IP Right Cessation
- 2016-09-23 MX MX2018003565A patent/MX2018003565A/es unknown
- 2016-09-23 US US15/761,304 patent/US20180334447A1/en not_active Abandoned
- 2016-09-23 CA CA2995161A patent/CA2995161A1/en not_active Abandoned
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2018
- 2018-03-19 IL IL258217A patent/IL258217A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| EP3353163A1 (en) | 2018-08-01 |
| TW201726651A (zh) | 2017-08-01 |
| WO2017050978A1 (en) | 2017-03-30 |
| EP3353163B1 (en) | 2020-02-05 |
| BR112018005591A2 (pt) | 2018-10-09 |
| HK1254800A1 (zh) | 2019-07-26 |
| CA2995161A1 (en) | 2017-03-30 |
| AU2016328589A1 (en) | 2018-03-01 |
| US20180334447A1 (en) | 2018-11-22 |
| JP2018527387A (ja) | 2018-09-20 |
| EA035026B1 (ru) | 2020-04-20 |
| EA201890769A1 (ru) | 2018-09-28 |
| MX2018003565A (es) | 2018-06-18 |
| CN108026069A (zh) | 2018-05-11 |
| IL258217A (en) | 2018-05-31 |
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| PA0105 | International application |
Patent event date: 20180412 Patent event code: PA01051R01D Comment text: International Patent Application |
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| PC1203 | Withdrawal of no request for examination |