KR20190127779A - 약제학적 활성 지환족-치환된 피라졸로[1,5-a]피리미딘 유도체 - Google Patents
약제학적 활성 지환족-치환된 피라졸로[1,5-a]피리미딘 유도체 Download PDFInfo
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- KR20190127779A KR20190127779A KR1020197028833A KR20197028833A KR20190127779A KR 20190127779 A KR20190127779 A KR 20190127779A KR 1020197028833 A KR1020197028833 A KR 1020197028833A KR 20197028833 A KR20197028833 A KR 20197028833A KR 20190127779 A KR20190127779 A KR 20190127779A
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- KR
- South Korea
- Prior art keywords
- methyl
- formula
- carboxylic acid
- pyrazolo
- trans
- 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.)
- Ceased
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- LDIJKUBTLZTFRG-UHFFFAOYSA-N pyrazolo[1,5-a]pyrimidine Chemical class N1=CC=CN2N=CC=C21 LDIJKUBTLZTFRG-UHFFFAOYSA-N 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 130
- 238000000034 method Methods 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 18
- 239000002207 metabolite Substances 0.000 claims abstract description 15
- 239000000651 prodrug Substances 0.000 claims abstract description 15
- 229940002612 prodrug Drugs 0.000 claims abstract description 15
- 239000003814 drug Substances 0.000 claims abstract description 14
- 239000012453 solvate Substances 0.000 claims abstract description 14
- 238000011282 treatment Methods 0.000 claims abstract description 14
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 11
- 230000003281 allosteric effect Effects 0.000 claims abstract description 11
- 150000004677 hydrates Chemical class 0.000 claims abstract description 9
- 229940126027 positive allosteric modulator Drugs 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 3
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 76
- 125000000217 alkyl group Chemical group 0.000 claims description 69
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 40
- 125000005843 halogen group Chemical group 0.000 claims description 29
- -1 4,4-difluorocyclohexyl Chemical group 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- 239000002253 acid Substances 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 19
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 18
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 18
- 239000004480 active ingredient Substances 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 17
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 16
- 230000003287 optical effect Effects 0.000 claims description 16
- 210000001072 colon Anatomy 0.000 claims description 14
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 12
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- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 8
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims description 6
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 6
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 claims description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 5
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- 125000003277 amino group Chemical group 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 claims description 4
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- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
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- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 4
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- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical class N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
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- UZVNCLCLJHPHIF-NOJKMYKQSA-J zinc;(1e)-2-(ethylcarbamoylamino)-n-methoxy-2-oxoethanimidoyl cyanide;manganese(2+);n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[Zn+2].[S-]C(=S)NCCNC([S-])=S.[S-]C(=S)NCCNC([S-])=S.CCNC(=O)NC(=O)C(\C#N)=N\OC UZVNCLCLJHPHIF-NOJKMYKQSA-J 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
- C07D491/147—Ortho-condensed systems the condensed system containing one ring with oxygen as ring hetero atom and two rings with nitrogen as ring hetero atom
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Psychiatry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HUP1700108 | 2017-03-13 | ||
| HU1700108A HU231058B1 (hu) | 2017-03-13 | 2017-03-13 | Gyógyászatilag hatékony aliciklusos-szubsztituált pirazolo[1,5-a]pirimidin származékok |
| PCT/IB2018/051599 WO2018167630A1 (en) | 2017-03-13 | 2018-03-12 | PHARMACOLOGICALLY ACTIVE ALICYCLIC-SUBSTITUTED PYRAZOLO[1,5-a]PYRIMIDINE DERIVATIVES |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20190127779A true KR20190127779A (ko) | 2019-11-13 |
Family
ID=89992389
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020197028833A Ceased KR20190127779A (ko) | 2017-03-13 | 2018-03-12 | 약제학적 활성 지환족-치환된 피라졸로[1,5-a]피리미딘 유도체 |
Country Status (32)
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN117510468A (zh) | 2017-03-13 | 2024-02-06 | 灵北拉荷亚研究中心公司 | 双重magl和faah抑制剂 |
| HU231057B1 (hu) | 2017-03-13 | 2020-04-28 | Richter Gedeon Nyrt | Gyógyászatilag hatékony aril-szubsztituált pirazolo[1,5-a]pirimidin származékok |
| IL296716A (en) | 2020-03-26 | 2022-11-01 | Richter Gedeon Nyrt | History of naphthyridine and pyrido[4,3-c]pyridazine as gabaa alpha 5 receptor modulators |
| CN116075514A (zh) * | 2020-08-05 | 2023-05-05 | 吉瑞工厂 | 药理学活性的杂环取代的吡唑并[1,5-a]嘧啶衍生物 |
| HU231691B1 (hu) | 2021-09-29 | 2025-10-28 | Richter Gedeon Nyrt | GABAA ALFA5 receptor modulátor hatású biciklusos aminszármazékok |
| CN115872095A (zh) * | 2022-11-28 | 2023-03-31 | 南通三鑫车灯配件有限公司 | 一种汽车车灯反光罩的生产线流转装置 |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE367163T1 (de) | 2004-03-02 | 2007-08-15 | Hoffmann La Roche | 4-(sulfanylpyrimidin-4-ylmethyl)morpholin- derivate und verwandte verbindungen als gaba- rezeptorliganden zur behandlung von angst, depression und epilepsie |
| GB0512844D0 (en) | 2005-06-23 | 2005-08-03 | Novartis Ag | Organic compounds |
| KR100753017B1 (ko) | 2006-05-25 | 2007-08-30 | 한국화학연구원 | 7-(3,4-디알콕시페닐)-피라졸로[1,5-ａ]피리미딘 화합물을포함하는 관절염, 아토피 피부염, 백혈병을 포함한 암 및알쯔하이머, 우울증 또는 기억력 감소 등의 뇌질환의 치료및 예방을 위한 약제학적 조성물 |
| WO2009123986A1 (en) * | 2008-03-31 | 2009-10-08 | Takeda Pharmaceutical Company Limited | Apoptosis signal-regulating kinase 1 inhibitors |
| TWI648281B (zh) | 2013-10-17 | 2019-01-21 | 日商安斯泰來製藥股份有限公司 | 含硫二環式化合物 |
| EP3286192A1 (en) | 2015-04-20 | 2018-02-28 | AbbVie Deutschland GmbH & Co KG | Substituted pyrazolopyrimidines and method of use |
| JP2018199623A (ja) | 2015-10-22 | 2018-12-20 | 大正製薬株式会社 | 含窒素縮合複素環化合物 |
| HU231057B1 (hu) | 2017-03-13 | 2020-04-28 | Richter Gedeon Nyrt | Gyógyászatilag hatékony aril-szubsztituált pirazolo[1,5-a]pirimidin származékok |
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2017
- 2017-03-13 HU HU1700108A patent/HU231058B1/hu not_active IP Right Cessation
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2018
- 2018-03-12 MY MYPI2019004947A patent/MY195262A/en unknown
- 2018-03-12 LT LTEPPCT/IB2018/051599T patent/LT3596080T/lt unknown
- 2018-03-12 EP EP18713016.6A patent/EP3596080B1/en active Active
- 2018-03-12 HU HUE18713016A patent/HUE056562T2/hu unknown
- 2018-03-12 PL PL18713016T patent/PL3596080T3/pl unknown
- 2018-03-12 PT PT18713016T patent/PT3596080T/pt unknown
- 2018-03-12 SG SG11201907864YA patent/SG11201907864YA/en unknown
- 2018-03-12 BR BR112019018843A patent/BR112019018843A2/pt not_active Application Discontinuation
- 2018-03-12 AU AU2018235266A patent/AU2018235266B2/en not_active Ceased
- 2018-03-12 PE PE2019001773A patent/PE20191646A1/es unknown
- 2018-03-12 MX MX2019011000A patent/MX2019011000A/es unknown
- 2018-03-12 WO PCT/IB2018/051599 patent/WO2018167630A1/en not_active Ceased
- 2018-03-12 US US16/493,453 patent/US11026946B2/en active Active
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- 2018-03-12 KR KR1020197028833A patent/KR20190127779A/ko not_active Ceased
- 2018-03-12 UA UAA201910328A patent/UA124783C2/uk unknown
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- 2018-03-12 ES ES18713016T patent/ES2893824T3/es active Active
- 2018-03-12 CN CN201880017859.XA patent/CN110431142A/zh active Pending
- 2018-03-12 RS RS20211334A patent/RS62533B1/sr unknown
- 2018-03-12 DK DK18713016.6T patent/DK3596080T3/da active
- 2018-03-12 JP JP2019549366A patent/JP7153662B2/ja active Active
- 2018-03-12 SI SI201830495T patent/SI3596080T1/sl unknown
- 2018-03-12 CA CA3056185A patent/CA3056185A1/en active Pending
- 2018-03-13 AR ARP180100580A patent/AR111176A1/es unknown
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2019
- 2019-08-26 IL IL26892319A patent/IL268923A/en unknown
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