ES2893824T3 - Derivados de pirazolo[1,5-a]pirimidina con sustitución alicíclica farmacológicamente activos - Google Patents
Derivados de pirazolo[1,5-a]pirimidina con sustitución alicíclica farmacológicamente activos Download PDFInfo
- Publication number
- ES2893824T3 ES2893824T3 ES18713016T ES18713016T ES2893824T3 ES 2893824 T3 ES2893824 T3 ES 2893824T3 ES 18713016 T ES18713016 T ES 18713016T ES 18713016 T ES18713016 T ES 18713016T ES 2893824 T3 ES2893824 T3 ES 2893824T3
- Authority
- ES
- Spain
- Prior art keywords
- methyl
- pyrazolo
- formula
- trifluoromethyl
- 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.)
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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 description 7
- 125000002723 alicyclic group Chemical group 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 118
- -1 racemates Chemical class 0.000 claims abstract description 37
- 150000003839 salts Chemical class 0.000 claims abstract description 32
- 125000005843 halogen group Chemical group 0.000 claims abstract description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
- 239000001257 hydrogen Substances 0.000 claims abstract description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 20
- 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 14
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 11
- 150000004677 hydrates Chemical class 0.000 claims abstract description 11
- 239000012453 solvate Substances 0.000 claims abstract description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 9
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 8
- 125000006555 (C3-C5) cycloalkyl group Chemical group 0.000 claims abstract description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000003277 amino group Chemical group 0.000 claims abstract description 6
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 6
- 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 claims abstract description 5
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
- 239000001301 oxygen Substances 0.000 claims abstract description 5
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 5
- 239000011593 sulfur Substances 0.000 claims abstract description 5
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims abstract description 5
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims abstract description 5
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims abstract 2
- 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 35
- 125000000217 alkyl group Chemical group 0.000 claims description 33
- 238000000034 method Methods 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- XJLSEXAGTJCILF-RXMQYKEDSA-N (R)-nipecotic acid zwitterion Chemical compound OC(=O)[C@@H]1CCCNC1 XJLSEXAGTJCILF-RXMQYKEDSA-N 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 230000003287 optical effect Effects 0.000 claims description 18
- 239000004480 active ingredient Substances 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 10
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 8
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- 238000010992 reflux Methods 0.000 claims description 6
- 125000001424 substituent 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
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 4
- 208000035475 disorder Diseases 0.000 claims description 4
- CUONGYYJJVDODC-UHFFFAOYSA-N malononitrile Chemical class N#CCC#N CUONGYYJJVDODC-UHFFFAOYSA-N 0.000 claims description 4
- 208000019901 Anxiety disease Diseases 0.000 claims description 3
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 3
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- DMFLJSHKIOZINU-ULQDDVLXSA-N CC1=NC=2N(C(=C1C(C)C)N1C[C@H](CCC1)C(=O)O)N=C(C=2)[C@@H]1CC[C@H](CC1)C(F)(F)F Chemical compound CC1=NC=2N(C(=C1C(C)C)N1C[C@H](CCC1)C(=O)O)N=C(C=2)[C@@H]1CC[C@H](CC1)C(F)(F)F DMFLJSHKIOZINU-ULQDDVLXSA-N 0.000 claims description 2
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- RZWACFXRVLCYDS-QQMNAOGKSA-N FC[C@@]1(CN(CCC1)C1=C(C(=NC=2N1N=C(C=2)[C@@H]1CC[C@H](CC1)C(F)(F)F)C)C(C)C)C(=O)O Chemical compound FC[C@@]1(CN(CCC1)C1=C(C(=NC=2N1N=C(C=2)[C@@H]1CC[C@H](CC1)C(F)(F)F)C)C(C)C)C(=O)O RZWACFXRVLCYDS-QQMNAOGKSA-N 0.000 claims description 2
- RZWACFXRVLCYDS-SEPYTNNBSA-N FC[C@]1(CN(CCC1)C1=C(C(=NC=2N1N=C(C=2)[C@@H]1CC[C@H](CC1)C(F)(F)F)C)C(C)C)C(=O)O Chemical compound FC[C@]1(CN(CCC1)C1=C(C(=NC=2N1N=C(C=2)[C@@H]1CC[C@H](CC1)C(F)(F)F)C)C(C)C)C(=O)O RZWACFXRVLCYDS-SEPYTNNBSA-N 0.000 claims description 2
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
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- WHSWIVIVQJQEEG-RXSFTSLZSA-N FC=1C(=NN2C=1N=C(C(=C2N1C[C@](CCC1)(C(=O)O)C)OC)C)[C@@H]1CC[C@H](CC1)C(F)(F)F Chemical compound FC=1C(=NN2C=1N=C(C(=C2N1C[C@](CCC1)(C(=O)O)C)OC)C)[C@@H]1CC[C@H](CC1)C(F)(F)F WHSWIVIVQJQEEG-RXSFTSLZSA-N 0.000 claims 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims 2
- 150000002825 nitriles Chemical class 0.000 claims 2
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims 1
- NPSUCBFOGBVWFQ-JOCHJYFZSA-N (3R)-1-[2-(4,4-difluorocyclohexyl)-5-methyl-6-propan-2-ylpyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid Chemical compound FC1(CCC(CC1)C1=NN2C(N=C(C(=C2N2C[C@@](CCC2)(C(=O)O)C)C(C)C)C)=C1)F NPSUCBFOGBVWFQ-JOCHJYFZSA-N 0.000 claims 1
- UTYQOINWQJGILD-QHCPKHFHSA-N (3S)-1-[2-(4,4-difluorocyclohexyl)-5-methyl-6-propan-2-ylpyrazolo[1,5-a]pyrimidin-7-yl]-3-ethylpiperidine-3-carboxylic acid Chemical compound FC1(CCC(CC1)C1=NN2C(N=C(C(=C2N2C[C@](CCC2)(C(=O)O)CC)C(C)C)C)=C1)F UTYQOINWQJGILD-QHCPKHFHSA-N 0.000 claims 1
- NPSUCBFOGBVWFQ-QFIPXVFZSA-N (3S)-1-[2-(4,4-difluorocyclohexyl)-5-methyl-6-propan-2-ylpyrazolo[1,5-a]pyrimidin-7-yl]-3-methylpiperidine-3-carboxylic acid Chemical compound FC1(CCC(CC1)C1=NN2C(N=C(C(=C2N2C[C@](CCC2)(C(=O)O)C)C(C)C)C)=C1)F NPSUCBFOGBVWFQ-QFIPXVFZSA-N 0.000 claims 1
- LYVXPYOVFRWPFH-HOZJOUCCSA-N C(#N)C=1C(=NN2C=1N=C(C(=C2N1C[C@@](CCC1)(C(=O)O)C)C(C)C)C)[C@@H]1CC[C@H](CC1)C(F)(F)F Chemical compound C(#N)C=1C(=NN2C=1N=C(C(=C2N1C[C@@](CCC1)(C(=O)O)C)C(C)C)C)[C@@H]1CC[C@H](CC1)C(F)(F)F LYVXPYOVFRWPFH-HOZJOUCCSA-N 0.000 claims 1
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Classifications
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- 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)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (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 (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| 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 |
|---|---|
| ES2893824T3 true ES2893824T3 (es) | 2022-02-10 |
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| NZ797702A (en) | 2017-03-13 | 2026-03-27 | Lundbeck La Jolla Research Center Inc | Dual magl and faah inhibitors |
| HU231057B1 (hu) | 2017-03-13 | 2020-04-28 | Richter Gedeon Nyrt | Gyógyászatilag hatékony aril-szubsztituált pirazolo[1,5-a]pirimidin származékok |
| 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 |
| TWI907472B (zh) * | 2020-08-05 | 2025-12-11 | 匈牙利商羅特格登公司 | 具藥理活性之經雜環取代的吡唑并〔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 |
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| KR100802863B1 (ko) | 2004-03-02 | 2008-02-12 | 에프. 호프만-라 로슈 아게 | 불안증, 우울증 및 간질의 치료를 위한 ｇａｂａ 수용체리간드로서 4-(설파닐-피리미딘-4-일메틸)-모폴린 유도체및 관련 화합물 |
| 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 |
| EP2271646A1 (en) | 2008-03-31 | 2011-01-12 | 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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2019
- 2019-08-26 IL IL26892319A patent/IL268923A/en unknown
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2021
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