TWI402269B - 噻唑吡唑并嘧啶化合物 - Google Patents
噻唑吡唑并嘧啶化合物 Download PDFInfo
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- TWI402269B TWI402269B TW096135177A TW96135177A TWI402269B TW I402269 B TWI402269 B TW I402269B TW 096135177 A TW096135177 A TW 096135177A TW 96135177 A TW96135177 A TW 96135177A TW I402269 B TWI402269 B TW I402269B
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- pharmaceutically acceptable
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- OADLYIRTEOHBCF-UHFFFAOYSA-N 1h-pyrazolo[4,3-d]pyrimidine;1,3-thiazole Chemical class C1=CSC=N1.N1=CN=C2C=NNC2=C1 OADLYIRTEOHBCF-UHFFFAOYSA-N 0.000 title description 2
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- 238000002360 preparation method Methods 0.000 claims description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
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- CQCVDIVNBYMRNY-UHFFFAOYSA-N 4-bromo-5-(2,5-dimethyl-7-pentan-3-ylpyrazolo[1,5-a]pyrimidin-3-yl)-2-(2-methyl-1,2,4-triazol-3-yl)-1,3-thiazole Chemical compound CC1=NN2C(C(CC)CC)=CC(C)=NC2=C1C(=C(N=1)Br)SC=1C1=NC=NN1C CQCVDIVNBYMRNY-UHFFFAOYSA-N 0.000 claims description 4
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 4
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- RXMJMPNRLIALPQ-UHFFFAOYSA-N 4-bromo-5-(7-heptan-4-yl-2,5-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-2-(2-methyl-1,2,4-triazol-3-yl)-1,3-thiazole Chemical compound CC1=NN2C(C(CCC)CCC)=CC(C)=NC2=C1C(=C(N=1)Br)SC=1C1=NC=NN1C RXMJMPNRLIALPQ-UHFFFAOYSA-N 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
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- 101000878664 Homo sapiens Corticotropin-releasing factor receptor 2 Proteins 0.000 description 18
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- 238000009739 binding Methods 0.000 description 18
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 18
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 16
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Classifications
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- 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
-
- 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
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| EP2025674A1 (de) | 2007-08-15 | 2009-02-18 | sanofi-aventis | Substituierte Tetrahydronaphthaline, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
| CA2739422C (en) * | 2008-10-02 | 2013-03-12 | Eli Lilly And Company | Thiazolyl-pyrazolopyrimidine compounds as synthetic intermediates and related synthetic processes |
| EP2567959B1 (en) | 2011-09-12 | 2014-04-16 | Sanofi | 6-(4-hydroxy-phenyl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylic acid amide derivatives as kinase inhibitors |
| PT3096756T (pt) * | 2014-01-21 | 2024-08-26 | Neurocrine Biosciences Inc | Antagonistas do recetor crf1 para o tratamento da hiperplasia adrenal congénita |
| PL236355B1 (pl) * | 2015-04-02 | 2021-01-11 | Celon Pharma Spolka Akcyjna | Pochodne 7-(morfolin-4-ylo)pirazolo[1,5-α]pirymidyny jako inhibitory kinazy PI3 |
| CA3039026A1 (en) | 2016-09-07 | 2018-03-15 | The Regents Of The University Of California | Allosteric corticotropin-releasing factor receptor 1 (crfr1) antagonists that decrease p-tau and improve cognition |
| AU2018318990B2 (en) * | 2017-08-14 | 2023-01-05 | Spruce Biosciences, Inc. | Corticotropin releasing factor receptor antagonists |
| BR112020002967A2 (pt) * | 2017-08-14 | 2020-08-11 | Spruce Biosciences, Inc. | antagonistas de receptor de fator de liberação de corticotropina |
| WO2019210266A1 (en) * | 2018-04-27 | 2019-10-31 | Spruce Biosciences, Inc. | Methods for treating testicular and ovarian adrenal rest tumors |
| CN109134481B (zh) * | 2018-08-07 | 2021-05-14 | 中山大学 | 一种取代吡咯色原酮类化合物或其药学上可接受的盐及其制备方法和应用 |
| TWI714231B (zh) * | 2018-09-04 | 2020-12-21 | 美商美國禮來大藥廠 | 2,6-二胺基吡啶化合物 |
| MA54395A (fr) | 2018-12-07 | 2022-03-16 | Neurocrine Biosciences Inc | Antagoniste du récepteur crf1, formulations pharmaceutiques et formes solides correspondantes pour le traitement de l'hyperplasie surrénalienne congénitale |
| EP3986416A4 (en) * | 2019-07-19 | 2023-06-28 | Spruce Biosciences, Inc. | Methods of treating congenital adrenal hyperplasia |
| US12383536B2 (en) | 2019-09-27 | 2025-08-12 | Neurocrine Biosciences, Inc. | CRF receptor antagonists and methods of use |
| EP4069697B1 (en) * | 2019-12-04 | 2025-07-16 | Neurocrine Biosciences, Inc. | Crf receptor antagonists and methods of use |
| GR1010096B (el) * | 2020-07-02 | 2021-10-08 | Uni-Pharma Κλεων Τσετης Φαρμακευτικα Εργαστηρια Αβεε, | Πυραζολο[1,5-a]πυριμιδινες με δραση αναστολης της αυτοταξινης |
| WO2022036123A1 (en) | 2020-08-12 | 2022-02-17 | Spruce Biosciences, Inc. | Methods and compositions for treating polycystic ovary syndrome |
| US20240024330A1 (en) | 2020-08-26 | 2024-01-25 | Neurocrine Biosciences, Inc. | Crf receptor antagonists and methods of use |
| EP4308553A4 (en) | 2021-03-19 | 2025-01-22 | Crinetics Pharmaceuticals, Inc. | Melanocortin subtype-2 receptor (mc2r) antagonist for the treatment of disease |
| KR20240109274A (ko) * | 2021-11-19 | 2024-07-10 | 스프루스 바이오사이언시스 인코포레이티드 | 틸다서폰트의 결정질 조성물 및 이의 사용 및 제조 방법 |
| US11708372B2 (en) | 2021-11-19 | 2023-07-25 | Spruce Biosciences, Inc. | Crystalline composition of tildacerfont and methods of use and preparation thereof |
| WO2023163945A1 (en) * | 2022-02-23 | 2023-08-31 | Crinetics Pharmaceuticals, Inc. | Treatment of congenital adrenal hyperplasia and polycystic ovary syndrome |
| WO2025188842A1 (en) * | 2024-03-08 | 2025-09-12 | Spruce Biosciences, Inc. | Amorphous solid dispersion of tildacerfont formulations |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994013676A1 (en) * | 1992-12-17 | 1994-06-23 | Pfizer Inc. | Pyrrolopyrimidines as crf antagonists |
| WO1997029109A1 (en) * | 1996-02-07 | 1997-08-14 | Janssen Pharmaceutica N.V. | Pyrazolopyrimidines as crf receptor antagonists |
| WO1998003510A1 (en) * | 1996-07-24 | 1998-01-29 | Du Pont Pharmaceuticals Company | Azolo triazines and pyrimidines |
| WO1998008847A1 (en) * | 1996-08-28 | 1998-03-05 | Pfizer Inc. | Substituted 6,5-hetero-bicyclic derivatives |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ299451B6 (cs) * | 1996-07-24 | 2008-07-30 | Bristol-Myers Squibb Pharma Company | [1,5-a]-Pyrazolo-1,3,5- triaziny jejich použití afarmaceutické kompozice na jejich bázi |
| EP1040831A3 (en) * | 1999-04-02 | 2003-05-02 | Pfizer Products Inc. | Use of corticotropin releasing factor (CRF) antagonists to prevent sudden death |
| WO2000059908A2 (en) | 1999-04-06 | 2000-10-12 | Du Pont Pharmaceuticals Company | Pyrazolopyrimidines as crf antagonists |
| CZ20021089A3 (cs) | 1999-09-30 | 2002-11-13 | Neurogen Corporation | Aminosustituované pyrazolo[1,5-a]-1,5-pyrimidiny a pyrazolo[1,5-a]-1,3,5-triaziny |
| RS50863B (sr) | 2001-03-13 | 2010-08-31 | Bristol-Myers Squibb Pharma Company | 4-(2-butilamino)-2,7-dimetil-8-(2-metil-6-metoksipirid-3-il) pirazolo/1,5a/-1,3,5-triazin,njegovi enantiomeri i farmaceutski prihvatljive soli kao ligandi receptora za faktor koji oslobađa kortikotropin |
| RU2394035C2 (ru) * | 2003-12-22 | 2010-07-10 | Эс Би ФАРМКО ПУЭРТО РИКО ИНК. | Антагонисты crf-рецепторов и способы, относящиеся к ним |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1994013676A1 (en) * | 1992-12-17 | 1994-06-23 | Pfizer Inc. | Pyrrolopyrimidines as crf antagonists |
| WO1997029109A1 (en) * | 1996-02-07 | 1997-08-14 | Janssen Pharmaceutica N.V. | Pyrazolopyrimidines as crf receptor antagonists |
| WO1998003510A1 (en) * | 1996-07-24 | 1998-01-29 | Du Pont Pharmaceuticals Company | Azolo triazines and pyrimidines |
| WO1998008847A1 (en) * | 1996-08-28 | 1998-03-05 | Pfizer Inc. | Substituted 6,5-hetero-bicyclic derivatives |
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