Title:
RETINOIC ACID RECEPTOR AGONIST, PREPARATION METHOD THEREFOR, INTERMEDIATE, PHARMACEUTICAL COMPOSITION AND USE
Document Type and Number:
WIPO Patent Application WO/2022/228409
Kind Code:
A1
Abstract:
Disclosed are a retinoic acid receptor agonist, a preparation method therefor, an intermediate, a pharmaceutical composition and a use. The structure of the compound is as shown in formula (I). The compound has relatively high agonist activity for retinoic acid receptor γ and selectivity to retinoic acid receptor γ, and has relatively low liver cell stability. It is shown that the compound has better activity in local skin, and is metabolized faster in liver cells after entering the systemic circulation. It is indicated that the drug is safer and excellent in druggability, and can potentially be used for treating diseases associated with retinoic acid receptors.
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Inventors:
XU WENFANG (CN)
TAN YUN (CN)
TAN YUN (CN)
Application Number:
PCT/CN2022/089139
Publication Date:
November 03, 2022
Filing Date:
April 26, 2022
Export Citation:
Assignee:
SHANGHAI XUCHENG PHARMATECH CO LTD (CN)
International Classes:
C07F7/08; A61K31/695; A61P17/00; A61P17/06; A61P17/10
Domestic Patent References:
| WO2015149072A1 | 2015-10-01 | |||
| WO2007068580A1 | 2007-06-21 | |||
| WO2005056516A1 | 2005-06-23 |
Foreign References:
| CN1430596A | 2003-07-16 | |||
| CN101087752A | 2007-12-12 |
Other References:
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NGUYEN THANH V. Q., RODRÍGUEZ-SANTAMARÍA JOSÉ A., YOO WOO-JIN, KOBAYASHI SHŪ: "Incorporation of carbon dioxide into phthalides via ligand-free copper-catalyzed direct carboxylation of benzoxasiloles", GREEN CHEMISTRY, ROYAL SOCIETY OF CHEMISTRY, GB, vol. 19, no. 11, 1 January 2017 (2017-01-01), GB , pages 2501 - 2505, XP055980825, ISSN: 1463-9262, DOI: 10.1039/C7GC00917H
ISHIGA WATARU, OHTA MASAYA, KODAMA TAKUYA, TOBISU MAMORU: "Ruthenium-Catalyzed Isomerization of ortho -Silylanilines to Their para Isomers", ORGANIC LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 23, no. 17, 3 September 2021 (2021-09-03), US , pages 6714 - 6718, XP055980822, ISSN: 1523-7060, DOI: 10.1021/acs.orglett.1c02280
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EMILIEN DEMORY; KARTHIK DEVARAJ; ANDREAS ORTHABER; PAUL J. GATES; LUKASZ T. PILARSKI: "Boryl (Hetero)aryne Precursors as Versatile Arylation Reagents: Synthesis through CH Activation and Orthogonal Reactivity", ANGEWANDTE CHEMIE, WILEY - V C H VERLAG GMBH & CO. KGAA, DE, vol. 127, no. 40, 13 August 2015 (2015-08-13), DE , pages 11931 - 11935, XP071365825, ISSN: 0044-8249, DOI: 10.1002/ange.201503152
GLUYAS, J. B. G. ET AL.: "Disila-analogues of the Synthetic Retinoids EC23 and TTNN: Synthesis, Structure and Biological Evaluation", ORGANIC & BIOMOLECULAR CHEMISTRY, vol. 10, no. 34, 20 July 2012 (2012-07-20), XP055394454, ISSN: 1477-0520, DOI: 10.1039/c2ob25989c
SIMMONS, E. M. ET AL.: "Iridium-Catalyzed Arene Ortho-Silylation by Formal Hydroxyl-Directed C-H Activation", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 132, no. 48, 15 November 2010 (2010-11-15), XP055103551, ISSN: 0002-7863, DOI: 10.1021/ja1086547
NGUYEN THANH V. Q., RODRÍGUEZ-SANTAMARÍA JOSÉ A., YOO WOO-JIN, KOBAYASHI SHŪ: "Incorporation of carbon dioxide into phthalides via ligand-free copper-catalyzed direct carboxylation of benzoxasiloles", GREEN CHEMISTRY, ROYAL SOCIETY OF CHEMISTRY, GB, vol. 19, no. 11, 1 January 2017 (2017-01-01), GB , pages 2501 - 2505, XP055980825, ISSN: 1463-9262, DOI: 10.1039/C7GC00917H
ISHIGA WATARU, OHTA MASAYA, KODAMA TAKUYA, TOBISU MAMORU: "Ruthenium-Catalyzed Isomerization of ortho -Silylanilines to Their para Isomers", ORGANIC LETTERS, AMERICAN CHEMICAL SOCIETY, US, vol. 23, no. 17, 3 September 2021 (2021-09-03), US , pages 6714 - 6718, XP055980822, ISSN: 1523-7060, DOI: 10.1021/acs.orglett.1c02280
THOREAU, ETIENNE, JEAN-MARIE ARLABOSSE, CLAIRE BOUIX-PETER, SANDRINE CHAMBON, LAURENT CHANTALAT, SéBASTIEN DAVER, LAURENCE DU: "Structure-based design of Trifarotene ( CD 5789), a potent and selective RARy agonist for the treatment of acne", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 28, 15 April 2018 (2018-04-15), pages 1736 - 1741, XP055831809, DOI: 10.1016/j.bmcl.2018.04.036
LESLEY J, SCOTT, DRUGS, vol. 79, 2019, pages 1905 - 1909
THOREAU ET AL.: "reported in the literature", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 28, 2018, pages 1736 - 1741
Attorney, Agent or Firm:
SHANGHAI BESHINING LAW OFFICE (CN)
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