Title:
PENTACYCLIC TRITERPENE TGR5 RECEPTOR AGONIST AND PREPARATION METHOD THEREFOR AND USES THEREOF
Document Type and Number:
WIPO Patent Application WO/2021/078150
Kind Code:
A1
Abstract:
A pentacyclic triterpene TGR5 receptor agonist and a preparation method therefor and uses thereof. The structure of the pentacyclic triterpene TGR5 receptor agonist is as shown in formula I, and the definition of each substituent group is as described in the description and the claims. The solubility of a pentacyclic triterpene compound is increased, the permeability is improved and the activation activity of the TGR5 receptor is remarkably improved; and Caco-2 monolayer cells can be penetrated, and thus the in-vivo effect after oral administration of the compound can be guaranteed. The TGR5 receptor agonist is expected to be further developed into drugs for treating metabolic diseases represented by diabetes.
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Inventors:
NAN FAJUN (CN)
XIE XIN (CN)
ZHANG CHENLU (CN)
GUO SHIMENG (CN)
ZHUO NING (CN)
LIANG XIAOYING (CN)
ZHANG YANGMING (CN)
YUN YING (CN)
LIU HUANAN (CN)
XIE XIN (CN)
ZHANG CHENLU (CN)
GUO SHIMENG (CN)
ZHUO NING (CN)
LIANG XIAOYING (CN)
ZHANG YANGMING (CN)
YUN YING (CN)
LIU HUANAN (CN)
Application Number:
PCT/CN2020/122472
Publication Date:
April 29, 2021
Filing Date:
October 21, 2020
Export Citation:
Assignee:
SHANGHAI INST MATERIA MEDICA CAS (CN)
International Classes:
C07J63/00; A61K31/56; A61P3/00; A61P3/04; A61P3/06; A61P3/10
Domestic Patent References:
| WO2014071506A1 | 2014-05-15 |
Foreign References:
| CN110680820A | 2020-01-14 | |||
| CN104910239A | 2015-09-16 | |||
| CN109517022A | 2019-03-26 | |||
| CN104910238A | 2015-09-16 |
Other References:
WANG, XIAO-YIN ET AL.: "Highly lipophilic 3-epi-betulinic acid derivatives as potent and selective TGR5 agonists with improved cellular efficacy", ACTA PHARMACOLOGICA SINICA, vol. 35, 6 October 2014 (2014-10-06), pages 1463 - 1472, XP055304558, DOI: 10.1038/aps.2014.97
HELLER, LUCIE ET AL.: "Amino derivatives of platanic acid act as selective and potent inhibitors of butyrylcholinesterase", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 126, 30 November 2016 (2016-11-30), pages 652 - 668, XP029885661, DOI: 10.1016/j.ejmech.2016.11.056
ROLLINGER, JUDITH M. ET AL.: "11β-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 18, 11 January 2010 (2010-01-11), pages 1507 - 1515, XP026894814, DOI: 10.1016/j.bmc.2010.01.010
DATABASE REGISTRY Chemical Abstracts Service, Columbus, US; 20 September 2004 (2004-09-20), XP055805812, retrieved from STN Database accession no. RN 748120-13-0
DATABASE REGISTRY Chemical Abstracts Service, Columbus, US; 16 November 1984 (1984-11-16), XP055805801, retrieved from STN Database accession no. RN 71623-71-7
GENET，CÉDRIC ET AL.: "Structure-Activity Relationship Study of Betulinic Acid, A Novel and Selective TGR5 Agonist, and Its Synthetic Derivatives: Potential Impact in Diabetes", JOURNAL OF MEDICINAL CHEMISTRY, vol. 53, no. 1, 13 November 2009 (2009-11-13), pages 178 - 190, XP055043872, DOI: 10.1021/jm900872z
HELLER, LUCIE ET AL.: "Amino derivatives of platanic acid act as selective and potent inhibitors of butyrylcholinesterase", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 126, 30 November 2016 (2016-11-30), pages 652 - 668, XP029885661, DOI: 10.1016/j.ejmech.2016.11.056
ROLLINGER, JUDITH M. ET AL.: "11β-Hydroxysteroid dehydrogenase 1 inhibiting constituents from Eriobotrya japonica revealed by bioactivity-guided isolation and computational approaches", BIOORGANIC & MEDICINAL CHEMISTRY, vol. 18, 11 January 2010 (2010-01-11), pages 1507 - 1515, XP026894814, DOI: 10.1016/j.bmc.2010.01.010
DATABASE REGISTRY Chemical Abstracts Service, Columbus, US; 20 September 2004 (2004-09-20), XP055805812, retrieved from STN Database accession no. RN 748120-13-0
DATABASE REGISTRY Chemical Abstracts Service, Columbus, US; 16 November 1984 (1984-11-16), XP055805801, retrieved from STN Database accession no. RN 71623-71-7
GENET，CÉDRIC ET AL.: "Structure-Activity Relationship Study of Betulinic Acid, A Novel and Selective TGR5 Agonist, and Its Synthetic Derivatives: Potential Impact in Diabetes", JOURNAL OF MEDICINAL CHEMISTRY, vol. 53, no. 1, 13 November 2009 (2009-11-13), pages 178 - 190, XP055043872, DOI: 10.1021/jm900872z
Attorney, Agent or Firm:
XU & PARTNERS, LLC. (CN)
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