Title:
CHOLIC ACID DERIVATIVE, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF AS TGR5 ALLOSTERIC AGONIST
Document Type and Number:
WIPO Patent Application WO/2023/168974
Kind Code:
A1
Abstract:
A cholic acid derivative, a preparation method therefor, and an application thereof as a TGR5 allosteric agonist. using CA as a lead compound, modification is performed at positions 7, 12, and 24 thereof by means of a series of reactions, and a new cholic acid derivative is obtained. Pharmacological results show that most synthesized cholic acid derivatives have good agonistic activity on TGR5 and functional activity of positive allosteric modulation of CDCA.
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Inventors:
CHEN XIN (CN)
SUN JINGJING (CN)
QIAN MINGCHENG (CN)
ZHAO SHUAI (CN)
SUN JINGJING (CN)
QIAN MINGCHENG (CN)
ZHAO SHUAI (CN)
Application Number:
PCT/CN2022/131241
Publication Date:
September 14, 2023
Filing Date:
November 11, 2022
Export Citation:
Assignee:
UNIV CHANGZHOU (CN)
International Classes:
C07J41/00; A61P1/16; A61P3/06; A61P3/10; C07J9/00; C07J43/00
Foreign References:
| CN112851740A | 2021-05-28 | |||
| CN110845567A | 2020-02-28 |
Other References:
QIAN, MINGCHENG ET AL.: "Discovery of novel cholic acid derivatives as highly potent agonists for G protein-coupled bile acid receptor", BIOORGANIC CHEMISTRY, vol. 120, 30 December 2021 (2021-12-30), XP087090332, DOI: 10.1016/j.bioorg.2021.105588
SATO HIROYUKI, ET AL: "Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies.", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 51, no. 6, 27 March 2008 (2008-03-27), US , pages 1831 - 1841, XP002520339, ISSN: 0022-2623, DOI: 10.1021/jm7015864
NAKHI ALI ET AL.: "7‑Methylation of Chenodeoxycholic Acid Derivatives Yields a Substantial Increase in TGR5 Receptor Potency", JOURNAL OF MEDICINAL CHEMISTRY, vol. 62, 3 July 2019 (2019-07-03), XP055947715, DOI: 10.1021/acs.jmedchem.9b00770
DATABASE REGISTRY 16 November 1984 (1984-11-16), ANONYMOUS: "Ethanesulfonic acid, 2-[[(3α,5β,7α,12α)-3,7,12- trihydroxy-24-oxocholan-24-yl]amino]- (CA INDEX NAME)", XP093091310, retrieved from STNext Database accession no. 81-24-3
LIDA TAKASHI, SHINOHARA, TOSHIYUKI; MOMOSE, TOSHIAKI; TAMURA, TOSHITAKE; MATSUMOTO, TARO; NAMBARA, TOSHIO; CHANG, FREDERIC C.: "Potential bile acid metabolites; 12. Synthesis of stereoisomeric 3,7,12-trihydroxy-5α-cholanic acids and related compounds", SYNTHESIS, vol. 1986, no. 12, 31 December 1986 (1986-12-31), pages 998 - 1004, XP093091009
SATO HIROYUKI, ET AL: "Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies.", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 51, no. 6, 27 March 2008 (2008-03-27), US , pages 1831 - 1841, XP002520339, ISSN: 0022-2623, DOI: 10.1021/jm7015864
NAKHI ALI ET AL.: "7‑Methylation of Chenodeoxycholic Acid Derivatives Yields a Substantial Increase in TGR5 Receptor Potency", JOURNAL OF MEDICINAL CHEMISTRY, vol. 62, 3 July 2019 (2019-07-03), XP055947715, DOI: 10.1021/acs.jmedchem.9b00770
DATABASE REGISTRY 16 November 1984 (1984-11-16), ANONYMOUS: "Ethanesulfonic acid, 2-[[(3α,5β,7α,12α)-3,7,12- trihydroxy-24-oxocholan-24-yl]amino]- (CA INDEX NAME)", XP093091310, retrieved from STNext Database accession no. 81-24-3
LIDA TAKASHI, SHINOHARA, TOSHIYUKI; MOMOSE, TOSHIAKI; TAMURA, TOSHITAKE; MATSUMOTO, TARO; NAMBARA, TOSHIO; CHANG, FREDERIC C.: "Potential bile acid metabolites; 12. Synthesis of stereoisomeric 3,7,12-trihydroxy-5α-cholanic acids and related compounds", SYNTHESIS, vol. 1986, no. 12, 31 December 1986 (1986-12-31), pages 998 - 1004, XP093091009
Attorney, Agent or Firm:
CHANGZHOU INNOVATION PATENT AGENCY (CN)
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