Title:
BILE ACID DERIVATIVE, COMPOSITION AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2021/036998
Kind Code:
A1
Abstract:
Provided are a novel bile acid derivative for treating fatty liver disease, a pharmaceutical composition thereof, and a use in the preparation of a medicine for treating and improving diseases and symptoms mediated or caused by FXR or TGR5. The bile acid derivative of the present invention inhibits or delays the metabolism of bile acid by bacterial BSH/7a dehydroxylase in the intestine and greatly prolongs the effective survival time of bile acid in the intestine. The bile acid derivative and the pharmaceutical composition thereof can significantly stimulate bile acid membrane receptor TGR5, promote the secretion of glucagon-like peptide-1 from enteroendocrine cells, reduce liver fat accumulation, significantly improve liver function and increase glucose tolerance, thereby having an excellent effect on treating fatty liver disease.
Inventors:
JIA WEI (CN)
XIE GUOXIANG (CN)
ZHAI NING (CN)
ZHAO AIHUA (CN)
ZHENG XIAOJIAO (CN)
XIE GUOXIANG (CN)
ZHAI NING (CN)
ZHAO AIHUA (CN)
ZHENG XIAOJIAO (CN)
Application Number:
PCT/CN2020/110851
Publication Date:
March 04, 2021
Filing Date:
August 24, 2020
Export Citation:
Assignee:
SHENZHEN YUNHE PHARMACEUTICAL TECH PARTNERSHIP LIMITED (CN)
International Classes:
C07J9/00; A61K31/575; A61P1/16; A61P3/00; A61P9/00; A61P9/10
Foreign References:
| CN109364269A | 2019-02-22 | |||
| ITMI981079A1 | 1999-11-15 | |||
| CN102712672A | 2012-10-03 |
Other References:
SONG C., ET AL.: "SELECTIVE ACTIVATION OF LIVER X RECEPTOR ALPHA BY 6ALPHA-HYDROXY BILE ACIDS AND ANALOGS.", STEROIDS, ELSEVIER SCIENCE PUBLISHERS, NEW YORK, NY., US, vol. 65., no. 08., 1 January 2000 (2000-01-01), US, pages 423 - 427., XP000952749, ISSN: 0039-128X, DOI: 10.1016/S0039-128X(00)00127-6
DJ. MANGELSDORF ET AL., CELL, vol. 83, no. 6, 1995, pages 841 - 850
D. PARKS ET AL., SCIENCE, vol. 284, no. 5418, 1999, pages 1362 - 1365
J. HOLT ET AL., GENES DEV., vol. 17, no. 13, 2003, pages 1581 - 1591
T. INAGAKI ET AL., CELL METAB., vol. 2, no. 4, 2005, pages 217 - 225
KAWAMATA ET AL., J. BIO. CHEM., vol. 278, 2003, pages 9435
TAKEDA ET AL., FEBS LETT, vol. 520, 2002, pages 97 - 101
KAWAMATA, Y. ET AL., J. BIOL. CHEM., vol. 278, 2003, pages 9435 - 9440
WATANABE, M. ET AL., NATURE, vol. 439, 2006, pages 484 - 489
MARUYAMA, T. ET AL., J. ENDOCRINOL., vol. 191, 2006, pages 197 - 205
KATSUMA, S., BIOCHEM. BIOPHYS. RES. COMMUN., vol. 329, 2005, pages 386 - 390
See also references of EP 4019528A4
DJ. MANGELSDORF ET AL., CELL, vol. 83, no. 6, 1995, pages 841 - 850
D. PARKS ET AL., SCIENCE, vol. 284, no. 5418, 1999, pages 1362 - 1365
J. HOLT ET AL., GENES DEV., vol. 17, no. 13, 2003, pages 1581 - 1591
T. INAGAKI ET AL., CELL METAB., vol. 2, no. 4, 2005, pages 217 - 225
KAWAMATA ET AL., J. BIO. CHEM., vol. 278, 2003, pages 9435
TAKEDA ET AL., FEBS LETT, vol. 520, 2002, pages 97 - 101
KAWAMATA, Y. ET AL., J. BIOL. CHEM., vol. 278, 2003, pages 9435 - 9440
WATANABE, M. ET AL., NATURE, vol. 439, 2006, pages 484 - 489
MARUYAMA, T. ET AL., J. ENDOCRINOL., vol. 191, 2006, pages 197 - 205
KATSUMA, S., BIOCHEM. BIOPHYS. RES. COMMUN., vol. 329, 2005, pages 386 - 390
See also references of EP 4019528A4
Attorney, Agent or Firm:
SHANGHAI L&W INTELLECTUAL PROPERTY LAW OFFICE, LLC (CN)
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