Title:
HALOGENATED TETRACYCLIC TRITERPENE DERIVATIVE, PREPARATION AND APPLICATION THEREOF
Document Type and Number:
WIPO Patent Application WO/2021/043194
Kind Code:
A1
Abstract:
Provided are a halogenated tetracyclic triterpene derivative as represented by general formula A, a preparation and an application thereof. R 1 is a halogen, R 2 is H, and the halogen is selected from fluorine, chlorine, bromine or iodine; or R 1 and R 2 are fluorine, separately, and R 3 is amine, alcohol, amino acid, peptide or organophosphate linked to oxygen by means of an acyl group. A pharmacokinetic study is performed on the derivative, which is relatively stable in whole blood of rats, and the absolute bioavailability of male rats after single intragastric administration is 15.6%. The absolute bioavailability of female rats after single intragastric administration is 28.4%, and the average bioavailability thereof is 22%. The effect of the derivative is better than that of enalapril and sacubitril/valsartan. Also provided is a hydrophilic prodrug of the tetracyclic triterpene derivative, which has an improved solubility and stronger druggability. The derivative can be used in the preparation of drugs for treating cardiovascular diseases.
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Inventors:
ZHANG WEIDONG (CN)
SUN QINGYAN (CN)
YUAN HU (CN)
LIU XIA (CN)
SUN QINGYAN (CN)
YUAN HU (CN)
LIU XIA (CN)
Application Number:
PCT/CN2020/113149
Publication Date:
March 11, 2021
Filing Date:
September 03, 2020
Export Citation:
Assignee:
SHANGHAI KING X BIOTECH CO LTD (CN)
International Classes:
C07D307/04; A61K31/341; A61P9/00
Domestic Patent References:
| WO2008063128A1 | 2008-05-29 |
Foreign References:
| CN1793132A | 2006-06-28 | |||
| CN102448308A | 2012-05-09 | |||
| CN102939011A | 2013-02-20 | |||
| CN1642558A | 2005-07-20 |
Other References:
EUR. J. DRUG METAB. PH., vol. 30, no. 4, 2005, pages 269 - 273
BASIC. CLIN. PHARMACOL. TOXICOL., vol. 95, no. 6, 2004, pages 295 - 298
EUR. J. DRUG METAB. PH., vol. 31, no. 1, 2006, pages 5 - 10
DRUG METAB. PHARMACOKINET., vol. 25, no. 5, 2010, pages 477 - 486
See also references of EP 4043447A4
BASIC. CLIN. PHARMACOL. TOXICOL., vol. 95, no. 6, 2004, pages 295 - 298
EUR. J. DRUG METAB. PH., vol. 31, no. 1, 2006, pages 5 - 10
DRUG METAB. PHARMACOKINET., vol. 25, no. 5, 2010, pages 477 - 486
See also references of EP 4043447A4
Attorney, Agent or Firm:
SHANGHAI SUNHOLD LAW FIRM (CN)
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