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Discovery of pentacyclic triterpene 3β-ester derivatives as a new class of cholesterol ester transfer protein inhibitors.

Abstract：

:A series of pentacyclic triterpene 3β-ester derivatives were designed, synthesized and evaluated as a new class of cholesteryl ester transfer protein (CETP) inhibitors for the treatment of dyslipidemia. In vitro screening assay showed that 5 out of 30 compounds displayed moderate inhibiting human CETP activity with IC50s less than 10 μM. Among them, compound 20 (IC50 = 2.3 μM) had the most potent biological activity, and effectively ameliorated plasma lipid levels of human adipose tissue specific CETP transgenic (ap2-CETPTg) mice and guinea pigs. Additional safety evaluation (no blood pressure elevation in guinea pigs) and pharmacokinetics studies indicated that the potential druggability for compound 20 which is a promising lead for development of a new class of CETP inhibitors for the treatment of dyslipidemia.

journal_name

Eur J Med Chem

journal_title

European journal of medicinal chemistry

authors

Chen D,Huang X,Zhou H,Luo H,Wang P,Chang Y,He X,Ni S,Shen Q,Cao G,Sun H,Wen X,Liu J

doi

10.1016/j.ejmech.2017.08.012

subject

Has Abstract

pub_date

2017-10-20 00:00:00

pages

201-213

eissn

0223-5234

issn

1768-3254

pii

S0223-5234(17)30615-3

journal_volume

139

pub_type

杂志文章

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