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Identification and characterization of pyrrolidine diastereoisomers as potent functional agonists and antagonists of the human melanocortin-4 receptor.

Abstract：

:A series of trans-4-phenylpyrrolidine-3-carboxamides were synthesized and characterized as potent ligands of the human melanocortin-4 receptor. Interestingly, a pair of diastereoisomers 13b displayed potent functional agonist and antagonist activity, respectively. Thus, the 3S,4R-pyrrolidine 13b-1 possessed a Ki of 1.0 nM and an EC50 of 3.8 nM, while its 3R,4S-isomer 13b-2 exhibited a Ki of 4.7 and an IC50 of 64 nM. Both compounds were highly selective over other melanocortin receptor subtypes. The MC4R agonist 13b-1 also demonstrated efficacy in a diet-induced obesity model in rats.

journal_name

Bioorg Med Chem Lett

journal_title

Bioorganic & medicinal chemistry letters

authors

Chen C,Jiang W,Tran JA,Tucci FC,Fleck BA,Markison S,Wen J,Madan A,Hoare SR,Foster AC,Marinkovic D,Chen CW,Arellano M,Saunders J

doi

10.1016/j.bmcl.2007.10.115

subject

Has Abstract

pub_date

2008-01-01 00:00:00

pages

129-36

issue

1

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(07)01308-X

journal_volume

18

pub_type

杂志文章

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