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Bioorg Med Chem Lett. 2005 Oct 15;15(20):4574-8.

Design, synthesis, and structure-activity relationship of podocarpic acid amides as liver X receptor agonists for potential treatment of atherosclerosis.

Author information

1
Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065, USA. weiguo_liu@merck.com

Abstract

A series of podocarpic acid amides were identified as potent agonists for Liver X receptor alpha and beta subtypes, which are members of a nuclear hormone receptor superfamily that are involved in the regulation of a variety of metabolic pathways including cholesterol metabolism. We recently reported podocarpic acid anhydride and imide dimers as potent LXR agonists. Through parallel organic synthesis, we rapidly identified a series of new podocarpate leads with stable structures exemplified by adamantyl- and phenylcyclohexylmethyl-podocarpic acid amides (14 and 18). Compound 18 exhibited LXRalpha/beta 50/20 nM (binding affinity) and 33.7/35.3-fold receptor inductions. Synthesis, SAR, and biological activities of new podocarpate analogs are discussed.

PMID:
16125384
DOI:
10.1016/j.bmcl.2005.06.100
[Indexed for MEDLINE]

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