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Bioorg Med Chem Lett. 2008 Oct 15;18(20):5554-8. doi: 10.1016/j.bmcl.2008.09.009. Epub 2008 Sep 6.

Optimization and structure-activity relationship of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides: identification of MK-0873, a potent and effective PDE4 inhibitor.

Author information

1
Merck Frosst Center for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Québec, Canada H9R 4P8. daniel_guay@merck.com

Abstract

A SAR study of a series of 1-phenyl-1,8-naphthyridin-4-one-3-carboxamides is described. Optimization of the series was based on in vitro potency against PDE4, inhibition of the LPS-induced production of TNF-alpha in human whole blood and minimizing affinity for the hERG potassium channel. From these studies, compounds 18 and 20 (MK-0873) were identified as optimized PDE4 inhibitors with good overall in vitro and in vivo profiles and selected as development candidates.

PMID:
18835163
DOI:
10.1016/j.bmcl.2008.09.009
[Indexed for MEDLINE]

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