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J Med Chem. 2008 Feb 14;51(3):400-6. doi: 10.1021/jm070623o. Epub 2008 Jan 12.

Identification of novel, water-soluble, 2-amino-N-pyrimidin-4-yl acetamides as A2A receptor antagonists with in vivo efficacy.

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1
Department of Medicinal Chemistry, Pharmacology and Lead Discovery, Neuroscience, Chemical Development and Preclinical Development, Neurocrine Biosciences, San Diego, CA 92130, USA. dslee@neurocrine.com

Abstract

Potent adenosine hA2A receptor antagonists are often accompanied by poor aqueous solubility, which presents issues for drug development. Herein we describe the early exploration of the structure-activity relationships of a lead pyrimidin-4-yl acetamide series to provide potent and selective 2-amino-N-pyrimidin-4-yl acetamides as hA2A receptor antagonists with excellent aqueous solubility. In addition, this series of compounds has demonstrated good bioavailability and in vivo efficacy in a rodent model of Parkinson's disease, despite having reduced potency for the rat A2A receptor versus the human A2A receptor.

PMID:
18189346
DOI:
10.1021/jm070623o
[Indexed for MEDLINE]
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