Hit-to-lead optimization of a series of carboxamides of ethyl 2-amino-4-phenylthiazole-5-carboxylates as novel adenosine A2A receptor antagonists.

Autor: Sams AG; Medicinal Chemistry Research, H. Lundbeck A/S, Valby, Denmark. anette.sams@leo-pharma.com, Mikkelsen GK, Larsen M, Torup L, Brennum LT, Schrøder TJ, Bang-Andersen B
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Sep 01; Vol. 20 (17), pp. 5241-4. Date of Electronic Publication: 2010 Jul 24.
DOI: 10.1016/j.bmcl.2010.06.138
Abstrakt: Herein we describe the discovery of a series of novel adenosine A(2A) receptor antagonists. A successful hit-to-lead optimization of an HTS hit led to replacement of a metabolically labile ester moiety with a heteroaromatic group. A compound from the series, (cyclopropanecarboxylic acid [5-(5-methyl-[1,2,4]oxadiazol-3-yl)-4-phenyl-thiazol-2-yl]-amide, compound 13), was shown to be effective in reversing haloperidol-induced hypolocomotion, a model of motor dysfunction in Parkinson's Disease.
(Copyright 2010 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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