Hit-to-lead optimization of a series of carboxamides of ethyl 2-amino-4-phenylthiazole-5-carboxylates as novel adenosine A2A receptor antagonists
| Autor: | Lise T. Brennum, Mogens Larsen, Tenna Juul Schrøder, Lars Torup, Benny Bang-Andersen, Anette Graven Sams, Gitte Mikkelsen |
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| Rok vydání: | 2010 |
| Předmět: |
Receptor
Adenosine A2A medicine.drug_class Stereochemistry Chemistry Organic Chemistry Clinical Biochemistry Antagonist Carboxylic Acids Pharmaceutical Science Carboxamide Biological activity Hit to lead Biochemistry Chemical synthesis Adenosine Amides Structure-Activity Relationship Purinergic P1 Receptor Antagonists In vivo Drug Discovery medicine Molecular Medicine Moiety Molecular Biology medicine.drug |
| Zdroj: | Bioorganicmedicinal chemistry letters. 20(17) |
| ISSN: | 1464-3405 |
| Popis: | Herein we describe the discovery of a series of novel adenosine A2A 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. |
| Databáze: | OpenAIRE |
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