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Discovery of LAS101057: A Potent, Selective, and Orally Efficacious A2B Adenosine Receptor Antagonist.

ABSTRACT: The structure-activity relationships for a series of pyrazine-based A2B adenosine receptor antagonists are described. From this work, LAS101057 (17), a potent, selective, and orally efficacious A2B receptor antagonist, was identified as a clinical development candidate. LAS101057 inhibits agonist-induced IL-6 production in human fibroblasts and is active in an ovalbumin (OVA)-sensitized mouse model after oral administration, reducing airway hyperresponsiveness to methacholine, Th2 cytokine production, and OVA-specific IgE levels.

SUBMITTER: Eastwood P

PROVIDER: S-EPMC4018059 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Discovery of LAS101057: A Potent, Selective, and Orally Efficacious A2B Adenosine Receptor Antagonist.

Eastwood Paul P Esteve Cristina C González Jacob J Fonquerna Silvia S Aiguadé Josep J Carranco Inés I Doménech Teresa T Aparici Mònica M Miralpeix Montserrat M Albertí Joan J Córdoba Mónica M Fernández Raquel R Pont Mercè M Godessart Núria N Prats Neus N Loza María Isabel MI Cadavid María Isabel MI Nueda Arsenio A Vidal Bernat B

ACS medicinal chemistry letters 20101220 3

The structure-activity relationships for a series of pyrazine-based A2B adenosine receptor antagonists are described. From this work, LAS101057 (17), a potent, selective, and orally efficacious A2B receptor antagonist, was identified as a clinical development candidate. LAS101057 inhibits agonist-induced IL-6 production in human fibroblasts and is active in an ovalbumin (OVA)-sensitized mouse model after oral administration, reducing airway hyperresponsiveness to methacholine, Th2 cytokine produ ...[more]

PMID: 24900298

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