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.

中文翻译：

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LAS101057的发现：高效，选择性和口服有效的A2B腺苷受体拮抗剂。

描述了一系列基于吡嗪的A2B腺苷受体拮抗剂的结构活性关系。从这项工作中，LAS101057（17）是一种有效，选择性和口服有效的A2B受体拮抗剂，被确定为临床开发的候选药物。LAS101057抑制人成纤维细胞中激动剂诱导的IL-6产生，并在口服后在卵清蛋白（OVA）致敏的小鼠模型中具有活性，从而降低气道对乙酰甲胆碱，Th2细胞因子产生和OVA特异性IgE水平的高反应性。