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

被引：17

作者：

Eastwood, Paul ^{[1
]}

Esteve, Cristina ^{[1
]}

Gonzalez, Jacob ^{[1
]}

Fonquerna, Silvia ^{[1
]}

Aiguade, Josep ^{[1
]}

Carranco, Ines ^{[1
]}

Domenech, Teresa ^{[1
]}

Aparici, Monica ^{[1
]}

Miralpeix, Montserrat ^{[1
]}

Alberti, Joan ^{[1
]}

Cordoba, Monica ^{[1
]}

Fernandez, Raquel ^{[1
]}

Pont, Merce ^{[1
]}

Godessart, Nuria ^{[1
]}

Prats, Neus ^{[1
]}

Isabel Loza, Maria ^{[2
]}

Isabel Cadavid, Maria ^{[2
]}

Nueda, Arsenio ^{[1
]}

Vidal, Bernat ^{[1
]}

机构：

[1] Almirall, R&D Ctr, Barcelona 08980, Spain

[2] Univ Santiago Compostela, Fac Pharm, Discovery Grp BioFarma, Santiago De Compostela 15782, Spain

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2011年 / 2卷 / 03期

关键词：

A(2B) adenosine receptor antagonist; ovalbumin mouse model; clinical candidate; PULMONARY INFLAMMATION;

D O I：

10.1021/ml100249e

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The structure activity relationships for a series of pyrazine-based A(2B) adenosine receptor antagonists are described. From this work, LAS101057 (17), a potent, selective, and orally efficacious A(2B) 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.

引用

收藏

页码：213 / 218

页数：6

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