基于计算机虚拟筛选得到的命中化合物开发的新型选择性口服活性CRTH2拮抗剂，用于治疗过敏性炎症。
Novel selective orally active CRTH2 antagonists for allergic inflammation developed from in silico derived hits.
作者信息
Ulven Trond, Receveur Jean-Marie, Grimstrup Marie, Rist Øystein, Frimurer Thomas M, Gerlach Lars-Ole, Mathiesen Jesper Mosolff, Kostenis Evi, Uller Lena, Högberg Thomas
机构信息
7TM Pharma, Fremtidsvej 3, DK-2970 Hørsholm, Denmark.
出版信息
J Med Chem. 2006 Nov 16;49(23):6638-41. doi: 10.1021/jm060657g.
Hits from an in silico derived focused library for CRTH2 were transformed into highly selective antagonists with favorable ADME properties. Oral administration of 4-bromo-2-(1-phenyl-1H-pyrazole-4-carbonyl)phenoxyacetic acid (19) inhibited peribronchial eosinophilia and mucus cell hyperplasia in a mouse model of allergic asthma, supporting the therapeutic potential of this novel compound class. In addition, this selective pharmacological tool compound provides further evidence for CRTH2 as a relevant therapeutic target for treatment of Th2- and eosinophil-related inflammation.
针对CRTH2的计算机虚拟衍生聚焦文库中的活性化合物被转化为具有良好药代动力学性质的高选择性拮抗剂。口服4-溴-2-(1-苯基-1H-吡唑-4-羰基)苯氧基乙酸（19）可抑制过敏性哮喘小鼠模型中的支气管周围嗜酸性粒细胞增多和黏液细胞增生，支持了这类新型化合物的治疗潜力。此外，这种选择性药理工具化合物为CRTH2作为治疗Th2和嗜酸性粒细胞相关炎症的相关治疗靶点提供了进一步的证据。
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