Heptares Therapeutics Limited, BioPark, Broadwater Road, Welwyn Garden City, Hertfordshire AL7 3AX, UK.
J Med Chem. 2012 Mar 8;55(5):1898-903. doi: 10.1021/jm201376w. Epub 2012 Jan 27.
Potent, ligand efficient, selective, and orally efficacious 1,2,4-triazine derivatives have been identified using structure based drug design approaches as antagonists of the adenosine A(2A) receptor. The X-ray crystal structures of compounds 4e and 4g bound to the GPCR illustrate that the molecules bind deeply inside the orthosteric binding cavity. In vivo pharmacokinetic and efficacy data for compound 4k are presented, demonstrating the potential of this series of compounds for the treatment of Parkinson's disease.
使用基于结构的药物设计方法，已经鉴定出强效、配体高效、选择性和口服有效的 1,2,4-三嗪衍生物，它们是腺苷 A(2A)受体的拮抗剂。化合物 4e 和 4g 与 GPCR 结合的 X 射线晶体结构表明，这些分子深深地结合在正构结合腔内。本文呈现了化合物 4k 的体内药代动力学和疗效数据，证明了该系列化合物在治疗帕金森病方面的潜力。
