Lewis Richard T, Blackaby Wesley P, Blackburn Timothy, Jennings Andrew S R, Pike Andrew, Wilson Rowan A, Hallett David J, Cook Susan M, Ferris Pushpinder, Marshall George R, Reynolds David S, Sheppard Wayne F A, Smith Alison J, Sohal Bindi, Stanley Joanna, Tye Spencer J, Wafford Keith A, Atack John R
The Neuroscience Research Centre, Merck Sharp & Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, United Kingdom.
J Med Chem. 2006 Apr 20;49(8):2600-10. doi: 10.1021/jm051144x.
The development of a series of GABA(A) alpha2/alpha3 subtype selective pyridazine based benzodiazepine site agonists as anxiolytic agents with reduced sedative/ataxic potential is described, including the discovery of 16, a remarkably alpha3-selective compound ideal for in vivo study. These ligands are antagonists at the alpha1 subtype, with good CNS penetration and receptor occupancy, and excellent oral bioavailability.
描述了一系列基于哒嗪的苯二氮䓬位点激动剂作为具有降低镇静/共济失调潜力的抗焦虑药物的开发，包括发现16，这是一种非常适合体内研究的α3选择性化合物。这些配体是α1亚型的拮抗剂，具有良好的中枢神经系统渗透性和受体占有率，以及出色的口服生物利用度。
