新一代非典型抗精神病药物鉴定的研究
Studies towards the identification of a new generation of atypical antipsychotic agents.
作者信息
Garzya Vincenzo, Forbes Ian T, Gribble Andrew D, Hadley Mike S, Lightfoot Andrew P, Payne Andrew H, Smith Alexander B, Douglas Sara E, Cooper David G, Stansfield Ian G, Meeson Malcom, Dodds Emma E, Jones Declan N C, Wood Martyn, Reavill Charlie, Scorer Carol A, Worby Angela, Riley Graham, Eddershaw Peter, Ioannou Chris, Donati Daniele, Hagan Jim J, Ratti Emiliangelo A
机构信息
Psychiatry Centre of Excellence for Drug Discovery, New Frontiers Science Park, Harlow, Essex CM19 5AW, UK.
出版信息
Bioorg Med Chem Lett. 2007 Jan 15;17(2):400-5. doi: 10.1016/j.bmcl.2006.10.036. Epub 2006 Oct 19.
A rational structure-activity relationship study around compound (1) is reported. The lead optimisation programme led to the identification of sulfonamide (25), a molecule combining dopamine D2/D3 receptor antagonism with serotonin 5-HT2A, 5-HT2C, 5-HT6 receptor antagonism for an effective treatment of schizophrenia. Compound (25) was shown to possess the required in vivo activity with no EPS liability.
报道了围绕化合物（1）的合理构效关系研究。先导化合物优化计划导致了磺酰胺（25）的发现，该分子兼具多巴胺D2/D3受体拮抗作用和5-羟色胺5-HT2A、5-HT2C、5-HT6受体拮抗作用，可有效治疗精神分裂症。化合物（25）显示出所需的体内活性且无锥体外系反应倾向。
Zotero 插件