3-芳基-5-苯甲氧基-1,3-恶唑烷-2-酮作为 mGluR2 的正变构调节剂用于治疗精神分裂症：从命中化合物到先导化合物的优化。
3-Aryl-5-phenoxymethyl-1,3-oxazolidin-2-ones as positive allosteric modulators of mGluR2 for the treatment of schizophrenia: Hit-to-lead efforts.
机构信息
Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA.
出版信息
Bioorg Med Chem Lett. 2010 May 15;20(10):3129-33. doi: 10.1016/j.bmcl.2010.03.089. Epub 2010 Mar 31.
PMID:20409708
Abstract
Hit to lead optimization of (5R)-5-hexyl-3-phenyl-1,3-oxazolidin-2-one as a positive allosteric modulator of mGluR2 is described. Improvements in potency and metabolic stability were achieved through SAR on both ends of the oxazolidinone. An optimized lead compound was found to be brain penetrant and active in a rat ketamine-induced hyperlocomotion model for antipsychotic activity.
摘要
（5R）-5-己基-3-苯基-1,3-恶唑烷-2-酮作为 mGluR2 的正变构调节剂的命中到先导优化被描述。通过对恶唑烷酮两端的 SAR 研究，提高了化合物的效力和代谢稳定性。发现一种优化的先导化合物具有脑渗透性，并在大鼠氯胺酮诱导的抗精神病活性的过度活动模型中具有活性。
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