螺环脲类化合物：通过计算机辅助药物设计发现的可口服生物利用的 11β-HSD1 抑制剂。
Spirocyclic ureas: orally bioavailable 11 beta-HSD1 inhibitors identified by computer-aided drug design.
机构信息
Vitae Pharmaceuticals, 502 West Office Center Drive, Fort Washington, PA 19034, USA.
出版信息
Bioorg Med Chem Lett. 2010 Feb 1;20(3):881-6. doi: 10.1016/j.bmcl.2009.12.082. Epub 2010 Jan 4.
PMID:20064717
Abstract
Structure-guided drug design led to the identification of a class of spirocyclic ureas which potently inhibit human 11beta-HSD1 in vitro. Lead compound 10j was shown to be orally bioavailable in three species, distributed into adipose tissue in the mouse, and its (R) isomer 10j2 was efficacious in a primate pharmacodynamic model.
摘要
基于结构的药物设计导致了一类螺环脲类化合物的发现，这类化合物能够在体外有效地抑制人源 11β-HSD1。先导化合物 10j 在三种动物中具有口服生物利用度，在小鼠中分布到脂肪组织中，其（R）异构体 10j2 在灵长类药效学模型中具有疗效。
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