1,5-取代 1H-四唑对 11β-羟甾醇脱氢酶 1 活性的调节。
Modulation of 11beta-hydroxysteroid dehydrogenase type 1 activity by 1,5-substituted 1H-tetrazoles.
机构信息
Endocrinology Unit, Centre for Cardiovascular Science, The Queen's Medical Research Institute, University of Edinburgh, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
出版信息
Bioorg Med Chem Lett. 2010 Jun 1;20(11):3265-71. doi: 10.1016/j.bmcl.2010.04.055. Epub 2010 Apr 18.
Abstract
Inhibitors of 11beta-hydroxysteroid dehydrogenase (11beta-HSD1) show promise as drugs to treat metabolic disease and CNS disorders such as cognitive impairment. A series of 1,5-substituted 1H-tetrazole 11beta-HSD1 inhibitors has been discovered and chemically modified. Compounds are selective for 11beta-HSD1 over 11beta-HSD2 and possess good cellular potency in human and murine 11beta-HSD1 assays. A range of in vitro stabilities are observed in human liver microsome assays.
摘要
11β-羟类固醇脱氢酶（11β-HSD1）抑制剂有望成为治疗代谢疾病和中枢神经系统疾病（如认知障碍）的药物。已经发现并对一系列 1,5-取代的 1H-四唑 11β-HSD1 抑制剂进行了化学修饰。这些化合物对 11β-HSD1 的选择性优于 11β-HSD2，并且在人源和鼠源 11β-HSD1 测定中具有良好的细胞效力。在人肝微粒体测定中观察到一系列不同的体外稳定性。
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