环状磺酰胺衍生物作为11β-羟基类固醇脱氢酶1抑制剂的合成及生物学评价
Synthesis and biological evaluation of cyclic sulfamide derivatives as 11β-hydroxysteroid dehydrogenase 1 inhibitors.
作者信息
Kim Se Hoan, Bok Ju Han, Lee Jae Hong, Kim Il Hyang, Kwon Sung Wook, Lee Gui Bin, Kang Seung Kyu, Park Ji Seon, Jung Won Hoon, Kim Hee Yeon, Rhee Sang Dal, Ahn Sung Hoon, Bae Myung Ae, Ha Deok Chan, Kim Ki Young, Ahn Jin Hee
机构信息
Bio-Organic Science Division, Korea Research Institute of Chemical Technology , Yuseong-Gu, Daejeon, 305-600, Korea ; Department of Chemistry, Korea University , Sungbuk-gu, Seoul 136-701, Korea.
Bio-Organic Science Division, Korea Research Institute of Chemical Technology , Yuseong-Gu, Daejeon, 305-600, Korea.
出版信息
ACS Med Chem Lett. 2012 Jan 17;3(2):88-93. doi: 10.1021/ml200226x. eCollection 2012 Feb 9.
Abstract
A new series of cyclic sulfamide derivatives were synthesized and evaluated for their ability to inhibit 11β-HSD1. Among this series, 18e showed good in vitro activity toward human 11β-HSD1, selectivity against 11β-HSD2, microsomal stability, and pharmacokinetic and safety profiles (hERG, CYP, and acute toxicity). Additionally, 18e exhibited good in vivo efficacy in rat and monkey models.
摘要
合成了一系列新的环状磺酰胺衍生物，并对其抑制11β-羟基类固醇脱氢酶1（11β-HSD1）的能力进行了评估。在该系列中，18e对人11β-HSD1表现出良好的体外活性、对11β-HSD2的选择性、微粒体稳定性以及药代动力学和安全性特征（人ether-à-go-go相关基因（hERG）、细胞色素P450（CYP）和急性毒性）。此外，18e在大鼠和猴模型中表现出良好的体内疗效。
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