Structure-activity relationships of 3,5-disubstituted benzamides as glucokinase activators with potent in vivo efficacy
Structure-activity relationships of 3,5-disubstituted benzamides as glucokinase activators with potent in vivo efficacy
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DOI：
10.1016/j.bmc.2009.04.040
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发表时间：
2009-06-01
影响因子：
3.5
通讯作者：
Nishimura, Teruyuki
中科院分区：
文献类型：
--
作者：
Iino, Tomoharu;Hashimoto, Noriaki;Nishimura, Teruyuki
描述了将我们的先导GK激活剂2a优化为3-[（1 S）-2-羟基-1-甲基乙氧基]-5-[4-（甲基磺酰基）苯氧基]-N-1，3-噻唑-2-基苯甲酰胺（6 g），其是一种具有良好口服利用度的强效GK激活剂，包括解偶联效力和疏水性之间的关系。口服给药后，该化合物在糖尿病模型啮齿动物中表现出稳健的葡萄糖降低。(C)2009爱思唯尔有限公司版权所有。
The optimization of our lead GK activator 2a to 3-[(1S)-2-hydroxy-1-methylethoxy]-5-[4-(methylsulfonyl) phenoxy]-N-1,3-thiazol-2-ylbenzamide (6g), a potent GK activator with good oral availability, is described, including to uncouple the relationship between potency and hydrophobicity. Following oral administration, this compound exhibited robust glucose lowering in diabetic model rodents. (C) 2009 Elsevier Ltd. All rights reserved.