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Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators
Weiwei Mao1, Mengmeng Ning, Zhiqing Liu
1Synthetic Organic and Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Abstract:
A series of benzamide derivatives were assembled by using the privileged-fragment-merging (PFM) strategy and their SAR studies as glucokinase activators were described. Compounds 5 and 16b were identified having a suitable balance of potency and activation profile. They showed EC(50) values of 28.3 and 44.8 nM, and activation folds of 2.4 and 2.2, respectively. However, both compounds displayed a minor reduction in plasma glucose levels on imprinting control region (ICR) mice. Unfavorable pharmacokinetic profiles (PK) were also observed on these two compounds.
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