期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 20, 期 9, 页码 2982-2991出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2012.03.008
关键词
Type 2 diabetes (T2D); Glucokinase activator; Benzamide derivatives; Privileged-fragment-merging; Aminothiazole
资金
- Chinese National Science Foundation [81125021, 81072528]
- National Basic Research Program of China (973 Program) [2009CB522300]
- National Science & Technology Major Project on 'Key New Drug Creation and Manufacturing Program', China [2012ZX09103-101-035]
- Shanghai postdoctoral research funding program [11R21417900]
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 EC50 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. (C) 2012 Elsevier Ltd. All rights reserved.
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