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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2982-2991 |
| Number of pages | 10 |
| Journal | Bioorganic and Medicinal Chemistry |
| Volume | 20 |
| Issue number | 9 |
| DOIs | |
| State | Published - May 1 2012 |
Keywords
- Aminothiazole
- Benzamide derivatives
- Glucokinase activator
- Privileged-fragment-merging
- Type 2 diabetes (T2D)
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Pharmaceutical Science
- Drug Discovery
- Clinical Biochemistry
- Organic Chemistry
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Mao, W., Ning, M., Liu, Z., Zhu, Q., Leng, Y., & Zhang, A. (2012). Design, synthesis, and pharmacological evaluation of benzamide derivatives as glucokinase activators. Bioorganic and Medicinal Chemistry, 20(9), 2982-2991. https://doi.org/10.1016/j.bmc.2012.03.008