1212-04-0Relevant articles and documents
Discovery of N-(2-(Benzylamino)-2-oxoethyl)benzamide analogs as a novel scaffold of pancreatic β-cell protective agents against endoplasmic reticulum stress
Eeda, Venkateswararao,Herlea-Pana, Oana,Lim, Hui-Ying,Wang, Weidong
, p. 388 - 393 (2020/01/02)
Endoplasmic reticulum (ER) stress-induced pancreatic β-cell dysfunction and death play important roles in the development of diabetes. The 1,2,3-triazole derivative 1 is one of only a few structures that have thus far been identified that protect β cells against ER stress. However, this compound has narrow activity range and limited aqueous solubility. To overcome these, we designed and synthesized a new scaffold in which the triazole pharmacophore was substituted with a glycine-like amino acid. Structure–activity relationship studies on this scaffold identified a N-(2-(Benzylamino)-2-oxoethyl)benzamide analog WO5m that possesses β-cell protective activity against ER stress with much improved potency (maximal activity at 100% with EC50 at 0.1?±?0.01?μm) and water solubility. Identification of this novel β-cell protective scaffold thus provides a new promising modality for the treatment of diabetes.
