Discovery of a series of phosphonic acid-containing thiazoles and orally bioavailable diamide prodrugs that lower glucose in diabetic animals through inhibition of …

…, J DaRe, F Tian, W Li, T Gibson, R Lemus…

Index: Dang, Qun; Liu, Yan; Cashion, Daniel K.; Kasibhatla, Srinivas Rao; Jiang, Tao; Taplin, Frank; Jacintho, Jason D.; Li, Haiqing; Sun, Zhili; Fan, Yi; Dare, Jay; Tian, Feng; Li, Wenyu; Gibson, Tony; Lemus, Robert; Van Poelje, Paul D.; Potter, Scott C.; Erion, Mark D. Journal of Medicinal Chemistry, 2011 , vol. 54, # 1 p. 153 - 165

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Citation Number: 66

Abstract

Oral delivery of previously disclosed purine and benzimidazole fructose-1, 6- bisphosphatase (FBPase) inhibitors via prodrugs failed, which was likely due to their high molecular weight (> 600). Therefore, a smaller scaffold was desired, and a series of phosphonic acid-containing thiazoles, which exhibited high potency against human liver FBPase (IC50 of 10− 30 nM) and high selectivity relative to other 5′- ...