In 2011,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. published 《Discovery of a series of phosphonic acid-containing thiazoles and orally bioavailable diamide prodrugs that lower glucose in diabetic animals through inhibition of fructose-1,6-bisphosphatase》.Journal of Medicinal Chemistry published the findings.Category: esters-buliding-blocks The information in the text is summarized as follows:
Oral delivery of previously disclosed purine and benzimidazole fructose-1,6-bisphosphatase (FBPase) inhibitors via prodrugs failed, which was likely due to their high mol. 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′-adenosinemonophosphate (AMP)-binding enzymes, were discovered using a structure-guided drug design approach. The initial lead compound I produced profound glucose lowering in rodent models of type 2 diabetes mellitus (T2DM) after parenteral administration. Various phosphonate prodrugs were explored without success, until a novel phosphonic diamide prodrug approach was implemented, which delivered compound I with good oral bioavailability (OBAV) (22-47%). Extensive lead optimization of both the thiazole FBPase inhibitors and their prodrugs culminated in the discovery of compound II (MB06322) as the first oral FBPase inhibitor advancing to human clin. trials as a potential treatment for T2DM.Ethyl 2-amino-2-thioxoacetate(cas: 16982-21-1Category: esters-buliding-blocks) was used in this study.
Ethyl 2-amino-2-thioxoacetate(cas: 16982-21-1) belongs to anime. Left-handed and right-handed forms (mirror-image configurations, known as optical isomers or enantiomers) are possible when all the substituents on the central nitrogen atom are different (i.e., the nitrogen is chiral). With amines, there is extremely rapid inversion in which the two configurations are interconverted.Category: esters-buliding-blocks
Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics