100615-73-4

Upstream product

• 121426-39-9 methyl (4S)-5-oxo-4-[[(phenylmethoxy)carbonyl]amino]-5-[(2-phenylethyl)amino]pentanoate 
• 16450-41-2 L-glutamic acid diethyl ester 
• 64-04-0 phenethylamine 
• 4652-65-7 (S)-2-Benzyloxycarbonylamino-pentanedioic acid 5-methyl ester 
• 4931-66-2 methyl (S)-pyroglutamate 

Downstream Products

• 101737-97-7 1-((S)-2-methyl-butyryl)-5-oxo-L-proline-phenethylamide 

Relevant academic research and scientific papers

Discovery of highly functionalized scaffolds: Pyrroloimidazolediones as P2X7 receptor antagonists

A broad range of pyrroloimidazolediones, new highly functionalized bicyclic heterocycles, was obtained by a cycloaddition reaction between L-pyroglutamide derivatives and Bredereck's reagent. Methanolysis of subsequent pyrroloimidazolediones provided antagonists of P2X7 receptor, with retention of initial stereoconfiguration, with potential applications in the treatment of inflammatory and neurological diseases. We have thus developed a new synthesis of lactamic nitrogen free enaminones which is currently the easiest method cited in the literature to access these compounds.

On the discovery of new potent human farnesyltransferase inhibitors: Emerging pyroglutamic derivatives

In the current context of lack of emergence of innovative human farnesyltransferase inhibitors families, and given all new therapeutic perspectives that open up for such molecules in rare diseases (e.g. Hutchinson-Gilford progeria syndrome), and in delta hepatitis, cardiovascular or neuroinflammatory diseases, we have just discovered a new series of powerful inhibitors. These molecules are pyroglutamic acid derivatives, and were evaluated on human farnesyltransferase in vitro then modeled in silico on the active site of the protein. Three main points of the pyroglutamic acid cycle have undergone chemical modulations pyroglutamides in position 5 (compounds 7a-h), constrained bicyclic analogues of pyrroloimidazoledione type (compounds 1a-h), modulation of the position 3 (compounds 2-5 and 8), and allowed the first SAR in the field. Five derivatives in the current work have IC50 values in the small nanomolar range (2-5 nM). These new lead compounds open the way for the next generation of farnesyltransferase inhibitors.