1093683-80-7Relevant academic research and scientific papers
Isosorbide-2-benzyl carbamate-5-salicylate, a peripheral anionic site binding subnanomolar selective butyrylcholinesterase inhibitor
Carolan, Ciaran G.,Dillon, Gerald P.,Khan, Denise,Ryder, Sheila A.,Gaynor, Joanne M.,Reidy, Sean,Marquez, Juan F.,Jones, Mike,Holland, Valerie,Gilmer, John F.
experimental part, p. 1190 - 1199 (2010/08/05)
Isosorbide-2-benzyl carbamate-5-benzoate is a highly potent and selective BuChE inhibitor. Meanwhile, isosorbide-2-aspirinate-5-salicylate is a highly effective aspirin prodrug that relies on the salicylate portion to interact productively with human BuChE. By integrating the salicylate group into the carbamate design, we have produced isosorbide-2-benzyl carbamate-5-salicylate, an inhibitor of high potency (150 pM) and selectivity for human BuChE over AChE (666000) and CES2 (23000). Modeling and mutant studies indicate that it achieves its exceptional potency because of an interaction with the polar D70/Y332 cluster in the PAS of BuChE in addition to pseudosubstrate interactions with the active site.
Discovery of a "true" aspirin prodrug
Moriarty, Louise M.,Lally, Maeve N.,Carolan, Ciaran G.,Jones, Michael,Clancy, John M.,Gilmer, John F.
supporting information; experimental part, p. 7991 - 7999 (2009/12/07)
Aspirin prodrugs formed by derivatization at the benzoic acid group are very difficult to obtain because the promoiety accelerates the rate of hydrolysis by plasma esterases at the neighboring acetyl group, generating salicylic acid derivatives. By tracing the hydrolysis pattern of the aspirin prodrug isosorbide-2,5-diaspirinate (ISDA) in human plasma solution, we were able to identify a metabolite, isosorbide-2-aspirinate-5-salicylate, that undergoes almost complete conversion to aspirin by human plasma butyrylcholinesterase, making it the most successful aspirin prodrug discovered to date.
