206556-91-4Relevant academic research and scientific papers
EFFICIENT ASPIRIN PRODRUGS
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Page/Page column 32-33, (2009/07/25)
Aspirin is one of the most widely used drugs in the treatment of inflammation, pain and fever. It has more recently found application in the prevention of heart attacks and stroke and is being studied as a cancer chemopreventative agent. Despite its value aspirin continues to be underutilized because it causes gastric bleeding. The technology under development potentially removes this problem. It is designed to reduce contact between the drug and the intestinal lining. An isosorbide aspirinate prodrug compound is thus provided. The compound has the general structure as shown in general formula (I) wherein Y is a C1 - C8 alkyl ester, a C1 - C8 alkoxy ester, a C3 - C10 cycloalkyl ester, an arylester, a C1 - C8 alkylaryl ester or -C(O)ORring, wherein Rring is a 5-membered aromatic or nonaromatic 5-member ring having at least one heteroatom substituted for a carbon of the ring system, which can be unsubstituted or substituted with at least one nitric oxide releasing group.
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.
