1093683-85-2Relevant academic research and scientific papers
COMPOUNDS AND COMPOSITIONS FOR USE IN TREATING PSORIASIS
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Paragraph 00100, (2018/10/19)
Compounds and pharmaceutical compositions for use in the treatment of psoriasis are disclosed. Preferred compounds have demonstrated efficacy in reducing skin scaling, erythema and skin thickness in the mouse model of Aldara-induced psoriasis.
Isosorbide-based aspirin prodrugs: Integration of nitric oxide releasing groups
Jones, Michael,Inkielewicz, Iwona,Medina, Carlos,Santos-Martinez, Maria Jose,Radomski, Anna,Radomski, Marek W.,Lally, Maeve N.,Moriarty, Louise M.,Gaynor, Joanne,Carolan, Ciaran G.,Khan, Denise,O'Byrne, Paul,Harmon, Shona,Holland, Valerie,Clancy, John M.,Gilmer, John F.
supporting information; experimental part, p. 6588 - 6598 (2010/04/25)
Aspirin prodrugs and related nitric oxide releasing compounds hold significant therapeutic promise, but they are hard to design because aspirin esterification renders its acetate group very susceptible to plasma esterasemediated hydrolysis. Isosorbide-2-aspirinate-5-salicylate is a true aspirin prodrug in human blood because it can be effectively hydrolyzed to aspirin upon interactionwith plasma BuChE. We show that the identity of the remote 5-ester dictates whether aspirin is among the products of plasma-mediated hydrolysis. By observing the requirements for aspirin release from an initial panel of isosorbide-based esters,we were able to introduce nitroxymethyl groups at the 5-position while maintaining ability to release aspirin. Several of these compounds are potent inhibitors of platelet aggregation. The design of these compounds will allow better exploration of cross-talk between COX inhibition and nitric oxide release and potentially lead to the development of selective COX-1 acetylating drugs without gastric toxicity.
EFFICIENT ASPIRIN PRODRUGS
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Page/Page column 27, (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.
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.
