PMID: 3761311Oct 1, 1986Paper

Acyl, N-protected alpha-aminoacyl, and peptidyl derivatives as prodrug forms of the alcohol deterrent agent cyanamide

Journal of Medicinal Chemistry
C H KwonF N Shirota

Abstract

Cyanamide (H2NC identical to N), a potent aldehyde dehydrogenase (AlDH) inhibitor that is used therapeutically as an alcohol deterrent agent, is known to be rapidly metabolized and excreted in the urine as acetylcyanamide (1). On the basis of our observation that 1 is deacetylated to cyanamide in vivo, albeit very slightly, thereby serving as a precursor of prodrug form of the latter, several acyl derivatives of cyanamide were synthesized specifically as prodrugs, including benzoylcyanamide (2), pivaloylcyanamide (3), and 1-adamantoylcyanamide (4), as well as long- and medium-chain fatty acyl derivatives such as palmitoyl- (6), stearoyl- (7), and n-butyrylcyanamide (5). N-Protected alpha-aminoacyl and peptidyl derivatives of cyanamide were also synthesized, and these include N-carbobenzoxyglycyl- (10), hippuryl- (13), N-benzoyl-L-leucyl- (14), N-carbobenzoxyglycyl-L-leucyl- (18), N-carbobenzoxy-L-pyroglutamyl- (22), L-pyroglutamyl-L-leucyl- (19), and L-pyroglutamyl-L-phenylalanylcyanamide (20). All of these prodrugs of cyanamide raised ethanol-derived blood acetaldehyde levels in rats significantly over controls 3 h after ip drug administration, and some of these were still capable of elevating blood acetaldehyde 16 h post drug...Continue Reading

Citations

Dec 13, 2006·Angewandte Chemie·Aurore ServaisMax Malacria
Jun 16, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Elisabete C B A AlegriaArmando J L Pombeiro
Oct 14, 2017·The Journal of Organic Chemistry·Linda ÅkerbladhLuke R Odell

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