Potential latent nitrogen mustard derivatives designed to target monoamine oxidase rich cells.
The monoamine oxidases A and B (MAO-A and MAO-B) catalyze the alpha-carbon oxidation of a variety of 4-substituted 1-methyl-1,2,3,6-tetrahydropyridine derivatives to yield the corresponding 2,3-dihydropyridinium species. When the substituent at C-4 of the tetrahydropyridine moiety is a carbamoyloxy functionality, the resulting dihydropyridinium metabolite undergoes spontaneous hydrolytic cleavage to yield 1-methyl-5,6-dihydro-4-pyridone, CO2, and the corresponding secondary amine. In this paper we summarize our efforts to exploit this metabolic pathway to develop latent nitrogen mustard derivatives related to the oxazaphosphorine antitumor agent cyclophosphamide which may target MAO-A and/or MAO-B rich cells.
Wang
Y X
YX
Department of Chemistry, Virginia Tech, Blacksburg 24061-0212, U.S.A.
Castagnoli
N
N
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D006801:Humans; D007700:Kinetics; D008995:Monoamine Oxidase / Q000378:metabolism*; D009588:Nitrogen Mustard Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D000970:Antineoplastic Agents; D009588:Nitrogen Mustard Compounds; D008995:Monoamine Oxidase