The central nature of nicotinamide in metabolic processes as a part of the NAD and NADP coenzyme systems prompted the synthesis of a series of N-nicotinyl- and N-isonicotinyl-N'- (substituted)ureas as potential metabolite antagonists of the vitamin. The compounds which were synthesized may be represented by the following general structure, where R = hydrogen, methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl, n-hexyl, cyclohexyl, phenyl and a-naphthyl. The observed toxicity of the N-nicotinyl-N'-(substituted)urea analogs may be attributed to the formation of a non-functional N-nicotinyl-N'-(substituted)urea-NAD analog through an exchange reaction catalyzed by NAD-ases in the cell. Support for this view was obtained by an in vitro enzymic synthesis of Nnicotinyl- N'-ethylurea-NAD analog employing N-nicotinyl-7- 1 4CN'- ethylurea. The labeled derivative was characterized through spectral, chromatographic, and chemical reaction studies.

The purpose of this investigation is threefold: (1) to examine in detail the cycloaddition of halogenated ketenes and carbonyl compounds, (2) to study the decarboxylation of the resulting halogenated 2-oxetanones,and (3) to investigate the effect of halogens in the halogenated 2-oxetanones on the nucleophilic addition reaction.