2,2-Difluoro-5-hexyne-1,4-diamine: A potent enzyme-activated inhibitor of ornithine decarboxylase

Article abstract of DOI:10.1021/jm00121a031

2,2-Difluoro-5-hexyne-1,4-diamine was prepared in an eight-step sequence from ethyl 2,2-difluoro-4-pentenoate and tested as an inhibitor of mammalian ornithine decarboxylase. It produces a time-dependent inhibition of the enzyme in vitro which shows saturation kinetics, with K(I) = 10 μM and τ( 1/2 ) = 2.4 min. In rats, it produces a rapid, long-lasting, and dose-dependent decrease of ornithine decarboxylase activity in the ventral prostate, testis, and thymus. In contrast with the nonfluorinated analogue 5-hexyne-1,4-diamine (Danzin et al. Biochem. Pharmacol. 1983, 32, 941), 2,2-difluoro-5-hexyne-1,4-diamine is not a substrate of mitochondrial monoamine oxidase.