2,2-Difluoro-5-hexyne-1,4-diamine: a potent enzyme-activated inhibitor of ornithine decarboxylase.
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 KI = 10 microM and tau 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.
Kendrick
D A
DA
Merrell Dow Research Institute, Strasbourg Center, France.
Danzin
C
C
Kolb
M
M
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D003959:Diamines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D008297:Male; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
D003959:Diamines; D065108:Ornithine Decarboxylase Inhibitors; C058108:2,2-difluoro-5-hexyne-1,4-diamine