N-1-Z-1,4-diaminobutane

As is evident from the above summary of the recent literature, plus many other papers not cited here, there is an extensive literature indicating the physiological significance of these amines. The most important studies can be summarized as follows. (a) Polyamines and their biosynthetic enzymes are ubiquitous. (b) Microbiological mutants have been described in which there is a definite requirement of polyamines for growth. (c) The concentration of polyamines and their biosynthesis enzymes increase when the growth rate increases. These increases usually precede or are simultaneous with increases in RNA, DNA, and protein levels. (d) Ornithine decarboxylase has a remarkably fast turnover rate in animal cells, and the level of this enzyme rapidly changes after a variety of growth stimuli. (e) Polyamines have a high affinity for nucleic acids and stabilize their secondary structure. They are found associated with DNA in bacteriophages and have a variety of stimulatory effects on DNA and RNA biosynthesis in vitro. (f) Polyamines stimulate protein synthesis in vivo and in vitro. (g) Polyamines protect spheroplasts and halophilic organisms for lysis, indicating their ability to stabilize membranes. Despite these observations, no specific mechanism has been firmly established for the action of the polyamines in vivo. It is clear that these compounds are physiologically important, however, and further work is necessary to establish the mechanism of their action.

The degradation pattern of bacterial poly-3-hydroxybutyrate (PHB) in dimethylformamide (DMF) and dioxane solutions at 100 °C assisted by ethylenediamine, 1,4-diaminobutane and monoaminoethanol was studied. When diamines were introduced into the PHB solution in DMF in the amount of 1 mol of the reagent to 5 or 10 mol of PHB monomers, a rapid decrease in the molecular weight of the polymer was observed. The initial value of the weight average molecular weight (Mw) 840 kDa had decreased by 20-30 times within the first 10-20 min of the experiment, followed by its gradual decrease to several thousand Da. When a similar molar quantity of aminoethanol was added, the molecular weight decreased slower. PHB had been degrading much slower in the dioxane solution than in DMF. By varying the number of reagents, it was possible to reach stabilization of the Mw at 1000-3000 Da when using diamines and 8000-20,000 Da using aminoethanol. 1H NMR analysis of the oligomers revealed of amino and amido groups forming in their structure. From the opposite end of the polymer chain, residues of 3-hydroxybutyric, crotonic and isocrotonic acids were formed during degradation. Differential scanning calorimetry indicated that after oligomerization there was a decrease in the melting point from 178 °C to 140-170 °C depending on the decrease in the molecular weight. The method proposed can be used for obtaining aminated PHB oligomers.

Inhibitors for polyamine oxidizing enzymes, spermine oxidase (SMOX) and N1-acetylpolyamine oxidase (PAOX), were designed and evaluated for their effectiveness in a photochemically induced thrombosis (PIT) mouse model. N1-Nonyl-1,4-diaminobutane (C9-4) and N1-tridecyl-1,4-diaminobutane (C13-4) competitively inhibited the activity of PAOX and SMOX in a manner comparable to N1,N4-bis(2,3-butadienyl)-1,4-butanediamine (MDL72527), an irreversible inhibitor of both enzymes. The two compounds were then tested for their effects in the PIT model. Both intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) administration of C9-4 decreased infarct volumes significantly. By contrast, C13-4 reduced the volume of brain infarction by i.c.v. administration, but no reduction was observed after i.p. administration. C9-4 administered by i.p. injection reduced the volume of brain infarction significantly at doses of more than 3 mg/kg, and the dosage of 5 mg/kg or 10 mg/kg demonstrated the most potent effect and were more effective than equivalent doses of the other inhibitors such as MDL72527 and N-benzylhydroxylamine. I.P. injection of 5 mg/kg of C9-4 provided a therapeutic time window of longer than 12 h. This report demonstrates that C9-4 is a potent inhibitor of the polyamine oxidizing enzymes and is useful lead compound for candidate drugs with a long therapeutic time window, to be used in the treatment of ischemic stroke.