Pg. Penketh et al., STUDIES ON THE MECHANISM OF DECOMPOSITION AND STRUCTURAL FACTORS AFFECTING THE AQUEOUS STABILITY OF 1,2-BIS(SULFONYL)-1-ALKYLHYDRAZINES, Journal of medicinal chemistry, 37(18), 1994, pp. 2912-2917
1,2-Bis(sulfonyl)-1-alkylhydrazines are highly active experimental ant
ineoplastic agents which decompose with first-order kinetics in neutra
l aqueous solutions. These agents generate approximately 2 mol of the
corresponding sulfinate, 1 mol of nitrogen, and 1 mol of the appropria
te alcohol, produced as a consequence of the alkylation of water. Incr
easing the leaving-group ability of the sulfonyl moiety on N-1 shorten
s the half-life, while the converse happens with N-2 substitutions. Li
near Hammett relationships are found for both types of substitutions.
The predictable kinetics of decomposition makes these agents potential
candidates for use in regional chemotherapy, where compounds with tun
able short half-lives may offer some advantage. Prodrugs of extremely
short-lived derivatives of this class may also have utility as targete
d alkylating agents.