Michael E. Perlman

Solution-phase, parallel synthesis and pharmacological evaluation of acylguanidine derivatives as potential sodium channel blockers.

Solution-phase synthesis of various acylguanidine derivatives and the evaluation of a small library of compounds as potential sodium channel blockers are described.

Chemical mechanism of the radiation potentiating effects of 2,2-Dimethylaziridine-type antitumor agents☆

Abstract Three 2,2-dimethyl phosphoraziridines, bis(2,2-dimethylaziridinyl)phosphinyl urethane (AB-132, NSC 51325), ethyl bis(2,2-dimethylaziridinyi)phosphinate (AB-163 NSC 108878) and bis(2,2-dimethylaziridinyl)-N-hydroxyurethane (AB-182, NSC 200724) which have shown synergistic antitumor effects in conjunction with X-irradiation, are characterized by their rapid hydrolysis via S N 1-mechanism and via the formation of transient 5-membered cyclic intermediates exhibiting phosphorylating activities. It was shown that the formation of the latter correlates with the observed maxima in the cholinesterase inhibitory effects of these compounds. It is proposed that the same intermediate hydrolysis products may block the repair of X-irradiation induced breaks in the DNA strands by phosphorylating their free YOH end groups. Additional mechanisms of the radiation potentiating effects of these compounds (not shown by their C-unsubstituted analogs), involving free radical-ion formation, are currently under investigation.