Chemical Protection against Ionizing Radiation: III. Mercaptoalkylguanidines and Related Isothiuronium Compounds with Protective Activity

Abstract

A series of 16 isothiuronium salts, 27 amino or substituted aminoalkylisothiuronium salts, 13 thiazolines and 18 mercaptoalkylguanidines were tested for toxicity and screened for activity in mice given a lethal dose of X-radiation. The results clearly indicate that for high protective activity in this class of compounds, a guanido group must be within 2 or 3 carbon atoms of a thiol group. 2-Mercaptoethylguanidine (MEG), and 3-mercaptopropylguanidine (MPG), were more active and less toxic than 2-mercaptoethylamine (MEG), with an intraperitoneal therapeutic ratio of 2 to 1. Both MEG and MPG can be readily prepared in a pure state from the corresponding aminoalkylisothiuronium salts. The synthesis of S, 2-aminoethylisothiuronium Br HBr (AET) and evidence for its conversion to MEG are given.