Antiradiation Drugs: The Synthesis of Mercapto Amidines.
Final scientific rept. 1 Apr 69-31 Aug 72,
ILLINOIS UNIV MEDICAL CENTER CHICAGO
Pagination or Media Count:
N-Substituted-2-mercaptoacetamidines and functional derivatives, including the corresponding disulfides, Bunte salts, and phosphorothioates, have been synthesized and found as a class to be highly effective antiradiation agents. Variations in the N substituent include alkyl, cycloalkyl, cycloalkylalkyl, aralkyl, hydroxalkyl, cycloalkyloxyalkyl, aryloxyalkyl, thioethers, and heteroaralkyl groups. A synthesis other than the conventional ones was needed and developed for the key intermediate, N-substituted-ethyl 2-chloroacetimidate salt, in which the substituent possessed a bulky carbon skeleton. Treatment of 2-chloroacetamides with Meerweins reagent gave ethyl 2-chloroacetimidate fluoroborates I R1 or R2H or 2-chloro-1-ethoxyethylidenemethylammonium tetrafluoroborates I R1 and R2 do not equal H. This allowed displacement of alkoxide by NH3 rather than by a bulky amine. Half-life determinations in EtOH were made of purified samples of I in an attempt to correlate stability with successful preparation of 2-chloroacetamidine II. Use of 1-amino-2-propanol in the Pinner amidine synthesis resulted in a rearrangement to give an unusual diester, mercaptoacetic acid, 2-amino-1-methylethyl ester, S-thiosulfate ester III. Antiradiation data for 84 compds are presented. Survival rates of 90-100 in the 30-day tests were obtained for many compds given either ip or po at doses well below toxic levels. Modified author abstract
- Organic Chemistry