Accession Number : AD0760626

Title :   Antiradiation Drugs: The Synthesis of Mercapto Amidines.

Descriptive Note : Final scientific rept. 1 Apr 69-31 Aug 72,

Corporate Author : ILLINOIS UNIV MEDICAL CENTER CHICAGO

Personal Author(s) : Bauer,Ludwig

Report Date : 25 APR 1973

Pagination or Media Count : 18

Abstract : 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 Meerwein's reagent gave ethyl 2-chloroacetimidate fluoroborates (I) (R(1) or R(2)=H) or (2-chloro-1-ethoxyethylidene)methylammonium tetrafluoroborates (I) (R(1) and R(2) 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)

Descriptors :   (*RADIOPROTECTIVE AGENTS, SYNTHESIS(CHEMISTRY)), (*ORGANIC SULFUR COMPOUNDS, SYNTHESIS(CHEMISTRY)), SALTS, AMINES, THIOLS, THIOSULFATES

Subject Categories : Radiobiology
      Pharmacology
      Organic Chemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE