Edward F. Faslager, Judith L. Johnson, L. M. Werbel
Aug 1, 1973
Citations
0
Influential Citations
6
Citations
Journal
Journal of Heterocyclic Chemistry
Abstract
The condensation of 5-chloro-3-(trichloromethyl)-1,2,4-thiadiazole (VIII) with N,N-dimelhyl-1,3-propanediamine gave 5-¶ [3-(dimethylammo)propyl]amino¶-3-(trichloromethyl)-1,2,4-thia-diazole(5) and 5,5′-¶[3-(dimethylamino)propyl]imino)¶bis[3-(triehloromethyl)-1,2,4-tliiadiazole] (14), together with 5,5′-[(3-¶ methyl[ 3-(trichloromethyl)-1,2,4-thiadiazol-5-yl ]amino Jpropyl)-imino]bis[3-(trichloromethyl)-1,2,4-thiadiazole] (17) which was formed via an unusual displacement of the distal methyl group of 14. The remarkable antimalarial activity of 14 prompted the synthesis of an array of 5-amino-3-(trichloromethyl, methyl, and 3,4-dichlorophenyl)-1,2,4-thiadiazoles and 5,5′-¶[(dialkylamino)alkyl]imino¶bis[3-(trichloromethyl, methyl, and 3,4-dichlorophenyl)-1,2,4-thiadiazoles] from an amine and the requisite 5-chloro-3-substituted-1,2,4-thiadiazoles, which were prepared from the appropriate amidine and trichloromethylsull'enyl chloride. 5-¶3-[(Diethylamino)methyl]-p-anisidino ¶-3-(triehloromethyl)-1,2,4-thiadiazole (13) was active against a chloroquine-resistant line of Plasrnodium berghei in the mouse, and compound 14, the most promising member of the series overall, was designated for expanded antimalarial and toxicological studies. Structure-activity relationships against P. berghei in mice and P. gallinaceum in chicks are discussed.