Synthesis and evaluation of novel 2,4-disubstituted arylthiazoles against T. brucei.

ABSTRACT

The design, synthesis and pharmacological evaluation of the 4-substituted-2-[3-(adamant-1-yl)-4-fluorophenyl]thiazoles 1a-j, the 4-substituted-2-[4-(adamant-1-yl)phenyl]thiazoles 2a-h, the 2-substituted-4-[4-(adamant-1-yl)phenyl]thiazoles 3a-e, the N-substituted 2-phenylthiazol-4-ethylamides 4a, b and the N-substituted 4-phenylthiazol-2-ethylamides 4c, d is described. Compounds 1a and 2a exhibit trypanocidal activity in the range of IC50 = 0.42 µM and IC50 = 0.80 µM, respectively. Both of these derivatives bear a lipophilic end, which consists of a 4-(1-adamantyl) phenyl or a 3-(1-adamantyl)phenyl moiety, a 1,3-thiazole ring and a functional end, which comprises of an alkylamine and can be considered as promising candidates for the treatment of Trypanosoma brucei infections.