SYNTHESIS, LIPOPHILICITY AND BIOLOGICAL EVALUATION OF INDOLE-CONTAINING DERIVATIVES OF 1,3,4-THIADIAZOLE AND 1,2,4-TRIAZOLE

3-[ (2-Methyl-1H-3-indolyl)methyl]-4-aryl-4, 5-dihydro-1H-1,2,4-triazo le-5-thiones 6a-c and their respective N-{5-[ (2-methyl-1H-3-indolyl) methyl] -1,3,4-thiadiazol-2-yl}-N-arylamines 7a,b have been prepared. The antidepressant profile of 6a,c and 7a was studied on mice with res pect to that of the analogous yl)-4-aryl-4,5-dihydro-1H-1,2,4-triazole -5-thiones 1a-c and the respective N-{5-[ (2-methyl-1H-3-indolyl) meth yl ]-1,3,4-thiadiazol-2-yl}-N-arylamines 2a-c, the synthesis and antim icrobial potency of which we have recently reported. Behavioral effect s, induced by the members of both series,in conjunction with their act ivity in some specific tests (forced swim, pentetrazole convulsions) o n mice, show that these derivatives cross the blood-brain barrier and could develop an antidepressant activity comparable to that of imipram ine. Blood-brain barrier penetration is also supported by the lipophil icity data obtained for all analogs. (C) 1998 Elsevier Science S.A. Al l rights reserved.