Synthesis and pharmacological activity of malonoyl/oxaloyl hydrazones of 5-substituted indole-3-carboxaldehydes, 3-terephthaloyl bis-1-(5 '-substituted-2 '-phenyl inbol-3 '-yl)-3-thioureas and their derivatives

Abstract

Malonoyl/oxaloyl hydrazones (IIIa-f) of 5-substituted-2-phenyl indole-3-carboxaldehydes were subjected to oxidative cyclization with ferric chloride and acetic acid to get respective methylene bis-2-[5-(5'-substituted-2'-phenyl indol-3'-yl)] yl-1,3,4-oxadiazoles (IVa-f), which on further reaction with hydrazine hydrate/phenyl hydrazine afforded the respective methylene bis/bis-2-[1-amino/1-phenylamino-5-(5'-substituted-2'-phenyl indol-3'-yl)]yl-1,3,4-oxadiazoles (Va-f and Vla-f) respectively. Compounds (IIIa-f) were converted into methylene bis/bis-3-carboxamidyl-[2-(5'-substituted-2'-phenyl indol-3'-yl)]-1,3-thiazolidin-4-ones (VIIa-f) by their reaction with thioglycollic acid in dry benzene. Compounds (IIIa-f) when allowed to react with malonic acid in acetyl chloride to give methylene bis/bis-4-(5'-substituted-2'-phenyl indol-3'-yl)-1-carboxamidyl azetidin-2-ones (VIIIa-f). 3-Terephthaloyl bis-1-(5'-substituted-2'-phenyl indol3'-yl)-3-thioureas (Xla-c) were synthesised by the reaction of 5-substituted-2-phenyl-3-amino indoles (Xa-c), terephthaloyl chloride and ammonium thiocyanate in dry acetone. These compounds (Xla-c) on reaction with chloroacetic acid in dioxan ethanol mixture in presence of catalytic amount of pyridine, chloroacetic acid in presence of sodium acetate in dimethylformamide and malonic acid in acetyl chloride afforded 3-terephthaloyl bis-1-(5'-substituted-2'-phenyl indol-3'-yl)-3-yl-2-thiohydantoins (XIIac), terephthaloyl bis-2-(5'-substituted-2'-phenyl indol3'-yl) imino-3-yl-thiazolidin-4-ones (XIIIa-c) and 3-terephthaloyl bis-1-(5'-substituted-2'-phenyl indol-3'-yl)-2-thioxo-4H, 5H, 6H-pyrimidine-4,6-diones (XIVa-c) respectively, some of the synthesised compounds were screened for their antiinflammatory and antimicrobial activity against the organisms E. coli, S. aureus, P. vulgaris, A. niger and C. albicans. Few compounds exhibited significant antiinflammatory and antimicrobial activity.