N-(piperazinoacyl) and N-(piperazinoalkyl) derivatives of 4-cyclopentylaniline and related compounds: Synthesis and pharmacological screening

Five N-(4-cyclopentylphenyl)haloalkanecarboxamides were reacted with 1-methylpiperazine and 1-(2-hydroxyethyl)piperazine to give the corresponding N-(4-cyclopentylphenyl)piperazinoalkanecarboxamides Iab -Vab. Their reduction with lithium aluminium hydride afforded the triamines VIIab - XIab. Acylation of the N-(4-methylpiperazino)alkyl-4-cyclopentylanilines Xa and XIa with propionyl chloride resulted in the propionanilides XIVa and XVa, whereas a similar reaction of the N-(4-(2-hydroxyethyl)piperazino)alkyl-4-cyclopentylanilines VIIb and IXb - XIb produced the propionoxypropionanilides XIIc - XVc. Ethanolysis of these compounds afforded corresponding hydroxypropionanilides XIIb - XVb. Many of the basic amides showed local anaesthetic and papaverine-like antispasmodic activity. The propionanilides XIIb, XIVc, and XVa proved interesting analgesic effects in the peritoneal test in mice.

Basic amides of 2,4,5-trichlorophenoxyacetic, 2,4,6-trimethylphenoxyacetic and 4-bromo-3,5-dimethylphenoxyacetic acid and some related compounds; Synthesis and pharmacological screening

Reactions of methyl esters II of 2,4,5-trichlorophenoxyacetic (Ia), 2,4,6-trimethylphenoxyacetic (Ib) and 4-bromo-3,5-dimethylphenoxyacetic acid (Ic) with 2-diethylaminoethylamine, 2-morpholinoethylamine, 3-morpholinopropylamine, 1-methylpiperazine, 3-(4-methylpiperazino)propylamine, 3-[4-(2-tolyl)piperazino]propylamine and 1,4-bis(3-aminopropyl)piperazine in boiling ethanol gave the basic amides Va-XIc which were isolated as hydrochlorides. Reactions of the acid chlorides IVa and IVb with 1,4-bis(2-hydroxyethyl)piperazine and 1,4-bis(3-hydroxypropyl)piperazine in dimethylformamide resulted directly in dihydrochlorides of diesters XIIab and XIIIab. The compounds prepared have only weak CNS effects (mostly of the depressant type); they have local anaesthetic, mild hypotensive (some of them adrenolytic), antiarrhythmic and peripheral vasodilating activities.