Paper
NAPHTHYLPIPERAZINES AND TETRALYLPIPERAZINES: SYNTHESIS AND PHARMACOLOGICAL PROPERTIES*
Published Jan 1, 1975 · DOI · I. Červená, A. Dlabač, J. Němec
Collection of Czechoslovak Chemical Communications
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Abstract
Heating of 1- and 2-naphthylamine hydrochlorides and of 5- and 6-tetralylamine hydrochlorides with diethanolamine hydrochloride produced naphthylpiperazines la and Ila and tetralylpiperazines Ilia and IVa. These secondary amines were treated with ethyl chloroformate or with acetic anhydride and then reduced; or underwent an addition of methyl acrylate or acrylonitrile and then were reduced; or finally underwent alkylation by 4-methoxyphen acyl bromide and 4-chloro^-fluorobutyrophenone to the corresponding N-alkyl derivatives which were evaluated pharmacologically. l-(6-Tetralyl)-4-methylpiperazine ( IVd) displayed a marked antireserpine effect in the test of eyelid ptosis in mice, 4-[3-(4-fluorobenzoyl)propyl]-l-(6-tetralyl)piperazine (IVk) was active neuroleptically. 1-Arylpiperazine derivatives have been often reported as neurotropic and cardiovascular agents; for the case that the aryl substituent is phenyl or a substituted phenyl, several examples of this type were reported recently1. The aryl in these compounds can also be bicyclic or tricyclic and can contain heteroatoms; thus, e.g., l-(2-pyridyl)piperazine derivative "azaperone" is a sedative used in veterinary practice2, the l-(2-pyrimidyl)piperazine derivative "piribedil" has the properties of a peripheral vasodilatant and a potential antiparkinsonic3 , l-(2-quinolyl) piperazine is the "quipazine"4 with serotoninergic and antitremorine activity, the l-(2-purinyl)piperazines are central depressants5, l-(thieno [2,3-d] pyrimidine-4-yl)piperazines show antihistamine activity6, l-(5-methyl-5if-pyrimido [3,4-6]-l,4-benzoxazin-3-yl)-4-methylpiperazine is the antidepressant agent "azaphene"7; on the other hand, l-(2- and 3-phenothiazinyl)piperazines displayed no interesting pharmacodynamic activity8. Little attention has been devoted to the napThthylpiperazines; patents9,10 report a central depressant activity for l-(l-aryl-2-propyl)-4-(naphthyl)piperazines and a sedative, myorelaxant and analgesic activity for l-(dihydronaphthyl)piperazines. The present communication contributes to the present knowledge of the pharmacodynamics of naphthylpiperazines and tetralylpiperazines. Prelog and Blazek11 described the preparation of l-(l-naphthyl )piperazine (la) and l-(2-naphthyl)piperazine (II a) by reactions of naphthylamine s with bis(2-bromo
Naphthylpiperazines and tetralylpiperazines show potential as neurotropic and cardiovascular agents, with l-(6-Tetralyl)-4-methylpiperazine showing neuroleptic activity.
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