SYNTHESIS AND CENTRAL NERVOUS SYSTEM DEPRESSANT ACTIVITY OF NEW PIPERAZINE AND RELATED DERIVATIVES .3.

Several N1,N4-disubstituted piperazine derivatives, in which N1 substituents are 3,4,5-trimethoxybenzoylacetyl, 3,4,5-trimethoxycinnamoyl or -hydrocinnamoyl, 3,4,5-trimethoxyphenylpropyl, and 3,4,5-trimethoxybenzoylalkyl and N4 substituents are benzyl, m-methyl- or p-t-butylbenzyl, p-chloro-α-phenylbenzyl, phenyl, chloro-, fluoro-, or methoxyphenyl, tolyl α,α,α,-trifluorotolyl, 2-pyridyl, 2-pyrimidyl, or 2-thiazoyl groups, have been synthesized. Analogous compounds with other alkyl and heterocyclic amines in place of piperazine have also been synthesized. All these compounds have been screened for CNS activity. A few of these compounds exhibited significant CNS depressant activity. The 3,4,5-trimethoxyphenyl moiety was found to be the most essential for CNS activity as stepwise omission of the methoxy groups of most active compounds resulted in loss of activity. © 1969, American Chemical Society. All rights reserved.