Abstract: A series of indolylalkylphenylpiperazines (Ⅰ) was recently reported to be active central depressants. Variation in the length of the alkyl chains and change of substituents on the indole moiety or on the phenyl group influenced only the strength and specificity of the activity. However, removal of the phenyl group or replacement of it by an alkyl or arylalkyl group caused the loss of almost all of the central activities. It would seem possible to get even more favourable central depressants on further modification of the indole moiety, as long as the N-phenyl group was retained. The authors, therefore,synthesized a number of N-phenyl and chlorophenyl piperazine derivatives, the substituents on the other nitrogen being either isosteres of indole or pharmacologically interesting groups. These compounds were synthesized either by condensation of appropriate halides with N-phenyl or chlorophenyl piperazine, or by reduction of the corresponding amides (Ⅳ) by means of lithium aluminium hydride. The amides were in turn prepared by the interaction of acyl chlorides or acyl azides and N-phenyl or chlorophenyl piperazine respectively. Two of the amides were afforded on application of the Arndt-Eistert reaction. Two of these compounds, 1-(3,4,5-trimethoxyphenethyl)-4-phenylpiperazine and 1-(3,4,5-trimethoxyphenethyl)-4-(p-chlorophenyl)-piperazine exhibited marked tranquilizing activity in preliminary pharmacological examinations.