130564-54-4Relevant academic research and scientific papers
SYNTHESIS OF 1-ACYL- AND 1-(THIOACYL)-4-BENZYLPIPERAZINES AS POTENTIAL ANTIDEPRESSANTS
Kmonicek, Vojtech,Svatek, Emil,Holubek, Jiri,Ryska, Miroslav,Valchar, Martin,Protiva, Miroslav
, p. 1817 - 1827 (2007/10/02)
2-Nitro, 3-nitro- and 4-nitrobenzoyl chloride were reacted with 1-benzylpiperazine in benzene in the presence of triethylamine and gave the amides IV-VI, the first of which is considered a bioisostere of the antidepressant agent piberaline (I). 2-Dimethylamino-, 3-dimethylamino- and 4-dimethylaminobenzoic acid were treated with thionyl chloride in benzene in the presence of triethylamine or pyridine, and the acid chlorides formed were reacted in situ with 1-benzylpiperazine affording the amides VII-IX.The amides I and IV - VI were transformed by treatment with phosphorus pentasulfide in pyridine to the thioamides X - XIII. 4-(Dimethylaminomethyl)benzoic acid was reacted with 1-benzylpiperazine in dimethylformamide in the presence of N,N'carbonyldiimidazole and afforded the amide XIV.Heating of ethyl 5-methylimidazole-4-carboxylate with 1-benzylpiperazine to 200 - 210 deg C gave the amide XV together with the unexpected 1-benzyl-4-ethylpiperazine (XVI).The oily or crystalline bases of the amino amides or thioamides were mostly transformed to crystalline salts and characterized by spectra.Out of the compounds prepared only X (VUFB-17070) and XIV (VUFB-17114) showed indications of efficacy in tests which are considered indicative of antidepressant activity.Compounds VII, VIII, and X appeared to be mildly antidopaminergic-similarly like piberaline (I), and compounds IV, V, XI, XIV, and XV on the contrary showed signs of dopaminominetic activity.
