Search for new tuberculostatics is an important task for medicinal chemistry. A series of new O-aroyl-β-(4-phenylpiperazin-1-yl)propioamidoximes were synthesized and tested for antituberculous activity in vitro. The synthesis of the target substances consists of 3 - 4 stages. At the first stage, β-(4-phenylpiperazin-1-yl)propionitrile was obtained with a yield of 79%; the second stage yields β-(4-phenylpiperazin-1-yl)propioamidoxime at an amount of 75%. The subsequent aroylation of this amidoxime by substituted benzoic acid chlorides in the presence of Et3N leads to the target O-aroyl-β-(4-phenylpiperazin-1-yl)propioamidoximes with a yield of 61 - 93%. Hydrochlorides of O-aroylated products were obtained with a yield of 72 - 94% by the action of ethereal HCl on the base solutions. 1H NMR spectra of hydrochlorides of O-aroylated products show evidence of a slow inversion of heterocycle at β-position and the coordination of HCl molecule at N1 atom of 4-phenylpiperazine fragment. Some bases and hydrochlorides of O-aroyl-β-(4-phenylpiperazin-1-yl)propioamidoximes exhibited interesting antituberculous properties when tested in vitro on sensitive, stable, and multi-drug-resistant strains of M. tuberculosis.
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