M. B. Navrotskii
Sep 1, 2003
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Journal
Pharmaceutical Chemistry Journal
Abstract
It was reported that 5-alkyl-2-(alkoxy)-6-(arylmethyl)4(3H)-pyrimidinones [1], as well as their sulfurous analogs 5-alkyl-2-(alkylthio)-6-(arylmethyl)-4(3H)-pyrimidinones [2], exhibit anti-HIV-1 activity. In a systematic investigation of the role of the nature of substituents at the sulfur atom on the biological activity spectrum of pyrimidinone derivatives, we have synthesized and studied a series of new 2-(alkylthio)6-benzhydryl-4(3H)-pyrimidinones (Ia – Ii). The new compounds were synthesized using a four-stage procedure proceeding from 2,2-diphenylacetic acid. In the first step, this acid was converted into chloroanhydride (I) under the action of phosphorus pentachloride in toluene as described in [3]. In the next step, 2,2-diphenylacetyl chloride (II) was converted into methyl-4,4-diphenyl-3-oxobutanoate (III) via a modified Oikawa – Yonemitsu method [4]. Then, compound III was condensed with thiourea in the presence of sodium methylate so as to obtain 6-benzhydryl-2-thioxo-2,3dihydro-4(1H)-pyrimidinone (IV). Finally, reactions of the latter compound with various alkylating agents (Table 1) yielded the target 2-(alkylthio)6-benzhydryl-4(3H)-pyrimidinones (Ia – Ii), some properties of which are presented in Table 2.