Pyrazolo[3,4-d]pyrimidine ribonucleosides as anticoccidials. 3. Synthesis and activity of some nucleosides of 4-[(arylalkenyl)thio]pyrazolo[3,4-d]pyrimidines

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Abstract
Ribonucleosides of 4-(alkylthio)-1H-pyrazdo[3,4-d]pyrimidines have been shown to be useful anticoccidial agents [Krenitsky, et. al.]. The unsaturated 4-allylthio and 4-crotylthio derivatives were more active in vivo against Eimeria tenella than their saturated congeners; therefore, some unsaturated (arylalkyl)thio derivatives were synthesized and investigated as anticoccidial agents. The novel compounds were prepared by the alkylation of 4-mercapto-1-.beta.-D-ribofuranosyl-1H-pyrazolo[3,4-d]pyrimidine, which was prepared by an enzymatic method. The (E)-4-cinnamylthio derivative and the 5''-monophosphate were the most active compounds against E. tenella in vivo. None of the analogs with substituents in the aryl moiety was more active than the (E)-4-cinnamylthio derivative in vivo. The geometry about the double bond was important, since the (Z)-4-cinnamylthio derivative was inactive both in vitro and in vivo. The 4-(3-phenylpropynyl)thio and 4-(5-phenyl-2,4-pentadienyl)thio derivatives were at least as active as the (E)-4-cinnaylthio derivative in vitro; they were less active than the (E)-4-cinnamylthio derivative in vivo. The (E)-4-cinnamylthio derivative was effective in vivo against E. tenella, E. necatrix, E. maxima and E. brunetti; these Eimeria spp. were controlled when the (E)-4-cinnamylthio derivative was given in the diet at levels up to 100 ppm. Infections in vivo due to E. acervulina were controlled by the (E)-4-cinnamylthio derivative only at .apprx. 800 ppm. The broad spectrum of anticoccidial activity shown by 2 represents a significant improvement over the activities reported for related compounds, et. al. 1982.

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