Trichomoniasis is a sexually transmitted disease that affects 153 million adults worldwide and 3.1 million in the United States. Trichomoniasis is an infection by the protozoan Trichomonas vaginalis. In recent years the resistance of T. vaginalis to current treatments, such as 5-nitroimidazole class of antitrichomonal drugs, has drastically increased. This accentuates the need for a novel treatment of trichomoniasis. One strategy is the inhibition of uridine nucleoside ribo-hydrolase (UNH), as T. vaginalis cannot produce its own purine or pyrimidine, and acquires these bases from their host. Previous studies showed 3-(3-methylpyridin-2-yl) benzonitrile displayed promising inhibition of UNH. Therefore, this compound’s motif was used as a starting point to create an array of analogs to test for UNH inhibition. Methylpyridin-2-yl-3-benzonitriles were synthesized under palladium catalyzed Suzuki coupling conditions using readily available cyanophenylboronic acids and 3-methyl-2-bromopyridine. Basic transformations such as hydrolysis were carried out at the cyano group to produce the amide and carboxylic acid moieties. In addition, the 3-methyl-2-bromopyridine was coupled with o- and p-phenolboronic acids. Similarly, 3-(4-methylpyridin-2-yl)benzonitrile was synthesized under Suzuki coupling conditions. Future work will include the hydrolysis the cyano group of 3-(4-methylpyridin-2-yl)benzonitrile to the amide and carboxylic acid moieties as well as the synthesis of 4-(4-methylpyridin-2-yl)phenol and 3-(4-methylpyridin-2-yl)phenol. The synthesis and UNH inhibitions of these compounds will be presented.

Synthesis of phenyl pyridine analogs via Suzuki coupling to inhibit uridine nucleoside ribohydrolase

2019 Spring National Meeting

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