In recent years, polo-like kinase-1 (PLK1) has attracted much attention as a primary drug development target in proliferative diseases. During our efforts to find novel and potent PLK1 inhibitors, 5,6-dihydroimidazo-[1,5-f]pteridine-7-carbonitrile core was discovered, with promising in vitro/in vivo activity. However, the synthetic route was lengthy, suffered from poor yields and lacked a late stage diversification point for efficient analog production. In this poster, we present the development of shorter and higher yielding synthetic route, enabling multigram preparation of advanced intermediates. In addition, the details of a key cyclization step to form the imidazole moiety will be presented.

Development of a novel synthetic route to highly potent and efficacious 5,6-dihydroimidazo[1,5-f]pteridine-7-carbonitrile inhibitors of polo-like kinase-1

243rd National Meeting (2012)

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