The research group specializes in Polo-like kinases (PLK) – a family of serine/threonine enzymes playing a critical role in the regulation of mitosis – and the inhibition of these. In a series of studies they have described the stereoselective synthesis of (1R,2S)-2-(1H-indazol-6-yl)spiro[cyclopropane-1,3′-indolin]-2′-ones as PLK4 Inhibitors, and now report one of these as a novel clinical candidate for cancer therapy.
Microwave reactions were performed on a Biotage® Initiator+ microwave synthesizer, and subsequent purification of intermediates and final products on an Isolera™ One flash purification system with Biotage® SNAP KP-Sil flash cartridges.
Sampson PB, Liu Y, Forrest B, Cumming G, Li SW, Patel NK, Edwards L, Laufer R, Feher M, Ban F, Awrey DE, Mao G, Plotnikova O, Hodgson R, Beletskaya I, Mason JM, Luo X, Nadeem V, Wei X, Kiarash R, Madeira B, Huang P, Mak TW, Pan G, Pauls HW. 2015. The discovery of Polo-like kinase 4 inhibitors: identification of (1R,2S).2-(3-((E).4-(((cis).2,6-dimethylmorpholino)methyl)styryl). 1H.indazol-6-yl)-5'-methoxyspiro[cyclopropane-1,3'-indolin]-2'-one (CFI-400945) as a potent, orally active antitumor agent. J Med Chem. 2015 Jan 8;58(1):147-69
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