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New class of azaheptapyridine FPT inhibitors as potential cancer therapy agents
Hugh Y Zhu1, Jagdish Desai1, Alan B Cooper1
1Merck Research Laboratories, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA.
Abstract:
Tertiary hydroxyl class of C-imidazole bridgehead azaheptapyridine FPT inhibitors were prepared in an attempt to block in vivo oxidation of secondary hydroxyl series. One representative compound 5a exhibited potent enzyme (IC50=1.4 nM) and cellular activities (soft agar IC50=1.3 nM) with excellent oral pharmacokinetic profiles in rats, mice, monkeys and dogs. The in vivo study in wap-ras TG mouse models showed dose dependent tumor growth inhibition and regression.
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