1. AMRI, Medicinal Chemistry Department, 26 Corporate Circle, PO Box 15098, Albany, NY 12212-5098, USA;2. Albany Medical College, Center for Immunology and Microbial Disease, 47 New Scotland Avenue, Albany, NY 12208-3479, USA
Abstract:
The introduction of an aryl ring onto the 4-position of the C-6 benzyl amino group of the Cdk inhibitor roscovitine (2), maintained the potent Cdk inhibition demonstrated by roscovitine (2) as well as greatly improving the antiproliferative activity. A series of C-6 biarylmethylamino derivatives was prepared addressing modifications on the C-6 biaryl rings, N-9 and C-2 positions to provide compounds that displayed potent cytotoxic activity against tumor cell lines. In particular, derivative 21h demonstrated a >750-fold improvement in the growth inhibition of HeLa cells compared to roscovitine (2).