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3,5,6-Trisubstituted naphthostyrils as CDK2 inhibitors. | LitMetric

3,5,6-Trisubstituted naphthostyrils as CDK2 inhibitors.

Bioorg Med Chem Lett

Department of Discovery Chemistry, Hoffmann-La Roche Inc., 340 Kingsland Street, Nutley, NJ 07110, USA.

Published: August 2003

A novel class of 3,5,6-trisubstituted naphthostyril analogues was designed and synthesized to study the structure-activity relationship for inhibition of cyclin-dependent kinase 2 (CDK2). These compounds, particularly molecules with side-chain modifications providing additional hydrogen bonding capability, were demonstrated to be potent CDK2 inhibitors with cellular activities consistent with CDK2 inhibition. These molecules inhibited tumor cell proliferation and G1-S and G2-M cell-cycle progression in vitro. The X-ray crystal structure of a 2-aminoethyleneamine derivative bound to CDK2, refined to 2.5A resolution, is presented.

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http://dx.doi.org/10.1016/s0960-894x(03)00488-8DOI Listing

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