MEDI 354 |
| Cyclin-dependent kinases (CDKs) are members of a family of serine-threonine protein kinases responsible for regulation of the eukaryotic cell cycle. A number of CDK inhibitors, such as flavopiridol, 7-hydroxystaurosporine (UCN-01), roscovitine (CYC202), BMS-387032 (SNS-032), PD0332991, and R547, have been studied in clinical trials for the treatment of cancer. Towards developing CDK inhibitors as anti-cancer agents, we recently reported that 3-benzoimidazoyl pyrazolopyridines (1) are novel potent anti-cancer CDK inhibitors and anti-proliferative agents. To discover structurally different CDK inhibitors with improved pharmacokinetic and solubility properties, we have designed, synthesized, and evaluated two related series of 3,4-disubstituted pyrazole analogs, in particular, 3-(imidazol-2-yl)-4-(2-pyridin-3-yl-vinyl)-pyrazole analogs (2) and 3-(benzoimidazol-2-yl)-4-(2-pyridin-3-yl-vinyl)-pyrazole analogs (3), as novel CDK inhibitors. The design, synthesis, and preliminary biological evaluation of these pyrazole compounds will be presented.
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Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Medicinal Chemistry |
