MEDI 456 |
| Several cyclin-dependent kinase (CDK) inhibitors have entered clinical evaluation for the treatment of cancer. These include flavopiridol, 7-hydroxystaurosporine (UCN-01), roscovitine (CYC202), BMS-387032 (SNS-032), and R547. In our program to develop CDK inhibitors as anti-cancer agents, we recently reported that 1-acyl-1H-[1,2,4]triazole-3,5-diamine analogs (1) and 2-amino-3-benzoyl-6-anilinopyridine analogs (2) are novel 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 several other series of compounds. Herein a series of 3,5-disubstituted pyrazolo[3,4-b]pyridine analogs (3) were synthesized as novel CDK inhibitors. These compounds showed potent and selective CDK inhibitory activities and inhibited in vitro cellular proliferation in various human tumor cells. Selected compounds were evaluated for efficacy in in vivo tumor xenograft studies. The synthesis, SAR study, and biological evaluation of these pyrazolopyridine compounds will be presented.
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General Oral Session
9:00 AM-12:20 PM, Thursday, August 23, 2007 BCEC -- 210B, Oral
Division of Medicinal Chemistry |
