The cyclin dependent kinases (Cdk) are a family of at least nine Ser/Thr protein kinases. Regulatory subunits called cyclins (Cyc) bind specific Cdk partners to form activated Cdk/Cyc complexes. These activated complexes play important roles in cell cycle control, transcription, and apoptosis. Cdk4/CycD1, Cdk2/CycE, Cdk2/CycA, and Cdk1/CycB have been identified as key regulators of the eukaryotic cell cycle. Defects in cell cycle machinery can lead to unregulated cell proliferation, and it has been shown that unregulated Cdk activity is a common feature of tumor development. Inhibitors of the Cdk/Cyc complexes would be expected to behave as cytostatic/cytotoxic agents for the treatment of cancer. This presentation describes the synthesis and SAR of a series of indenopyrazoles as broad-spectrum, potent inhibitors of the cyclin dependent kinases. The leading candidates that we have identified, RGB-286199 and RGB-286638, show potential for clin. activity.