Cyclin-dependent kinases (CDKs) are serine/threonine kinases that play key roles in the regulation of cell cycle progression. Disruptions in regular CDK activity is known to be associated with cancer, proliferative renal diseases, and neurodegenerative disorders making them prime targets for therapeutics. It is currently known that CDK1, 2, 4, and 6 are directly involved in the cell cycle regulation, while CDK7 and 9 control processes such as transcription. CDK5 is highly expressed in the nervous system and studies have shown it to be deregulated in several neuronal diseases. Developmental origin of the tumors dictate the requirements of specific interphase CDKs for different types of cancers based on their origin. Identification of CDK isozyme-specific inhibitors has been challenging with very little success mainly due to their high sequence homology. The goal of the project is to use molecular modeling tools to design molecules that act as isozyme specific inhibitors of CDK. This is done by designing and synthesizing new derivatives of indazolones and phthalimides as potential ATP-competitive inhibitors of CDKs. The synthetic protocol for the derivatization of the phthalimides and indazolones has been established paving the way for the synthesis of newly designed derivatives.

Synthesis of indazolones and pthalimides as potential cyclin dependent kinase inhibitors

251st National Meeting (2016)

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