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pubmed:abstractText |
Structure-based design approach was successfully used to guide the evolution of imidazopyridine scaffold yielding new structural class of highly selective inhibitors of cyclin dependent kinases that were able to form a new interaction with an identified residue of the protein, Lys89. Compounds from this series have shown no detectable effect when tested against a representative set of other serine/threonine kinases such as GSK3beta, CAMKII, PKA, PKC-alpha,beta,epsilon,gamma. Compound 2i inhibits proliferation in HCT 116 cells in tissue culture. Synthesis, co-crystal structure of CDK2 in complex with compound 2i, and preliminary SAR study are disclosed.
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pubmed:affiliation |
Lilly Research Laboratories, A Division of Eli Lilly and Company, Lilly Corporate Center, DC: 0540, Indianapolis, IN 46285, United States. hamdouchi_chafiq@lilly.com
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