504413-28-9Relevant academic research and scientific papers
Structure-based design of a new class of highly selective aminoimidazo[1,2-a]pyridine-based inhibitors of cyclin dependent kinases
Hamdouchi, Chafiq,Zhong, Boyu,Mendoza, Jose,Collins, Elizabeth,Jaramillo, Carlos,De Diego, Jose Eugenio,Robertson, Daniel,Spencer, Charles D.,Anderson, Bryan D.,Watkins, Scott A.,Zhang, Faming,Brooks, Harold B.
, p. 1943 - 1947 (2005)
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 GSK3β, CAMKII, PKA, PKC-α,β,ε,γ. 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.
Aminoimidazo[1,2-a]pyridines as a new structural class of cyclin-dependent kinase inhibitors. Part 1: Design, synthesis, and biological evaluation
Jaramillo, Carlos,De Diego, J. Eugenio,Hamdouchi, Chafiq,Collins, Elizabeth,Keyser, Heather,Sánchez-Martínez, Concha,Del Prado, Miriam,Norman, Bryan,Brooks, Harold B.,Watkins, Scott A.,Spencer, Charles D.,Dempsey, Jack Alan,Anderson, Bryan D.,Campbell, Robert M.,Leggett, Tellie,Patel, Bharvin,Schultz, Richard M.,Espinosa, Juan,Vieth, Michal,Zhang, Faming,Timm, David E.
, p. 6095 - 6099 (2007/10/03)
Synthesis of 2-aminoimidazo[1,2-a]pyridines 1 and their evaluation as CDK2 inhibitors is described. We have identified a novel structural class of protein serine/threonine kinase inhibitors comprised of an aminoimidazo[1,2-a]pyridine nucleus. Compounds from this family are shown to potently inhibit cyclin-dependent kinases by competing with ATP for binding to a catalytic subunit of the protein. Structure-based design approach was used to direct this chemical scaffold toward generating potent and selective CDK2 inhibitors. The discovery of this new class of ATP-site directed protein kinase inhibitors, aminoimidazo[1,2-a]pyridines, provides the basis of new medicinal chemistry tool in search for an effective treatment of cancer and other diseases that involve protein kinase signaling pathways.
Regioselective synthesis of 3,6-disubstituted-2-aminoimidazo[1,2-a]pyridines
Jaramillo, Carlos,Carretero, Juan Carlos,De Diego, J.Eugenio,Del Prado, Miriam,Hamdouchi, Chafiq,Roldán, José Luis,Sánchez-Martínez, Concha
, p. 9051 - 9054 (2007/10/03)
A convenient synthesis of 3,6-disubstituted-2-aminoimidazo[1,2-a]pyridines 3 is described. A halogen-metal exchange study on building block 1 showed that use of i-propyl magnesium chloride is most effective for chemoselective functionalization at position
