Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics.

@article{Fraley2002OptimizationOA,
  title={Optimization of a pyrazolo[1,5-a]pyrimidine class of KDR kinase inhibitors: improvements in physical properties enhance cellular activity and pharmacokinetics.},
  author={Mark E. Fraley and Robert S. Rubino and William F. Hoffman and Scott R. Hambaugh and Kenneth L. Arrington and Randall W. Hungate and Mark T Bilodeau and Andrew J. Tebben and Ruth Z. Rutledge and Richard L. Kendall and Rosemary C. McFall and William R. Huckle and Kathleen E. Coll and Kenneth A. Thomas},
  journal={Bioorganic \& medicinal chemistry letters},
  year={2002},
  volume={12 24},
  pages={
          3537-41
        }
}
We have introduced solubilizing functionality to a 3,6-disubstituted pyrazolo[1,5-a]pyrimidine series of KDR kinase inhibitors to improve the physical properties of these compounds. The addition of a basic side-chain to the 6-aryl ring, introduction of 3-pyridyl groups, and most significantly, incorporation of a 4-pyridinonyl substituent at the 6-position of the core are modifications that maintain and often enhance the intrinsic potency of this class of inhibitors. Moreover, the improvements… 

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