During the study,
the first natural product inhibitor of Tie-2 kinase was
reported(103; Scheme 18) from the plant Acacia aulacocarpa,
and a set of four papers from another research group
demonstrated the activity of synthetic pyrrolo[2,3-d]pyrimidines
as inhibitors of the same class of kinases. The
details of the models used, the chemistry leading to the
nakijiquinone-based compounds, and the ribbon structures
of the kinase domain of the insulin receptor, with the
corresponding homology domains of the as yet uncrystallized
VEGFR-2 and Tie-2, have been fully reviewed