Download (4Mb) - Etheses - Saurashtra University

Chapter – 4 Studies on different types of reactions…..
demonstrated that the cyclopropane moiety is critical in optimizing effective
molecular interactions. (Fig. 4.3)
2-Indolinone derivatives have recently been established as anti cancer
compounds 108 and more specifically as tyrosine kinase inhibitors (SU5416,
SU5614, SU6668, SU6597, SU6663 and SU6561-Fig. 4.4) that block kit
activation and growth of small cell in lung cancer. 109 Targeting receptor
kinase by novel indolinone derivatives like BIBF1000 in multiple myeloma
abrogration of stroma derived interleukin-6 secretion and induction of
apoptosis in cytogenetically with definite subgroups has been identified. 110
Various other analogs have been evaluated as kinase inhibitors, anticancer
and antiangiogenic agents with encouraging results. 111
After the first report of fibroblast growth factor receptor (FGFr-1) cocrystallization
with SU4984 and SU5402, the crystal structure of a receptor
tyrosine kinase (RTK) bound to a competitive inhibitor of ATP was identified.
112
These compounds are also inhibitors of both the vascular endothelial
growth factor receptor (TK flk-1) and vascular endothelial growth factor
(VEGF). SU4984 and SU5402 inhibit the autophosphorylation of FGFr with
IC50 values of 10-40 µM. 113
Fig. 4.3
Department of Chemistry, Saurashtra University, Rajkot – 360 005 194