Discovery of a new potent bisamide FMS kinase inhibitor.

FMS is a type III receptor tyrosine kinase that binds to the macrophage or monocyte colony stimulating factor (M-CSF or CSF-1). Signal transduction through that binding results in survival, proliferation, and differentiation of monocyte/macrophage lineage. In this study, we report the discovery of a new potent inhibitor of FMS kinase. The synthesized pyrrolo[3,2-c]pyridine derivative (compound 1) was initially tested at a single concentration of 1 microM against 47 different kinases. At this concentration, the% inhibitions of the enzymatic activities of FMS and KDR kinases were 90% and 71%, respectively, while the inhibition in activity was less than 58% for all of the other kinases. For compound 1, the IC(50) values against FMS and KDR were 96 and 1058 nM, respectively. So, compound 1 was found to be 11 times more selective for FMS kinase than KDR kinase. Compound 1 can be used as a promising lead for the development of new selective inhibitors of FMS kinase, which can be used as useful therapeutic tools for treatment of several inflammatory and cancer disorders.