TYRPHOSTINS .5. POTENT INHIBITORS OF PLATELET-DERIVED GROWTH-FACTOR RECEPTOR TYROSINE KINASE - STRUCTURE-ACTIVITY-RELATIONSHIPS IN QUINOXALINES, QUINOLINES, AND INDOLE TYRPHOSTINS

A series of 3-indoleacrylonitrile tyrphostins, 2-chloro-3-phenylquinol ines, and 3-arylquinoxalines were prepared and tested for inhibition o f platelet-derived growth factor receptor tyrosine kinase (PDGF-RTK) a ctivity. The potency of the inhibitors was found to be quinoxalines > quinolines > indoles. Lipophilic groups (methyl, methoxy) in the 6 and 7 positions and phenyl at the 3 position of quinoxalines and quinolin es were essential for potency, in contrast to the hydrophilic catechol group in tyrphostins active against EGFR kinase inhibition at differe nt sites. The inhibitors showed selectivity for PDGF and were not acti ve against EGF receptor and HER-2/c-ErbB-2 receptor.