(6,7-Dimethoxy-2,4-dihydroindeno[1,2-<i>c</i>]pyrazol-3-yl)phenylamines:  Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitors with Broad Antiproliferative Activity against Tumor Cells

Abstract

A series of (6,7-dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines has been optimized to preserve both potent kinase inhibition activity against the angiogenesis target, the receptor tyrosine kinase of Platelet-Derived Growth Factor-BB (PDGF-BB), and to improve the broad tumor cell antiproliferative activity of these compounds. This series culminates in the discovery of 17 (JNJ-10198409), a compound with anti-PDGFR-beta kinase activity (IC(50)=0.0042 microM) and potent antiproliferative activity in six of eight human tumor cell lines (IC(50) < 0.033 microM).