(6,7-Dimethoxy-2,4-dihydroindeno[1,2-c]pyrazol-3-yl)phenylamines: Platelet-Derived Growth Factor Receptor Tyrosine Kinase Inhibitors with Broad Antiproliferative Activity against Tumor Cells
Journal of Medicinal Chemistry2005Vol. 48(26), pp. 8163–8173
Citations Over TimeTop 24% of 2005 papers
Chih Y. Ho, Donald Ludovici, Umar S. M. Maharoof, Jay Mei, Jan L. Sechler, Robert W. Tuman, Eric D. Strobel, Laura Andraka, Hwa-Kwo Yen, Gregory C. Leo, Jian Li, Harold R. Almond, Hongfang Lu, Ann Devine, Rose Tominovich, Judith F. Baker, Stuart L. Emanuel, Robert H. Gruninger, Steven A. Middleton, Dana L. Johnson, Robert A. Galemmo
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).
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