- (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.
(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 chemistry (2005-12-22)
Chih Y Ho, Donald W Ludovici, Umar S M Maharoof, Jay Mei, Jan L Sechler, Robert W Tuman, Eric D Strobel, Laura Andraka, Hwa-Kwo Yen, Gregory Leo, Jian Li, Harold Almond, Hong Lu, Ann DeVine, Rose M Tominovich, Judith Baker, Stuart Emanuel, Robert H Gruninger, Steven A Middleton, Dana L Johnson, Robert A Galemmo
PMID16366598
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).
MATERIALS