(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

  • J Med Chem. 2005 Dec 29;48(26):8163-73. doi: 10.1021/jm050680m.
Chih Y Ho  1 ,  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 Jr
Affiliations
  • 1. Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Spring House Research and Early Development Site, Spring House, Pennsylvania 19477, USA.
PMID: 16366598 DOI: 10.1021/jm050680m
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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