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(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.

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).
AuthorsChih 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 Jr
JournalJournal of medicinal chemistry (J Med Chem) Vol. 48 Issue 26 Pg. 8163-73 (Dec 29 2005) ISSN: 0022-2623 [Print] United States
PMID16366598 (Publication Type: Journal Article)
Chemical References
  • (6,7-dimethoxy-2,4-dihydroindeno(1,2-c)pyrazol-3-yl)(3-fluorophenyl)amine
  • Antineoplastic Agents
  • Indans
  • Platelet-Derived Growth Factor
  • Proto-Oncogene Proteins c-sis
  • Pyrazoles
  • Becaplermin
  • Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor
Topics
  • Antineoplastic Agents (chemical synthesis, pharmacology)
  • Becaplermin
  • Cell Line
  • Cell Line, Tumor
  • Endothelium, Vascular (drug effects)
  • Humans
  • Indans (chemical synthesis, pharmacology)
  • Inhibitory Concentration 50
  • Platelet-Derived Growth Factor (antagonists & inhibitors)
  • Protein-Tyrosine Kinases (antagonists & inhibitors)
  • Proto-Oncogene Proteins c-sis
  • Pyrazoles (chemical synthesis, pharmacology)
  • Receptors, Platelet-Derived Growth Factor (antagonists & inhibitors)

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