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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Authors | 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 Jr |
Journal | Journal of medicinal chemistry
(J Med Chem)
Vol. 48
Issue 26
Pg. 8163-73
(Dec 29 2005)
ISSN: 0022-2623 [Print] United States |
PMID | 16366598
(Publication Type: Journal Article)
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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
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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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