7-[1H-Indol-2-yl]-2,3-dihydro-isoindol-1-ones as dual Aurora-A/VEGF-R2 kinase inhibitors: design, synthesis, and biological activity.
A novel series of 7-[1H-indol-2-yl]-2,3-dihydro-isoindol-1-ones designed to be inhibitors of VEGF-R2 kinase was synthesized and found to potently inhibit VEGF-R2 and Aurora-A kinases. The structure-based design, synthesis, and initial SAR of the series are discussed.
Hughes
Terry V
TV
Johnson & Johnson Pharmaceutical Research and Development, L.L.C, PO Box 300, 1000 Route 202, Raritan, NJ 08869, USA. hughe007@hotmail.com
Emanuel
Stuart L
SL
O'Grady
Harold R
HR
Connolly
Peter J
PJ
Rugg
Catherine
C
Fuentes-Pesquera
Angel R
AR
Karnachi
Prabha
P
Alexander
Richard
R
Middleton
Steven A
SA
D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D007211:Indoles; D042442:Vascular Endothelial Growth Factors; D020794:Receptor Protein-Tyrosine Kinases; C576918:Aurka protein, mouse; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases