Simplified staurosporine analogs as potent JAK3 inhibitors.
Simplification of bottom ring and regioselective functionalization of the indolocarbazole unit of staurosporine (2) are described. The modification led to a new series of simplified staurosporine analogs, which exhibited significant inhibitory activity against Janus kinase 3 (JAK3). The structure-activity relationships (SAR) are discussed and a proposed binding model is also highlighted.
Yang
Shyh-Ming
SM
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, NJ 08512, USA. syang9@prdus.jnj.com
Malaviya
Ravi
R
Wilson
Lawrence J
LJ
Argentieri
Rochelle
R
Chen
Xin
X
Yang
Cangming
C
Wang
Bingbing
B
Cavender
Druie
D
Murray
William V
WV
D000255:Adenosine Triphosphate / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D007202:Indicators and Reagents; D053616:Janus Kinase 3 / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D011485:Protein Binding; D019311:Staurosporine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D000255:Adenosine Triphosphate; D053616:Janus Kinase 3; D019311:Staurosporine