title: Simplified staurosporine analogs as potent JAK3 inhibitors.
abstract: 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.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, L.L.C., 8 Clarke Drive, Cranbury, NJ 08512, USA. syang9@prdus.jnj.com
authors.forename: Shyh-Ming
authors.initials: SM
authors.lastname: Yang
authors.forename: Ravi
authors.initials: R
authors.lastname: Malaviya
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Wilson
authors.forename: Rochelle
authors.initials: R
authors.lastname: Argentieri
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.forename: Cangming
authors.initials: C
authors.lastname: Yang
authors.forename: Bingbing
authors.initials: B
authors.lastname: Wang
authors.forename: Druie
authors.initials: D
authors.lastname: Cavender
authors.forename: William V
authors.initials: WV
authors.lastname: Murray
mesh_terms: 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
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D000255:Adenosine Triphosphate; D053616:Janus Kinase 3; D019311:Staurosporine