title: Indole RSK inhibitors. Part 2: optimization of cell potency and kinase selectivity.
abstract: A series of inhibitors for the 90 kDa ribosomal S6 kinase (RSK) based on an 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide scaffold were optimized for cellular potency and kinase selectivity. This led to the identification of compound 24, BIX 02565, an attractive candidate for use in vitro and in vivo to explore the role of RSK as a target for the treatment heart failure.
authors: Department of Medicinal Chemistry, Boehringer-Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, PO Box 368, Ridgefield, CT 06877, USA. tom.kirrane@boehringer-ingelheim.com
authors: Thomas M
authors: TM
authors: Kirrane
authors: Stephen J
authors: SJ
authors: Boyer
authors: Jennifer
authors: J
authors: Burke
authors: Xin
authors: X
authors: Guo
authors: Roger J
authors: RJ
authors: Snow
authors: Lida
authors: L
authors: Soleymanzadeh
authors: Alan
authors: A
authors: Swinamer
authors: Yunlong
authors: Y
authors: Zhang
authors: Jeffery B
authors: JB
authors: Madwed
authors: Mohammed
authors: M
authors: Kashem
authors: Stanley
authors: S
authors: Kugler
authors: Margaret M
authors: MM
authors: O'Neill
mesh_terms: D000577:Amides / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D008968:Molecular Conformation; D009584:Nitrogen / Q000737:chemistry; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D004791:Enzyme Inhibitors; D007211:Indoles; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D009584:Nitrogen