title: Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.
abstract: Based on the lead compound BX-517, a series of C-4' substituted indolinones have been synthesized and evaluated for PDK1 inhibition. Modification at C-4' of the pyrrole afforded potent compounds (7b and 7d) with improved solubility and ADME properties. In this letter, we describe the synthesis, selectivity profile, and pharmacokinetic data of selected compounds.
authors.affiliation: Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA. imadulislam@yahoo.com
authors.forename: Imadul
authors.initials: I
authors.lastname: Islam
authors.forename: Greg
authors.initials: G
authors.lastname: Brown
authors.forename: Judi
authors.initials: J
authors.lastname: Bryant
authors.forename: Paul
authors.initials: P
authors.lastname: Hrvatin
authors.forename: Monica J
authors.initials: MJ
authors.lastname: Kochanny
authors.forename: Gary B
authors.initials: GB
authors.lastname: Phillips
authors.forename: Shendong
authors.initials: S
authors.lastname: Yuan
authors.forename: Marc
authors.initials: M
authors.lastname: Adler
authors.forename: Marc
authors.initials: M
authors.lastname: Whitlow
authors.forename: Dao
authors.initials: D
authors.lastname: Lentz
authors.forename: Mark A
authors.initials: MA
authors.lastname: Polokoff
authors.forename: James
authors.initials: J
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Shen
authors.forename: Janette
authors.initials: J
authors.lastname: Walters
authors.forename: Elena
authors.initials: E
authors.lastname: Ho
authors.forename: Babu
authors.initials: B
authors.lastname: Subramanyam
authors.forename: Daguang
authors.initials: D
authors.lastname: Zhu
authors.forename: Richard I
authors.initials: RI
authors.lastname: Feldman
authors.forename: Damian O
authors.initials: DO
authors.lastname: Arnaiz
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D045744:Cell Line, Tumor; D006801:Humans; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C522901:BX 517; D007211:Indoles; D047428:Protein Kinase Inhibitors; D014508:Urea; D064413:3-Phosphoinositide-Dependent Protein Kinases; C578562:PDPK1 protein, human; D017346:Protein Serine-Threonine Kinases