title: Identification and optimization of a novel series of indoleamine 2,3-dioxygenase inhibitors.
abstract: The discovery of a series of structurally-novel biaryl urea IDO inhibitors is described. Optimization of a micromolar hit through iterative cycles of synthesis and screening in an assay measuring IDO-mediated intracellular conversion of tryptophan to kynurenine led to potent inhibitors with favorable selectivity and metabolic stability profiles.
authors.affiliation: Oncology Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States. Electronic address: jay.markwalder@bms.com.
authors.forename: Jay A
authors.initials: JA
authors.lastname: Markwalder
authors.affiliation: Oncology Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Seitz
authors.affiliation: Mechanistic Biochemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States.
authors.forename: Yuval
authors.initials: Y
authors.lastname: Blat
authors.affiliation: Lead Discovery & Optimization, Bristol-Myers Squibb Research and Development, Wallingford, CT 06492, United States.
authors.forename: Lisa
authors.initials: L
authors.lastname: Elkin
authors.affiliation: Oncology Biology, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States.
authors.forename: John T
authors.initials: JT
authors.lastname: Hunt
authors.affiliation: Oncology Biology, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States.
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Pabalan
authors.affiliation: Oncology Biology, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States.
authors.forename: Maria N
authors.initials: MN
authors.lastname: Jure-Kunkel
authors.affiliation: Oncology Chemistry, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Vite
authors.affiliation: Oncology Biology, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543-5400, United States.
authors.forename: Kelly
authors.initials: K
authors.lastname: Covello
mesh_terms: D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D057166:High-Throughput Screening Assays; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014508:Urea
keywords: IDO; Immuno-oncology; Indoleamine 2,3-dioxygenase; Kynurenine