title: Identification of novel and potent isoquinoline aminooxazole-based IMPDH inhibitors.
abstract: Screening of our in-house compound collection led to the discovery of 5-bromo-6-amino-2-isoquinoline 1 as a weak inhibitor of IMPDH. Subsequent optimization of 1 afforded a series of novel 2-isoquinolinoaminooxazole-based inhibitors, represented by 17, with single-digit nanomolar potency against the enzyme.
authors.affiliation: Discovery Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA. ping.chen@bms.com
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.forename: Derek
authors.initials: D
authors.lastname: Norris
authors.forename: Kristin D
authors.initials: KD
authors.lastname: Haslow
authors.forename: T G
authors.initials: TG
authors.lastname: Murali Dhar
authors.forename: William J
authors.initials: WJ
authors.lastname: Pitts
authors.forename: Scott H
authors.initials: SH
authors.lastname: Watterson
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Cheney
authors.forename: Donna A
authors.initials: DA
authors.lastname: Bassolino
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Fleener
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Rouleau
authors.forename: Diane L
authors.initials: DL
authors.lastname: Hollenbaugh
authors.forename: Robert M
authors.initials: RM
authors.lastname: Townsend
authors.forename: Joel C
authors.initials: JC
authors.lastname: Barrish
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Iwanowicz
mesh_terms: D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors*; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*; D009243:NAD / Q000378:metabolism; D010080:Oxazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010080:Oxazoles; D009243:NAD; D007168:IMP Dehydrogenase