title: Discovery, synthesis and biological evaluation of novel glucokinase activators.
abstract: The identification, synthesis and SAR of a novel series of glucokinase activators is described. The interplay between lipophilicity, potency and physical properties is discussed, and compound 22 highlighted as having a suitable balance. In vivo pharmacokinetic and acute efficacy studies on this compound are also presented.
authors.affiliation: Cardiovascular and Gastrointestinal Research Area, AstraZeneca UK, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. darren.mckerrecher@astrazeneca.com <darren.mckerrecher@astrazeneca.com>
authors.forename: Darren
authors.initials: D
authors.lastname: McKerrecher
authors.forename: Joanne V
authors.initials: JV
authors.lastname: Allen
authors.forename: Suzanne S
authors.initials: SS
authors.lastname: Bowker
authors.forename: Scott
authors.initials: S
authors.lastname: Boyd
authors.forename: Peter W R
authors.initials: PW
authors.lastname: Caulkett
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Currie
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Davies
authors.forename: Mark L
authors.initials: ML
authors.lastname: Fenwick
authors.forename: Harold
authors.initials: H
authors.lastname: Gaskin
authors.forename: Emma
authors.initials: E
authors.lastname: Grange
authors.forename: Rod B
authors.initials: RB
authors.lastname: Hargreaves
authors.forename: Barry R
authors.initials: BR
authors.lastname: Hayter
authors.forename: Roger
authors.initials: R
authors.lastname: James
authors.forename: Keith M
authors.initials: KM
authors.lastname: Johnson
authors.forename: Craig
authors.initials: C
authors.lastname: Johnstone
authors.forename: Clifford D
authors.initials: CD
authors.lastname: Jones
authors.forename: Sarah
authors.initials: S
authors.lastname: Lackie
authors.forename: John W
authors.initials: JW
authors.lastname: Rayner
authors.forename: Rolf P
authors.initials: RP
authors.lastname: Walker
mesh_terms: D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004789:Enzyme Activation / Q000502:physiology; D020536:Enzyme Activators / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D005941:Glucokinase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013844:Thiazoles / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D020536:Enzyme Activators; C476008:RO-28-0450; D013844:Thiazoles; D005941:Glucokinase