Discovery, synthesis and biological evaluation of novel glucokinase activators

Darren McKerrecher; Joanne V Allen; Suzanne S Bowker; Scott Boyd; Peter W R Caulkett; Gordon S Currie; Christopher D Davies; Mark L Fenwick; Harold Gaskin; Emma Grange; Rod B Hargreaves; Barry R Hayter; Roger James; Keith M Johnson; Craig Johnstone; Clifford D Jones; Sarah Lackie; John W Rayner; Rolf P Walker

doi:10.1016/j.bmcl.2005.01.087

Discovery, synthesis and biological evaluation of novel glucokinase activators

Bioorg Med Chem Lett. 2005 Apr 15;15(8):2103-6. doi: 10.1016/j.bmcl.2005.01.087.

Affiliation

¹ Cardiovascular and Gastrointestinal Research Area, AstraZeneca UK, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK. darren.mckerrecher@astrazeneca.com <darren.mckerrecher@astrazeneca.com>

PMID: 15808477
DOI: 10.1016/j.bmcl.2005.01.087

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.

MeSH terms

Animals
Drug Evaluation, Preclinical / methods
Enzyme Activation / physiology
Enzyme Activators / chemical synthesis*
Enzyme Activators / pharmacology
Female
Glucokinase / metabolism*
Rats
Rats, Wistar
Thiazoles / chemical synthesis
Thiazoles / pharmacology

Substances

Enzyme Activators
RO-28-0450
Thiazoles
Glucokinase