Xiong, Yusheng published the artcileDiscovery of a novel glucagon receptor antagonist N-[(4-{(1S)-1-[3-(3, 5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine (MK-0893) for the treatment of type II diabetes, COA of Formula: C9H12BClO3, the publication is Journal of Medicinal Chemistry (2012), 55(13), 6137-6148, database is CAplus and MEDLINE.
A potent, selective glucagon receptor antagonist I was discovered by optimization of a previously identified lead. Compound I is a reversible and competitive antagonist with high binding affinity (IC50 of 6.6 nM) and functional cAMP activity (IC50 of 15.7 nM). It is selective for glucagon receptor relative to other family B GPCRs, showing IC50 values of 1020 nM for GIPR, 9200 nM for PAC1, and >10000 nM for GLP-1R, VPAC1, and VPAC2. Compound I blunted glucagon-induced glucose elevation in hGCGR mice and rhesus monkeys. It also lowered ambient glucose levels in both acute and chronic mouse models: in hGCGR ob/ob mice it reduced glucose (AUC 0-6 h) by 32% and 39% at 3 and 10 mpk single doses, resp. In hGCGR mice on a high fat diet, compound I at 3, and 10 mpk po in feed lowered blood glucose levels by 89% and 94% at day 10, resp., relative to the difference between the vehicle control and lean hGCGR mice. On the basis of its favorable biol. and DMPK properties, compound I (MK-0893) was selected for further preclin. and clin. evaluations.
Journal of Medicinal Chemistry published new progress about 1256345-74-0. 1256345-74-0 belongs to chlorides-buliding-blocks, auxiliary class Chloride,Boronic acid and ester,Benzene,Ether,Boronic Acids,Boronic acid and ester, name is (3-Chloro-5-propoxyphenyl)boronic acid, and the molecular formula is C10H15ClO3S, COA of Formula: C9H12BClO3.
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