870823-05-5

Basic information

• Product Name: N-{4-[1-(5-(6-methoxy-2-naphthyl)-3-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrazol-1-yl)ethyl]benzoyl}-β-alaninate
• Synonyms: N-{4-[1-(5-(6-methoxy-2-naphthyl)-3-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrazol-1-yl)ethyl]benzoyl}-β-alaninate
• CAS NO: 870823-05-5
• Molecular Weight: 647.672
• Mol File: 870823-05-5.mol

Chemical Properties

• CAS DataBase Reference: N-{4-[1-(5-(6-methoxy-2-naphthyl)-3-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrazol-1-yl)ethyl]benzoyl}-β-alaninate(CAS DataBase Reference)
• NIST Chemistry Reference: N-{4-[1-(5-(6-methoxy-2-naphthyl)-3-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrazol-1-yl)ethyl]benzoyl}-β-alaninate(870823-05-5)
• EPA Substance Registry System: N-{4-[1-(5-(6-methoxy-2-naphthyl)-3-{[(trifluoromethyl)sulfonyl]oxy}-1H-pyrazol-1-yl)ethyl]benzoyl}-β-alaninate(870823-05-5)

Safety Data

• Hazardous Substances Data: 870823-05-5(Hazardous Substances Data)

Upstream product

• 62550-56-5 ethyl 3-(6-methoxy-2-naphthyl)-3-oxopropanoate 
• 58601-32-4 6-methoxy-2-naphthoyl chloride 
• 1383937-88-9 5-(6-methoxy-2-naphthyl)-2,4-dihydro-3H-pyrazol-3-one 
• 870823-04-4 tert-butyl N-[4-(1-hydroxyethyl)benzoyl]-β-alaninate 
• 870823-02-2 3-(6-methoxy-2-naphthyl)-1H-pyrazol-5-yl trifluoromethanesulfonate 
• 870823-02-2 3-(6-methoxy-2-naphthyl)-1H-pyrazol-5-yl trifluoromethanesulfonate 

Downstream Products

• 870824-64-9 N-[(4-{1-[3-(3,4-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl)carbonyl]-β-alanine 
• 870824-59-2 N-({4-[1-{3-[2-fluoro-5-(trifluoromethyl)phenyl]-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl}ethyl]phenyl}carbonyl)-β-alanine 

Relevant articles and documents

Discovery of a novel glucagon receptor antagonist N-[(4-{(1 S)-1-[3-(3, 5-dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1 H -pyrazol-1-yl]ethyl}phenyl) carbonyl]-β-alanine (MK-0893) for the treatment of type II diabetes

A potent, selective glucagon receptor antagonist 9m, N-[(4-{(1S)-1-[3-(3,5- dichlorophenyl)-5-(6-methoxynaphthalen-2-yl)-1H-pyrazol-1-yl]ethyl}phenyl) carbonyl]-β-alanine, was discovered by optimization of a previously identified lead. Compound 9m 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 9m 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, respectively. In hGCGR mice on a high fat diet, compound 9m at 3, and 10 mpk po in feed lowered blood glucose levels by 89% and 94% at day 10, respectively, relative to the difference between the vehicle control and lean hGCGR mice. On the basis of its favorable biological and DMPK properties, compound 9m (MK-0893) was selected for further preclinical and clinical evaluations.

Pyrazole derivatives, compositions containing such compounds and methods of use

Pyrazoles having a naphthyl group attached are disclosed. The compounds are useful for treating type 2 diabetes and related conditions. Pharmaceutical compositions and methods of treatment are also included.