1044586-82-4

Basic information

• Product Name: N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-4-yl]-1H-pyrazole-4-carboxamide
• CAS NO: 1044586-82-4
• Molecular Weight: 527.837
• Mol File: 1044586-82-4.mol
• Article Data: 3

Chemical Properties

• CAS DataBase Reference: N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-4-yl]-1H-pyrazole-4-carboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-4-yl]-1H-pyrazole-4-carboxamide(1044586-82-4)
• EPA Substance Registry System: N-[(4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridine-4-yl]-1H-pyrazole-4-carboxamide(1044586-82-4)

Safety Data

• Hazardous Substances Data: 1044586-82-4(Hazardous Substances Data)

Upstream product

• 37718-11-9 1H-pyrazole-4-carboxylic acid 
• 1044588-31-9 (4R)-6-(4-chlorophenyl)-7-(2,4-dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-amine 

Relevant articles and documents

Discovery of N -[(4 R)-6-(4-Chlorophenyl)-7-(2,4-dichlorophenyl)-2,2- dimethyl-3,4-dihydro-2 H -pyrano[2,3- b ]pyridin-4-yl]-5-methyl-1 H -pyrazole-3-carboxamide (MK-5596) as a novel cannabinoid-1 receptor (CB1R) inverse agonist for the treatment of obesity

This paper describes the discovery of N-[(4R)-6-(4-chlorophenyl)-7-(2,4- dichlorophenyl)-2,2-dimethyl-3,4-dihydro-2H-pyrano[2,3-b]pyridin-4-yl] -5-methyl-1H-pyrazole-3-carboxamide (MK-5596, 12c) as a novel cannabinoid-1 receptor (CB1R) inverse agonist for the treatment of obesity. Structure-activity relationship (SAR) studies of lead compound 3, which had off-target hERG (human ether-a-go-go related gene) inhibition activity, led to the identification of several compounds that not only had attenuated hERG inhibition activity but also were subject to glucuronidation in vitro providing the potential for multiple metabolic clearance pathways. Among them, pyrazole 12c was found to be a highly selective CB1R inverse agonist that reduced body weight and food intake in a DIO (diet-induced obese) rat model through a CB1R-mediated mechanism. Although 12c was a substrate of P-glycoprotein (P-gp) transporter, its high in vivo efficacy in rodents, good pharmacokinetic properties in preclinical species, good safety margins, and its potential for a balanced metabolism profile in man allowed for the further evaluation of this compound in the clinic.

SUBSTITUTED PYRANO[2,3-B]PYRIDINE DERIVATIVES AS CANNABINOID-1 RECEPTOR MODULATORS

Novel compounds of the structural Formula (I) are antagonists and/or inverse agonists of the Cannabinoid-1 (CB1) receptor and are useful in the treatment, prevention and suppression of diseases mediated by the CB1 receptor. The compounds of the present in