1449691-93-3

Basic information

• Product Name: 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl]-1H-pyrazole-3-carboxamide
• CAS NO: 1449691-93-3
• Molecular Weight: 476.061
• Mol File: 1449691-93-3.mol
• Article Data: 1

Chemical Properties

• CAS DataBase Reference: 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl]-1H-pyrazole-3-carboxamide(CAS DataBase Reference)
• NIST Chemistry Reference: 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl]-1H-pyrazole-3-carboxamide(1449691-93-3)
• EPA Substance Registry System: 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2R,4S)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-yl]-1H-pyrazole-3-carboxamide(1449691-93-3)

Safety Data

• Hazardous Substances Data: 1449691-93-3(Hazardous Substances Data)

Upstream product

• 192702-07-1 5-(4-chloro-3-methyl-phenyl)-1-[(4-methylphenyl)methyl]-1H-pyrazole-3-carboxylic acid 
• 255714-97-7 C₁₀H₁₉N*ClH 
• 192703-20-1 1-(4-methylbenzyl)-5-(4-chloro-3-methylphenyl)pyrazole-3-carboxylic acid chloride 
• 251576-26-8 C₁₀H₁₉N 
• 76-22-2 (-)-camphor 
• 1449691-95-5 ethyl 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-1H-pyrazole-3-carboxylate 
• 1029295-67-7 ethyl 5-(4-chloro-3-methylphenyl)-1H-pyrazole-3-carboxylate 

Relevant articles and documents

The importance of hydrogen bonding and aromatic stacking to the affinity and efficacy of cannabinoid receptor CB2 antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3, 3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528)

Despite the therapeutic promise of the subnanomolar affinity cannabinoid CB2 antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl) methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl] -1H-pyrazole-3-carboxamide (SR144528, 1), little is known about its binding site interactions and no primary interaction site for 1 at CB2 has been identified. We report here the results of Glide docking studies in our cannabinoid CB 2 inactive state model that were then tested via compound synthesis, binding, and functional assays. Our results show that the amide functional group of 1 is critical to its CB2 affinity and efficacy and that aromatic stacking interactions in the TMH5/6 aromatic cluster of CB2 are also important. Molecular modifications that increased the positive electrostatic potential in the region between the fenchyl and aromatic rings led to more efficacious compounds. This result is consistent with the EC-3 loop negatively charged amino acid, D275 (identified via Glide docking studies) acting as the primary interaction site for 1 and its analogues.