1,2,3-Triazole derivatives as new cannabinoid CB1 receptor antagonists.
This letter reports the new entry of novel 1,2,3-triazole derivatives as CB1 receptor antagonists. The design, synthesis and biological evaluation of N1 and N2 substituted 1,2,3-trizoles are described. The N2 substituted, symmetrical 1,2,3-triazoles are more potent ligands than the unsymmetrical analogues. The in vitro activity of these triazoles is further improved by inserting a methylene group between the central core and the carbonyl side chain. The most potent antagonists prepared in this series (IC(50)<20 nM) are the triazoles containing benzyl amides. These triazoles also show excellent selectivity between CB1 and CB2 receptors (IC(50)>10 microM for CB2; CB2/CB1>1000).
Hou
Duen-Ren
DR
Department of Chemistry, National Central University, 300 Jhong-Da Road, Jhongli City, Taoyuan, Taiwan. drhou@ncu.edu.tw
Alam
Safiul
S
Kuan
Ting-Chun
TC
Ramanathan
Mani
M
Lin
Tsung-Pang
TP
Hung
Ming-Shiu
MS
D000577:Amides / Q000737:chemistry; D001554:Benzene / Q000737:chemistry; D002186:Cannabinoids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008024:Ligands; D008956:Models, Chemical; D009765:Obesity / Q000188:drug therapy; D011485:Protein Binding; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D043885:Receptor, Cannabinoid, CB2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry*
D000577:Amides; D002186:Cannabinoids; D008024:Ligands; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D014230:Triazoles; D001554:Benzene