Design, synthesis and biological evaluation of piperazine analogues as CB1 cannabinoid receptor ligands.

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Song KS, Lee SH, Chun HJ, Kim JY, Jung ME, Ahn K, Kim SU, Kim J, Lee J

Design, synthesis and biological evaluation of piperazine analogues as CB1 cannabinoid receptor ligands.

Bioorg Med Chem. 2008 Apr 1;16(7):4035-51. doi: 10.1016/j.bmc.2008.01.023. Epub 2008 Jan 19.

PubMed ID

18243711 [ View in PubMed

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Abstract

After the CB1 receptor antagonist SR141716 (rimonabant) was previously reported to modulate food intake, CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. Several series of urea, carbamate, amide, sulfonamide and oxalamide derivatives based on 1-benzhydrylpiperazine scaffold were synthesized and tested for CB1 receptor binding affinity. The SAR studies to optimize the CB1 binding affinity led to the potent urea derivatives. After the additional SAR studies to optimize the substituents of diphenyl rings, the combination of 2-chlorophenyl and 4-chlorophenyl turned out to be the most potent scaffold. The CB2 binding affinity assay as well as functional assay was also conducted on these compounds. Herein we wish to introduce several novel CB1 antagonists with IC(50) values less than 100 nM for the CB1 receptor binding.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rimonabant	Cannabinoid receptor 1	IC 50 (nM)	120	N/A	N/A	Details