Send to

Choose Destination
See comment in PubMed Commons below
Bioorg Med Chem. 2008 Feb 1;16(3):1111-24. Epub 2007 Nov 1.

Imine derivatives as new potent and selective CB2 cannabinoid receptor agonists with an analgesic action.

Author information

  • 1Medicinal Chemistry Laboratories, Taisho Pharmaceutical Co., Ltd, Saitama-shi, Saitama 331-9530, Japan.


In this study, a novel series of CB(2) receptor agonist imine derivatives, 1-6, was synthesized and evaluated for activity against the CB(2) receptor. In a previous paper we reported the synthesis and SARs of thiazole derivative 1, a potent CB(2) receptor agonist, but we had not assessed chemical modifications of the 5-membered heteroring of 1. In the present study, we therefore tried chemically modifying the 5-membered heteroring of 1 in an attempt to further improve binding affinity for the CB(2) receptor. In the course of making the structural modifications, we discovered that a novel pyrazole derivative 6b (CBS0550) had high affinity for the CB(2) receptor (IC(50)=2.9 nM, EC(50)=1.8 nM, E(max)=85%), high selectivity for CB(2) (CB(1) IC(50)/CB(2) IC(50)=1400), and good physicochemical properties (solubility in water: 5.9 mg/100mL at 25 degrees C). Oral administration of 6b to rats at a dose of 10mg/kg resulted in significant plasma concentrations, and orally administered compound 6b significantly reversed mechanical hyperalgesia in the Randall-Selitto model of inflammatory pain in rats.

[PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Other Literature Sources

Chemical Information


PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center