Sulfonamide derivatives as new potent and selective CB2 cannabinoid receptor agonists
| Autor: | Yoshihisa Toda, Tomoko Ishizaka, Hiroshi Ohta, Aki Morita, Shuji Saito, Mitsukane Yoshinaga, Yasumitsu Tomishima |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Agonist
Cannabinoid receptor medicine.drug_class Stereochemistry medicine.medical_treatment Clinical Biochemistry Pharmaceutical Science Biochemistry Chemical library Receptor Cannabinoid CB2 chemistry.chemical_compound Structure-Activity Relationship Drug Discovery medicine Cannabinoid receptor type 2 Humans Molecular Biology IC50 chemistry.chemical_classification Sulfonamides Chemistry Organic Chemistry Cannabinoid Receptor Agonists Sulfonamide Molecular Medicine lipids (amino acids peptides and proteins) Cannabinoid |
| Zdroj: | Bioorganicmedicinal chemistry letters. 17(18) |
| ISSN: | 0960-894X |
| Popis: | A novel series of sulfonamide derivatives 3, the CB(2) receptor agonists, was synthesized and evaluated for activity against the human CB(2) receptor. We first identified sulfonamide 3a, which was obtained by random screening of our in-house chemical library as a moderately active (CB(2) IC(50)=340nM) CB(2) receptor agonist. We then attempted to test its analogues to identify compounds with a high affinity for the CB(2) receptor. One of these, compound 3f, exhibited high affinity for the human CB(2) receptor (IC(50)=16nM) and high selectivity for CB(2) over CB(1) (CB(1) IC(50)/CB(2)IC(50)=106), and behaved as a full CB(2) receptor agonist in the [(35)S]GTPgammaS binding assay (CB(2) EC(50)=7.2nM, E(max)=100%). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect