Biaryl cannabinoid mimetics--synthesis and structure-activity relationship.
Synthesis, in vitro biological evaluation, and structure-activity relationships of a biaryl cannabinoid mimetic 2 are reported. Variations in the substitution pattern yielded a number of agonists with low nanomolar affinity. Replacing the phenol group by a methyl morpholino acetate group led to compound 28, a 500-fold selective CB(2) receptor agonist.
Worm
Karin
K
Department of Chemistry, Adolor Corporation, 700 Pennsylvania Drive, Exton, PA, USA. kworm@adolor.com <kworm@adolor.com>
Zhou
Q Jean
QJ
Stabley
Gabriel J
GJ
DeHaven
Robert N
RN
Dolle
Roland E
RE
D002186:Cannabinoids / Q000138:chemical synthesis* / Q000737:chemistry*; D002264:Carboxylic Acids / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006859:Hydrogen / Q000737:chemistry; D006860:Hydrogen Bonding; D007166:Immunosuppressive Agents / Q000737:chemistry; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D010276:Parasympatholytics; D019800:Phenol / Q000737:chemistry; D011485:Protein Binding
D002186:Cannabinoids; D002264:Carboxylic Acids; D007166:Immunosuppressive Agents; D010276:Parasympatholytics; D019800:Phenol; D006859:Hydrogen