TY - JOUR
T1 - Design, synthesis, binding, and molecular modeling studies of new potent ligands of cannabinoid receptors
AU - Brizzi, Antonella
AU - Cascio, Maria Grazia
AU - Brizzi, Vittorio
AU - Bisogno, Tiziana
AU - Dinatolo, Maria Teresa
AU - Martinelli, Adriano
AU - Tuccinardi, Tiziano
AU - Di Marzo, Vincenzo
N1 - Funding Information:
We thank MIUR (PRIN 2004037521) and the Università degli Studi di Siena, Italy, for financial support. We thank Mr. Marco Allarà for technical assistance with assays.
PY - 2007/8/15
Y1 - 2007/8/15
N2 - In our ongoing program aimed at the design, synthesis, and biological evaluation of novel cannabinoid receptor ligands derived from olivetol and hexyl-resorcinol, we have designed a structural model for new derivatives on the basis of a previous study. Here we report the synthesis, binding, and molecular modeling studies of new potent compounds with high affinity toward CB1 and CB2 receptors. Compounds with amidic 'heads' with alkyloxy chains varying in length from 8 to 12 carbon atoms showed nanomolar affinity for both receptors, depending on the type of aromatic backbone. Two of the new compounds, although not very potent, exhibit selectivity for CB1 receptors (CB1/CB2 = 0.07 and 0.08, respectively). Molecular modeling studies fitted this new class of cannabinoid ligands into a CB1 receptor model, and the qualitative analysis of the results was in general agreement with the CB1 affinity constants observed experimentally for these derivatives.
AB - In our ongoing program aimed at the design, synthesis, and biological evaluation of novel cannabinoid receptor ligands derived from olivetol and hexyl-resorcinol, we have designed a structural model for new derivatives on the basis of a previous study. Here we report the synthesis, binding, and molecular modeling studies of new potent compounds with high affinity toward CB1 and CB2 receptors. Compounds with amidic 'heads' with alkyloxy chains varying in length from 8 to 12 carbon atoms showed nanomolar affinity for both receptors, depending on the type of aromatic backbone. Two of the new compounds, although not very potent, exhibit selectivity for CB1 receptors (CB1/CB2 = 0.07 and 0.08, respectively). Molecular modeling studies fitted this new class of cannabinoid ligands into a CB1 receptor model, and the qualitative analysis of the results was in general agreement with the CB1 affinity constants observed experimentally for these derivatives.
KW - Anandamide
KW - Cannabinoid receptors
KW - Docking
KW - Endocannabinoids
UR - http://www.scopus.com/inward/record.url?scp=34250693214&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2007.05.060
DO - 10.1016/j.bmc.2007.05.060
M3 - Article
C2 - 17561406
AN - SCOPUS:34250693214
VL - 15
SP - 5406
EP - 5416
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
SN - 0968-0896
IS - 16
ER -