Neoclerodane diterpenes as a novel scaffold for mu opioid receptor ligands.
Structural modification of salvinorin A, the active component of Salvia divinorum, has resulted in the synthesis of novel neoclerodane diterpenes with opioid receptor affinity and activity. We report in this study a nonnitrogenous neoclerodane diterpene with mu opioid receptor affinity (13) that is an agonist at mu opioid receptors. This represents the identification of a novel structural class of mu opioid receptor agonists.
Harding
Wayne W
WW
Division of Medicinal & Natural Products Chemistry, College of Pharmacy, The University of Iowa, Iowa City, Iowa 52242, USA.
Tidgewell
Kevin
K
Byrd
Nathan
N
Cobb
Howard
H
Dersch
Christina M
CM
Butelman
Eduardo R
ER
Rothman
Richard B
RB
Prisinzano
Thomas E
TE
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045785:Diterpenes, Clerodane; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011869:Radioligand Assay; D017465:Receptors, Opioid, delta / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000819:agonists*; D027544:Salvia; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
C502982:9-(benzoyloxy)-2-(3-furanyl)dodecahydro-6a,10b-dimethyl-4,10-dioxo-2H-naphtho(2,1-c)pyran-7-carboxylic acid methyl ester; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D005663:Furans; D008024:Ligands; D011753:Pyrones; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C468586:neoclerodane; C090499:salvinorin A