TY - JOUR
T1 - Synthetic studies of neoclerodane diterpenes from Salvia divinorum
T2 - Role of the furan in affinity for opioid receptors
AU - Simpson, Denise S.
AU - Lovell, Kimberly M.
AU - Lozama, Anthony
AU - Han, Nina
AU - Day, Victor W.
AU - Dersch, Christina M.
AU - Rothman, Richard B.
AU - Prisinzano, Thomas E.
PY - 2009
Y1 - 2009
N2 - Further synthetic modification of the furan ring of salvinorin A (1), the major active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. A computational study has predicted 1 to be a reproductive toxicant in mammals and is suggestive that use of 1 may be associated with adverse effects. We report in this study that piperidine 21 and thiomorpholine 23 have been identified as selective partial agonists at kappa opioid receptors. This indicates that additional structural modifications of 1 may provide ligands with good selectivity for opioid receptors but with reduced potential for toxicity.
AB - Further synthetic modification of the furan ring of salvinorin A (1), the major active component of Salvia divinorum, has resulted in novel neoclerodane diterpenes with opioid receptor affinity and activity. A computational study has predicted 1 to be a reproductive toxicant in mammals and is suggestive that use of 1 may be associated with adverse effects. We report in this study that piperidine 21 and thiomorpholine 23 have been identified as selective partial agonists at kappa opioid receptors. This indicates that additional structural modifications of 1 may provide ligands with good selectivity for opioid receptors but with reduced potential for toxicity.
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U2 - 10.1039/b905148a
DO - 10.1039/b905148a
M3 - Article
C2 - 19707679
AN - SCOPUS:69649104682
SN - 1477-0520
VL - 7
SP - 3748
EP - 3756
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 18
ER -