Synthesis and in vitro pharmacological studies of C(4) modified salvinorin A analogues

David Y W Lee; Minsheng He; Leelakrishna Kondaveti; Lee-Yuan Liu-Chen; Zhongze Ma; Yulin Wang; Yong Chen; Jian-Guo Li; Cecile Beguin; William A Carlezon Jr; Bruce Cohen

doi:10.1016/j.bmcl.2005.06.092

Synthesis and in vitro pharmacological studies of C(4) modified salvinorin A analogues

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4169-73. doi: 10.1016/j.bmcl.2005.06.092.

Authors

David Y W Lee¹, Minsheng He, Leelakrishna Kondaveti, Lee-Yuan Liu-Chen, Zhongze Ma, Yulin Wang, Yong Chen, Jian-Guo Li, Cecile Beguin, William A Carlezon Jr, Bruce Cohen

Affiliation

¹ Bioorganic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.

PMID: 16051487
DOI: 10.1016/j.bmcl.2005.06.092

Abstract

Salvinorin A is the most potent naturally occurring opioid agonist with a high selectivity and affinity for kappa-opioid receptor. To explore its structure-activity relationships, modifications at the C(4) position have been studied and a series of salvinorin A derivatives were prepared. These C(4)-modified salvinorin A analogues were screened for binding and functional activities at the human kappa-opioid receptor and several potent new agonists have been identified.

MeSH terms

Analgesics, Opioid / chemical synthesis*
Analgesics, Opioid / pharmacology
Diterpenes / chemical synthesis*
Diterpenes / chemistry
Diterpenes / pharmacology
Diterpenes, Clerodane
Drug Evaluation, Preclinical
Guanosine 5'-O-(3-Thiotriphosphate) / metabolism
Humans
Inhibitory Concentration 50
Receptors, Opioid, kappa / agonists*
Receptors, Opioid, kappa / metabolism
Structure-Activity Relationship

Substances

Analgesics, Opioid
Diterpenes
Diterpenes, Clerodane
Receptors, Opioid, kappa
Guanosine 5'-O-(3-Thiotriphosphate)
salvinorin A