title: Synthesis and in vitro pharmacological evaluation of salvinorin A analogues modified at C(2).
abstract: Salvinorin A is the only known non-nitrogenous and specific kappa-opioid agonist. A series of salvinorin A derivatives were prepared and tested for in vitro activity at the kappa-opioid receptor. Unsubstituted carbamate 9 was a potent kappa-agonist (EC(50) = 6.2 nM) and should be more stable than salvinorin A toward metabolic transformations. Compound 10, containing an N-methyl carbamate at C(2), showed partial agonist activity with 81% efficacy when compared with the full agonist U50,488H. No antagonist ligands were observed.
authors.affiliation: Molecular Pharmacology Laboratory, McLean Hospital, Belmont, MA 02478, USA.
authors.forename: Cécile
authors.initials: C
authors.lastname: Béguin
authors.forename: Michele R
authors.initials: MR
authors.lastname: Richards
authors.forename: Yulin
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Lee-Yuan
authors.initials: LY
authors.lastname: Liu-Chen
authors.forename: Zhongze
authors.initials: Z
authors.lastname: Ma
authors.forename: David Y W
authors.initials: DY
authors.lastname: Lee
authors.forename: William A
authors.initials: WA
authors.lastname: Carlezon
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D004353:Drug Evaluation, Preclinical
chemical_list: D004224:Diterpenes; D045785:Diterpenes, Clerodane; C090499:salvinorin A