Synthesis and in vitro pharmacological studies of new C(4)-modified salvinorin A analogues.
Salvinorin A, a compound isolated from the plant Salvia divinorum, is a potent and highly selective agonist for the kappa opioid receptor. For exploration of its structure and activity relationships, further modifications, such as reduction 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 new full agonists have been identified.
Lee
David Y W
DY
Bioorganic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
He
Minsheng
M
Liu-Chen
Lee-Yuan
LY
Wang
Yulin
Y
Li
Jian-Guo
JG
Xu
Wei
W
Ma
Zhongze
Z
Carlezon
William A
WA
Cohen
Bruce
B
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004224:Diterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D006801:Humans; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism*
D004224:Diterpenes; D045785:Diterpenes, Clerodane; D017473:Receptors, Opioid, kappa; C090499:salvinorin A