Synthesis and in vitro pharmacological studies of C(4) modified salvinorin A analogues.
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.
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
Kondaveti
Leelakrishna
L
Liu-Chen
Lee-Yuan
LY
Ma
Zhongze
Z
Wang
Yulin
Y
Chen
Yong
Y
Li
Jian-Guo
JG
Beguin
Cecile
C
Carlezon
William A
WA
Cohen
Bruce
B
D000701:Analgesics, Opioid / Q000138:chemical synthesis* / Q000494:pharmacology; D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045785:Diterpenes, Clerodane; D004353:Drug Evaluation, Preclinical; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000378:metabolism; D013329:Structure-Activity Relationship
D000701:Analgesics, Opioid; D004224:Diterpenes; D045785:Diterpenes, Clerodane; D017473:Receptors, Opioid, kappa; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C090499:salvinorin A