Synthesis and in vitro pharmacological studies of new C(2) modified salvinorin A analogues.
Salvinorin A is the most potent naturally occurring opioid agonist yet discovered with high selectivity and affinity for kappa-opioid receptor. To explore its structure and activity relationships, a series of salvinorin A derivatives modified at the C2 position were prepared and studied. These salvinorin A derivatives were screened for binding and functional activities at the human kappa-opioid receptor. Compound 4, containing a methoxymethyl group at the 2-position, was a full kappa-agonist with an EC50 value at 0.6 nM, which is about 7 times more potent than salvinorin A.
Bioorganic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA.
David Y W
DY
Lee
Vishnu V R
VV
Karnati
Minsheng
M
He
Lee-Yuan
LY
Liu-Chen
Leelakrishna
L
Kondaveti
Zhongze
Z
Ma
Yulin
Y
Wang
Yong
Y
Chen
Cecile
C
Beguin
William A
WA
Carlezon
Bruce
B
Cohen
D004224:Diterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045785:Diterpenes, Clerodane; D006801:Humans; D008968:Molecular Conformation; D017473:Receptors, Opioid, kappa / Q000819:agonists; D013329:Structure-Activity Relationship
D004224:Diterpenes; D045785:Diterpenes, Clerodane; D017473:Receptors, Opioid, kappa; C090499:salvinorin A