New Salvinorin Analog

[RoboCop]

There was recently a new Salvinorin A analog made that is seven times as potent as Salvinorin A. Here is a small article on it.

Synthesis and in vitro pharmacological studies of new C(2) modified salvinorin A analogues

David Y.W. Leea, Vishnu V.R. Karnatia, Minsheng Hea, Lee-Yuan Liu-Chenb, Leelakrishna Kondaretia, Zhongze Maa, Yulin Wangb, Yong Chenb, Cecile Beguind, William A. Carlezon, Jr.c and Bruce Cohend, ,

aBioorganic and Natural Products Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA
bDepartment of Pharmacology, School of Medicine, Temple University, 3420 N. Broad St, Philadelphia, PA 19140, USA
cBehavioral Genetics Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA
dMolecular Pharmacology Laboratory, McLean Hospital, Harvard Medical School, 115 Mill Street, Belmont, MA 02478, USA

Received 18 March 2005; revised 16 May 2005; accepted 17 May 2005. Available online 1 July 2005.




Abstract
Salvinorin A is the most potent naturally occurring opioid agonist yet discovered with high selectivity and affinity for ê-opioid receptor. To explore its structure and activity relationships, a series of salvinorin A derivatives modified at the C(2) position were prepared and studied. These salvinorin A derivatives were screened for binding and functional activities at the human ê-opioid receptor. Compound 4, containing a methoxymethyl group at the 2-position, was a full ê-agonist with an EC50 value at 0.6 nM, which is about 7 times more potent than salvinorin A.


Graphical abstract
A series of salvinorin A derivatives modified at the C(2) position were prepared and screened for binding and functional activities at the human ê-opioid receptor. A highly selective ê-agonist (EC50 = 0.6 nM) was identified.



Keywords: ê Opioid-receptor; Salvinorin A; Diterpenoid; Agonist; Binding activity