Bioorganic & Medicinal Chemistry Letters
September 1, 2018
Shun Hirasawa, Min Cho, Tarsis F Brust et al.
Salvinorin A (SalA) is a potent and selective agonist of the kappa-opioid receptor (KOR), but its instability has frustrated medicinal chemistry efforts. Treatment of SalA with weak bases like DBU leads to C8 epimerization with loss of receptor affinity and signaling potency. Here we show that replacement of C20 with H and replacement of O6 with CH2 stabilizes the SalA scaffold relative to its...
Bioorganic & Medicinal Chemistry Letters
March 12, 2018
Jeremy J Roach, Ryan A Shenvi
The plant metabolite salvinorin A potently and selectively agonizes the human kappa-opioid receptor, an emerging target for next-generation analgesics. Here we review analogs of the salvinorin chemotype and their effects on selectivity, affinity and potency. Extensive peripheral modifications using isolated salvinorin A have delivered a trove of SAR information. More deep-seated changes are now...
Bioorganic & Medicinal Chemistry Letters
February 1, 2016
Nicholas V. Cozzi, Paul F. Daley
24 citations
N,N-Diallyltryptamine (DALT) and 5-methoxy-N,N-diallyltryptamine (5-MeO-DALT) are two tryptamines synthesized and tested by Alexander Shulgin. In self-experiments, 5-MeO-DALT was reported to be psychoactive in the 12-20mg range, while the unsubstituted compound DALT had few discernible effects in the 42-80 mg range. Recently, 5-MeO-DALT has been used in nonmedical settings for its psychoactive...
Bioorganic & Medicinal Chemistry Letters
June 1, 2013
Warunya Arunotayanun, Jeffrey W Dalley, Xi-Ping Huang et al.
41 citations
Novel Psychoactive Drugs (NPD) can be sold without restriction and are often synthetic analogues of controlled drugs. The tryptamines are an important class of NPD as they bind to the various serotonin (5-HT) receptor subtypes and cause psychosis and hallucinations that can lead to injury or death through misadventure. Here we report on the structure elucidation and receptor binding profiles of...
Bioorganic & Medicinal Chemistry Letters
May 15, 2013
Prabhakar R Polepally, Kate White, Eyal Vardy et al.
24 citations
Salvinorin A, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective κ-opioid receptor agonist. To better understand the ligand-receptor interactions, a series of dicarboxylic ester-type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at κ-, δ- and μ-opioid receptors....
Bioorganic & Medicinal Chemistry Letters
October 1, 2010
David Y W Lee, Lu Yang, Wei Xu et al.
Salvinorin A (1), the main active ingredient of Salvia divinorum, is a potent and selective κ opioid receptor (KOPR) agonist. Based on the SAR, its C-2 position is one of the key binding sites and has very little space tolerance (3-4 carbons atoms) and limited to only lipophilic groups. In our attempt to prepare PET brain imaging agent for mapping KOPR, a series of C-2 halogenated analogs have...
Bioorganic & Medicinal Chemistry Letters
March 1, 2009
Lu Yang, Wei Xu, Feng Chen et al.
Salvinorin A (1), the main active ingredient of Salvia divinorum, is a potent and selective kappa-opioid receptor (KOPR) agonist. A series of C-12 triazole analogs and the oxadiazole (4) analog of 1 are synthesized and screened for binding affinity at kappa, mu (MOPR), or delta (DOPR). Surprisingly, all triazole analogs have shown negligible binding affinity at opioid receptors and the...
Bioorganic & Medicinal Chemistry Letters
November 15, 2007
Kenneth G Holden, Kevin Tidgewell, Alfred Marquam et al.
Modification of the C-1 ketone of salvinorin A (2a) produces analogues with opioid antagonist properties. Of particular significance is the finding that 1-deoxo-1,10-dehydrosalvinorin A (11a) is a moderately potent antagonist at all three opioid receptor subtypes, and that herkinorin (2b), a mu agonist, is converted to a weak antagonist by removal of the C-1 ketone (3b and 11b). These...
Bioorganic & Medicinal Chemistry Letters
August 3, 2005
Howard Sard, Govindaraj Kumaran, Cynthia Morency et al.
78 citations
An SAR study of psilocybin and psilocin derivatives reveals that 1-methylpsilocin is a selective agonist at the h5-HT(2C) receptor. The corresponding phosphate derivative, 1-methylpsilocybin, shows efficacy in an animal model for obsessive-compulsive disorder, as does 4-fluoro-N,N-dimethyltryptamine. These results suggest a new area for development of novel 5-HT(2C) agonists with applications...
Bioorganic & Medicinal Chemistry Letters
October 18, 2004
Kevin Tidgewell, Wayne W Harding, Mark S Schmidt et al.
68 citations
Salvinorin A is a novel hallucinogen isolated from the widely available leaves of Salvia divinorum. Based on its mechanism of action, salvinorin A has shown potential as a stimulant abuse therapeutic. However, there are no methods for the detection of salvinorin A or its metabolites in biological fluids. In order to begin developing salvinorin A as a potential therapeutic, an understanding of...