MedChemComm
December 1, 2011
Katherine M Prevatt-Smith, Kimberly M Lovell, Denise S Simpson et al.
50 citations
A modified compound, initially derived from a potent natural hallucinogen, surprisingly offers a new avenue for treating drug addiction. Scientists hypothesized that slight structural changes could enhance its therapeutic benefits. Through synthesizing and evaluating new versions, particularly focusing on their interaction with opioid receptors and impact on drug-seeking behaviors in rats, a specific analog was identified. This novel compound not only matched the original's potency at key brain receptors but also effectively reduced cocaine-induced drug-seeking. This discovery represents the first instance of such a modified compound demonstrating anti-addictive capabilities.
Bioorganic & medicinal chemistry
May 1, 2012
Kimberly M Lovell, Tamara Vasiljevik, Juan J Araya et al.
35 citations
A palladium-catalyzed cross-coupling reaction (Liebeskind-Srogl) applied to a modified natural product scaffold produces ketone analogs of salvinorin A at neutral pH and room temperature, expanding synthetic access to this class. A one-step microwave method converts salvinorin A to its 12-epimer, previously requiring multiple steps. Several new analogs (alkene 9 and aromatic compounds 12, 19, 23, 25, 26) retain affinity and selectivity for kappa opioid receptors (KOP), and the furan-2-yl analog (31) shows similar affinity to the parent compound. These results indicate that diverse aromatic groups attached to the decalin core may be tolerated by KOP receptors, potentially yielding additional ligands.
Organic & biomolecular chemistry
September 21, 2009
Denise S Simpson, Kimberly M Lovell, Anthony Lozama et al.
Modifying the furan ring of salvinorin A, the active component of Salvia divinorum, produced new compounds with activity at opioid receptors. A computational study predicted salvinorin A to be a reproductive toxicant in mammals, suggesting its use may have adverse effects. Two new compounds, piperidine 21 and thiomorpholine 23, were identified as selective partial agonists at kappa opioid receptors. This suggests further structural changes could yield ligands with good opioid receptor selectivity but lower toxicity.