Synthesis and biological evaluation of new salvinorin A analogues incorporating natural amino acids.
The synthesis and in vitro evaluation of a new series of salvinorin A analogues substituted at the C(2) position with natural amino acids is reported. Compound 12, containing Val, displayed high affinity and full agonist activity at the kappa-opioid receptor. Analogues with bulky and/or aromatic residues were inactive, showing the importance of size and electronegativity of C(2)-substituents for binding affinity of salvinorin A derivatives.
Department of Pharmacognosy and Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, MS38677-1848, USA.
Jakub
J
Fichna
Kevin
K
Lewellyn
Feng
F
Yan
Bryan L
BL
Roth
Jordan K
JK
Zjawiony
D000596:Amino Acids / Q000737:chemistry*; D045785:Diterpenes, Clerodane / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000378:metabolism; D013329:Structure-Activity Relationship; D014633:Valine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
C557403:2-(2'-amino-3-methylbutanoate)salvinorin B; D000596:Amino Acids; D045785:Diterpenes, Clerodane; D017473:Receptors, Opioid, kappa; D014633:Valine; C090499:salvinorin A