|Title||Synthesis and biological evaluation of new opioid agonist and neurokinin-1 antagonist bivalent ligands.|
|Publication Type||Journal Article|
|Year of Publication||2011|
|Authors||Vardanyan R, Kumirov VK, Nichol GS, Davis P, Liktor-Busa E, Rankin D, Varga E, Vanderah T, Porreca F, Lai J, Hruby VJ|
|Journal||Bioorg Med Chem|
|Date Published||2011 Oct 15|
|Keywords||Analgesics, Opioid, Animals, Binding Sites, Drug Design, Guinea Pigs, Humans, Ligands, Male, Mice, Mice, Inbred ICR, Neurokinin-1 Receptor Antagonists, Receptors, Neurokinin-1|
Newly designed bivalent ligands-opioid agonist/NK1-antagonists have been synthesized. The synthesis of new starting materials-carboxy-derivatives of Fentanyl (1a-1c) was developed. These products have been transformed to 'isoimidium perchlorates' (2a-c). The new isoimidium perchlorates have been successfully implemented in nucleophilic addition reactions, with l-tryptophan 3,5-bis(trifluoromethyl)benzyl ester to give the target compounds-amides (3a-c). Perchlorates (2a-c) successfully undergo reactions with other nucleophiles such as alcohols, amines or hydrazines. The obtained compound 3b exhibited μ-opioid agonist activity and NK1-antagonist activity and may serve as a useful lead compound for the further design of a new series of opioid agonist/NK1-antagonist compounds.
|Alternate Journal||Bioorg. Med. Chem.|
|PubMed Central ID||PMC4137774|
|Grant List||DA 06284 / DA / NIDA NIH HHS / United States |
DA 06789 / DA / NIDA NIH HHS / United States
DA 13449 / DA / NIDA NIH HHS / United States
P01 DA006284 / DA / NIDA NIH HHS / United States
R01 DA013449 / DA / NIDA NIH HHS / United States
Synthesis and biological evaluation of new opioid agonist and neurokinin-1 antagonist bivalent ligands.
Faculty Member Reference:
Victor Hruby, Ph.D.
Josephine Lai , Ph.D.
Frank Porreca, PhD
Todd Vanderah, PhD
Eva Varga, Ph.D.