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ID: ALA1833807

Journal: Bioorg Med Chem

Title: Synthesis and biological evaluation of new opioid agonist and neurokinin-1 antagonist bivalent ligands.

Authors: Vardanyan R, Kumirov VK, Nichol GS, Davis P, Liktor-Busa E, Rankin D, Varga E, Vanderah T, Porreca F, Lai J, Hruby VJ.

Abstract: 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.

CiteXplore: 21925887

DOI: 10.1016/j.bmc.2011.08.027