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ID: ALA2146448

Journal: Bioorg Med Chem

Title: Synthesis of quinolinomorphinan derivatives as highly selective δ opioid receptor ligands.

Authors: Ida Y, Matsubara A, Nemoto T, Saito M, Hirayama S, Fujii H, Nagase H.

Abstract: We have reported previously the novel δ opioid agonist KNT-127 which showed high affinity and selectivity for the δ receptor. Moreover, the analgesic effect of subcutaneously administered KNT-127 was more potent than that of a prototypical δ agonist (-)-TAN-67 in the acetic acid writhing test. This study of the structure-activity relationship of KNT-127 derivatives focused on the introduction of substituents onto the 5'-, 6'-, 7'- or 8'-position of the quinoline ring and revealed that many derivatives with 5'- or 8'-substituents showed high affinities and selectivities for the δ receptor. Especially, SYK-153 with an 8'-OH group showed the highest affinity and the most balanced and highest selectivity for the δ receptor among the synthesized compounds.

CiteXplore: 22967810

DOI: 10.1016/j.bmc.2012.08.004