Effects of -Substituents on the Functional Activities of Naltrindole Derivatives for the δ Opioid Receptor: Synthesis and Evaluation of Sulfonamide Derivatives

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2020 Aug 23

PMID 32825410

Citations 5

Authors

Chiharu Iwamatsu

Daichi Hayakawa

Tomomi Kono

Ayaka Honjo

Saki Ishizaki

Shigeto Hirayama

Hiroaki Gouda

Hideaki Fujii

Affiliations

Soon will be listed here.

Abstract

We have recently reported that -alkyl and -acyl naltrindole (NTI) derivatives showed activities for the δ opioid receptor (DOR) ranging widely from full inverse agonists to full agonists. We newly designed sulfonamide-type NTI derivatives in order to investigate the effects of the -substituent on the functional activities because the side chain and S=O part in the sulfonamide moiety located in spatially different positions compared with those in the alkylamine and amide moieties. Among the tested compounds, cyclopropylsulfonamide (SYK-839) was the most potent full inverse agonist for the DOR, whereas phenethylsulfonamide (SYK-901) showed full DOR agonist activity with moderate potency. These NTI derivatives are expected to be useful compounds for investigation of the molecular mechanism inducing these functional activities.

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