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Discovery of highly selective κ-opioid receptor agonists: 10α-Hydroxy TRK-820 derivatives
Shinya Suzuki1, Yuji Sugawara1, Riichiro Tsuji1
1Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan.
Abstract:
κ-Opioid receptor agonists with high selectivity over the μ-opioid receptor are attractive targets in the development of drugs for pain and pruritus. We previously reported the synthesis of 10α-hydroxy TRK-820 (1). In this study, we elucidated the biological properties of 1 and optimized its 6-acyl unit by modifying our synthetic route. Among the 10α-hydroxy TRK-820 derivatives prepared, 26 showed the most potent κ-opioid agonist activity (EC50=0.00466nM) and excellent selectivity and 22 was the most κ-selective agonist.
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