Bioorganic & Medicinal Chemistry Letters 2010-11-01

Design and synthesis of KNT-127, a δ-opioid receptor agonist effective by systemic administration.

Hiroshi Nagase, Toru Nemoto, Ayaka Matsubara, Manabu Saito, Naoshi Yamamoto, Yumiko Osa, Shigeto Hirayama, Mayumi Nakajima, Kaoru Nakao, Hidenori Mochizuki, Hideaki Fujii

Index: Bioorg. Med. Chem. Lett. 20(21) , 6302-5, (2010)

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Abstract

We have reported previously the novel δ-opioid agonist, SN-28, which was more potent in in vitro assays than the prototype δ-agonists, TAN-67 and SNC-80. However, when administered by subcutaneous injection, this compound showed no analgesic effect at dosages greater than 30mg/kg in the acetic acid writhing test. We speculated that SN-28 was not effective in the test because the presence of the charged ammonium groups prevented its penetration through the blood-brain barrier. On the basis of our proposal, we designed the novel δ-agonist, KNT-127, which was effective with systemic administration.Copyright © 2010 Elsevier Ltd. All rights reserved.