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

文献索引：Bioorg. Med. Chem. Lett. 20(21) , 6302-5, (2010)

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摘要

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.