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

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

• Book ID: 104004806
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 646 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.08.083

✦ Synopsis

We have reported previously the novel d-opioid agonist, SN-28, which was more potent in in vitro assays than the prototype d-agonists, TAN-67 and SNC-80. However, when administered by subcutaneous injection, this compound showed no analgesic effect at dosages greater than 30 mg/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 d-agonist, KNT-127, which was effective with systemic administration.