Laboratory of Medicinal Chemistry, School of Pharmacy , Kitasato University , 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641 , Japan.
Medicinal Research Laboratories, School of Pharmacy , Kitasato University , 5-9-1, Shirokane, Minato-ku, Tokyo 108-8641 , Japan.
ACS Chem Neurosci. 2019 May 15;10(5):2237-2242. doi: 10.1021/acschemneuro.9b00067. Epub 2019 Apr 1.
The cyclopropylmethyl group in classical δ opioid receptor (DOR) antagonist NTI, BNTX, and NTB was replaced with various electron-withdrawing groups to develop DOR inverse agonists. N-Benzyl NTB derivative SYK-657 was a potent DOR full inverse agonist and its potency was over 10-fold potent than that of a reference compound ICI-174,864. Intraperitoneal administration of SYK-657 induced the short-term memory improving effect in mice without abnormal behaviors.
经典 δ 阿片受体（DOR）拮抗剂 NTI、BNTX 和 NTB 中的环丙甲基基团被各种吸电子基团取代，以开发 DOR 反向激动剂。N-苄基 NTB 衍生物 SYK-657 是一种有效的 DOR 完全反向激动剂，其效力超过参考化合物 ICI-174,864 的 10 倍以上。SYK-657 腹腔给药可诱导小鼠产生短期记忆改善作用，而无异常行为。
