Design and synthesis of novel delta opioid receptor agonists and their pharmacologies
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- 作者：Hiroshi Nagase ; Yumiko Osa ; Toru Nemoto ; Hideaki Fujii ; Masayuki Imai ; Takashi Nakamura ; Toshiyuki Kanemasa ; Akira Kato ; Hiroaki Gouda ; Shuichi Hirono
- 关键词：Opioid ; Naltrexone ; Analgesics ; δ ; Receptor
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2009
- 出版时间：15 May 2009
- 年：2009
- 卷：19
- 期：10
- 页码：2792-2795
- 全文大小：570 K
文摘
We re-examined the accessory site of the 4,5-epoxymorphinan skeleton by camdas conformational analysis in an effort to deign novel δ opioid receptor antagonists. We synthesized three novel compounds (SN-11, 23 and 28) with a 10-methylene bridge and without a 4,5-epoxy ring. Among them, compounds SN-23 (17-isobutyl derivative) and SN-28 (17-methyl derivative) showed very strong agonist activity (over 10 times more than TAN-67). SN-28 also showed high δ selectivity. The δ agonist activity of SN-23 was weaker than that of SN-28, but in terms of the δ selectivity, SN-23 was higher than that of SN-28. These unexpected results indicated that the 4,5-epoxy ring, but not the 10-methylene bridge, was an accessory site in δ opioid receptor agonists.