Amino Acids and Peptides. LVI. Synthesis of pyrazinone ring-containing opioid mimetics and examination of their opioid receptor binding activity

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• 作者：Okada ; Yoshio ; Fukumizu ; Atsuko ; Takahashi ; Motohiro ; Yamazaki ; Junpei ; Yokoi ; Toshio ; Tsuda ; Yuko ; et. al.
• 关键词：dipeptidyl chloromethyl ketone ; cyclization ; pyrazinone ring-containing amino acids ; opioid mimetics
• 刊名：Tetrahedron
• 出版年：1999
• 出版时间：December 10, 1999
• 年：1999
• 卷：55
• 期：50
• 页码：14391-14406
• 全文大小：830 K

文摘

Cyclization of dipeptidyl chloromethyl ketones gave 6-(4-aminobutyl)-3-carboxyethyl-5-methyl-2(1H)-pyrazinone (3), 3-(4-aminobutyl)-6-carboxyethyl-5-methyl-2(1H)-pyrazinone (6), and 3,6-bis(4-aminobutyl)-5-methyl-2(1H)-pyrazinone (15). Using above pyrazinone derivatives, three opioid mimetics were prepared (III-V). Derivatives containing 3 and 6 demonstrated weak μ and δ-opioid receptor affinities ranging from 1.6 mM to 4.1 mM while the opioid mimetic containing derivative 15 displayed higher μ-opioid receptor binding affinity (K_iμ = 61 nM) and selectivity (K_iμ/K_iδ = 31).