Novel Cyclic Biphalin Analogue with Improved Antinociceptive Properties
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- 作者：Adriano Mollica ; Alfonso Carotenuto ; Ettore Novellino ; Antonio Limatola ; Roberto Costante ; Francesco Pinnen ; Azzurra Stefanucci ; Stefano Pieretti ; Anna Borsodi ; Reza Samavati ; Ferenc Zador ; S谩ndor Benyhe ; Peg Davis ; Frank Porreca ; Victor J. Hruby
- 刊名：ACS Medicinal Chemistry Letters
- 出版年：2014
- 出版时间：September 11, 2014
- 年：2014
- 卷：5
- 期：9
- 页码：1032-1036
- 全文大小：323K
- ISSN：1948-5875
文摘
Two novel opioid analogues have been designed by substituting the native d-Ala residues in position 2,2鈥?of biphalin with two residues of d-penicillamine or l-penicillamine and by forming a disulfide bond between the thiol groups. The so-obtained compound 9 containing d-penicillamines showed excellent 渭/未 mixed receptor affinities (Ki未 = 5.2 nM; Ki渭 = 1.9 nM), together with an efficacious capacity to trigger the second messenger and a very good in vivo antinociceptive activity, whereas product 10 was scarcely active. An explanation of the two different pharmacological behaviors of products 9 and 10 was found by studying their conformational properties.