加拉米克的合成：一种非肽类甘丙肽受体激动剂。
Synthesis of galmic: a nonpeptide galanin receptor agonist.
作者信息
Ceide Susana Conde, Trembleau Laurent, Haberhauer Gebhard, Somogyi Laszlo, Lu Xiaoying, Bartfai Tamas, Rebek Julius
机构信息
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
出版信息
Proc Natl Acad Sci U S A. 2004 Nov 30;101(48):16727-32. doi: 10.1073/pnas.0407543101. Epub 2004 Nov 19.
Abstract
Galanin is a neuropeptide with a wide variety of biological functions. Few nonpeptide ligands, capable of activating galanin receptors, are available today. Based on known pharmacophores of galanin and the tripeptidomimetic galnon, a combinatorial library was formulated, synthesized, and screened against the galanin receptor. An active compound, galmic, was identified and tested in vitro and in vivo for its affinity and efficacy at galanin receptors. The present work describes the total synthesis of galmic, the synthesis of its oxazole precursors, the coupling of the building blocks into a linear trimer, and the macrolactamization reaction.
摘要
甘丙肽是一种具有多种生物学功能的神经肽。目前能够激活甘丙肽受体的非肽配体很少。基于甘丙肽已知的药效基团和三肽模拟物甘诺，构建、合成了一个组合文库，并针对甘丙肽受体进行筛选。鉴定出一种活性化合物加尔米克，并在体外和体内测试了其对甘丙肽受体的亲和力和功效。本研究描述了加尔米克的全合成、其恶唑前体的合成、将各个结构单元偶联成线性三聚体以及大环内酰胺化反应。
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本文引用的文献
1
Galmic, a nonpeptide galanin receptor agonist, affects behaviors in seizure, pain, and forced-swim tests.加尔米克（Galmic）是一种非肽类甘丙肽受体激动剂，可影响癫痫、疼痛和强迫游泳试验中的行为。
Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10470-5. doi: 10.1073/pnas.0403802101. Epub 2004 Jul 6.
2
Anticonvulsant activity of a nonpeptide galanin receptor agonist.一种非肽类甘丙肽受体激动剂的抗惊厥活性。
Proc Natl Acad Sci U S A. 2002 May 14;99(10):7136-41. doi: 10.1073/pnas.102163499.
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Exp Clin Endocrinol Diabetes. 2001;109 Suppl 2:S109-21. doi: 10.1055/s-2001-18574.
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Pharmacological evidence supporting a role for galanin in cognition and affect.支持甘丙肽在认知和情感中发挥作用的药理学证据。
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