...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Medicinal Chemistry >Methyl substitution of 2-aminobicyclo[3.1.0]hexane 2,6-dicarboxylate (LY354740) determines functional activity at metabotropic glutamate receptors: Identification of a subtype selective mGlu2 receptor agonist
【24h】

Methyl substitution of 2-aminobicyclo[3.1.0]hexane 2,6-dicarboxylate (LY354740) determines functional activity at metabotropic glutamate receptors: Identification of a subtype selective mGlu2 receptor agonist

机译：2-氨基双环[3.1.0]己烷2,6-二羧酸酯（LY354740）的甲基取代决定对代谢型谷氨酸受体的功能活性：亚型选择性mGlu2受体激动剂的鉴定

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

LY354740 (1) is a highly potent and selective agonist of metabotropic glutamate (mGlu) receptors 2 and 3. In the present study, we have prepared C3- and C4-methyl-substituted variants of rac-1, compounds 5, 9, and 13. Each of these racemic methyl-substituted analogues displaced specific binding of the mGlu2/3 receptor antagonist H-3-2S-2-amino-2-(1S,2S-2-carboxycycloprop-1-yl)-3-(xanth-9-yl)propanoic acid (H-3-LY341495) from membranes expressing mGlu2 or mGlu3 receptor subtypes. Evaluation of the functional effects of this series on second messenger responses in cells expressing human mGrlu2 or mGlu3 receptors revealed C3β-methyl analogue 5 to possess antagonist properties at both mGlu2 and mGlu3 receptors while C4β-methyl analogue 9 acts as a full agonist at each of these targets. Unexpectedly, we found that incorporation of a methyl substituent at the C4α-position as in analogue 13 results in a mixed mGlu2 agonist/mGlu3 antagonist pharmacological profile. All of the mGlu2 agonist and mGlu3 antagonist activity of rac-13 was found to reside in its resolved (+)-isomer.
机译：LY354740（1）是代谢型谷氨酸（mGlu）受体2和3的高效选择性激动剂。在本研究中，我们制备了rac-1，化合物5、9和9的C3和C4甲基取代的变体。 13.这些外消旋的甲基取代的类似物均取代了mGlu2 / 3受体拮抗剂H-3-2S-2-氨基-2-（1S，2S-2-羧基环丙-1-基）-3-（黄嘌呤）的特异性结合来自表达mGlu2或mGlu3受体亚型的膜的-9-基）丙酸（H-3-LY341495）。评价该系列对表达人mGrlu2或mGlu3受体的细胞中第二信使反应的功能作用后发现，C3β-甲基类似物5在mGlu2和mGlu3受体上均具有拮抗特性，而C4β-甲基类似物9在每个受体上均具有完全的激动剂作用。这些目标。出乎意料的是，我们发现在类似物13中的C4α位置掺入甲基取代基会导致混合的mGlu2激动剂/ mGlu3拮抗剂药理学特征。发现rac-13的所有mGlu2激动剂和mGlu3拮抗剂活性均位于其拆分的（+）-异构体中。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号