(3S,4aS,6S,8aR)-6-(5-methoxy-2-cyano-phenoxy)-2-tert-butoxycarbonyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid ethyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3S,4aS,6S,8aR)-6-(5-methoxy-2-cyano-phenoxy)-2-tert-butoxycarbonyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid ethyl ester
• 英文别名: ethyl (3S,4aS,6S,8aR)-6-(5-methoxy-2-cyano-phenoxy)-2-tert-butoxycarbonyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate；2-O-tert-butyl 3-O-ethyl (3S,4aS,6S,8aR)-6-(2-cyano-5-methoxyphenoxy)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-2,3-dicarboxylate
• 化学式: C₂₅H₃₄N₂O₆
• 分子量: 458.555
• InChiKey: VGGPKWWLCFGGMF-YHELAOLJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  98.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3S,4aS,6S,8aR)-6-(5-methoxy-2-cyano-phenoxy)-2-tert-butoxycarbonyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid ethyl ester 在 三正丁基叠氮化锡 作用下， 生成
  参考文献：
  名称：

  GluK1 antagonists from 6-(tetrazolyl)phenyl decahydroisoquinoline derivatives: In vitro profile and in vivo analgesic efficacy

  摘要：

  We have explored the decahydroisoquinoline scaffold, bearing a phenyl tetrazole, as GluK1 antagonists with potential as oral analgesics. We have established the optimal linker atom between decahydroisoquinoline and phenyl rings and demonstrated an improvement of both the affinity for the GluK1 receptor and the selectivity against the related GluA2 receptor with proper phenyl substitution. In this Letter, we also disclose in vivo data that led to the discovery of LY545694 center dot HCl, a compound with oral efficacy in two persistent pain models. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.045

文献信息

• GluK1 antagonists from 6-(tetrazolyl)phenyl decahydroisoquinoline derivatives: In vitro profile and in vivo analgesic efficacy
  作者：Jose A. Martinez-Perez、Smriti Iyengar、Harlan E. Shannon、David Bleakman、Andrew Alt、David K. Clawson、Brian M. Arnold、Michael G. Bell、Thomas J. Bleisch、Ana M. Castaño、Miriam Del Prado、Esteban Dominguez、Ana M. Escribano、Sandra A. Filla、Ken H. Ho、Kevin J. Hudziak、Carrie K. Jones、Ana Mateo、Brian M. Mathes、Edward L. Mattiuz、Ann Marie L. Ogden、Rosa Maria A. Simmons、Douglas R. Stack、Robert E. Stratford、Mark A. Winter、Zhipei Wu、Paul L. Ornstein

  DOI：10.1016/j.bmcl.2013.09.045

  日期：2013.12

  We have explored the decahydroisoquinoline scaffold, bearing a phenyl tetrazole, as GluK1 antagonists with potential as oral analgesics. We have established the optimal linker atom between decahydroisoquinoline and phenyl rings and demonstrated an improvement of both the affinity for the GluK1 receptor and the selectivity against the related GluA2 receptor with proper phenyl substitution. In this Letter, we also disclose in vivo data that led to the discovery of LY545694 center dot HCl, a compound with oral efficacy in two persistent pain models. (C) 2013 Elsevier Ltd. All rights reserved.