(3S,4aS,6S,8aR)-6-((2-ethoxycarbonyl-5-chlorophenyl)thio)-2-methoxycarbonyl-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-((2-ethoxycarbonyl-5-chlorophenyl)thio)-2-methoxycarbonyl-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-((2-ethoxycarbonyl-5-chlorophenyl)thio)-2-methoxycarbonyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate；Ethyl(3S, 4aS, 6S, 8aR)6-((2-ethoxycarbonyl-5-chlorophenyl)thio)-2-methoxycarbonyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate；3-O-ethyl 2-O-methyl (3S,4aS,6S,8aR)-6-(5-chloro-2-ethoxycarbonylphenyl)sulfanyl-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-2,3-dicarboxylate
• 化学式: C₂₃H₃₀ClNO₆S
• 分子量: 484.013
• InChiKey: FQCBFXOXEAJAGB-HIRMHNASSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  107
• 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-((2-ethoxycarbonyl-5-chlorophenyl)thio)-2-methoxycarbonyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid ethyl ester 在 盐酸 作用下， 以 水 为溶剂， 生成 (3S,4aS,6S,8aR)-6-((2-carboxy-5-chlorophenyl)thio)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid
  参考文献：
  名称：

  GluK1 antagonists from 6-(carboxy)phenyl decahydroisoquinoline derivatives. SAR and evaluation of a prodrug strategy for oral efficacy in pain models

  摘要：

  The synthesis and structure-activity relationship of decahydroisoquinoline derivatives with various benzoic acid substitutions as GluK1 antagonists are described. Potent and selective antagonists were selected for a tailored prodrug approach in order to facilitate the evaluation of the new compounds in pain models after oral administration. Several diester prodrugs allowed for acceptable amino acid exposure and moderate efficacy in vivo. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.046
• 作为产物：
  描述：

  ethyl (3S,4aR,8aR)-6-oxo-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate 在 sodium tetrahydroborate 、 cerium(III) chloride heptahydrate 、 potassium carbonate 、 三乙胺 作用下， 以 乙醇 、 丙酮 为溶剂， 生成 (3S,4aS,6S,8aR)-6-((2-ethoxycarbonyl-5-chlorophenyl)thio)-2-methoxycarbonyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  GluK1 antagonists from 6-(carboxy)phenyl decahydroisoquinoline derivatives. SAR and evaluation of a prodrug strategy for oral efficacy in pain models

  摘要：

  The synthesis and structure-activity relationship of decahydroisoquinoline derivatives with various benzoic acid substitutions as GluK1 antagonists are described. Potent and selective antagonists were selected for a tailored prodrug approach in order to facilitate the evaluation of the new compounds in pain models after oral administration. Several diester prodrugs allowed for acceptable amino acid exposure and moderate efficacy in vivo. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.046

文献信息

• Excitatory amino acid receptor antagonists
  申请人：Eli Lilly and Company

  公开号：US07205313B2

  公开（公告）日：2007-04-17

  The present invention provides novel compounds of Formula (I) and Formula (I(a)), or the pharmaceutically acceptable salts thereof; methods for treating neurological disorders and neurodegenerative diseases, particularly pain and migraine, comprising administering a compound of Formula (I) or Formula (I(a)); and processes for preparing compounds of Formula (I) or Formula (I(a)).

  本发明提供了式(I)和式(I(a))的新型化合物，或其药学上可接受的盐；用于治疗神经系统疾病和神经退行性疾病，特别是疼痛和偏头痛的方法，包括给予式(I)或式(I(a))的化合物；以及制备式(I)或式(I(a))的化合物的方法。
• GluK1 antagonists from 6-(carboxy)phenyl decahydroisoquinoline derivatives. SAR and evaluation of a prodrug strategy for oral efficacy in pain models
  作者：Jose A. Martinez-Perez、Smriti Iyengar、Harlan E. Shannon、David Bleakman、Andrew Alt、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.2013.09.046

  日期：2013.12

  The synthesis and structure-activity relationship of decahydroisoquinoline derivatives with various benzoic acid substitutions as GluK1 antagonists are described. Potent and selective antagonists were selected for a tailored prodrug approach in order to facilitate the evaluation of the new compounds in pain models after oral administration. Several diester prodrugs allowed for acceptable amino acid exposure and moderate efficacy in vivo. (C) 2013 Elsevier Ltd. All rights reserved.