(3S,4aS,6S,8aR)-6-((2-carboxy-4-chlorophenyl)thio)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid | 754973-98-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (3S,4aS,6S,8aR)-6-((2-carboxy-4-chlorophenyl)thio)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid
• 英文别名: (3S,4aS,6S,8aR)-6-[(2-Carboxy-4-chlorophenyl)thio]decahydro-3-isoquinolinecarboxylic acid；(3S,4aS,6S,8aR)-6-(2-carboxy-4-chlorophenyl)sulfanyl-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid
• CAS: 754973-98-3
• 化学式: C₁₇H₂₀ClNO₄S
• 分子量: 369.869
• InChiKey: CSOIIZJOPHPJBD-QPPBUOOMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (3S,4aS,6S,8aR)-6-((2-ethoxycarbonyl-4-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-4-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

文献信息

• EXCITATORY AMINO ACID RECEPTOR ANTAGONISTS
  申请人：Martinez-Perez Jose Antonio

  公开号：US20100094014A1

  公开（公告）日：2010-04-15

  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)).

  本发明提供了公式（I）和公式（I（a））的新化合物，或其药学上可接受的盐；治疗神经系统疾病和神经退行性疾病的方法，特别是治疗疼痛和偏头痛，包括给予公式（I）或公式（I（a））的化合物；以及制备公式（I）或公式（I（a））化合物的过程。
• Excitatory amino acid receptor antagonists
  申请人：Eli Lilly & Company

  公开号：EP2166003A1

  公开（公告）日：2010-03-24

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

  本发明提供了新型的式 I 和式 I(a)化合物或其药学上可接受的盐；它们在治疗神经系统疾病和神经退行性疾病，尤其是疼痛和偏头痛方面的用途，以及制备式 I 或式 I(a)化合物的工艺。
• US7205313B2
  申请人：——

  公开号：US7205313B2

  公开（公告）日：2007-04-17
• US7601738B2
  申请人：——

  公开号：US7601738B2

  公开（公告）日：2009-10-13
• 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.