(3S,4aR,8aR)-6-oxo-2-(tert-butoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid ethyl ester | 1027374-85-1

• 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,4aR,8aR)-6-oxo-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,8aR)6-oxo-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,8aR)-6-oxo-1,3,4,4a,5,7,8,8a-octahydroisoquinoline-2,3-dicarboxylate
• CAS: 1027374-85-1
• 化学式: C₁₇H₂₇NO₅
• 分子量: 325.405
• InChiKey: PKEFQSLNTJXAEE-SCRDCRAPSA-N

物化性质

• 沸点：
  426.4±45.0 °C(Predicted)
• 密度：
  1.132±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3S,4aR,8aR)-6-oxo-2-(tert-butoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid ethyl ester 在 sodium tetrahydroborate 、 cerium(III) chloride heptahydrate 作用下， 以 乙醇 为溶剂， 生成 ethyl (3S,4aR,6R,8aR)-6-hydroxy-2-(tert-butoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate
  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 碘代三甲硅烷 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 (3S,4aR,8aR)-6-oxo-2-(tert-butoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  [EN] PHARMACEUTICAL COMPOSITIONS OF 6-(2-(2H-TETRAZOL-5-YL)ETHYL)-6-FLUORODECAHYDROISOQUINOLINE-3-CARBOXYLIC ACID AND ESTER DERIVATIVES THEREOF
  [FR] COMPOSITIONS PHARMACEUTIQUES D'ACIDE 6-(2-(2H-TÉTRAZOL-5-YL)ÉTHYL)-6-FLUORODÉCAHYDROISOQUINOLÉINE-3-CARBOXYLIQUE ET DE DÉRIVÉS ESTERS DE CELUI-CI

  摘要：

  公开了式子为6-(2-(2H-四唑-5-基)乙基)-6-氟十氢异喹啉-3-羧酸和6-(2-(2H-四唑-5-基)乙基)-6-氟十氢异喹啉-3-羧酸的烃基酯衍生物，以及使用这些化合物的药物组合物和治疗疼痛、癫痫、惊厥和抽搐的方法。

  公开号：

  WO2022006537A1

文献信息

• [EN] PHARMACEUTICAL COMPOSITIONS OF 6-(2-(2H-TETRAZOL-5-YL)ETHYL)-6-FLUORODECAHYDROISOQUINOLINE-3-CARBOXYLIC ACID AND ESTER DERIVATIVES THEREOF<br/>[FR] COMPOSITIONS PHARMACEUTIQUES D'ACIDE 6-(2-(2H-TÉTRAZOL-5-YL)ÉTHYL)-6-FLUORODÉCAHYDROISOQUINOLÉINE-3-CARBOXYLIQUE ET DE DÉRIVÉS ESTERS DE CELUI-CI
  申请人：SEA PHARMACEUTICALS LLC

  公开号：WO2022006537A1

  公开（公告）日：2022-01-06

  6-(2-(2H-tetrazol-5-yl)ethyl)-6-fluorodecahydroisoquinoline-3-carboxylic acid and 6-(2-(2H-tetrazol-5-yl)ethyl)-6-fluorodecahydroisoquinoline-3-carboxylic acid hydrocarbyl ester derivatives of formula are disclosed, as are pharmaceutical compositions and methods for the treatment of pain, epilepsy, convulsions, and seizures employing those compositions.

  公开了式子为6-(2-(2H-四唑-5-基)乙基)-6-氟十氢异喹啉-3-羧酸和6-(2-(2H-四唑-5-基)乙基)-6-氟十氢异喹啉-3-羧酸的烃基酯衍生物，以及使用这些化合物的药物组合物和治疗疼痛、癫痫、惊厥和抽搐的方法。
• 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。
• Two Prodrugs of Potent and Selective GluR5 Kainate Receptor Antagonists Actives in Three Animal Models of Pain
  作者：Esteban Dominguez、Smriti Iyengar、Harlan E. Shannon、David Bleakman、Andrew Alt、Brian M. Arnold、Michael G. Bell、Thomas J. Bleisch、Jennifer L. Buckmaster、Ana M. Castano、Miriam Del Prado、Ana Escribano、Sandra A. Filla、Ken H. Ho、Kevin J. Hudziak、Carrie K. Jones、Jose A. Martinez-Perez、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：10.1021/jm0491952

  日期：2005.6.1

  Amino acids 5 and 7, two potent and selective competitive GluR5 KA receptor antagonists, exhibited high GluR5 receptor affinity over other glutamate receptors. Their ester prodrugs 6 and 8 were orally active in three models of pain: reversal of formalin-induced paw licking, carrageenan-induced thermal hyperalgesia, and capsaicin-induced mechanical hyperalgesia.
• WO2023/130008
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.