8-Isoquinolinecarboxamide,N-[4-chloro-3-(trifluoromethyl)phenyl]-1,2,3,4,4a,7,8,8a-octahydro-1-oxo-2-(phenylmethyl)-,(4aR,8S,,8aR)- | 1219700-72-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 8-Isoquinolinecarboxamide,N-[4-chloro-3-(trifluoromethyl)phenyl]-1,2,3,4,4a,7,8,8a-octahydro-1-oxo-2-(phenylmethyl)-,(4aR,8S,,8aR)-
• 英文别名: (4aR,8S,8aR)-2-benzyl-N-[4-chloro-3-(trifluoromethyl)phenyl]-1-oxo-3,4,4a,7,8,8a-hexahydroisoquinoline-8-carboxamide
• CAS: 1219700-72-7
• 化学式: C₂₄H₂₂ClF₃N₂O₂
• 分子量: 462.899
• InChiKey: BSPPZJZWKVYWNH-DJPFJPOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (4aR,8S,8aR)-1-((R)-phenylprop-2-yn-1-yl)-2-benzyl-1-oxo-1,2,3,4,4a,7,8,8a-octahydroisoquinoline-8-carboxylate 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 copper(l) chloride 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 8-Isoquinolinecarboxamide,N-[4-chloro-3-(trifluoromethyl)phenyl]-1,2,3,4,4a,7,8,8a-octahydro-1-oxo-2-(phenylmethyl)-,(4aR,8S,,8aR)-
  参考文献：
  名称：

  在中性条件下使用铜 (I) 促进去除炔丙酯来拆分羧酸

  摘要：

  描述了羧酸的光学拆分方法。外消旋羧酸与手性末端炔丙醇缩合得到可分离的非对映体酯。色谱分离，然后在甲醇中加热单个非对映异构体和催化卤化铜 (I)，以良好的收率和≥94% 的对映体比率再生羧酸。该方法对于拆分与常规酯水解不相容的羧酸特别有用。

  DOI：

  10.1021/jo200433w

文献信息

• SYNTHESIS OF FUNCTIONALIZED OCTAHYDRO-ISOQUINOLIN-1-ONE-8-CARBOXYLIC ESTERS AND ANALOGS, AND THERAPEUTIC METHODS
  申请人：University of Kansas

  公开号：US20140243333A1

  公开（公告）日：2014-08-28

  A functionalized polycyclic compound can have a structure of Formula 1 or salt, prodrug, analog, or derivative thereof, which compound can be prepared by providing a diene; reacting the diene with a dienophile under sufficient conditions for a combined Diels-Alder/acylation reaction so as to provide a polycyclic compound having a carboxylic acid; and coupling the carboxylic acid with an amine-containing compound or a hydroxyl-containing compound so as to form an amide or an ester and producing a compound having a structure of Formula 1. The compound can be used for modulating an opioid receptor, which can be conducted by administering to an opioid receptor a functionalized polycyclic compound as described herein in an effective amount to modulate the functionality of the opioid receptor. Such opioid modulation can provide a biological benefit to a subject.

  一种功能化多环化合物可以具有公式1或其盐、前药、类似物或衍生物的结构，该化合物可以通过提供二烯；在足够条件下将二烯与二烯丙酮反应，从而提供具有羧酸的多环化合物，并将羧酸与含胺化合物或含羟基化合物偶联，以形成酰胺或酯，并产生具有公式1结构的化合物进行制备。该化合物可用于调节阿片受体，这可通过向阿片受体中施用本文所述的功能化多环化合物的有效量来进行，以调节阿片受体的功能。这种阿片调节可以为主体提供生物学上的益处。
• <i>N</i>-Alkyl-octahydroisoquinolin-1-one-8-carboxamides: Selective and Nonbasic κ-Opioid Receptor Ligands
  作者：Kevin J. Frankowski、Partha Ghosh、Vincent Setola、Thuy B. Tran、Bryan L. Roth、Jeffrey Aubé

  DOI：10.1021/ml100040t

  日期：2010.8.12

  Herein, we report that N-alkyl-octahydroisoquinolin-1-one-8-carboxamides are a novel class of readily synthesized, selective K-opioid receptor (KOR) ligands. A striking feature of this class of compounds is the absence of any basic nitrogen atoms. Many of these compounds have demonstrated exclusive affinity for the KOR over not only the delta-opioid receptor and the mu-opioid receptor but also 38 other G protein-coupled receptor targets. The general binding affinity of this class of compounds for the KOR combined with a streamlined route for analogue synthesis provide strong motivation for pursuing this interesting new scaffold as a basis toward new probes targeting the KOR.
• SYNTHESIS OF FUNCTIONALIZED OCTAHYDRO-ISOQUINOLIN-1-ONE-8- CARBOXAMIDES, OCTAHYDRO-ISOQUINOLIN-1-ONE-8-CARBOXYLIC ESTERS AND ANALOGS, AND THERAPEUTIC METHODS
  申请人：Aube Jeffrey

  公开号：US20100256142A1

  公开（公告）日：2010-10-07

  A functionalized polycyclic compound can have a structure of Formula 1 or salt, prodrug, analog, or derivative thereof, which compound can be prepared by providing a diene; reacting the diene with a dienophile under sufficient conditions for a combined Diels-Alder/acylation reaction so as to provide a polycyclic compound having a carboxylic acid; and coupling the carboxylic acid with an amine-containing compound or a hydroxyl-containing compound so as to form an amide or an ester and producing a compound having a structure of Formula 1. The compound can be used for modulating an opioid receptor, which can be conducted by administering to an opioid receptor a functionalized polycyclic compound as described herein in an effective amount to modulate the functionality of the opioid receptor. Such opioid modulation can provide a biological benefit to a subject.
• US8735391B2
  申请人：——

  公开号：US8735391B2

  公开（公告）日：2014-05-27
• Resolution of Carboxylic Acids Using Copper(I)-Promoted Removal of Propargylic Esters under Neutral Conditions
  作者：Partha Ghosh、Jeffrey Aubé

  DOI：10.1021/jo200433w

  日期：2011.5.20

  A method for the optical resolution of carboxylic acids is described. Condensation of racemic carboxylic acids with chiral terminal propargyl alcohols gave separable diastereomeric esters. Chromatographic separation followed by heating the individual diastereomers in methanol with catalytic copper(I) halide regenerated the carboxylic acids in good yields and in enantiomeric ratios of ≥94%. This method

  描述了羧酸的光学拆分方法。外消旋羧酸与手性末端炔丙醇缩合得到可分离的非对映体酯。色谱分离，然后在甲醇中加热单个非对映异构体和催化卤化铜 (I)，以良好的收率和≥94% 的对映体比率再生羧酸。该方法对于拆分与常规酯水解不相容的羧酸特别有用。