5-chloro-2-(methoxybenzyl)-benzylamine | 793695-93-9

• 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: 5-chloro-2-(methoxybenzyl)-benzylamine
• 英文别名: 2-benzyloxy-5-chloro-benzamide；5-chloro-2-phenylmethoxybenzamide
• CAS: 793695-93-9
• 化学式: C₁₄H₁₂ClNO₂
• mdl: MFCD08253245
• 分子量: 261.708
• InChiKey: HJKXFSRXSSJOHI-UHFFFAOYSA-N

物化性质

• 熔点：
  110-112 °C
• 沸点：
  399.2±37.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.071
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-chloro-2-(methoxybenzyl)-benzylamine 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 6.0h， 生成 (1'S,2'R,3'S,4'R,5'S)-4'-[6-(5-chloro-2-benzyloxybenzylamino)-2-chloropurin-9-yl]-2',3'-O-isopropylidenebicyclo[3.1.0]haxane-1'-carboxylic acid ethyl ester
  参考文献：
  名称：

  (N)-Methanocarba 2,N⁶-Disubstituted Adenine Nucleosides as Highly Potent and Selective A₃ Adenosine Receptor Agonists

  摘要：

  A series of ring-constrained (N)-methanocarba-5 '-uronamide 2,N-6-disubstituted adenine nucleosides have been synthesized via Mitsunobu condensation of the nucleobase precursor with a pseudosugar ring containing a 5 '-ester functionality. Following appropriate functionalization of the adenine ring, the ester group was converted to the 5 '-N-methylamide. The compounds, mainly 2-chloro-substituted derivatives, were tested in both binding and functional assays at human adenosine receptors (ARs), and many were found to be highly potent and selective A(3)AR agonists. Selected compounds were compared in binding to the rat A(3)AR to assess their viability for testing in rat disease models. The N-6-(3-chlorobenzyl) and N-6-(3-bromobenzyl) analogues displayed K-i values at the human A(3)AR of 0.29 and 0.38 nM, respectively. Other subnanomolar affinities were observed for the following N-6 derivatives: 2,5-dichlorobenzyl, 5-iodo-2-methoxybenzyl, trans-2-phenyl-1-cyclopropyl, and 2,2-diphenylethyl. Selectivity for the human A3AR in comparison to the A(3)AR was the following (fold): the N-6-(2,2-diphenylethyl) analogue 34 (1900), the N-6-(2,5-dimethoxybenzyl) analogue 26 (1200), the N-6-(2,5-dichlorobenzyl) and N-6-(2-phenyl-1-cyclopropyl) analogues 20 and 33 (1000), and the N-6-(3-substituted benzyl) analogues 17, 18, 28, and 29 (700-900). Typically, even greater selectivity ratios were obtained in comparison with the A(2A) and A(2B)ARs. The (N)-methanocarba-5 '-uronamide analogues were full agonists at the A(3)AR, as indicated by the inhibition of forskolin-stimluated adenylate cyclase at a concentration of 10 mu M. The N-6-(2,2-diphenylethyl) derivative was an A(3)AR agonist in the (N)-methanocarba-5 '-uronamide series, although it was an antagonist in the ribose series. Thus, many of the previously known groups that enhance A(3)AR affinity in the 9-riboside series, including those that reduce intrinsic efficacy, may be adapted to the (N)-methanocarba nucleoside series of full agonists.

  DOI：

  10.1021/jm049580r
• 作为产物：
  描述：

  溴甲苯 、 5-氯-2-羟基苯甲酰胺 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以81%的产率得到5-chloro-2-(methoxybenzyl)-benzylamine
  参考文献：
  名称：

  [EN] HETEROCYCLYL COMPOUNDS
  [FR] COMPOSES HETEROCYCLYLES

  摘要：

  公式（I）的化合物或其药学上可接受的衍生物：其中W、X、Y、Z、R1、R2a、R2b、Rx、R8和R9如规范中定义，制备这种化合物的方法，包含这种化合物的药物组合物以及这种化合物在医学中的用途。

  公开号：

  WO2005040128A1

文献信息

• [EN] PURINE DERIVATIVES AS A3 AND A1 ADENOSINE RECEPTOR AGONISTS<br/>[FR] DERIVES DE PURINE COMME AGONISTES DU RECEPTEUR D'ADENOSINE A3 ET A1
  申请人：US GOV HEALTH & HUMAN SERV

  公开号：WO2006031505A1

  公开（公告）日：2006-03-23

  Disclosed are (N)-methanocarba adenine nucleosides of the formula: [Formula] as highly potent A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R1-R6 are as defined in the specification. These nucleosides are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. The invention also provides compounds that are agonists of both A1 and A3 adenosine receptors for use in cardioprotection.

  揭示了一种公式为[N-甲烷卡巴腺嘌呤核苷]的高效A3腺苷受体激动剂，包括这种核苷的制药组合物，以及这些核苷的使用方法，其中R1-R6如规范中所定义。这些核苷被考虑用于治疗多种疾病，例如炎症、心肌缺血、中风、哮喘、糖尿病和心律失常。该发明还提供了既是A1受体又是A3受体激动剂的化合物，用于心脏保护。
• [EN] HETEROCYCLYL COMPOUNDS<br/>[FR] COMPOSES HETEROCYCLYLES
  申请人：GLAXO GROUP LTD

  公开号：WO2005040128A1

  公开（公告）日：2005-05-06

  Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein W, X, Y, Z, R1, R2a, R2b, and Rx, R8, and R9 are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine.

  公式（I）的化合物或其药学上可接受的衍生物：其中W、X、Y、Z、R1、R2a、R2b、Rx、R8和R9如规范中定义，制备这种化合物的方法，包含这种化合物的药物组合物以及这种化合物在医学中的用途。
• Purine Derivatives as A3 and A1 Adenosine Receptor Agonists
  申请人：Jacobson A. Kenneth

  公开号：US20070232626A1

  公开（公告）日：2007-10-04

  Disclosed are (N)-methanocarba adenine nucleosides of the formula: [Formula] as highly potent A 3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R 1 -R 6 are as defined in the specification. These nucleosides are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. The invention also provides compounds that are agonists of both A 1 and A 3 adenosine receptors for use in cardioprotection.

  本发明公开了一种(N)-甲烷卡巴腺嘌呤核苷，其化学式为：[Formula]，作为高效的A3腺苷受体激动剂，包括这种核苷的制药组合物和使用这些核苷的方法，其中R1-R6如规范中所定义。这些核苷可用于治疗多种疾病，例如炎症，心脏缺血，中风，哮喘，糖尿病和心律失常。本发明还提供了既是A1受体激动剂又是A3受体激动剂的化合物，用于心脏保护。
• Heterocyclyl compounds
  申请人：Giblin Martin Paul Gerard

  公开号：US20070060596A1

  公开（公告）日：2007-03-15

  Compounds of formula (I) or a pharmaceutically acceptable derivative thereof: wherein W, X, Y, Z, R 1 , R 2a , R 2b , and R x , R 8 and R 9 are as defined in the specification, a process for the preparation of such compounds, pharmaceutical compositions comprising such compounds and the use of such compounds in medicine.

  式(I)或其药学上可接受的衍生物的化合物： 其中W、X、Y、Z、R1、R2a、R2b和Rx、R8和R9如规范中所定义，制备这种化合物的过程，包括这种化合物的制药组合物以及这种化合物在医学上的应用。
• Purine derivatives as A3 and A1 adenosine receptor agonists
  申请人：The United States of America as represented by the Department of Health and Human Services

  公开号：US07825126B2

  公开（公告）日：2010-11-02

  Disclosed are (N)-methanocarba adenine nucleosides of the formula: as highly potent A3 adenosine receptor agonists, pharmaceutical compositions comprising such nucleosides, and a method of use of these nucleosides, wherein R1-R6 are as defined in the specification. These nucleosides are contemplated for use in the treatment a number of diseases, for example, inflammation, cardiac ischemia, stroke, asthma, diabetes, and cardiac arrhythmias. The invention also provides compounds that are agonists of both A1 and A3 adenosine receptors for use in cardioprotection.

  本发明涉及一种公式为(N)-methanocarba腺嘌呤核苷的化合物，其具有高效的A3腺苷受体激动剂作用，包括这些核苷的制药组合物和使用这些核苷的方法，其中R1-R6如规范所定义。这些核苷可用于治疗多种疾病，例如炎症、心脏缺血、中风、哮喘、糖尿病和心律失常。本发明还提供了既是A1受体又是A3受体激动剂的化合物，用于心脏保护。