N-(2,5-二氯苄基)邻苯二甲酰亚胺 | 793695-86-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 中文名称: N-(2,5-二氯苄基)邻苯二甲酰亚胺
• 英文名称: 2-(2,5-dichlorobenzyl)isoindoline-1,3-dione
• 英文别名: N-(2,5-dichlorobenzyl)phthalimide；N-(2,5-dichlorobenzyl phthalimide)；2-[(2,5-Dichlorophenyl)methyl]isoindole-1,3-dione
• CAS: 793695-86-0
• 化学式: C₁₅H₉Cl₂NO₂
• 分子量: 306.148
• InChiKey: DSBSFLYYULWOIS-UHFFFAOYSA-N

物化性质

• 熔点：
  145-146 °C
• 沸点：
  443.7±35.0 °C(Predicted)
• 密度：
  1.494±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(2,5-二氯苄基)邻苯二甲酰亚胺 在 肼 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 2,5-二氯苄胺
  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：

  potassium phtalimide 、 2,5-二氯苄基溴 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-(2,5-二氯苄基)邻苯二甲酰亚胺
  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

文献信息

• [EN] COMPOSITIONS FOR PROMOTING READTHROUGH OF PREMATURE TERMINATION CODONS, AND METHODS OF USING THE SAME<br/>[FR] COMPOSITIONS PERMETTANT DE FAVORISER LA TRANSLECTURE DE CODONS DE TERMINAISON PRÉMATURÉE, ET LEURS PROCÉDÉS D'UTILISATION
  申请人：THE CENTRE FOR DRUG RES AND DEV

  公开号：WO2017049409A1

  公开（公告）日：2017-03-30

  Disclosed are compounds of general formula (I) that promote readthrough of a premature termination codon (PTC) of an RNA molecule in a translation system, and their use, alone or in combination with other compounds, such as aminoglycoside, to treat diseases or disorders ameliorated by modulation of a premature termination codon (PTC) of an RNA molecule in a translation system. The disorder or disease may be Dystrophic epidermolysis bullosa, Batten disease, Duchenne muscular dystrophy, cancer, and spinal muscular atrophy. Ar-L-B (I)

  公开了通式(I)的化合物，它们能够促进RNA分子在翻译系统中过早终止密码子(PTC)的通读，以及它们单独或与其他化合物如氨基糖苷的组合使用，用于治疗通过调节翻译系统中RNA分子的过早终止密码子(PTC)而得到改善的疾病或失调。该疾病或失调可能是营养不良性表皮松解症、贝敦病、杜氏肌营养不良症、癌症和脊髓性肌萎缩症。Ar-L-B (I)
• [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。
• 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。
• PURINE DERIVATIVES AS A3 AND A1 ADENOSINE RECEPTOR AGONISTS
  申请人：The Government of the United States of America, as repres. by the Secretary of Health and Human Services, Nat. Inst. of Health

  公开号：EP1794162A1

  公开（公告）日：2007-06-13
• US7825126B2
  申请人：——

  公开号：US7825126B2

  公开（公告）日：2010-11-02