2-溴甲基-1-氯-4-碘苯 | 793695-85-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-溴甲基-1-氯-4-碘苯
• 中文别名: 2-氯-5-碘苄溴；2-氯-5-碘溴苄
• 英文名称: 2-bromomethyl-1-chloro-4-iodo-benzene
• 英文别名: 2-Chloro-5-iodobenzyl bromide；2-(bromomethyl)-1-chloro-4-iodobenzene
• CAS: 793695-85-9
• 化学式: C₇H₅BrClI
• 分子量: 331.378
• InChiKey: DFDCZEQSQMAKJJ-UHFFFAOYSA-N

物化性质

• 熔点：
  94-95 °C
• 沸点：
  309.1±32.0 °C(Predicted)
• 密度：
  2.166±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  0
• 氢给体数：
  0
• 氢受体数：
  0

安全信息

• 包装等级：
  II
• 危险类别：
  8
• 危险性防范说明：
  P260,P264,P270,P280,P301+P330+P331,P302+P352,P303+P361+P353,P304+P340,P305+P351+P338,P310,P332+P313,P362,P405,P501
• 危险品运输编号：
  3261
• 危险性描述：
  H302,H315,H314
• 储存条件：
  应存于室温、避光且在惰性气体保护下。

反应信息

• 作为反应物：
  描述：

  2-溴甲基-1-氯-4-碘苯 在 三乙胺 、 肼 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 (1'S,2'R,3'S,4'R,5'S)-4'-[6-(2-chloro-5-iodobenzylamino)-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：

  2-氯-5-碘甲苯 在 N-溴代丁二酰亚胺(NBS) 、 过氧化苯甲酰 作用下， 以 四氯化碳 为溶剂， 生成 2-溴甲基-1-氯-4-碘苯
  参考文献：
  名称：

  第一次接触：7-苯基-2-氨基喹啉，有效的和选择性的神经元一氧化氮合酶抑制剂，针对同工型特异性天冬氨酸。

  摘要：

  抑制神经元一氧化氮合酶（nNOS）是一种涉及神经退行性疾病的酶，是治疗或预防这些疾病的有吸引力的策略。我们以前开发了几类基于2-氨基喹啉的nNOS抑制剂，但是这些化合物的缺点包括脱靶混杂，对人nNOS的活性低以及对nNOS的选择性比相关酶适度。在这项研究中，我们合成了基于7-苯基-2-氨基喹啉的新型nNOS抑制剂，并针对大鼠和人类nNOS，人类eNOS和鼠类（在某些情况下）对人类iNOS进行了测定。在氨基喹啉和带正电荷的尾部之间具​​有元关系的化合物很有效，对人nNOS的选择性比对人eNOS的选择性高近900倍。X射线晶体学分析表明某些化合物的氨基占据了nNOS特异性天冬氨酸残基（eNOS中不存在）周围充满水的口袋。诱变研究证实了这种相互作用，使7-苯基-2-氨基喹啉成为第一个与该残基相互作用的氨基喹啉。

  DOI：

  10.1021/acs.jmedchem.9b01573

文献信息

• MODULATORS OF TOLL-LIKE RECEPTORS
  申请人：Halcomb Randall L.

  公开号：US20110098248A1

  公开（公告）日：2011-04-28

  The present application includes novel modulators of TLRs, compositions containing such compounds, therapeutic methods that include the administration of such compounds.

  本申请涵盖了TLR的新型调节剂，包含这类化合物的组合物，以及包括这类化合物的给药的治疗方法。
• CARBON-LINKED TETRAHYDRO-PYRAZOLO-PYRIDINE MODULATORS OF CATHEPSIN S
  申请人：Ameriks Michael K.

  公开号：US20080200454A1

  公开（公告）日：2008-08-21

  Carbon-linked tetrahydro-pyrazolo-pyridine compounds are described, which are useful as cathepsin S modulators. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by cathepsin S activity, such as psoriasis, pain, multiple sclerosis, atherosclerosis, and rheumatoid arthritis.

  描述了与碳相连的四氢吡唑吡啶化合物，这些化合物可作为cathepsin S调节剂。这些化合物可用于制备药物组合物和治疗疾病状态、疾病和病况的方法，这些疾病状态、疾病和病况是由cathepsin S活性介导的，如银屑病、疼痛、多发性硬化症、动脉粥样硬化和类风湿性关节炎。
• [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。
• 1-氯-2-(4-乙氧基苄基)-4-碘代苯的合成方 法
  申请人：南京红杉生物科技有限公司

  公开号：CN109232199B

  公开（公告）日：2021-11-30

  本发明属于药物合成领域，公开了一种1‑氯‑2‑(4‑乙氧基苄基)‑4‑碘代苯的合成方法：S1：将4‑溴苯乙醚混合于溶剂中，加入镁，在碘的催化下进行反应，即得到格氏试剂；S2：将2‑(溴甲基)‑4‑碘氯苯混合于溶剂中，并加入至S1制得的格氏试剂中，在碘化亚铜催化下进行反应，即得到中间体1‑氯‑2‑(4‑乙氧基苄基)‑4‑碘代苯。该方法合成路线短，最终产品纯度高达99.5％，产率高达95.9％，有利于产业化生产。
• 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。