(5-氯-2-羟基苄基)氨基甲酸叔丁酯 | 195517-88-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 中文名称: (5-氯-2-羟基苄基)氨基甲酸叔丁酯
• 中文别名: 叔丁基5-氯-2-羟基苄基氨基甲酸酯
• 英文名称: (5-chloro-2-hydroxybenzyl)carbamic acid tert-butyl ester
• 英文别名: tert-butyl (5-chloro-2-hydroxybenzyl)carbamate；(5-chloro-2-hydroxy-benzyl)-carbamic acid tert-butyl ester；N-t-butoxycarbonyl-2-hydroxy-5-chlorobenzylamine；Tert-butyl 5-chloro-2-hydroxybenzylcarbamate；tert-butyl N-[(5-chloro-2-hydroxyphenyl)methyl]carbamate
• CAS: 195517-88-5
• 化学式: C₁₂H₁₆ClNO₃
• 分子量: 257.717
• InChiKey: IEXNKDQSZTYMTI-UHFFFAOYSA-N

物化性质

• 熔点：
  124-126 °C
• 沸点：
  397.1±32.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5-氯-2-羟基苄基)氨基甲酸叔丁酯 在 potassium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.75h， 生成 (1'S,2'R,3'S,4'R,5'S)-4'-[6-(5-chloro-2-(aminocarbonylmethyloxy)benzylamino)-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：

  5-氯-2-羟基苯甲酰胺 在 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 7.5h， 生成 (5-氯-2-羟基苄基)氨基甲酸叔丁酯
  参考文献：
  名称：

  一种二甲硝咪唑衍生物及其应用

  摘要：

  本发明公开了一种二甲硝咪唑衍生物或其药用盐，结构通式为以下结构的一种：#imgabs0#本发明的化合物体外抗菌活性测试表现出良好的抗具核梭杆菌活性和特异性的特点；衍生物B2具有优秀的体外抗具核梭杆菌活性和选择性，结直肠癌小鼠移植瘤体内模型研究发现，化合物B2在单独使用时，对于由具核梭杆菌引起的移植瘤具有一定的抗肿瘤效果，且化合物B2与PD‑1抗体联合给药时，表现出优秀的体内抗肿瘤活性，能够较好的逆转具核梭杆菌感染的结直肠癌对PD‑1抗体的耐药，本发明化合物可以用于治疗由具核梭杆菌引起的结直肠癌以及治疗中出现的肿瘤转移和耐药。

  公开号：

  CN117024368A

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。
• Continued Exploration of Trifunctional Alkyl 4-Chloro-2-diazo-3-oxobutanoates: Streamlined Entry into [1,2,3]Triazolo[5,1-c][1,4]benzoxazines and [1,2,3]Triazolo[5,1-c][1,4]benzoxazepines
  作者：Dmitry Dar’in、Mikhail Krasavin、Anton V. Budeev、Grigory Kantin

  DOI：10.1055/a-1348-9031

  日期：2021.6

  o-aminophenols followed by deprotection provided a convenient entry into [1,2,3]triazolo[5,1-c][1,4]benzoxazines, which are of high medicinal importance, as documented in the literature. The same approach applied to N-protected substituted o-(aminomethyl)phenols afforded [1,2,3]triazolo[5,1-c][1,4]benzoxazepines, which are practically unexplored compounds from a medicinal chemistry perspective. The syntheses

  进一步探索先前引入的4-氯-2-重氮-3-氧代丁酸烷基酯在与N保护的取代的邻氨基苯酚反应后进行脱保护的三功能特征，这为[1,2,3] triazolo [5， 1-c] [1,4]苯并恶嗪具有很高的医学重要性，如文献所记载。将相同的方法应用于N保护的取代邻-（氨基甲基）苯酚可提供[1,2,3]三唑并[5,1-c] [1,4]苯并x氮平，从医药化学的角度来看，它们实际上是未经探索的化合物。合成从苯酚的SN2型烷基化开始。除去保护基会触发亚胺的形成，然后合成Wolff 1,2,3-三唑。
• Pyridinone thrombin inhibitors
  申请人：Merck & Co., Inc.

  公开号：US05792779A1

  公开（公告）日：1998-08-11

  Compounds of the invention are useful in inhibiting thrombin and associated thrombotic occlusions and have the following structure: ##STR1## for example: ##STR2##

  本发明的化合物在抑制凝血酶和相关的血栓闭塞方面是有用的，其结构如下：##STR1## 例如：##STR2##
• Thrombin inhibitors
  申请人：Merck & Co., Inc.

  公开号：US06017934A1

  公开（公告）日：2000-01-25

  A compound which inhibits human thrombin and where has the structure ##STR1##

  这是一种抑制人类凝血酶的化合物，其结构式为##STR1##。
• 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。