N-4-<<(benzyloxy)carbonyl>amino>phenylacetate N-hydroxysuccinimidyl ester | 149414-91-5

• 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: N-4-<<(benzyloxy)carbonyl>amino>phenylacetate N-hydroxysuccinimidyl ester
• 英文别名: N-[4-(benzyloxycarbonylamino)phenylethanoyloxy]succinimide；(2,5-dioxopyrrolidin-1-yl) 2-[4-(phenylmethoxycarbonylamino)phenyl]acetate
• CAS: 149414-91-5
• 化学式: C₂₀H₁₈N₂O₆
• 分子量: 382.373
• InChiKey: DGKSHZBXDRVYPW-UHFFFAOYSA-N

物化性质

• 熔点：
  143.4-144.3 °C
• 密度：
  1.38±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-4-<<(benzyloxy)carbonyl>amino>phenylacetate N-hydroxysuccinimidyl ester 在 palladium on activated charcoal 、 1,4-环己二烯 、 碳酸氢钠 、 溶剂黄146 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 5.0h， 生成 1-N-[4-aminophenylethanoyl]-6-O-[2-N-(4-butylamino)ethylamino]neamine
  参考文献：
  名称：

  Design of Novel Antibiotics that Bind to the Ribosomal Acyltransfer Site

  摘要：

  The structure of neamine bound to the A site of the bacterial ribosomal RNA was used in the design of novel aminoglycosides. The design took into account stereo and electronic contributions to interactions between RNA and aminoglycosides, as well as a random search of 273 000 compounds from the Cambridge structural database and the National Cancer Institute 3-D database that would fit in the ribosomal aminoglycoside-binding pocket. A total of seven compounds were designed and subsequently synthesized, with the expectation that they would bind to the A-site RNA. Indeed, all synthetic compounds were found to bind to the target RNA comparably to the parent antibiotic neamine, with dissociation constants in the lower micromolar range. The synthetic compounds were evaluated for antibacterial activity against a set of important pathogenic bacteria. These designer antibiotics showed considerably enhanced antibacterial activities against these pathogens, including organisms that hyperexpressed resistance enzymes to aminoglycosides. Furthermore, analyses of four of the synthetic compounds with two important purified resistance enzymes for aminoglycosides indicated that the compounds were very poor substrates; hence the activity of these synthetic antibiotics does not appear to be compromised by the existing resistance mechanisms, as supported by both in vivo and in vitro experiments. The design principles disclosed herein hold the promise of the generation of a large series of designer antibiotics uncompromised by the existing mechanisms of resistance.

  DOI：

  10.1021/ja011695m
• 作为产物：
  描述：

  对氨基苯乙酸 在 sodium hydroxide 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 为溶剂， 反应 4.0h， 生成 N-4-<<(benzyloxy)carbonyl>amino>phenylacetate N-hydroxysuccinimidyl ester
  参考文献：
  名称：

  Design of Novel Antibiotics that Bind to the Ribosomal Acyltransfer Site

  摘要：

  The structure of neamine bound to the A site of the bacterial ribosomal RNA was used in the design of novel aminoglycosides. The design took into account stereo and electronic contributions to interactions between RNA and aminoglycosides, as well as a random search of 273 000 compounds from the Cambridge structural database and the National Cancer Institute 3-D database that would fit in the ribosomal aminoglycoside-binding pocket. A total of seven compounds were designed and subsequently synthesized, with the expectation that they would bind to the A-site RNA. Indeed, all synthetic compounds were found to bind to the target RNA comparably to the parent antibiotic neamine, with dissociation constants in the lower micromolar range. The synthetic compounds were evaluated for antibacterial activity against a set of important pathogenic bacteria. These designer antibiotics showed considerably enhanced antibacterial activities against these pathogens, including organisms that hyperexpressed resistance enzymes to aminoglycosides. Furthermore, analyses of four of the synthetic compounds with two important purified resistance enzymes for aminoglycosides indicated that the compounds were very poor substrates; hence the activity of these synthetic antibiotics does not appear to be compromised by the existing resistance mechanisms, as supported by both in vivo and in vitro experiments. The design principles disclosed herein hold the promise of the generation of a large series of designer antibiotics uncompromised by the existing mechanisms of resistance.

  DOI：

  10.1021/ja011695m

文献信息

• Selective, Tight-Binding Inhibitors of Integrin α4β1 That Inhibit Allergic Airway Responses
  作者：Ko-chung Lin、Humayun S. Ateeq、Sherry H. Hsiung、Lillian T. Chong、Craig N. Zimmerman、Alfredo Castro、Wen-cherng Lee、Charles E. Hammond、Sandhya Kalkunte、Ling-Ling Chen、R. Blake Pepinsky、Diane R. Leone、Andrew G. Sprague、William M. Abraham、Alan Gill、Roy R. Lobb、Steven P. Adams

  DOI：10.1021/jm980673g

  日期：1999.3.1

  development of nonspecific airway hyperresponsiveness to carbachol. These results show that highly selective and potent small-molecule antagonists can be identified to integrins with primary specificity for peptide domains other than Arg-Gly-Asp (RGD); they confirm the generality of integrins as small molecule targets; and they validate alpha4beta1 as a therapeutic target for asthma.

  整联蛋白α4beta1介导白细胞募集，激活，介质释放和凋亡抑制，并且它在炎症病理生理学中发挥着核心作用。描述了基于来自细胞纤连蛋白交替剪接的连接段1（CS-1）肽的Leu-Asp-Val（LDV）序列的高亲和力，选择性的alpha4beta1抑制剂，该抑制剂采用了新型N端肽“上限”策略。一种抑制剂BIO-1211的效价比起始肽高约10（6）倍，并表现出紧密结合的特性（koff = 1.4 x 10（-4）s-1，KD = 70 pM），这是一个了不起的发现用于蛋白质受体的非共价小分子抑制剂。BIO-1211对激活形式的alpha4beta1也具有200倍的选择性，并且它刺激整联蛋白beta1亚基上配体诱导的表位的表达，与受体的配体结合位点的占有率一致的性质。用3毫克雾化剂量的BIO-1211预处理过敏羊可抑制抗原攻击后的早期和晚期气道反应，并防止非特异性气道对卡巴胆碱的过度反应。这些结果表
• Aminoglycosides as antibiotics
  申请人：Haddad Jalal

  公开号：US20050171035A1

  公开（公告）日：2005-08-04

  The present invention provides aminoglycosides and pharmaceutical compositions that include the aminoglycosides. The aminogylcosides are useful to treat or prevent infectious diseases (e.g., bacterial infections) in a mammal (e.g., human).

  本发明提供了氨基糖苷类化合物和包含该氨基糖苷类化合物的药物组合物。该氨基糖苷类化合物可用于治疗或预防哺乳动物（如人）的传染病（例如细菌感染）。
• AMINOGLYCOSIDES AS ANTIBIOTICS
  申请人：Haddad Jalal

  公开号：US20070203081A1

  公开（公告）日：2007-08-30

  The present invention provides aminoglycosides and pharmaceutical compositions that include the aminoglycosides. The aminoglycosides are useful to treat or prevent infectious diseases (e.g., bacterial infections) in a mammal (e.g., human).

  本发明提供了氨基糖苷和包括氨基糖苷的制药组合物。氨基糖苷可用于治疗或预防哺乳动物（如人类）的感染性疾病（如细菌感染）。
• US7220727B2
  申请人：——

  公开号：US7220727B2

  公开（公告）日：2007-05-22
• US7759482B2
  申请人：——

  公开号：US7759482B2

  公开（公告）日：2010-07-20