4-叠氮基水杨酸 N-羟基琥珀酰亚胺酯 | 96602-46-9

• 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: 4-叠氮基水杨酸 N-羟基琥珀酰亚胺酯
• 中文别名: 4-叠氮基-水杨酸琥珀酰亚胺酯；4-叠氮基水杨酸N-羟基琥珀酰亚胺酯
• 英文名称: succinimide 4-azidosalicylate
• 英文别名: 4-azido-2-hydroxybenzoic acid N-hydroxysuccinimide ester；N-hydroxysuccinimidyl ester of p-azidosalicylic acid；4-azido salicylic acid N-hydroxy succinimide ester；4-azidosalicylic acid N-hydroxysuccinimide ester；N-hydroxysuccinimidyl 4-azido-2-hydroxybenzoate；N-hydroxy-succinimidyl-4-azidosalicylic acid；(2,5-dioxopyrrolidin-1-yl) 4-azido-2-hydroxybenzoate
• CAS: 96602-46-9
• 化学式: C₁₁H₈N₄O₅
• 分子量: 276.208
• InChiKey: RBAFCMJBDZWZIV-UHFFFAOYSA-N

物化性质

• 熔点：
  81-83 °C
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  98.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-叠氮基水杨酸 N-羟基琥珀酰亚胺酯 在 chloroamine-T 、 sodium iodide 作用下， 以 乙腈 为溶剂， 反应 1.0h， 以42%的产率得到N-hydroxysuccinimidyl 4-azido-2-hydroxy-5-iodobenzoate
  参考文献：
  名称：

  使用氯胺T和碘化钠对苯酚进行碘化

  摘要：

  许多取代的苯酚加碘的简便方法是在DMF，DMSO或乙腈中使用氯胺T和碘化钠。

  DOI：

  10.1016/s0040-4039(00)94774-9
• 作为产物：
  描述：

  4-氨基水杨酸 在 吡啶 、 sodium azide 、 硫酸 、 sodium nitrite 作用下， 以 水 、 乙腈 为溶剂， 反应 16.0h， 生成 4-叠氮基水杨酸 N-羟基琥珀酰亚胺酯
  参考文献：
  名称：

  Synthesis and biological activity of iodinated and photosensitive derivatives of tetrabenazine

  摘要：

  DOI：

  10.1016/0223-5234(90)90121-i

文献信息

• Novel agents for preventing and treating disorders involving modulation of the RyR receptors
  申请人：Marks R. Andrew

  公开号：US20070049572A1

  公开（公告）日：2007-03-01

  The present invention provides novel compounds of Formula I and salts, hydrates, solvates, complexes, and prodrugs thereof. The present invention further provides methods for synthesizing compounds of Formula I. The invention additionally provides pharmaceutical compositions comprising the compounds of Formula I and methods of using the pharmaceutical compositions of Formula I to treat and prevent disorders and diseases associated with the RyR receptors that regulate calcium channel functioning in cells. Such disorders and diseases include, by way of example only, cardiac disorders and diseases, skeletal muscular disorders and diseases, cognitive disorders and diseases, malignant hyperthermia, diabetes, and sudden infant death syndrome. Cardiac disorder and diseases include, but are not limited to, irregular heartbeat disorders and diseases; exercise-induced irregular heartbeat disorders and diseases; sudden cardiac death; exercise-induced sudden cardiac death; congestive heart failure; chronic obstructive pulmonary disease; and high blood pressure. Irregular heartbeat disorders and diseases include and exercise-induced irregular heartbeat disorders and diseases include, but are not limited to, atrial and ventricular arrhythmia; atrial and ventricular fibrillation; atrial and ventricular tachyarrhythmia; atrial and ventricular tachycardia; catecholaminergic polymorphic ventricular tachycardia (CPVT); and exercise-induced variants thereof. Skeletal muscular disorder and diseases include, but are not limited to, skeletal muscle fatigue, exercise-induced skeletal muscle fatigue, muscular dystrophy, bladder disorders, and incontinence. Cognitive disorders and diseases include, but are not limited to, Alzheimer's Disease, forms of memory loss, and age-dependent memory loss.

  本发明提供了Formula I的新化合物及其盐、水合物、溶剂合物、络合物和前药。本发明还提供了合成Formula I化合物的方法。此外，该发明还提供了包含Formula I化合物的药物组合物，以及使用Formula I药物组合物治疗和预防与调节细胞中钙通道功能的RyR受体相关的疾病和疾病的方法。这些疾病包括但不限于心脏疾病、骨骼肌肉疾病、认知障碍和疾病、恶性高热、糖尿病和婴儿猝死综合征。心脏疾病包括但不限于心律不齐疾病、运动诱发的心律不齐疾病、猝死、运动诱发的猝死、充血性心力衰竭、慢性阻塞性肺疾病和高血压。心律不齐疾病和疾病包括运动诱发的心律不齐疾病，但不限于心房和心室心律失常、心房和心室颤动、心房和心室快速心律失常、心房和心室快速心跳、儿茶酚胺多形性心室心动过速（CPVT）及其运动诱发的变体。骨骼肌肉疾病包括但不限于骨骼肌疲劳、运动诱发的骨骼肌疲劳、肌肉萎缩、膀胱疾病和失禁。认知障碍和疾病包括但不限于阿尔茨海默病、各种记忆丧失形式和年龄相关的记忆丧失。
• Pharmaceutical uses and synthesis of nicotinamides
  申请人：Darwin Molecular Corporation

  公开号：US06777432B1

  公开（公告）日：2004-08-17

  A compound of the formula and pharmaceutically acceptable salts thereof, wherein R1 is selected from (R3)C(═O)—N(R4)— and (R3)(R4)N—C(═O)—; R2 is selected from —OR5 and —N(R5)(R6); n is 0, 1, 2 or 3; X is selected from oxygen and sulfur; and R3, R4, R5 and R6 are independently selected from hydrogen, alkyl, heteroalkyl, aryl, aryl(akylene), heteroaryl, heteroaryl(alkylene), carbocycle, carbocycle(alkylene), heterocycle, and heterocycle(alkylene); as well as pharmaceutical compositions containing said compound. The compounds and compositions are useful in, for example, the treatment of inflammatory events in an animal subject.

  该化合物的公式及其药用盐，其中R1从(R3)C(═O)—N(R4)—和(R3)(R4)N—C(═O)—中选择；R2从—OR5和—N(R5)(R6)中选择；n为0、1、2或3；X从氧和硫中选择；R3、R4、R5和R6独立地从氢、烷基、杂原子烷基、芳基、芳基(烷基)、杂原子芳基、杂原子芳基(烷基)、碳环、碳环(烷基)、杂环和杂环(烷基)中选择；以及含有该化合物的药物组合物。这些化合物和组合物在例如治疗动物体内的炎症事件方面是有用的。
• Structure−Activity Relationships of Methoctramine-Related Polyamines as Muscular Nicotinic Receptor Noncompetitive Antagonists. 2. Role of Polymethylene Chain Lengths Separating Amine Functions and of Substituents on the Terminal Nitrogen Atoms
  作者：Michela Rosini、M. Gabriele Bixel、Gabriella Marucci、Roberta Budriesi、Michael Krauss、Maria L. Bolognesi、Anna Minarini、Vincenzo Tumiatti、Ferdinand Hucho、Carlo Melchiorre

  DOI：10.1021/jm011067f

  日期：2002.4.1

  compounds, like prototype 1, were noncompetitive antagonists of nicotinic receptors while being competitive antagonists at M(2) and M(3) mAChRs. The biological profile of polyamines 4-7 revealed that increasing the number of amine functions and the chain length separating these nitrogen atoms led to a significant improvement in potency at nAChRs. Moreover, the role of the number and type of amine functions

  聚亚甲基四胺甲辛胺（1）是一种典型的抗毒蕈碱配体，对肌肉nAChR具有显着的亲和力。因此，根据通用模板方法，对1进行结构修饰以提高对肌肉型nAChR的亲和力和选择性。合成的多胺衍生物分别在蛙直肌和鱼雷nAChRs和豚鼠左心房（M（2））和回肠纵肌（M（3））mAChRs上进行测试。所有化合物，如原型1，都是烟碱样受体的非竞争性拮抗剂，同时是M（2）和M（3）mAChRs的竞争性拮抗剂。多胺4-7的生物学特性表明，增加胺官能团的数量和分隔这些氮原子的链长导致nAChRs的效力显着提高。此外，通过合成化合物9和10，进一步研究了胺官能团的数量和类型在与nAChRs相互作用中的作用，显示了四胺8和11，在氮原子之间带有相当刚性的间隔基，而不是非常柔软的聚亚甲基链，在nAChRs处的分布类似于1，而在mAChRs处观察到效力显着降低。带有2-甲氧基苯乙基的四胺12的效力比1低，而带有二苯乙基部分的
• C10-Oe-N-(4-azido-5-125iodo salicyloyl)-β-alanyl-β alanyl ryanodine (Az-βAR), a novel photo-affinity ligand for the ryanodine binding site
  作者：Keshore R. Bidasee、Henry R. Besch、Sangyeol Kwon、Jeffrey T. Emmick、Kurt T. Besch、Koert Gerzon、Rod A. Humerickhouse

  DOI：10.1002/jlcr.2580340106

  日期：1994.1

  A high affinity, photoactivatable, radio-iodinated ligand for the ryanodine binding site(s) of the sarcoplasmic reticulum calcium-release-channel, C10-Oeq-N-(4-azido-5-125iodo salicyloyl)-β-alanyl-β-alanyl ryanodine (Az-βAR), was synthesized at a specific activity of 1400mCi/mmol. Prepared by condensing the versatile synthon, N-(4-azido-5125iodo salicyloyl)-β-alanine with C10-Oeq-β-alanyl ryanodine, Az-βAR, like [3H] ryanodine, does not demonstrate saturation binding kinetics. 127Az-βAR exhibits an IC50 of 27.2 ± 2 × 10−9 M (mean ± SD) compared to ryanodine's 6.2 ± 0.4 × 10−9 M for the ryanodine receptor/calcium release channel of sarcoplasmic reticulum vesicles isolated from rabbit skeletal muscle.

  我们合成了一种与肌质网钙释放通道的雷诺丁结合位点具有高亲和力、可光激活的放射性碘化配体--C10-Oeq-N-（4-叠氮-5-125 碘水杨酰）-β-丙氨酰-β-丙氨酰雷诺丁（Az-βAR），其比活度为 1400mCi/mmol。Az-βAR 是由多功能合成物 N-（4-叠氮-5125 碘水杨酰）-β-丙氨酸与 C10-Oeq-β-丙氨酰雷诺丁缩合而成，与 [3H] 雷诺丁一样，Az-βAR 不显示饱和结合动力学。127Az-βAR 对分离自家兔骨骼肌的肌质网囊泡的雷诺丁受体/钙释放通道的 IC50 为 27.2 ± 2 × 10-9 M（平均值 ± SD），而雷诺丁的 IC50 为 6.2 ± 0.4 × 10-9 M。
• Synthesis of sparsomycin derivatives, addressing its binding to the large ribosomal subunit
  作者：L. A. G. M. van den Broek、A. J. J. Antonisse、H. C. J. Ottenheijm、A. San Felix、E. Lázaro、J. P. G. Ballesta、P. Lelieveld

  DOI：10.1002/recl.19921110401

  日期：——

  Apparently, the uracil ring plays an important role in the interaction of sparsomycin with the ribosomal peptidyl transferase and its unmodified presence is crucial for displaying activity. The photoprobes, carrying modifications in the “eastern C” fragment of 1, do interact with the ribosome, but less effectively than sparsomycin itself.

  化合物的合成14-19，6- methyluracilacryloyl衍生物，和27-29，抗肿瘤抗生素稀疏霉素光反应性叠氮芳基类似物（1）中描述。1的6-甲基尿嘧啶丙烯酰基部分的所有修饰都是通过选择性还原或通过选择性的6的N-和O-甲基化来实现的（方案2）。合成方案中与光亲和性类似物的关键步骤是使氯甲基亚砜20和21与在液氨中得到适当保护的胱胺22反应，得到由Sparsomycin N保护的胺分别如图23和24所示（方案4）。随后，光反应基团即。一个p -azidosalicylyl和4-叠氮基-2-硝基苯基，分别加上这些胺。为了评估所制备化合物的生物学活性，研究了两种无细胞测定法中蛋白质生物合成的抑制，液体培养基中大肠杆菌的细胞生长抑制和软琼脂中鼠白血病L1210菌落形成的抑制。在的“西方”片段引入的所有变型1使药物失去生物学活性。显然，尿嘧啶环在稀疏霉素与核糖体肽基转移酶的相互作用中