四氮唑-1-乙酸甲酯 | 55633-19-7

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 四氮唑-1-乙酸甲酯
• 中文别名: 四唑-1-乙酸甲酯
• 英文名称: (1H-tetrazol-1-yl)-2-acetic acid methyl ester
• 英文别名: 1H-tetrazole-1-acetic acid methyl ester；methyl 1H-tetrazol-1-ylacetate；methyl 2-(tetrazol-1-yl)acetate
• CAS: 55633-19-7
• 化学式: C₄H₆N₄O₂
• mdl: MFCD03650761
• 分子量: 142.117
• InChiKey: CGQJVEFCNZKVRS-UHFFFAOYSA-N

物化性质

• 熔点：
  50-52 °C
• 沸点：
  262.2±42.0 °C(Predicted)
• 密度：
  1.47±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  10
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  69.9
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2933990090
• 包装等级：
  III
• 危险类别：
  4.1
• 危险性防范说明：
  P210,P264,P280,P302+P352,P337+P313,P305+P351+P338,P362+P364,P332+P313
• 危险品运输编号：
  1325
• 危险性描述：
  H315,H319,H228
• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  四氮唑-1-乙酸甲酯 在 肼 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 四唑-1-乙酸酰肼
  参考文献：
  名称：

  Compounds useful in therapy

  摘要：

  式(I)的化合物，或其药学上可接受的衍生物，其中： X代表—[CH 2 ] a —R或—[CH 2 ] a —O—[CH 2 ] b —R；a代表从0到6中选择的数字；b代表从0到6中选择的数字； R代表H，CF 3 或Het；Het代表一个可选择取代的5-或6-成员饱和、部分饱和或芳香杂环环； Y代表一个或多个取代基，独立地选择自—[O] c —[CH 2 ] d —R 1 ，每次出现时可能相同也可能不同；c在每次出现时独立地代表从0或1中选择的数字；d在每次出现时独立地代表从0到6中选择的数字； R 1 在每次出现时独立地代表H，卤素，CF 3 ，CN或Het 1 ； Het 1 在每次出现时独立地代表一个5-或6-成员不饱和杂环环；V代表一个直链或—O—；环A代表一个可选择取代的5-到7-成员饱和杂环环，或一个苯基团； Q代表一个直链或—N(R 2 )—； R 2 代表氢或C 1-6 烷基； Z代表—[O] e —[CH 2 ] f —R 3 ，一个苯环（可选择与苯环或Het 2 融合，并且整体作为可选择取代的团），或Het 3 （可选择与苯环或Het 4 融合，并且整体作为可选择取代的团）； R 3 代表C 1-6 烷基（可选择取代），C 3-6 环烷基，C 3-6 环烯基，苯基（可选择取代），Het 5 或NR 4 R 5 ；e代表从0或1中选择的数字；f代表从0到6中选择的数字； Het 2 和Het 5 独立地代表可选择取代的5-或6-成员饱和、部分饱和或芳香杂环环； Het 3 代表一个可选择取代的4到6-成员饱和、部分饱和或芳香杂环环； Het 4 代表一个可选择取代的6-成员芳香杂环环； R 4 和R 5 独立地代表可选择取代的C 1-6 烷基，C 1-6 烷氧基，C 3-8 环烷基（可与C 3-8 环烷基融合），Het 6 ，或氢； Het 6 代表一个可选择取代的5-或6-成员饱和、部分饱和或芳香杂环环；适用于治疗需要V1 a 拮抗剂的紊乱。

  公开号：

  US20050154024A1
• 作为产物：
  描述：

  重氮甲烷 、 四氮唑乙酸 以 甲醇 为溶剂， 以73%的产率得到四氮唑-1-乙酸甲酯
  参考文献：
  名称：

  One-Pot Chemoenzymatic Synthesis of 3‘-Functionalized Cephalosporines (Cefazolin) by Three Consecutive Biotransformations in Fully Aqueous Medium

  摘要：

  We illustrate a new chemoenzymatic synthesis of cefazolin from cephalosporin C, involving three consecutive biotransformations in full aqueous medium. This one-pot three-step synthesis includes the D-amino acid oxidase catalyzed oxidative deamination of the cephalosporin C side chain, hydrolysis of the resulting glutaryl derivative catalyzed by glutaryl acylase, and the final penicillin G acylase (PGA)-catalyzed acylation of 7-aminocephalosporanic acid (1, 7-ACA). The product, 7-[(1H-tetrazol-1-yl)acetamido]-3-(acetoxymethyl)-Delta(3)-cephem-4-carboxylic acid (5), was used as an intermediate for cefazolin synthesis by 3'-acetoxy group displacement with 2-mercapto-5-methyl-1,3,4-thiadiazole. Very high yields have been achieved with all the enzymatic reactions performed; high product concentrations were obtained in short reaction times. This synthetic approach presents several advantages when compared with the conventional chemical processes. The use of the toxic reagents and chlorinated solvents is avoided, while the substrate specificity and chemoselectivity of the enzymes makes reactive group protection and intermediate purification unnecessary. The enzymatic deacylation of cephalosporin C was performed by the simultaneous use of D-amino acid oxidase and glutaryl acylase. The substrate specificity of PGA allowed the acylation of 7-ACA (1) to be performed without purification from the glutaric acid produced during the enzymatic deacylation. These results were achieved by optimization and correct assembly of the different biotransformations involved. Special attention has been applied to the kinetically controlled acylation reaction. High yields were obtained through a careful selection of the enzyme catalyst, experimental conditions, and synthetic strategy.

  DOI：

  10.1021/jo971166u

文献信息

• Modulation of the Microenvironment Surrounding the Active Site of Penicillin G Acylase Immobilized on Acrylic Carriers Improves the Enzymatic Synthesis of Cephalosporins
  作者：Paolo Bonomi、Teodora Bavaro、Immacolata Serra、Auro Tagliani、Marco Terreni、Daniela Ubiali

  DOI：10.3390/molecules181114349

  日期：——

  The catalytic properties of penicillin G acylase (PGA) from Escherichia coli in kinetically controlled synthesis of β-lactam antibiotics are negatively affected upon immobilization on hydrophobic acrylic carriers. Two strategies have been here pursued to improve the synthetic performance of PGA immobilized on epoxy-activated acrylic carriers. First, an aldehyde-based spacer was inserted on the carrier surface by glutaraldehyde activation (immobilization yield = 50%). The resulting 3-fold higher synthesis/hydrolysis ratio (vs/vh1 = 9.7 ± 0.7 and 10.9 ± 0.7 for Eupergit® C and Sepabeads® EC-EP, respectively) with respect to the unmodified support (vs/vh1 = 3.3 ± 0.4) was ascribed to a facilitated diffusion of substrates and products as a result of the increased distance between the enzyme and the carrier surface. A second series of catalysts was prepared by direct immobilization of PGA on epoxy-activated acrylic carriers (Eupergit® C), followed by quenching of oxiranes not involved in the binding with the protein with different nucleophiles (amino acids, amines, amino alcohols, thiols and amino thiols). In most cases, this derivatization increased the synthesis/hydrolysis ratio with respect to the non derivatized carrier. Particularly, post-immobilization treatment with cysteine resulted in about 2.5-fold higher vs/vh1 compared to the untreated biocatalyst, although the immobilization yield decreased from 70% (untreated Eupergit® C) to 20%. Glutaraldehyde- and cysteine-treated Eupergit® C catalyzed the synthesis of cefazolin in 88% (±0.9) and 87% (±1.6) conversion, respectively, whereas untreated Eupergit® C afforded this antibiotic in 79% (±1.2) conversion.

  大肠杆菌青霉素G酰化酶（PGA）的催化性质在动力学控制的β-内酰胺抗生素合成中，当其固定在疏水性丙烯酸载体上时会受到负面影响。本文采用两种策略来提高PGA固定在环氧活化丙烯酸载体上的合成性能。首先，通过戊二醛活化在载体表面插入基于醛基的间隔臂（固定化产率为50%）。与未修饰的载体相比，所得到的合成/水解比（vs/vh1）提高了3倍（分别为Eupergit® C和Sepabeads® EC-EP的9.7±0.7和10.9±0.7），这归因于由于酶与载体表面之间的距离增加，使得底物和产物的扩散更加容易。第二种催化剂系列是通过将PGA直接固定在环氧活化的丙烯酸载体（Eupergit® C）上，然后使用不同亲核试剂（氨基酸、胺、氨基醇、硫醇和氨基硫醇）淬灭未与蛋白质结合的环氧乙烷来制备的。在大多数情况下，这种衍生化相比于非衍生化载体增加了合成/水解比。特别是，用半胱氨酸进行后固定化处理使得vs/vh1比未处理的生物催化剂提高了约2.5倍，尽管固定化产率从70%（未处理的Eupergit® C）降至20%。经过戊二醛和半胱氨酸处理的Eupergit® C催化头孢唑啉的合成转化率分别为88%（±0.9）和87%（±1.6），而未处理的Eupergit® C则达到79%（±1.2）的转化率。
• Influence of Substrate Structure on PGA-Catalyzed Acylations. Evaluation of Different Approaches for the Enzymatic Synthesis of Cefonicid
  作者：Marco Terreni、Joseph Gapesie Tchamkam、Umberto Sarnataro、Silvia Rocchietti、Roberto Fernández-Lafuente、José M. Guisán

  DOI：10.1002/adsc.200404136

  日期：2005.1

  centre of PGA. The enzymatic acylation of these nuclei with R-methyl mandelate has been studied in order to evaluate different approaches for the enzymatic synthesis of cefonicid. The best results have been obtained in the acylation of 7-SACA. Cefonicid (8) was recovered from the reaction mixture as the disodium salt in 65% yield and about 95% of purity. Furthermore, through acylation of 7-ACA, a “one-pot”

  研究了底物结构对大肠杆菌中动态控制的酰化反应中青霉素G酰基转移酶（PGA）催化性能的影响。特别地，已经考虑了合成速率（v s）与酰化酯的水解速率（v h1）之间的比率，评估了不同的β-内酰胺核对活性位点的亲和力。7-氨基头孢烷酸（7-ACA）和7-氨基-3-（1-磺甲基-1,2,3,4-四唑-5-基）硫甲基-3-头孢4-4-羧酸（7-SACA）对PGA的活性中心表现出良好的亲和力。这些核被R酶促酰化对扁桃酸甲酯进行了研究，以评估头孢烯酮酶促合成的不同方法。在7-SACA的酰化中已获得最好的结果。从反应混合物中以二钠盐的形式回收头孢烯酮（8），产率为65％，纯度为约95％。此外，通过7-ACA的酰化反应，从头孢菌素C开始，使用三种酶依次进行了“一锅法”化学酶合成：D-氨基酸氧化酶（DAO），戊二酰酰基化酶（GA）和PGA。分三步获得头孢烯二钠盐，避免了任何中间纯化，总产率为35％，纯度为约9
• Novel thiol esters and process for preparing cephalosporin compounds
  申请人：Asahi Kasei Kogyo Kabushiki Kaisha

  公开号：US04258195A1

  公开（公告）日：1981-03-24

  An 1,3,4-thiadiazole-5-thiol ester of the formula, ##STR1## wherein R is a hydrogen atom or a methyl group, a process for their preparation and a process for preparing a cephalosporin compound of the formula, ##STR2## wherein R is the same as defined above, using the above described 1,3,4-thiadiazole-5-thiol ester.

  该文描述了一种化合物及其制备方法，该化合物为公式##STR1##中的1,3,4-噻二唑-5-硫醇酯，其中R为氢原子或甲基基团。同时，还描述了一种使用上述1,3,4-噻二唑-5-硫醇酯制备头孢菌素化合物的方法，所述头孢菌素化合物的化学式为##STR2##，其中R与上述定义相同。
• Triazolyl piperidine arginine vasopressin receptor modulators
  申请人：——

  公开号：US07745630B2

  公开（公告）日：2010-06-29

  Compounds of formula (I), or pharmaceutically acceptable derivatives thereof, wherein: Z, O, A, V, Y and Y′ are as defined herein; are useful for treating dysmenorreah.

  式(I)的化合物或其药学上可接受的衍生物，其中：Z、O、A、V、Y和Y'如本文所定义；适用于治疗痛经。
• Compounds Useful In Therapy
  申请人：Bryans Justin Stephen

  公开号：US20100317652A1

  公开（公告）日：2010-12-16

  The present invention provides compounds of formula (I), or pharmaceutically acceptable derivatives thereof wherein the variables Z, Q, Ring A, V, X, Y and Y′ are as defined herein, and pharmaceutical compositions comprising these compounds. The compounds of formula (I) and pharmaceutical compositions comprising them are useful for treating a disorder for which a V1a antagonist is indicated, in particular, dysmenorrhoea.

  本发明提供了式(I)的化合物或其药学上可接受的衍生物，其中变量Z，Q，环A，V，X，Y和Y'如此定义，并且包含这些化合物的药物组合物。式(I)的化合物和包含它们的药物组合物可用于治疗需要V1a拮抗剂的紊乱，特别是痛经。