benzhydryl (6R,7R)-3-(acetyloxymethyl)-7-ethynyl-8-oxo-7-(trifluoromethylsulfonyloxy)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate | 160032-69-9

• 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: benzhydryl (6R,7R)-3-(acetyloxymethyl)-7-ethynyl-8-oxo-7-(trifluoromethylsulfonyloxy)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
• CAS: 160032-69-9
• 化学式: C₂₆H₂₀F₃NO₈S₂
• 分子量: 595.574
• InChiKey: NRUPAGZTSXDJHW-JWQCQUIFSA-N

物化性质

• 沸点：
  681.4±55.0 °C(Predicted)
• 密度：
  1.55±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  150
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  benzhydryl (6R,7R)-3-(acetyloxymethyl)-7-ethynyl-8-oxo-7-(trifluoromethylsulfonyloxy)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate 在 铜 、 氯化铵 、 copper(I) bromide 、 lithium bromide 、 锌 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 0.58h， 生成
  参考文献：
  名称：

  7-亚烷基头孢菌素酯作为人白细胞弹性蛋白酶的抑制剂。

  摘要：

  作为其苯甲酰基酯的一系列7-亚烷基头孢菌素和7-亚乙烯基头孢菌素已被测试作为猪胰腺弹性蛋白酶和人白细胞弹性蛋白酶的抑制剂。发现选择的7-亚烷基头孢菌素酯是HLE的有效抑制剂。一类新抑制剂是7-（卤代亚烷基）头孢菌素。与以前报道的基于头孢菌素的弹性蛋白酶抑制剂相反，这些卤代亚烷基头孢显示出作为硫化物而不是作为砜的最佳抑制活性。它们是有效且不可逆的抑制剂。第二类活性化合物由二苯甲基酯7-（氰基亚甲基）头孢菌素砜代表。与这些新抑制剂的活性相反，基于机理的β-内酰胺酶抑制剂7-[（2' -吡啶基）亚甲基]-头孢菌素砜作为弹性蛋白酶抑制剂几乎没有抑制活性。尽管末端未取代的烯丙基硫醚显示出作为PPE抑制剂的活性，但7-亚乙烯基头孢菌素也是相对较弱的抑制剂。模型分析表明7-亚烷基取代基可以很容易地容纳在S1袋中。提出了抑制的潜在机制。

  DOI：

  10.1021/jm970351x
• 作为产物：
  描述：

  二苯基重氮甲烷 在 吡啶 、 盐酸 、 三氟甲磺酸酐 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 48.5h， 生成 benzhydryl (6R,7R)-3-(acetyloxymethyl)-7-ethynyl-8-oxo-7-(trifluoromethylsulfonyloxy)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
  参考文献：
  名称：

  7-亚烷基头孢菌素酯作为人白细胞弹性蛋白酶的抑制剂。

  摘要：

  作为其苯甲酰基酯的一系列7-亚烷基头孢菌素和7-亚乙烯基头孢菌素已被测试作为猪胰腺弹性蛋白酶和人白细胞弹性蛋白酶的抑制剂。发现选择的7-亚烷基头孢菌素酯是HLE的有效抑制剂。一类新抑制剂是7-（卤代亚烷基）头孢菌素。与以前报道的基于头孢菌素的弹性蛋白酶抑制剂相反，这些卤代亚烷基头孢显示出作为硫化物而不是作为砜的最佳抑制活性。它们是有效且不可逆的抑制剂。第二类活性化合物由二苯甲基酯7-（氰基亚甲基）头孢菌素砜代表。与这些新抑制剂的活性相反，基于机理的β-内酰胺酶抑制剂7-[（2' -吡啶基）亚甲基]-头孢菌素砜作为弹性蛋白酶抑制剂几乎没有抑制活性。尽管末端未取代的烯丙基硫醚显示出作为PPE抑制剂的活性，但7-亚乙烯基头孢菌素也是相对较弱的抑制剂。模型分析表明7-亚烷基取代基可以很容易地容纳在S1袋中。提出了抑制的潜在机制。

  DOI：

  10.1021/jm970351x

文献信息

• Synthesis and Mechanistic Evaluation of 7-Vinylidenecephem Sulfones as .beta.-Lactamase Inhibitors
  作者：John D. Buynak、Dipti Khasnis、Brian Bachmann、Kuangcong Wu、Grady Lamb

  DOI：10.1021/ja00103a010

  日期：1994.11

  Representative 7-vinylidenecephalosporins 1 were synthesized from 7-aminocephalosporanic acid and were biologically evaluated as beta-lactamase inhibitors. These chiral allenes were prepared stereospecifically from a cephalosporin-derived propargylic triflate using organocopper reagents. The sodium salts of a few such unsaturated cephalosporanates were evaluated as beta-lactamase inhibitors of the type C enzyme derived from Enterobacter cloacae strain P99. One compound, sodium 7-(2'alpha-tert-butylvinylidene)cephalasporanate sulfone (16),was found to be an excellent progressive inhibitor of this enzyme, exhibiting a second-order rate constant of inactivation of k(3)' = 1.7 x 10(6) 1/(mol.min) and a turnover number of 12. A potential mechanism of inhibition was investigated. The corresponding terminally deuterated allene sodium 7-(2'alpha-tert-butyl-2'-beta-deuteriovinylidene) sulfone (21) was prepared and biologically evaluated. The deuterated compound inhibited the enzyme with a rate constant of k(3)' = 2.7 x 10(5) 1/(mol.min), representing an isotope effect of 6.3. The deuterated compound had an IC50 value which was approximately twice that of the protio compound, and had a turnover number of 25. A mechanism of inhibition which is consistent with this data was proposed. The mechanism of inhibition involves an acyl enzyme which becomes stabilized toward hydrolysis through its conversion-to a vinylogous urethane (beta-aminoacrylate). This intermediate is formed by an elimination reaction which transforms the allene into an enyne. The inhibition disappears extremely slowly, presumedly due to hydrolysis of the stabilized acyl enzyme. This pattern of reactivity is further confirmed by a H-1 NMR study of the nonenzymatic hydrolysis of the inhibitor under basic conditions. A second type of enzymatic inhibition, which does not disappear with time, was also observed. This second (irreversible) type of inhibition required longer incubation times and higher ratios of inhibitor to enzyme and showed no isotope effect.