mono-trichloroethyl glutarate | 16326-47-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: mono-trichloroethyl glutarate
• 英文别名: 5-oxo-5-(2,2,2-trichloroethoxy)pentanoic acid
• CAS: 16326-47-9
• 化学式: C₇H₉Cl₃O₄
• 分子量: 263.505
• InChiKey: PLXUNZLMJZIJSG-UHFFFAOYSA-N

物化性质

• 沸点：
  430.4±45.0 °C(Predicted)
• 密度：
  1.493±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  mono-trichloroethyl glutarate 在 N,N-二甲基甲酰胺 草酰氯 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.67h， 生成 ethyl 6-({(2-chloro-4-fluorophenyl)[5-oxo-5-(2,2,2-trichloroethoxy)pentanoyl]amino}sulfonyl)cyclohex-1-ene-1-carboxylate
  参考文献：
  名称：

  EP2039681

  摘要：

  公开号：
• 作为产物：
  描述：

  戊二酸酐 、 2,2,2-三氯乙醇 在 4-二甲氨基吡啶 、 N-羟基丁二酰亚胺 、 三乙胺 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以90%的产率得到mono-trichloroethyl glutarate
  参考文献：
  名称：

  Rational Design of a β-Lactamase Inhibitor Achieved via Stabilization of the trans-Enamine Intermediate:  1.28 Å Crystal Structure of wt SHV-1 Complex with a Penam Sulfone

  摘要：

  beta-Lactamases are one of the major causes of antibiotic resistance in Gram negative bacteria. The continuing evolution of beta-lactamases that are capable of hydrolyzing our most potent beta-lactams presents a vexing clinical problem, in particular since a number of them are resistant to inhibitors. The efficient inhibition of these enzymes is therefore of great clinical importance. Building upon our previous structural studies that examined tazobactam trapped as a trans-enamine intermediate in a deacylation deficient SHV variant, we designed a novel penam sulfone derivative that forms a more stable trans-enamine intermediate. We report here the 1.28 A resolution crystal structure of wt SHV-1 in complex with a rationally designed penam sulfone, SA2-13. The compound is covalently bound to the active site of wt SHV-1 similar to tazobactam yet forms an additional salt-bridge with K234 and hydrogen bonds with S130 and T235 to stabilize the trans-enamine intermediate. Kinetic measurements show that SA2-13, once reacted with SHV-1 beta-lactamase, is about 10-fold slower at being released from the enzyme compared to tazobactam. Stabilizing the trans-enamine intermediate represents a novel strategy for the rational design of mechanism-based class A beta-lactamase inhibitors.

  DOI：

  10.1021/ja063715w

文献信息

• CYCLOALKENE DERIVATIVES, PROCESS FOR PRODUCTION OF THE DERIVATIVES, AND USE OF THE SAME
  申请人：Ichikawa Takashi

  公开号：US20090209585A1

  公开（公告）日：2009-08-20

  The present invention relates to a cycloalkene derivative represented by the formula (I): wherein each symbol is as defined in the specification, a pharmaceutical agent containing the derivative, and a production method thereof. The cycloalkene derivative of the present invention has high solubility in water and is suitable for use as an injection.

  本发明涉及一种由式(I)表示的环烷烯衍生物，其中每个符号如规范中定义，包含该衍生物的制药剂和其生产方法。本发明的环烷烯衍生物在水中具有高溶解度，适用于注射。
• US4847376A
  申请人：——

  公开号：US4847376A

  公开（公告）日：1989-07-11
• US4988497A
  申请人：——

  公开号：US4988497A

  公开（公告）日：1991-01-29
• EP2039681
  申请人：——

  公开号：——

  公开（公告）日：——
• Rational Design of a β-Lactamase Inhibitor Achieved via Stabilization of the <i>trans</i>-Enamine Intermediate:  1.28 Å Crystal Structure of <i>wt</i> SHV-1 Complex with a Penam Sulfone
  作者：Pius S. Padayatti、Anjaneyulu Sheri、Monica A. Totir、Marion S. Helfand、Marianne P. Carey、Vernon E. Anderson、Paul R. Carey、Christopher R. Bethel、Robert A. Bonomo、John D. Buynak、Focco van den Akker

  DOI：10.1021/ja063715w

  日期：2006.10.1

  beta-Lactamases are one of the major causes of antibiotic resistance in Gram negative bacteria. The continuing evolution of beta-lactamases that are capable of hydrolyzing our most potent beta-lactams presents a vexing clinical problem, in particular since a number of them are resistant to inhibitors. The efficient inhibition of these enzymes is therefore of great clinical importance. Building upon our previous structural studies that examined tazobactam trapped as a trans-enamine intermediate in a deacylation deficient SHV variant, we designed a novel penam sulfone derivative that forms a more stable trans-enamine intermediate. We report here the 1.28 A resolution crystal structure of wt SHV-1 in complex with a rationally designed penam sulfone, SA2-13. The compound is covalently bound to the active site of wt SHV-1 similar to tazobactam yet forms an additional salt-bridge with K234 and hydrogen bonds with S130 and T235 to stabilize the trans-enamine intermediate. Kinetic measurements show that SA2-13, once reacted with SHV-1 beta-lactamase, is about 10-fold slower at being released from the enzyme compared to tazobactam. Stabilizing the trans-enamine intermediate represents a novel strategy for the rational design of mechanism-based class A beta-lactamase inhibitors.