benzyl ethyl chlorophosphate | 73992-66-2

• 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: benzyl ethyl chlorophosphate
• 英文别名: O-ethyl benzylchlorophosphonate；[chloro(ethoxy)phosphoryl]oxymethylbenzene
• CAS: 73992-66-2
• 化学式: C₉H₁₂ClO₃P
• 分子量: 234.619
• InChiKey: HGXCPASPLWDAKG-UHFFFAOYSA-N

物化性质

• 沸点：
  325.9±21.0 °C(Predicted)
• 密度：
  1.254±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl ethyl chlorophosphate 在 sodium hydroxide 、 4 A molecular sieve 、 silver(l) oxide 作用下， 以 氯仿 、 水 、 异丙醇 为溶剂， 反应 5.0h， 生成 1-[ethoxy(phenylmethoxy)phosphoryl]-2-methyl-3-[2-[(5-methyl-1H-imidazol-4-yl)methylsulfanyl]ethyl]guanidine
  参考文献：
  名称：

  Zwitterionic analogs of cimetidine as H2 receptor antagonists

  摘要：

  A series of analogues of the H2 receptor histamine antagonist cimetidine have been synthesized in which the dipolar cyanoguanidine group has been replaced by a number of zwitterionic moieties. Although none of the compounds is more effective than cimetidine in blocking histamine-stimulated tachycardia on the isolated guinea pig atrium, the activities of most of the compounds possessing rigid dipoles can be accounted for on the basis of dipole orientation relative to the common side chain and by considering the active species in each case to be the zwitterion. These findings are in general agreement with those found for analogues having conjugated groups as dipoles.

  DOI：

  10.1021/jm00390a006
• 作为产物：
  描述：

  Ethyl-benzyl-phosphit 在 磺酰氯 作用下， 以 四氯化碳 为溶剂， 反应 1.0h， 生成 benzyl ethyl chlorophosphate
  参考文献：
  名称：

  New Synthesis of Phosphorous and Phosphoric Acid Esters

  摘要：

  在四烷氧基钛的存在下，醇与二烷基亚磷酸酯反应，会导致所用醇的 RO 基团取代两个或一个酯官能团。用这种方法制备的混合亚磷酸酯 (R3O)(R1O)P(O)H 可用作混合磷酸盐 (R4O)(R3O)(R1O)PO 的底物。

  DOI：

  10.1055/s-1991-26418

文献信息

• Amidines, their preparation and pharmaceutical compositions containing them.
  申请人：SMITH KLINE & FRENCH LABORATORIES LIMITED

  公开号：EP0007326A1

  公开（公告）日：1980-02-06

  Amidine phosphonate compounds have the structure in which Het is a 5- or 6- membered unsaturated nitrogen heterocycle, Z is sulphur or methylene, n is 2 or 3, R' is hydrogen, lower alkyl or Het-CH2Z(CH2)n2-, p is 0 or 1, R2 is hydrogen or lower alkyl, or R' and R2 together form a (CH2)2 or(CH2)3 group, R'is lower alkyl, aryl or aryl-(lower alkyl), and R4 is hydrogen when p is 0 and hydrogen, lower alkyl, aryl or aryl (lower alkyl) when p is 1. Those compounds where R4 is other than hydrogen are intermediates for the preparation of the compounds where R4 is hydrogen, which have histamine H2-antagonist activity and are the active ingredients of pharmaceutical compositions. The compounds are prepared by primary amine coupling reactions, phosphonylation and hydrolysis.

  膦酸脒化合物的结构如下 其中 Het 是 5 或 6 位不饱和氮杂环，Z 是硫或亚甲基，n 是 2 或 3，R'是氢、低级烷基或 Het-CH2Z(CH2)n2-，p 是 0 或 1，R2 是氢或低级烷基、或 R' 和 R2 共同形成 (CH2)2 或 (CH2)3 基团，R'为低级烷基、芳基或芳基（低级烷基），当 p 为 0 时，R4 为氢，当 p 为 1 时，R4 为氢、低级烷基、芳基或芳基（低级烷基）。R4不是氢的化合物是制备R4是氢的化合物的中间体，这些化合物具有组胺H2-拮抗剂活性，是药物组合物的活性成分。这些化合物是通过伯胺偶联反应、膦酰化反应和水解反应制备的。
• Covalent Inhibition of Serine β-Lactamases by Novel Hydroxamic Acid Derivatives
  作者：Ronak Tilvawala、R. F. Pratt

  DOI：10.1021/bi4003887

  日期：2013.5.28

  The effectiveness of beta-lactam antibiotics is greatly limited by the ability of bacteria to produce beta-lactamases. These enzymes catalyze the hydrolysis of beta-lactams and thus loss of their antibiotic activity. The search for inhibitors of beta-lactamases began soon after beta-lactams were introduced into medical practice and continues today. Some time ago, we introduced a new class of covalent serine beta-lactamase inhibitors, the O-aryloxycarbonyl hydroxamates, that inactivated these enzymes by a unique mechanism in which the active site became cross-linked. We describe in this paper some new variants of this class of inhibitor. First, we investigated compounds in which more polar hydroxamates were incorporated. These were generally not more active than the original compounds against representative class A and class C beta-lactamases, but one of them, 1-(benzoyl)-O-(phenoxycarbonyl)-3-hydroxyurea, was significantly more stable in solution, thus revealing a useful platform for further design. Second, we describe a series of O-(arylphosphoryl) hydroxamates that are also irreversible inactivators of class A and class C beta-lactamases, by phosphorylation of the enzyme, as revealed by mass spectra. These compounds did not, however, cross-link the enzyme active site A striking feature of their structure-activity profile was that hydroxamate remained the leaving group on enzyme phosphorylation rather than aryloxide, even though the aryloxide was intrinsically the better leaving group, as indicated by pK(a) values and demonstrated by the products of hydrolysis in free solution. Model building suggested that this phenomenon arises from the relative affinity of the enzyme active site components for the two leaving groups. The results obtained for both groups of inhibitors are important for further optimization of these inhibitors.
• US4190664A
  申请人：——

  公开号：US4190664A

  公开（公告）日：1980-02-26
• US4282213A
  申请人：——

  公开号：US4282213A

  公开（公告）日：1981-08-04
• Zwitterionic analogs of cimetidine as H2 receptor antagonists
  作者：Rodney C. Young、C. Robin Ganellin、Michael J. Graham、Robert C. Mitchell、Michael L. Roantree、Zev Tashma

  DOI：10.1021/jm00390a006

  日期：1987.7

  A series of analogues of the H2 receptor histamine antagonist cimetidine have been synthesized in which the dipolar cyanoguanidine group has been replaced by a number of zwitterionic moieties. Although none of the compounds is more effective than cimetidine in blocking histamine-stimulated tachycardia on the isolated guinea pig atrium, the activities of most of the compounds possessing rigid dipoles can be accounted for on the basis of dipole orientation relative to the common side chain and by considering the active species in each case to be the zwitterion. These findings are in general agreement with those found for analogues having conjugated groups as dipoles.