(4-methoxyphenyl)chlorophosphonic acid ethyl ester | 362477-53-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4-methoxyphenyl)chlorophosphonic acid ethyl ester
• 英文别名: 1-[Chloro(ethoxy)phosphoryl]-4-methoxybenzene
• CAS: 362477-53-0
• 化学式: C₉H₁₂ClO₃P
• 分子量: 234.619
• InChiKey: DWKYPUBNMRTDEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  4
• 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：

  (4-methoxyphenyl)chlorophosphonic acid ethyl ester 在 10percent Pd/C 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 (2R)-N-hydroxy-1-[(R)-ethoxy(4-methoxyphenyl)phosphoryl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  New Type of Metalloproteinase Inhibitor:  Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids

  摘要：

  A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K-i values against MMP-1, -3, -9, and TACE and also showed nanomolar IC50 values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.

  DOI：

  10.1021/jm0103211
• 作为产物：
  描述：

  4-methoxylphenyl phosphonic acid monoethyl ester 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 生成 (4-methoxyphenyl)chlorophosphonic acid ethyl ester
  参考文献：
  名称：

  Encounter with Unexpected Collagenase-1 Selective Inhibitor: Switchover of Inhibitor Binding Pocket Induced by Fluorine Atom

  摘要：

  Phosphonamide-based inhibitors having trifluoromethyl moiety showed highly selective inhibition against MMP-1. A possible mechanism of the selectivity of MMP-1 inhibitors through the switchover of the binding pocket was speculated by computational calculations. As a consequence of the unexpected selectivity, the specific interaction of CF3 group of the inhibitor and Arg214 in the S1' pocket of MMP-1 conducted a low binding energy. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00796-x

文献信息

• Process for preparing enamine derivatives, compounds so produced and process for preparing a 3-hydroxy-cephalosporin
  申请人：Lilly Industries Limited

  公开号：EP0019401A1

  公开（公告）日：1980-11-26

  There is described a process for preparing an enamine of formula (IX): where R2 is a carboxylic acid protecting group and R3 is the residue of a carboxylic acid derived acyl group and where R5 and R6 are the same or different C1-4 alkyl or C7-10 aralkyl groups; or taken together with the adjacent nitrogen atom form a heterocyclic ring containing from 4 to 8 carbon atoms and optionally a further heteroatom selected from oxygen and nitrogen; by reacting a compound of formula (XII) : with an amine of formula HNR5R6, the reactant of formula (XII) being prepared by reaction of an appropriate enol derivative with a phosphorus reagent. The enamines of formula (IX) are useful in the preparation of 3-hydroxycephalosporins.

  本发明描述了一种制备式(IX)烯胺的工艺： 其中 R2 是羧酸保护基，R3 是羧酸衍生酰基的残基，R5 和 R6 是相同或不同的 C1-4 烷基或 C7-10 芳烷基；或与相邻的氮原子一起形成含有 4 至 8 个碳原子和任选地另一个选自氧和氮的杂原子的杂环；通过使式 (XII) ： 与式 HNR5R6 的胺反应，式 (XII) 的反应物通过适当的烯醇衍生物与磷试剂反应制备。式（IX）的烯胺可用于制备 3-羟基头孢菌素。
• Discovery of selective phosphonamide-based inhibitors of tumor necrosis factor-α converting enzyme (TACE)
  作者：Masaaki Sawa、Kiriko Kurokawa、Yoshimasa Inoue、Hirosato Kondo、Kohichiro Yoshino

  DOI：10.1016/s0960-894x(03)00292-0

  日期：2003.6

  A novel series of phosphonamide-based inhibitors of tumor necrosis factor-a converting enzyme (TACE) was discovered by structural modification of tetrahydroisoquinoline derivative 1b, which was extremely weak inhibitor of TACE. (S)-Isomer at the phosphorus atom (7b) displayed potent inhibition for TACE, while selectivity sparing MMP-1, -3, and -9. (C) 2003 Elsevier Science Ltd. All rights reserved.
• US4301280A
  申请人：——

  公开号：US4301280A

  公开（公告）日：1981-11-17
• New Type of Metalloproteinase Inhibitor:  Design and Synthesis of New Phosphonamide-Based Hydroxamic Acids
  作者：Masaaki Sawa、Takao Kiyoi、Kiriko Kurokawa、Hiroshi Kumihara、Minoru Yamamoto、Tomohiro Miyasaka、Yasuko Ito、Ryoichi Hirayama、Tomomi Inoue、Yasuyuki Kirii、Eiji Nishiwaki、Hiroshi Ohmoto、Yu Maeda、Etsuko Ishibushi、Yoshimasa Inoue、Kohichiro Yoshino、Hirosato Kondo

  DOI：10.1021/jm0103211

  日期：2002.2.1

  A series of phosphonamide-based hydroxamate derivatives were synthesized, and the inhibitory activities were evaluated against various metalloproteinases in order to clarify its selectivity profile. Among the four diastereomeric isomers resulting from the chirality at the C-3 and P atoms, the compound with a (R,R)-configuration both at the C-3 position and the phosphorus atom was found to be potently active, while the other diastereomeric isomers were almost inactive. A number of (R,R)-compounds synthesized here exhibited broad spectrum activities with nanomolar K-i values against MMP-1, -3, -9, and TACE and also showed nanomolar IC50 values against HB-EGF shedding in a cell-based inhibition assay. The modeling study using X-ray structure of MMP-3 suggested the possible binding mode of the phosphonamide-based inhibitors.
• Encounter with Unexpected Collagenase-1 Selective Inhibitor: Switchover of Inhibitor Binding Pocket Induced by Fluorine Atom
  作者：Masaaki Sawa、Hirosato Kondo、Shin-ichiro Nishimura

  DOI：10.1016/s0960-894x(01)00796-x

  日期：2002.2

  Phosphonamide-based inhibitors having trifluoromethyl moiety showed highly selective inhibition against MMP-1. A possible mechanism of the selectivity of MMP-1 inhibitors through the switchover of the binding pocket was speculated by computational calculations. As a consequence of the unexpected selectivity, the specific interaction of CF3 group of the inhibitor and Arg214 in the S1' pocket of MMP-1 conducted a low binding energy. (C) 2002 Elsevier Science Ltd. All rights reserved.