(4-methoxyphenyl)phosphonic acid bis(2,2,2-trifluoroethyl) ester | 362477-47-2

• 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)phosphonic acid bis(2,2,2-trifluoroethyl) ester
• 英文别名: Phosphonic acid, (4-methoxyphenyl)-, bis(2,2,2-trifluoroethyl) ester；1-[bis(2,2,2-trifluoroethoxy)phosphoryl]-4-methoxybenzene
• CAS: 362477-47-2
• 化学式: C₁₁H₁₁F₆O₄P
• 分子量: 352.17
• InChiKey: UIPLWRUPEBEPQM-UHFFFAOYSA-N

物化性质

• 沸点：
  299.7±40.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (4-methoxyphenyl)phosphonic acid bis(2,2,2-trifluoroethyl) ester 在 10percent Pd/C 氢氧化钾 、 氯化亚砜 、 氢气 、 N,N-二异丙基乙胺 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 为溶剂， 反应 7.0h， 生成 (3R)-N-hydroxy-2-[(R)-(2,2,2-trifluoroethoxy)(4-methoxyphenyl)phosphoryl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide
  参考文献：
  名称：

  New Strategy for Antedrug Application:  Development of Metalloproteinase Inhibitors as Antipsoriatic Drugs

  摘要：

  Phosphonamide-based inhibitors were synthesized and evaluated for the inhibitory activities against the shedding of epidermal growth factors, amphiregulin and lieparin-binding EGF-like growth factor, that would participate in the development of psoriasis. All compounds exhibited excellent inhibitory activities for these EGF sheddings; however, they also inhibited matrix metalloproteinases (MMPs). To avoid adverse effects reported by the clinical development of MMP inhibitors, the antedrug concept was introduced. Among the phosphonamide inhibitors, the 2,2,2-trifluoroethyl ester 8d and 2,2-difluoroethyl ester 8c showed rapid decomposition in human plasma, which is an essential property for the antedrug. Topical applications of these compounds significantly suppressed TPA-induced epidermal hyperplasia in murin skin, a model of psoriasis. These results suggested that the phosphonamide-based inhibitors have a therapeutic potential for the treatment of psoriasis as an antedrug application.

  DOI：

  10.1021/jm010349c
• 作为产物：
  描述：

  2,2,2-三氟乙醇 、 4-甲氧苯基磷酸二氯 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以83%的产率得到(4-methoxyphenyl)phosphonic acid bis(2,2,2-trifluoroethyl) ester
  参考文献：
  名称：

  New Strategy for Antedrug Application:  Development of Metalloproteinase Inhibitors as Antipsoriatic Drugs

  摘要：

  Phosphonamide-based inhibitors were synthesized and evaluated for the inhibitory activities against the shedding of epidermal growth factors, amphiregulin and lieparin-binding EGF-like growth factor, that would participate in the development of psoriasis. All compounds exhibited excellent inhibitory activities for these EGF sheddings; however, they also inhibited matrix metalloproteinases (MMPs). To avoid adverse effects reported by the clinical development of MMP inhibitors, the antedrug concept was introduced. Among the phosphonamide inhibitors, the 2,2,2-trifluoroethyl ester 8d and 2,2-difluoroethyl ester 8c showed rapid decomposition in human plasma, which is an essential property for the antedrug. Topical applications of these compounds significantly suppressed TPA-induced epidermal hyperplasia in murin skin, a model of psoriasis. These results suggested that the phosphonamide-based inhibitors have a therapeutic potential for the treatment of psoriasis as an antedrug application.

  DOI：

  10.1021/jm010349c

文献信息

• 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.
• New Strategy for Antedrug Application:  Development of Metalloproteinase Inhibitors as Antipsoriatic Drugs
  作者：Masaaki Sawa、Takako Tsukamoto、Takao Kiyoi、Kiriko Kurokawa、Fumio Nakajima、Yuichiro Nakada、Koichi Yokota、Yoshimasa Inoue、Hirosato Kondo、Kohichiro Yoshino

  DOI：10.1021/jm010349c

  日期：2002.2.1

  Phosphonamide-based inhibitors were synthesized and evaluated for the inhibitory activities against the shedding of epidermal growth factors, amphiregulin and lieparin-binding EGF-like growth factor, that would participate in the development of psoriasis. All compounds exhibited excellent inhibitory activities for these EGF sheddings; however, they also inhibited matrix metalloproteinases (MMPs). To avoid adverse effects reported by the clinical development of MMP inhibitors, the antedrug concept was introduced. Among the phosphonamide inhibitors, the 2,2,2-trifluoroethyl ester 8d and 2,2-difluoroethyl ester 8c showed rapid decomposition in human plasma, which is an essential property for the antedrug. Topical applications of these compounds significantly suppressed TPA-induced epidermal hyperplasia in murin skin, a model of psoriasis. These results suggested that the phosphonamide-based inhibitors have a therapeutic potential for the treatment of psoriasis as an antedrug application.