3-[3-(3-Fluoro-phenoxy)-phenyl]-propionic acid ethyl ester | 156176-03-3

• 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: 3-[3-(3-Fluoro-phenoxy)-phenyl]-propionic acid ethyl ester
• 英文别名: Ethyl 3-[3-(3-fluorophenoxy)phenyl]propanoate
• CAS: 156176-03-3
• 化学式: C₁₇H₁₇FO₃
• 分子量: 288.319
• InChiKey: ROHJDMDKYYWBHZ-UHFFFAOYSA-N

物化性质

• 沸点：
  370.9±32.0 °C(Predicted)
• 密度：
  1.153±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-[3-(3-Fluoro-phenoxy)-phenyl]-propionic acid ethyl ester 在 potassium tert-butylate 、 溶剂黄146 、 氯乙酸 作用下， 反应 29.0h， 生成 5-[3-(3-fluorophenoxy)benzyl]uracil
  参考文献：
  名称：

  Inhibition of Uridine Phosphorylase. Synthesis and Structure−Activity Relationships of Aryl-Substituted 1-((2-Hydroxyethoxy)methyl)-5-(3-phenoxybenzyl)uracil

  摘要：

  Structure-activity relationship studies on a series of 1-((2-hydroxyethoxy)methyl)-5-(3(substituted-phenoxy)benzyl)uracils as inhibitors of murine liver uridine phosphorylase have led to compounds with IC(50)s as low as 1.4 nM. The two most potent compounds, 10j (3-cyanophenoxy) and 11f (3-chlorophenoxy) were tested in vivo for effects on steady-state concentrations of circulating uridine in mice and rats. Both compounds were substantially more efficacious than BAU (5-benzylacyclouridine) both in vitro and in vivo.

  DOI：

  10.1021/jm960688j
• 作为产物：
  描述：

  3-氟苯酚 在 platinum(IV) oxide palladium diacetate 、 氢气 、 sodium methylate 、 三乙胺 、 三(邻甲基苯基)磷 作用下， 以 乙醇 、 乙腈 为溶剂， 25.0~180.0 ℃ 、206.84 kPa 条件下， 反应 38.0h， 生成 3-[3-(3-Fluoro-phenoxy)-phenyl]-propionic acid ethyl ester
  参考文献：
  名称：

  Inhibition of Uridine Phosphorylase. Synthesis and Structure−Activity Relationships of Aryl-Substituted 1-((2-Hydroxyethoxy)methyl)-5-(3-phenoxybenzyl)uracil

  摘要：

  Structure-activity relationship studies on a series of 1-((2-hydroxyethoxy)methyl)-5-(3(substituted-phenoxy)benzyl)uracils as inhibitors of murine liver uridine phosphorylase have led to compounds with IC(50)s as low as 1.4 nM. The two most potent compounds, 10j (3-cyanophenoxy) and 11f (3-chlorophenoxy) were tested in vivo for effects on steady-state concentrations of circulating uridine in mice and rats. Both compounds were substantially more efficacious than BAU (5-benzylacyclouridine) both in vitro and in vivo.

  DOI：

  10.1021/jm960688j

文献信息

• Phosphonosulfonates Are Potent, Selective Inhibitors of Dehydrosqualene Synthase and Staphyloxanthin Biosynthesis in <i>Staphylococcus aureus</i>
  作者：Yongcheng Song、Fu-Yang Lin、Fenglin Yin、Mary Hensler、Carlos A. Rodrígues Poveda、Dushyant Mukkamala、Rong Cao、Hong Wang、Craig T. Morita、Dolores González Pacanowska、Victor Nizet、Eric Oldfield

  DOI：10.1021/jm801023u

  日期：2009.2.26

  Staphylococcus aureus produces a golden carotenoid virulence factor called staphyloxanthin (STX), and we report here the inhibition of the enzyme, dehydrosqualene synthase (CrtM), responsible for the first committed step in STX biosynthesis. The most active compounds are halogen-substituted phosphonosulfonates, with K-i values as low as 5 nM against the enzyme and IC50 values for STX inhibition in S. aureus as low as 11 nM. There is, however, only a poor correlation (R-2 = 0.27) between enzyme and cell pIC(50) (= -log(10) IC50) values. The ability to predict cell from enzyme data improves considerably (to R-2 = 0.72) with addition of two more descriptors. We also investigated the activity of these compounds against human squalene synthase (SQS), as a counterscreen, finding several potent STX biosynthesis inhibitors with essentially no squalene synthase activity. These results open up the way to developing potent and selective inhibitors of an important virulence factor in S. aureus, a major human pathogen.
• URACIL DERIVATIVES AS ENZYME INHIBITORS
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0649413A1

  公开（公告）日：1995-04-26
• [EN] URACIL DERIVATIVES AS ENZYME INHIBITORS<br/>[FR] DERIVES D'URACILE UTILISES COMME INHIBITEURS ENZYMATIQUES
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：WO1994001414A1

  公开（公告）日：1994-01-20

  (EN) Novel uracil derivatives of formula (I) and esters and prodrugs thereof wherein R1 is H, C1-8 straight or branched-chain alkyl, C2-6 alkenyl, or (C1-3 alkyl-C3-6 cycloalkyl-C1-3 alkyl) optionally substituted by 1 or 2 substituents selected from -OR8 or -NR8R9 (wherein R8 and R9 are the same or different and are selected from H, C1-6 straight or branched-chain alkyl, and aralkyl); or a -CH2ZR10, -ZCH2R10, or CH2ZR10aZR10 group (wherein R10a is selected from C1-6 straight or branched-chain alkylene and R10 is selected from C1-6 straight or branched chain alkyl) each of R10a and R10 being optionally substituted by 1 or 2 substituents independently selected from -OR8 and -NR8R9 (wherein R8 and R9 are as defined above) and Z is selected from O, S, -CH2O-, or -CH2S-); R2 is selected from O or S; R3 is selected from O, S, -SO, -SO2, -NR8, C=O, or -C1-6 straight or branched-chain alkyl; R4 is selected from H, C1-4 straight or branched-chain alkyl, halogen, -OR11 (wherein R11 is C1-4 straight or branched-chain alkyl optionally substituted by halogen, aryl, C3-6 cycloalkyl, (C1-3 alkyl-C3-6 cycloalkyl), C2-6alkenyl or C2-6alkynyl), methylenedioxy, -CX3 (wherein X is halogen), NO2, or CN; R5 is selected from H, halogen or -OR11; R6 is selected from H, or Y-Ar-R7(m) (wherein Y is selected from O, S, -SO, -SO2, -NR8, C=O, or -C1-6 straight or branched-chain alkyl, Ar is phenyl or naphthyl, m is 1-3 and R7 is selected from R8, -CO2R8, -COR8, -CONR8R9, R8aOR8 (wherein R8a is selected from C1-6 straight or branched-chain alkyl, and aralkyl), -CN, -CX3 (wherein X is halogen), -OR8, OCX3 (wherein X is halogen), -SR8, -SO2R8, -OR8aO- (when m=1), -NO2, -NR8R9, -NHCOR8, -NHSO2R8, fluoro, chloro, bromo, or iodo, or a combination thereof); provided that when R1 is H, CH2OCH2CH2OH or CH2OCH(CH2OH)2, R2 is O, R3 is -CH2 then R4, R5 and R6 are other than -OCH3, -OCH2CH3, -OCH2Ph, or -O-iso-propyl, pharmaceutical compositions containing them, their uses in medicine and the preparation of such compounds are disclosed.(FR) L'invention concerne de nouveaux dérivés de l'uracile de la formule (I) ainsi que leurs esters et précurseurs. Dans cette formule, R1 est un H, un (C1-C8)alkyle à chaîne droite ou ramifiée, un (C2-C6)alcényle ou un (C1-C3)alkyl(C3-C6)cycloalkyl(C1-C3))alkyle, le cas échéant substitués avec 1 ou 2 substituants choisis parmi -OR8 ou -NR8R9 (où R8 et R9 sont identiques ou différents et sont choisis parmi H, les groupes (C1C6)alkyle et ara(C1-C6)alkyle à chaîne droite ou ramifiée); ou un groupe -CH2ZR10, -ZCH2R10, ou CH2ZR10aZR10 (où R10a est choisi parmi les groupes (C1-C6)alkylène à chaîne droite ou ramifiée et R10 est choisi parmi les groupes (C1-C6)alkyle à chaîne droite ou ramifiée), chacun des deux groupes R10a et R10 étant le cas échéant substitués par 1 ou 2 substituants choisis indépendamment parmi -OR8 er -NR8R9 (où R8 et R9 sont comme défini ci-dessus) et Z est choisi parmi O, S, -CH2O-, ou -CH2S-); R2 est choisi parmi O ou S; R3 est choisi parmi O, S, -SO, -SO2, -NR8, C=O, ou les groupes (C1-C6)alkyle à chaîne droite ou ramifiée; R4 est choisi parmi H, les groupes (C1-C4)alkyle à chaîne droite ou ramifiée, un halogène, un -OR11 (où R11 est un (C1-C4)alkyle à chaîne droite ou ramifiée, le cas échéant substitué par un halogène, un aryle, un (C3-C6)cycloalkyle, un (C1-C3)alkyl(C3-C6)cycloalkyle, un (C2-C6)alcényle ou un (C2-C6)alcynyle), un méthylènedioxy, un -CX3 (où X est un halogène), un NO2, ou un CN; R5 est choisi parmi H, un halogène ou un -OR11; R6 est choisi parmi H, ou Y-Ar-R7(m) (où Y est choisi parmi O, S, -SO, -SO2, -NR8, C=O, ou un groupe (C1-C6)alkyle à chaîne droite ou ramifiée, Ar est un phényle ou un naphtyle, m est égal à 1-3 et R7 est choisi parmi R8, -CO2R8, -COR8, -CONR8R9, R8aOR8 (où R8a est choisi parmi les groupes (C1-C6)alkyle ou ara(C1-C6)alkyle à chaîne droite ou ramifiée, -CN, -CX3 (où X est un halogène), -OR8, OCX3 (où X est un halogène), -SR8, -SO2R8, -OR8aO- (quand m=1), -NO2, -NR8R9, -NHCOR8, -NHSO2R8, fluoro, chloro, bromo, ou iodo, ou une combinaison de ceux-ci); une condition à satisfaire étant que lorsque R1 est un H, un CH2OCH2CH2OH ou un CH2OCH(CH2OH)2, R2 est un O, R3 est un -CH2, à ce moment R4, R5 et R6 sont autres que -OCH3, -OCH2CH3, -OCH2Ph, ou -O-isopropyle. L'invention concerne également la préparation de ces composés, les compositions pharmaceutiques les contenant et leur utilisation en médecine.
• Inhibition of Uridine Phosphorylase. Synthesis and Structure−Activity Relationships of Aryl-Substituted 1-((2-Hydroxyethoxy)methyl)-5-(3-phenoxybenzyl)uracil
  作者：G. Faye Orr、David L. Musso、James L. Kelley、Suzanne S. Joyner、Stephen T. Davis、David P. Baccanari

  DOI：10.1021/jm960688j

  日期：1997.4.1

  Structure-activity relationship studies on a series of 1-((2-hydroxyethoxy)methyl)-5-(3(substituted-phenoxy)benzyl)uracils as inhibitors of murine liver uridine phosphorylase have led to compounds with IC(50)s as low as 1.4 nM. The two most potent compounds, 10j (3-cyanophenoxy) and 11f (3-chlorophenoxy) were tested in vivo for effects on steady-state concentrations of circulating uridine in mice and rats. Both compounds were substantially more efficacious than BAU (5-benzylacyclouridine) both in vitro and in vivo.