4-[3-(4-fluorophenoxy)phenyl]-3-butyn-2-ol | 188534-03-4

• 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: 4-[3-(4-fluorophenoxy)phenyl]-3-butyn-2-ol
• 英文别名: 4-[3-(4-Fluorophenoxy)phenyl]but-3-yn-2-ol
• CAS: 188534-03-4
• 化学式: C₁₆H₁₃FO₂
• 分子量: 256.276
• InChiKey: UATKCSOGBBYBBZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[3-(4-fluorophenoxy)phenyl]-3-butyn-2-ol 在 偶氮二甲酸二异丙酯 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 生成 N-[4-(3-(4-fluorophenoxy)phenyl)-3-butyn-2-yl]hydroxylamine
  参考文献：
  名称：

  Structure−Activity Relationships of N-Hydroxyurea 5-Lipoxygenase Inhibitors

  摘要：

  The discovery of second generation N-hydroxyurea 5-lipoxygenase inhibitors was accomplished through the development of a broad structure-activity relationship (SAR) study. This study identified requirements for improving potency and also extending duration by limiting metabolism. Potency could be maintained by the incorporation of heterocyclic templates substituted with selected lipophilic substituents. Duration of inhibition after oral administration was optimized by identification of structural features in the proximity of the N-hydroxyurea which correlated to low in vitro glucuronidation rates. Furthermore, the rate of in vitro glucuronidation was shown to be stereoselective for certain analogs. (R)-N-[3-[5-(4-Fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]-N-hy- droxyurea (17c) was identified and selected for clinical development.

  DOI：

  10.1021/jm9700474
• 作为产物：
  描述：

  4-氟-3’-碘二苯醚 、 三苯基膦 、 3-丁炔-2-醇 、 二异丙胺 、 氮气 在 碘化亚铜 、 双(乙腈)氯化钯(II) 氨 、 Brine 、 盐酸 、 碳酸氢钠 、 magnesium sulfate 、 碳 、 甲烷 、 甲基叔丁基醚 作用下， 以 甲基叔丁基醚 为溶剂， 反应 2.25h， 以to give a solution of 4-[3-(4-fluorophenoxy)phenyl]-3-butyn-2-ol in methyl t-butyl ether which的产率得到4-[3-(4-fluorophenoxy)phenyl]-3-butyn-2-ol
  参考文献：
  名称：

  Process for the preparation of arylalkynyl-N-hydroxyurea derivatives

  摘要：

  本发明提供了一种制备公式为##STR1##的化合物的方法，其中R是一种直链或支链烷基，其碳原子数为1至12；M代表氢或药学上可接受的阳离子；A选自可选择的取代的环烷基苯。

  公开号：

  US05714633A1

文献信息

• [EN] PROCESS FOR THE PREPARATION OF ARYLALKYNYL-N-HYDROXYUREA DERIVATIVES HAVING LIPOXYGENASE INHIBITORY ACTIVITY<br/>[FR] PROCEDE DE PREPARATION DE DERIVES D'ARYLALCYNYLE-N-HYDROXYUREE A ACTIVITE INHIBITRICE DE LA LIPOXYGENASE
  申请人：ABBOTT LABORATORIES

  公开号：WO1997010206A1

  公开（公告）日：1997-03-20

  (EN) The present invention provides a process for the preparation of a compound of formula (I), wherein R is a straight or branched alkyl group of from one to twelve carbon atoms; M represents hydrogen or a pharmaceutically acceptable cation; and A is selected from optionally substituted carbocyclic phenyl.(FR) Procédé de préparation d'un composé de formule (I) dans laquelle R est un groupe alkyle linéaire ou ramifié possédant un à douze atomes de carbone, M représente hydrogène ou un cation pharmaceutiquement acceptable et A est choisi parmi des phényles carbocycliques éventuellement substitués.

  本发明提供了一种制备式（I）化合物的方法，其中R是一种直链或支链烷基，其碳原子数为1到12；M代表氢或药学上可接受的阳离子；A选自可选取的取代的环烷基苯基。
• PROCESS FOR THE PREPARATION OF ARYLALKYNYL-N-HYDROXYUREA DERIVATIVES HAVING LIPOXYGENASE INHIBITORY ACTIVITY
  申请人：Abbott Laboratories

  公开号：EP0850217B1

  公开（公告）日：2000-04-05
• US5714633A
  申请人：——

  公开号：US5714633A

  公开（公告）日：1998-02-03
• Structure−Activity Relationships of <i>N</i>-Hydroxyurea 5-Lipoxygenase Inhibitors
  作者：Andrew O. Stewart、Pramila A. Bhatia、Jonathan G. Martin、James B. Summers、Karen E. Rodriques、Michael B. Martin、James H. Holms、Jimmie L. Moore、Richard A. Craig、Teodozyj Kolasa、James D. Ratajczyk、Hormoz Mazdiyasni、Francis A. J. Kerdesky、Shari L. DeNinno、Robert G. Maki、Jennifer B. Bouska、Patrick R. Young、Carmine Lanni、Randy L. Bell、George W. Carter、Clint D. W. Brooks

  DOI：10.1021/jm9700474

  日期：1997.6.1

  The discovery of second generation N-hydroxyurea 5-lipoxygenase inhibitors was accomplished through the development of a broad structure-activity relationship (SAR) study. This study identified requirements for improving potency and also extending duration by limiting metabolism. Potency could be maintained by the incorporation of heterocyclic templates substituted with selected lipophilic substituents. Duration of inhibition after oral administration was optimized by identification of structural features in the proximity of the N-hydroxyurea which correlated to low in vitro glucuronidation rates. Furthermore, the rate of in vitro glucuronidation was shown to be stereoselective for certain analogs. (R)-N-[3-[5-(4-Fluorophenoxy)-2-furyl]-1-methyl-2-propynyl]-N-hy- droxyurea (17c) was identified and selected for clinical development.
• Process for the preparation of arylalkynyl-N-hydroxyurea derivatives
  申请人：Abbott Laboratories

  公开号：US05714633A1

  公开（公告）日：1998-02-03

  The present invention provides a process for the preparation of a compound of formula ##STR1## wherein R is a straight or branched alkyl group of from one to twelve carbon atoms; M represents hydrogen or a pharmaceutically acceptable cation; and A is selected from optionally substituted carbocyclic phenyl.

  本发明提供了一种制备公式为##STR1##的化合物的方法，其中R是一种直链或支链烷基，其碳原子数为1至12；M代表氢或药学上可接受的阳离子；A选自可选择的取代的环烷基苯。