2-[(4-氟苯基)甲基]-5-碘噻吩 | 154355-88-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-[(4-氟苯基)甲基]-5-碘噻吩
• 英文名称: 5-((4-fluorophenyl)methyl)-2-iodothiophene
• 英文别名: 2-iodo-5-(4-fluorophenylmethyl)thiophene；5-(4-fluorobenzyl)-2-iodothiophene；2-(4-Fluorobenzyl)-5-iodothiophene；2-[(4-fluorophenyl)methyl]-5-iodothiophene
• CAS: 154355-88-1
• 化学式: C₁₁H₈FIS
• 分子量: 318.153
• InChiKey: PNRNSMBTRRXYBQ-UHFFFAOYSA-N

物化性质

• 沸点：
  333.7±37.0 °C(Predicted)
• 密度：
  1.723±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  28.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-[(4-氟苯基)甲基]-5-碘噻吩 、 (R)-N-(3-butyn-2-yl)-N-hydroxyurea 在 双(乙腈)氯化钯(II) 、 copper(l) iodide 、 二乙胺 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 以18%的产率得到1-[(2R)-4-[5-[(4-氟苯基)甲基]噻吩-2-基]丁-3-炔-2-基]-1-羟基脲
  参考文献：
  名称：

  Preparation of (R)-(+)-N-[3-[5-[(4-Fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (ABT-761), a second-generation 5-lipoxygenase inhibitor.

  摘要：

  Structure-activity optimization of inhibitory potency and duration of action of N-hydroxyurea containing 5-lipoxygenase inhibitors was conducted. The lipophilic heteroaryl template and the link group connnecting the template to the N-hydroxyurea pharmacophore were modified. Inhibition of 5-lipoxygenase was evaluated in vitro in a human whole blood assay. An in vitro assay using liver microsomes from monkey was used to evaluate congeners for comparative rates of glucuronidation. (3-Heteroaryl-1-methyl-2-propynyl)-N-hydroxyureas were found to be more resistant to in vitro glucuronidation. The promising inhibitor N-[3-[5-(4-fluorophenoxy)2-furyl]-1-methyl-2-propynyl]-N-hydroxyurea (6) was found to have stereoselective glucuronidation in monkey and man. The R enantiomer 7 provided longer duration of inhibition as evaluated by an ex vivo whole blood assay. Further optimization of the lipophilic template led to the discovery of (R)-(+)-N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (11) with more effective and prolonged inhibition of leukotriene biosynthesis than zileuton (1) and 7 in monkey and man. The optimized 5-lipoxygenase inhibitor 11 was selected for development as an investigational drug for leukotriene-mediated disorders.

  DOI：

  10.1021/jm00024a004
• 作为产物：
  描述：

  4-氟溴苄 在 N-碘代丁二酰亚胺 、 四(三苯基膦)钯 、 正丁基锂 、 溶剂黄146 作用下， 以 氯仿 为溶剂， 反应 2.5h， 生成 2-[(4-氟苯基)甲基]-5-碘噻吩
  参考文献：
  名称：

  Preparation of (R)-(+)-N-[3-[5-[(4-Fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (ABT-761), a second-generation 5-lipoxygenase inhibitor.

  摘要：

  Structure-activity optimization of inhibitory potency and duration of action of N-hydroxyurea containing 5-lipoxygenase inhibitors was conducted. The lipophilic heteroaryl template and the link group connnecting the template to the N-hydroxyurea pharmacophore were modified. Inhibition of 5-lipoxygenase was evaluated in vitro in a human whole blood assay. An in vitro assay using liver microsomes from monkey was used to evaluate congeners for comparative rates of glucuronidation. (3-Heteroaryl-1-methyl-2-propynyl)-N-hydroxyureas were found to be more resistant to in vitro glucuronidation. The promising inhibitor N-[3-[5-(4-fluorophenoxy)2-furyl]-1-methyl-2-propynyl]-N-hydroxyurea (6) was found to have stereoselective glucuronidation in monkey and man. The R enantiomer 7 provided longer duration of inhibition as evaluated by an ex vivo whole blood assay. Further optimization of the lipophilic template led to the discovery of (R)-(+)-N-[3-[5-[(4-fluorophenyl)methyl]-2-thienyl]-1-methyl-2-propynyl]-N-hydroxyurea (11) with more effective and prolonged inhibition of leukotriene biosynthesis than zileuton (1) and 7 in monkey and man. The optimized 5-lipoxygenase inhibitor 11 was selected for development as an investigational drug for leukotriene-mediated disorders.

  DOI：

  10.1021/jm00024a004
• 作为试剂：
  描述：

  1-(but-3-yn-2-yl)-1-hydroxyurea 、 2-[(4-氟苯基)甲基]-5-碘噻吩 在 2-[(4-氟苯基)甲基]-5-碘噻吩 作用下， 以88.7的产率得到非维匹仑
  参考文献：
  名称：

  PHENYLALKYL N-HYDROXYUREAS FOR TREATING LEUKOTRIENE RELATED PATHOLOGIES

  摘要：

  通过给予N-[3-[5-[(4-氟苯基)甲基]-2-噻吩基]-1-甲基-2-丙炔基]-N-羟基脲来治疗白三烯相关病理的方法，以及用于此用途的组合物。

  公开号：

  US20130190514A1

文献信息

• Substituted aryl- and heteroarylalkenyl-N-hydroxyurea inhibitors of
  申请人：Abbott Laboratories

  公开号：US05506261A1

  公开（公告）日：1996-04-09

  Compounds of the structure ##STR1## wherein Z is selected from optionally substituted thienyl, thiazolyl, oxazolyl and furyl are potent inhibitors of lipoxygenase enzymes and thus inhibit the biosynthesis of leukotrienes. These compounds are useful in the treatment or amelioration of allergic and inflammatory disease states.

  具有结构##STR1##的化合物，其中Z从选择性取代的噻吩基、噻唑基、噁唑基和呋喃基中选择，是脂氧酶酶的有效抑制剂，从而抑制白三烯的生物合成。这些化合物可用于治疗或改善过敏和炎症性疾病状态。
• Design, Synthesis, and Biological Evaluation of Conformationally Constrained <i>a</i><i>ci</i>-Reductone Mimics of Arachidonic Acid
  作者：Allen T. Hopper、Donald T. Witiak、John Ziemniak

  DOI：10.1021/jm970034q

  日期：1998.2.1

  with lithium acetylide ethylenediamine complex (LiAEDA, HMPA, -5 degrees C), and benzyl group cleavage (Ac2O, Pyr, BCl3). The utility of this synthetic method was demonstrated by the synthesis of analogues 10e-k. Biological testing revealed that certain of these antioxidants inhibit both cyclooxygenase (COX) and 5-lipoxygenase (5-LO) with comparable efficacy as reported for aspirin and zileuton, respectively

  已开发出一种有效且收敛的合成方法，用于生产3,4-二羟基-5- [4-（2-（（（2Z）-己烯基）苯基）-3-（1Z）-丁烯基] -2（5H） -呋喃酮（12天）。该疏水性抗氧化剂是花生四烯酸（AA）（1）及其各自的aci-还原酮类似物（2）的稳定的构象约束模拟物。Pd（0）催化的5-（3-丁炔基）-3,4-二羟基-2（5H）-呋喃酮（7）与2-（（2Z）-己烯基）碘苯（8d）然后是Lindlar的交叉偶联催化加氢产生12d。丁炔基中间体7由2-（苄氧基）-5-脱氧抗坏血酸（15）通过碘化（I2，PPh3，Imd），用乙炔锂乙二胺络合物（LiAEDA，HMPA，-5摄氏度）碘取代和苄基制得裂解（Ac2O，Pyr，BCl3）。通过合成类似物10e-k证明了这种合成方法的实用性。生物学测试表明，这些抗氧化剂中的某些可以同时抑制环氧化酶（COX）和5-脂氧化酶（5-LO），其功效与分别报道的阿司
• [DE] VERFAHREN ZUR HERSTELLUNG VON KLEINEN SPHÄRISCHEN PARTIKELN, DIE MINDESTENS EIN WASSERUNLÖSLICHES LINEARES POLYSACCHARID ENTHALTEN<br/>[EN] METHOD FOR THE PRODUCTION OF SMALL SPHERICAL PARTICLES CONTAINING AT LEAST ONE WATER-INSOLUBLE LINEAR POLYSACCHARIDE<br/>[FR] PROCEDE DE PREPARATION DE PETITES PARTICULES SPHERIQUES CONTENANT AU MOINS UN POLYSACCHARIDE LINEAIRE SOLUBLE DANS L'EAU
  申请人：AVENTIS RES & TECH GMBH & CO

  公开号：WO2000012589A1

  公开（公告）日：2000-03-09

  Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von kleinen sphärischen Partikeln, die ganz oder teilweise aus mindestens einem wasserunlöslichen linearen Polysaccharid bestehen, durch Lösen des mindestens einen wasserunlöslichen Polysaccharids in einem Lösungsmittel oder Lösungsmittelgemisch, Einbringen der Lösung in ein Fällmittel oder Fällmittelgemisch, gegebenenfalls Kühlen des dabei entstehenden Gemisches und Abtrennen der gebildeten kleinen Partikel, wobei als Fällungshilfsmittel mindestens ein heißwasserlösliches Poly-alpha-D-glucan eingesetzt wird, sowie nach diesem Verfahren erhältliche Partikel.

  本发明涉及一种制备小球形颗粒的方法，这些颗粒完全或部分由至少一种不溶于水的线性多糖组成，通过将至少一种不溶于水的多糖溶解于溶剂或溶剂混合物中，将溶液引入沉淀剂或沉淀剂混合物中，必要时冷却形成的混合物并分离形成的小颗粒，其中至少一个热水溶性聚α-D-葡聚糖被用作沉淀助剂，以及根据该方法获得的颗粒。
• Substituted arylalkynyl-and heteroarylalkynl-N-hydroxyurea inhibitors of
  申请人：Abbott Laboratories

  公开号：US05616596A1

  公开（公告）日：1997-04-01

  The invention relates to compounds having activity to inhibit lipoxygenase enzyme activity, to pharmaceutical compositions comprising these compounds, and to a medical method of treating. More particularly, this invention concerns certain substituted arylalkynyl- and ((heteroaryl)alkynyl)-N-hydroxy-ureas which inhibit leukotriene biosynthesis, to pharmaceutical compositions of these compounds and to a method of inhibiting leukotriene biosynthesis.

  本发明涉及具有抑制脂肪氧化酶酶活性的活性化合物，包括这些化合物的制药组合物，以及治疗的医疗方法。更具体地说，本发明涉及某些取代芳基炔基和((杂环)炔基)-N-羟基脲，这些化合物抑制白三烯生物合成，以及这些化合物的制药组合物和抑制白三烯生物合成的方法。
• Process for the preparation of N-4-[(substituted phenyl)alkylheterocyclic]-
  申请人：Abbott Laboratories

  公开号：US05580989A1

  公开（公告）日：1996-12-03

  A process for preparing a compound of the structure I ##STR1## where A is oxygen and sulfur and R.sup.1 is selected from the group consisting of hydrogen, halogen, alkyl of one to six carbon atoms, alkoxy of one to six carbon atoms, and trifluoromethyl, and R.sup.2 is alkyl of one to four carbon atoms, comprising coupling a compound of formula II: ##STR2## where X is bromine or iodine, with an N-hydroxyurea compound of formula III: ##STR3## in the presence of a palladium catalyst followed by reaction of the product thus formed with an alkali metal isocyante. The compounds of formula I are inhibitors of the enzyme 5-lipoxygenase and are thus useful as therapeutic agents for the treatment of allergic and inflammatory disease conditions.

  一种制备结构I的化合物的方法，其中A为氧和硫，R.sup.1选自氢，卤素，1至6个碳原子的烷基，1至6个碳原子的烷氧基和三氟甲基的群体，R.sup.2为1至4个碳原子的烷基，包括在钯催化剂存在下，将式II的化合物：##STR2## 其中X为溴或碘，与式III的N-羟基脲化合物：##STR3## 偶联，然后将所形成的产物与碱金属异氰酸酯反应。式I的化合物是5-脂氧合酶酶的抑制剂，因此可用作治疗过敏和炎症疾病的治疗剂。