2-(4-fluorophenyl)-4-hydroxy-5-phenylthiazole | 131786-86-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(4-fluorophenyl)-4-hydroxy-5-phenylthiazole
• 英文别名: 2-(4-fluorophenyl)-5-phenylthiazol-4-ol；2-(4-fluorophenyl)-5-phenyl-1,3-thiazol-4-ol
• CAS: 131786-86-2
• 化学式: C₁₅H₁₀FNOS
• 分子量: 271.315
• InChiKey: KUOOEYKNEXFFMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  α-溴苯乙酸甲酯 、 4-氟硫代苄胺 在 吡啶 作用下， 以 甲苯 为溶剂， 反应 2.0h， 以52%的产率得到2-(4-fluorophenyl)-4-hydroxy-5-phenylthiazole
  参考文献：
  名称：

  5-脂氧合酶的4-羟基噻唑抑制剂。

  摘要：

  4-羟基噻唑已被确定为体外5-脂氧合酶的有效抑制剂，其IC50值小于1 microM。对结构活性关系的研究表明，该系列最有效的抑制剂是5-苯基衍生物。发现相应的噻唑烷丁-4-酮类似物相对没有活性。在完整的大鼠多形核白细胞和人全血中，4-羟基噻唑都是针对5-脂氧合酶的活性抑制剂。该化合物还是5-脂氧合酶的选择性抑制剂，对其他相关酶环氧合酶和12-和15-脂氧合酶的活性很弱。

  DOI：

  10.1021/jm00111a035

文献信息

• 4-hydroxythiazoles as 5-lipoxygenase inhibitors
  申请人：Abbott Laboratories

  公开号：US05124342A1

  公开（公告）日：1992-06-23

  A composition for the inhibition of lipoxygenase enzymes comprising a pharmaceutically acceptable carrier and a compound of the formula: ##STR1## wherein R.sub.1 and R.sub.2 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, arylalkenyl, reduced heteroaryl, and reduced heteroarylalkyl and substituted derivatives thereof having one or more substituents independently selected from the group consisting of halogen, alkyl, halosubstituted alkyl, aryl, arylalkyl, reduced heteroaryl, arylalkoxy, cyano, nitro, COR.sub.4, SO.sub.2 R.sub.4, NR.sub.5 R.sub.6, OR.sub.6, COCX.sub.1 X.sub.2 NR.sub.6 R.sub.7, CON(OH)R.sub.6, NR.sub.6 COR.sub.4, CR.sub.5 (NH.sub.2)CO.sub.2 R.sub.5, NHCX.sub.1 X.sub.2 CO.sub.2 R.sub.5, N(OH)CONR.sub.5 R.sub.6, N(OH)COR.sub.4, NHCONR.sub.5 R.sub.6, C(NOH)NHOH and CONHNR.sub.5 R.sub.6 ; R.sub.3 is selected from the group consisting of hydrogen, a pharmaceutically acceptable salt, COR.sub.4, COCX.sub.1 X.sub.2 NR.sub.6 R.sub.7, CR.sub.8 R.sub.9 OR.sub.10, CH.sub.2 CR.sub.8 (OR.sub.10)CH.sub.2 OR.sub.11 and SiR.sub.12 R.sub.13 R.sub.14 ; R.sub.4 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, reduced heteroaryl, reduced heteroarylalkyl, OR.sub.5, NHCX.sub.1 X.sub.2 CO.sub.2 R.sub.5 and NR.sub.6 R.sub.7 ; R.sub.5 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, reduced heteroaryl, and reduced heteroarylalkyl; R.sub.6 and R.sub.7 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, reduced heteroaryl, reduced heteroarylalkyl and (CH.sub.2).sub.n OR.sub.5 where n is 2-4 and R.sub.5 is as defined above; R.sub.8, R.sub.9, R.sub.10 and R.sub.11 are independently selected from the group consisting of hydrogen, alkyl, aryl, arylalkyl and (CH.sub.2).sub.n OR.sub.5 or at least two of R.sub.8, R.sub.9, R.sub.10 and R.sub.11 together form a ring system containing 5-10 atoms wherein said ring system is carbocyclic, heterocyclic or reduced heterocyclic and R.sub.5 and n are as defined above; R.sub.12, R.sub.13 and R.sub.14 are independently selected from the group consisting of alkyl and aryl; and X.sub.1 and X.sub.2 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, aryl, and arylalkyl; and the acid addition salts thereof.

  一种抑制脂氧合酶酶活性的组合物，包括药学上可接受的载体和公式化合物：##STR1## 其中R.sub.1和R.sub.2分别选自由烷基，烯基，环烷基，环烯基，芳基，芳基烷基，芳基烯基，还原杂环芳基和还原杂环芳基烷基，以及其取代衍生物，其中每个取代基独立地选自卤素，烷基，卤代烷基，芳基，芳基烷基，还原杂环芳基，芳基烷氧基，氰基，硝基，COR.sub.4，SO.sub.2R.sub.4，NR.sub.5R.sub.6，OR.sub.6，COCX.sub.1X.sub.2NR.sub.6R.sub.7，CON（OH）R.sub.6，NR.sub.6COR.sub.4，CR.sub.5（NH.sub.2）CO.sub.2R.sub.5，NHCX.sub.1X.sub.2CO.sub.2R.sub.5，N（OH）CONR.sub.5R.sub.6，N（OH）COR.sub.4，NHCONR.sub.5R.sub.6，C（NOH）NHOH和CONHNR.sub.5R.sub.6；R.sub.3选自氢，药学上可接受的盐，COR.sub.4，COCX.sub.1X.sub.2NR.sub.6R.sub.7，CR.sub.8R.sub.9OR.sub.10，CH.sub.2CR.sub.8（OR.sub.10）CH.sub.2OR.sub.11和SiR.sub.12R.sub.13R.sub.14；R.sub.4选自氢，烷基，烯基，环烷基，环烯基，芳基，芳基烷基，还原杂环芳基，还原杂环芳基烷基，OR.sub.5，NHCX.sub.1X.sub.2CO.sub.2R.sub.5和NR.sub.6R.sub.7；R.sub.5选自氢，烷基，烯基，环烷基，芳基，芳基烷基，还原杂环芳基和还原杂环芳基烷基；R.sub.6和R.sub.7分别选自氢，烷基，烯基，环烷基，芳基，芳基烷基，还原杂环芳基，还原杂环芳基烷基和（CH.sub.2）.sub.nOR.sub.5，其中n为2-4，R.sub.5如上所定义；R.sub.8，R.sub.9，R.sub.10和R.sub.11独立地选自氢，烷基，芳基，芳基烷基和（CH.sub.2）.sub.nOR.sub.5，或者R.sub.8，R.sub.9，R.sub.10和R.sub.11中至少两个组成含5-10个原子的环系统，所述环系统为碳环，杂环或还原杂环，R.sub.5和n如上所定义；R.sub.12，R.sub.13和R.sub.14独立地选自烷基和芳基；X.sub.1和X.sub.2独立地选自氢，烷基，烯基，环烷基，芳基和芳基烷基；以及其酸加成盐。
• EP0457803A4
  申请人：——

  公开号：EP0457803A4

  公开（公告）日：1991-12-04
• 4-HYDROXYTHIAZOLES AS 5-LIPOXYGENASE INHIBITORS
  申请人：ABBOTT LABORATORIES

  公开号：EP0457803A1

  公开（公告）日：1991-11-27
• US5124342A
  申请人：——

  公开号：US5124342A

  公开（公告）日：1992-06-23
• [EN] 4-HYDROXYTHIAZOLES AS 5-LIPOXYGENASE INHIBITORS
  申请人：——

  公开号：WO1990009801A1

  公开（公告）日：1990-09-07

  [EN] A composition for the inhibition of lipoxygenase enzymes comprising a pharmaceutically acceptable carrier and a compound of formula (I), wherein R1 and R2 are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, arylalkenyl, reduced heteroaryl, and reduced heteroarylalkyl and substituted derivatives thereof having one or more substituents independently selected from the group consisting of halogen, alkyl, halosubstituted alkyl, aryl, arylalkyl, reduced heteroaryl, arylalkoxy, cyano, nitro, COR4, SO2R4, NR5R6, OR6, COCX1X2NR6R7, CON(OH)R6, NR6COR4, CR5(NH2)CO2R5, NHCX1X2CO2R5, N(OH)CONR5R6, N(OH)COR4, NHCONR5R6, C(NOH)NHOH and CONHNR5R6; R3 is selected from the group consisting of hydrogen, a pharmaceutically acceptable salt, COR4, COCX1X2NR6R7, CR8R9OR10, CH2CR8(OR10)CH2OR11 and SiR12R13R14; R4 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, arylalkyl, reduced heteroaryl, reduced heteroarylalkyl, OR5, NHCX1X2CO2R5 and NR6R7; R5 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, reduced heteroaryl, and reduced heteroarylalkyl; R6 and R7 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, aryl, arylalkyl, reduced heteroaryl, reduced heteroarylalkyl and (CH2)nOR5 where n is 2-4 and R5 is as defined above; R8, R9, R10 and R11 are independently selected from the group consisting of hydrogen, alkyl, aryl, arylalkyl and (CH2)nOR5 or at least two of R8, R9, R10 and R11 together form a ring system containing 5-10 atoms wherein said ring system is carbocyclic, heterocyclic or reduced heterocyclic and R5 and n are as defined above; R12, R13 and R14 are independently selected from the group consisting of alkyl and aryl; and X1 and X2 are independently selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, aryl, and arylalkyl; and the acid addition salts thereof.
  [FR] L'invention concerne une composition d'inhibition d'enzymes de lipoxygénase comprenant un support pharmaceutiquement acceptable ainsi qu'un composé de la formule (I), dans laquelle R1 et R2 sont indépendamment chosis dans le groupe composé d'alcoyle, alcényle, cycloalcoyle, cycloalcényle, aryle, arylalcoyle, arylacényle, hétéroaryle substitué, ainsi que de l'hétéroarylalcoyle réduit et des dérivés substitués de ceux-ci, comportant un ou plusieurs substituants choisis indépendamment dans le groupe composé d'halogène, alcoyle, alcoyle à substitution halo, aryle, arylalcoyle, hétéroaryle réduit, arylalkoxy, cyano, nitro, COR4, SO2R4, NR5R6, OR6, COCX1X2NR6R7, CON(OH)R6, NR6COR4, CR5(NH2)CO2R5, NHCX1X2CO2R5, N(OH)CONR5R6, N(OH)COR4, NHCONR5R6, C(NOH)NHOH et CONHNR5R6; R3 est choisi dans le groupe composé d'hydrogène, d'un sel pharmaceutiquement acceptable, de COR4, COCX1X2NR6R7, CR8R9OR10, CH2CR8(OR10)CH2OR11 et SiR12R13R14; R4 est choisi dans le groupe composé d'hydrogène, alcoyle, alcényle, cycloalcoyle, cycloalcényle, aryle, arylalcoyle, hétéroaryle réduit, hétéroarylalcoyle réduit, OR5, NHCX1X2CO2R5 et NR6R7; R5 est choisi dans le groupe composé d'hydrogène, alcoyle, alcényle, cycloalcoyle, aryle, arylalcoyle, hétéroaryle réduit, et hétéroarylalcoyle réduit; R6 et R7 sont indépendamment choisis dans le groupe composé d'hydrogène, alcoyle, alcényle, cycloalcoyle, aryle, arylalcoyle, hétéroaryle réduit, hétéroarylalcoyle réduit et (CH2)nOR5 ou n est compris entre 2 et 4 et R5 est défini comme ci-dessus; R8, R9, R10 et R11 sont indépendamment choisis dans le groupe composé d'hydrogène, alcoyle, aryle, arylalcoyle et (CH2)nOR5 ou au moins deux des éléments R8, R9, R10 et R11 forment ensemble un système annulaire contenant 5 à 10 atomes, ledit système annulaire étant carbocyclique, hétérocyclique ou hétérocyclique réduit, et R5 et n étant décrits tel que ci-dessus; R12, R13 et R14 sont indépendamment choisis dans le groupe composé d'alcoyle et aryle et X1 et X2 sont choisis indépendamment dans le groupe composé