1-<4-(phenylmethoxy)phenyl>-3-pyrazolidinone | 6080-54-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-<4-(phenylmethoxy)phenyl>-3-pyrazolidinone
• 英文别名: 1-(4-benzyloxy-phenyl)-pyrazolidin-3-one；1-(4-benzyloxyphenyl)-3-pyrazolidinone；1-(4-phenylmethoxyphenyl)pyrazolidin-3-one
• CAS: 6080-54-2
• 化学式: C₁₆H₁₆N₂O₂
• 分子量: 268.315
• InChiKey: QPCHJWPLHQBKHK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  41.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-<4-(phenylmethoxy)phenyl>-3-pyrazolidinone 在 三乙胺 、 lithium diisopropyl amide 作用下， 以 二氯甲烷 为溶剂， 反应 1.75h， 生成 1-(4-Benzyloxy-phenyl)-4-(2-methoxy-ethyl)-pyrazolidin-3-one
  参考文献：
  名称：

  5-Lipoxygenase inhibitors: the synthesis and structure-activity relationships of a series of 1-phenyl-3-pyrazolidinones

  摘要：

  A series of analogues of the 5-lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone, 1a) has been prepared via two complementary new synthetic methods. The reaction of various electrophiles with the dianion of 1a or with an N-silylpyrazolidinone anion gave the desired 4-substituted pyrazolidinones (Scheme I and II). A new procedure was developed for the resolution of 4-substituted pyrazolidinones (Scheme V). A regression study on 21 compounds in this series showed a correlation of increased inhibitor potency (pIC50) with increased compound lipophilicity (log P) and with an N-phenyl electronic effect as measured by the C-13 NMR chemical shift parameter CNMR1' (R2 = 0.79). The most potent 5-lipoxygenase inhibitor in this series was 4-(ethylthio)-1-phenyl-3-pyrazolidinone (1n) with an IC50 of 60 nM. Another member of this series, 4-(2-methoxyethyl)-1-phenyl-3-pyrazolidinone (1f, IC50 = 0-48-mu-M), although less potent than 1n, was better tolerated in the whole animal relative to phenidone (1a) and also displayed good oral activity in two models of 5-lipoxygenase inhibition. On the basis of a structure-activity relationship study, a mechanism for the inhibition of 5-lipoxygenase by this class of inhibitors was proposed.

  DOI：

  10.1021/jm00109a006
• 作为产物：
  描述：

  4-苄氧基苯肼盐酸盐 、 丙烯酸乙酯 在 sodium ethanolate 作用下， 以 乙醇 、 水 、 甲苯 为溶剂， 生成 1-<4-(phenylmethoxy)phenyl>-3-pyrazolidinone
  参考文献：
  名称：

  1-arylalkoxyphenyl-pyrazolines, ketones or enoles as anti-inflammatory

  摘要：

  本公开说明了一种新型药物组合物，具有有用的抗炎和抗过敏性能，其有效成分为式中的化合物：##STR1## 其中，Ar和Ar.sub.1各自独立地为苯基或萘基或氮、氧或硫杂环；Z是含有0至5个碳原子的主链烷基链，总共不超过7个碳原子；X为O或S；Y为.dbd.O；R和R.sub.1独立地为氢、羟基、低烷氧基、低烷酰氧基、卤素、氰基、羟基低烷氧基、羧基低烷基、芳氧基或苄氧基；R.sub.2和R.sub.3独立地为氢、低烷基、低芳基烷基、低烷基烯基、低烷基炔基、芳基或羧基低烷基，以及其药学上可接受的盐。

  公开号：

  US04668694A1

文献信息

• HLASTA, DENNIS J.;CASEY, FRANCIS B.;FERGUSON, EDWARD W.;GANGELL, SALLY J.+, J. MED. CHEM., 34,(1991) N, C. 1560-1570
  作者：HLASTA, DENNIS J.、CASEY, FRANCIS B.、FERGUSON, EDWARD W.、GANGELL, SALLY J.+

  DOI：——

  日期：——
• US4668694A
  申请人：——

  公开号：US4668694A

  公开（公告）日：1987-05-26
• 5-Lipoxygenase inhibitors: the synthesis and structure-activity relationships of a series of 1-phenyl-3-pyrazolidinones
  作者：Dennis J. Hlasta、Francis B. Casey、Edward W. Ferguson、Sally J. Gangell、Martha R. Heimann、Edward P. Jaeger、Rudolph K. Kullnig、Robert J. Gordon

  DOI：10.1021/jm00109a006

  日期：1991.5

  A series of analogues of the 5-lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone, 1a) has been prepared via two complementary new synthetic methods. The reaction of various electrophiles with the dianion of 1a or with an N-silylpyrazolidinone anion gave the desired 4-substituted pyrazolidinones (Scheme I and II). A new procedure was developed for the resolution of 4-substituted pyrazolidinones (Scheme V). A regression study on 21 compounds in this series showed a correlation of increased inhibitor potency (pIC50) with increased compound lipophilicity (log P) and with an N-phenyl electronic effect as measured by the C-13 NMR chemical shift parameter CNMR1' (R2 = 0.79). The most potent 5-lipoxygenase inhibitor in this series was 4-(ethylthio)-1-phenyl-3-pyrazolidinone (1n) with an IC50 of 60 nM. Another member of this series, 4-(2-methoxyethyl)-1-phenyl-3-pyrazolidinone (1f, IC50 = 0-48-mu-M), although less potent than 1n, was better tolerated in the whole animal relative to phenidone (1a) and also displayed good oral activity in two models of 5-lipoxygenase inhibition. On the basis of a structure-activity relationship study, a mechanism for the inhibition of 5-lipoxygenase by this class of inhibitors was proposed.
• 1-arylalkoxyphenyl-pyrazolines, ketones or enoles as anti-inflammatory
  申请人：USV Pharmaceutical Corporation

  公开号：US04668694A1

  公开（公告）日：1987-05-26

  This disclosure describes novel pharmaceutical compositions of matter which possess useful anti-inflammatory and anti-allergic properties, the active ingredients of said compositions of matter being compounds of the formula ##STR1## wherein Ar and Ar.sub.1 are each independently phenyl or naphthyl or a nitrogen, oxygen or sulfur-heterocyclic ring; Z is an alkylene chain containing from 0 up to 5 carbons in the principal chain and up to a total of 7 carbons; X is O or S; Y is .dbd.O; R and R.sub.1 are independently hydrogen, hydroxy, lower alkoxy, lower alkanoyloxy, halo, cyano, carboloweralkoxy, carboxyloweralkyl, aryloxy or benzyloxy; R.sub.2 and R.sub.3 are independently hydrogen, lower alkyl, lower aralkyl, lower alkenyl, lower alkynyl, aryl or carboxyloweralkyl and the pharmaceutically acceptable salts thereof.

  本公开说明了一种新型的药物组合物，具有有用的抗炎和抗过敏性能，该药物组合物的活性成分是化合物的公式：##STR1##其中Ar和Ar.sub.1各自独立地为苯基或萘基或氮、氧或硫杂环; Z是含有0至5个碳的主链的烷基链，并且总共最多有7个碳; X是O或S; Y是.dbd.O; R和R.sub.1各自独立地为氢、羟基、较低的烷氧基、较低的烷酰氧基、卤素、氰基、羧基较低的烷氧基、羧基较低的烷基、芳氧基或苄氧基; R.sub.2和R.sub.3各自独立地为氢、较低的烷基、较低的芳基烷基、较低的烯基、较低的炔基、芳基或羧基较低的烷基，以及其药学上可接受的盐。