4-(2-Azidomethyl-2-hydroxymethyl-5-oxo-pyrrolidin-1-yl)-3-(1-ethyl-propylamino)-benzoic acid | 623162-11-8

• 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-(2-Azidomethyl-2-hydroxymethyl-5-oxo-pyrrolidin-1-yl)-3-(1-ethyl-propylamino)-benzoic acid
• 英文别名: 4-[2-(Azidomethyl)-2-(hydroxymethyl)-5-oxo-pyrrolidin-1-yl]-3-(1-ethylpropylamino)benzoic acid；4-[2-(azidomethyl)-2-(hydroxymethyl)-5-oxopyrrolidin-1-yl]-3-(pentan-3-ylamino)benzoic acid
• CAS: 623162-11-8
• 化学式: C₁₈H₂₅N₅O₄
• 分子量: 375.428
• InChiKey: HIBXOFJYKXTXDG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  104
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(2-Azidomethyl-2-hydroxymethyl-5-oxo-pyrrolidin-1-yl)-3-(1-ethyl-propylamino)-benzoic acid 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.5h， 以84%的产率得到4-(2-Aminomethyl-2-hydroxymethyl-5-oxo-pyrrolidin-1-yl)-3-(1-ethyl-propylamino)-benzoic acid
  参考文献：
  名称：

  Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: modifications of essential pyrrolidinone ring substituents

  摘要：

  We recently reported the first benzoic acid, 1-[4-carboxy-2-(3-pentylamino)phenyl]-5,5-bis(hydroxymethyl)pyrrolidin-2-one (8), that is a potent inhibitor of avian influenza A neuraminidase (N9) and, unlike other reported potent neuraminidase inhibitors, does not contain a basic aliphatic amine or guanidine nor a simple N-acetyl grouping. However, 8 was a poor inhibitor of influenza B neuraminidase. In the present study we further evaluated 8 as an inhibitor of human influenza A NA isolates, and it was effective against N2 NA but found to be 160-fold less active against N1 NA. We also synthesized analogues of 8 involving moderate modifications of essential substituents on the pyrrolidinone ring. Specifically, the aminomethyl (9), hydroxyethyl (10), and aminoethyl (11) analogues were prepared. Only the most conservative change (compound 9) resulted in continued effective inhibition of influenza A, in addition to a noteworthy increase in the activity of 9 for N1 NA. The effectiveness of 9 against influenza B neuraminidase was furthermore improved 10-fold relative to 8, but this activity remained 50-fold poorer than for type A NA. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00271-2
• 作为产物：
  描述：

  1-(4-methoxycarbonyl-2-nitrophenyl)-5,5-bis(hydroxymethyl)pyrrolidin-2-one 在 sodium hydroxide 、 N-溴代丁二酰亚胺(NBS) 、 sodium azide 、 sodium dithionite 、 sodium cyanoborohydride 、 对甲苯磺酸 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 、 苯 为溶剂， 反应 127.0h， 生成 4-(2-Azidomethyl-2-hydroxymethyl-5-oxo-pyrrolidin-1-yl)-3-(1-ethyl-propylamino)-benzoic acid
  参考文献：
  名称：

  Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: modifications of essential pyrrolidinone ring substituents

  摘要：

  We recently reported the first benzoic acid, 1-[4-carboxy-2-(3-pentylamino)phenyl]-5,5-bis(hydroxymethyl)pyrrolidin-2-one (8), that is a potent inhibitor of avian influenza A neuraminidase (N9) and, unlike other reported potent neuraminidase inhibitors, does not contain a basic aliphatic amine or guanidine nor a simple N-acetyl grouping. However, 8 was a poor inhibitor of influenza B neuraminidase. In the present study we further evaluated 8 as an inhibitor of human influenza A NA isolates, and it was effective against N2 NA but found to be 160-fold less active against N1 NA. We also synthesized analogues of 8 involving moderate modifications of essential substituents on the pyrrolidinone ring. Specifically, the aminomethyl (9), hydroxyethyl (10), and aminoethyl (11) analogues were prepared. Only the most conservative change (compound 9) resulted in continued effective inhibition of influenza A, in addition to a noteworthy increase in the activity of 9 for N1 NA. The effectiveness of 9 against influenza B neuraminidase was furthermore improved 10-fold relative to 8, but this activity remained 50-fold poorer than for type A NA. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00271-2

文献信息

• Pyrrolidinobenzoic acid inhibitors of influenza virus neuraminidase: modifications of essential pyrrolidinone ring substituents
  作者：Wayne J Brouillette、Saroj N Bajpai、Shoukath M Ali、Sadanandan E Velu、Venkatram R Atigadda、Barbara S Lommer、James B Finley、Ming Luo、Gillian M Air

  DOI：10.1016/s0968-0896(03)00271-2

  日期：2003.7

  We recently reported the first benzoic acid, 1-[4-carboxy-2-(3-pentylamino)phenyl]-5,5-bis(hydroxymethyl)pyrrolidin-2-one (8), that is a potent inhibitor of avian influenza A neuraminidase (N9) and, unlike other reported potent neuraminidase inhibitors, does not contain a basic aliphatic amine or guanidine nor a simple N-acetyl grouping. However, 8 was a poor inhibitor of influenza B neuraminidase. In the present study we further evaluated 8 as an inhibitor of human influenza A NA isolates, and it was effective against N2 NA but found to be 160-fold less active against N1 NA. We also synthesized analogues of 8 involving moderate modifications of essential substituents on the pyrrolidinone ring. Specifically, the aminomethyl (9), hydroxyethyl (10), and aminoethyl (11) analogues were prepared. Only the most conservative change (compound 9) resulted in continued effective inhibition of influenza A, in addition to a noteworthy increase in the activity of 9 for N1 NA. The effectiveness of 9 against influenza B neuraminidase was furthermore improved 10-fold relative to 8, but this activity remained 50-fold poorer than for type A NA. (C) 2003 Elsevier Science Ltd. All rights reserved.