2-(Toluene-4-sulfonyl)-2-aza-bicyclo[2.2.2]octane-3-carboxylic acid ethyl ester | 521970-27-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(Toluene-4-sulfonyl)-2-aza-bicyclo[2.2.2]octane-3-carboxylic acid ethyl ester
• 英文别名: Ethyl 2-(4-methylphenyl)sulfonyl-2-azabicyclo[2.2.2]octane-3-carboxylate
• CAS: 521970-27-4
• 化学式: C₁₇H₂₃NO₄S
• 分子量: 337.44
• InChiKey: MJWNFGYRXJRTDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(Toluene-4-sulfonyl)-2-aza-bicyclo[2.2.2]octane-3-carboxylic acid ethyl ester 在 lithium hydroxide 、 氯化铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 锌 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 (S)-3-(4-Amino-phenyl)-2-{[2-(toluene-4-sulfonyl)-2-aza-bicyclo[2.2.2]octane-3-carbonyl]-amino}-propionic acid methyl ester
  参考文献：
  名称：

  Aza-bicyclic amino acid sulfonamides as α4β1/α4β7 integrin antagonists

  摘要：

  The design, synthesis, and biological activity of novel alpha(4)beta(1) and alpha(4)beta(7) integrin antagonists, containing a bridged azabicyclic nucleus, are reported. Conformational analysis of targets containing an azabicyclo[2.2.2]octane carboxylic acid and known integrin antagonists indicated that this azabicycle would be a suitable molecular scaffold. Variation of substituents on the pendant arylsulfonamide and phenylalanine groups resulted in potent alpha(4)beta(1)-selective and dual alpha(4)beta(1)/alpha(4)beta(7) antagonists. Potent compounds 11i, 11h, and 14 were effective in the antigen-sensitized sheep model of asthma. (C) 2003 Elsevier Science Ltd. All rights reserved. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.063
• 作为产物：
  描述：

  对甲苯磺酰氯 、 ethyl 2-azabicyclo[2.2.2]octane-3-carboxylate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-(Toluene-4-sulfonyl)-2-aza-bicyclo[2.2.2]octane-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Aza-bicyclic amino acid sulfonamides as α4β1/α4β7 integrin antagonists

  摘要：

  The design, synthesis, and biological activity of novel alpha(4)beta(1) and alpha(4)beta(7) integrin antagonists, containing a bridged azabicyclic nucleus, are reported. Conformational analysis of targets containing an azabicyclo[2.2.2]octane carboxylic acid and known integrin antagonists indicated that this azabicycle would be a suitable molecular scaffold. Variation of substituents on the pendant arylsulfonamide and phenylalanine groups resulted in potent alpha(4)beta(1)-selective and dual alpha(4)beta(1)/alpha(4)beta(7) antagonists. Potent compounds 11i, 11h, and 14 were effective in the antigen-sensitized sheep model of asthma. (C) 2003 Elsevier Science Ltd. All rights reserved. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.063

文献信息

• BRIDGED BICYCLE (1,4) BENZODIAZEPINE VASOPRESSIN RECEPTOR ANTAGONISTS
  申请人：Ortho-McNeil Pharmaceutical, Inc.

  公开号：EP1442040B1

  公开（公告）日：2007-05-23
• Aza-bicyclic amino acid sulfonamides as α4β1/α4β7 integrin antagonists
  作者：Alexey B Dyatkin、William J Hoekstra、William A Kinney、Maria Kontoyianni、Rosemary J Santulli、Edward S Kimball、M Carolyn Fisher、Stephen M Prouty、William M Abraham、Patricia Andrade-Gordon、Dennis J Hlasta、Wei He、Pamela J Hornby、Bruce P Damiano、Bruce E Maryanoff

  DOI：10.1016/j.bmcl.2003.11.063

  日期：2004.2

  The design, synthesis, and biological activity of novel alpha(4)beta(1) and alpha(4)beta(7) integrin antagonists, containing a bridged azabicyclic nucleus, are reported. Conformational analysis of targets containing an azabicyclo[2.2.2]octane carboxylic acid and known integrin antagonists indicated that this azabicycle would be a suitable molecular scaffold. Variation of substituents on the pendant arylsulfonamide and phenylalanine groups resulted in potent alpha(4)beta(1)-selective and dual alpha(4)beta(1)/alpha(4)beta(7) antagonists. Potent compounds 11i, 11h, and 14 were effective in the antigen-sensitized sheep model of asthma. (C) 2003 Elsevier Science Ltd. All rights reserved. (C) 2003 Elsevier Ltd. All rights reserved.