4-(4-hydroxybenzenesulfonylmethyl)piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester | 946857-56-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(4-hydroxybenzenesulfonylmethyl)piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester
• CAS: 946857-56-3
• 化学式: C₂₀H₂₉NO₇S
• 分子量: 427.519
• InChiKey: NBYOXEVSEYBZQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.75
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  110.21
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-(4-hydroxybenzenesulfonylmethyl)piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester 在 甲醇 、 sodium hydroxide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 caesium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 生成 4-((4-(but-2-ynyloxy)phenylsulfonyl)methyl)-N-hydroxy-1-(pyridin-4-yl)piperidine-4-carboxamide
  参考文献：
  名称：

  Identification of potent and selective TACE inhibitors via the S1 pocket

  摘要：

  By focusing on the P1 portion of the piperidine beta-sulfone ligands we identified a motif that induces selectivity and resulted in a series of TACE inhibitors that demonstrated excellent in vitro potency against isolated TACE enzyme and excellent selectivity over MMPs 1, 2, 9, 13, and 14.

  DOI：

  10.1016/j.bmcl.2006.10.004
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 potassium carbonate 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 59.0h， 生成 4-(4-hydroxybenzenesulfonylmethyl)piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester
  参考文献：
  名称：

  Design and synthesis of 3,3-piperidine hydroxamate analogs as selective TACE inhibitors

  摘要：

  Structure-based methods were used to design P-sulfone 3,3-piperidine hydroxamates as TACE inhibitors with the aim of improving selectivity for TACE versus MMP-13. Several compounds in this series were synthesized and evaluated in enzymatic and cell-based assays. These analogs exhibit excellent in vitro potency against isolated TACE enzyme and show good selectivity for TACE over the related metalloproteases MMP-2, -13, and -14. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.05.022

文献信息

• Structure-based design of TACE selective inhibitors: Manipulations in the S1′–S3′ pocket
  作者：Adrian Huang、Diane Joseph-McCarthy、Frank Lovering、Linhong Sun、Weiheng Wang、Weixin Xu、Yi Zhu、Junqing Cui、Yuhua Zhang、Jeremy I. Levin

  DOI：10.1016/j.bmc.2007.06.031

  日期：2007.9

  A series of beta-sulfonyl hydroxamate TACE inhibitors, bearing a butynylamino or a butynyloxy Pl' group, was designed and synthesized. Of the compounds investigated, 22 has excellent potency against isolated TACE enzyme, shows good selectivity over MMP-2 and MMP- 13, and oral activity in an in vivo mouse model of TNF-alpha( production. (c) 2007 Elsevier Ltd. All rights reserved.