4-(4-but-2-ynyloxy-benzenesulfonylmethyl)-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester | 287202-73-7

• 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-but-2-ynyloxy-benzenesulfonylmethyl)-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester
• 英文别名: 4-(4-But-2-ynyloxy-phenylsulfonylmethyl)-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester；4-[(4-but-2-ynoxyphenyl)sulfonylmethyl]-1-[(2-methylpropan-2-yl)oxycarbonyl]piperidine-4-carboxylic acid
• CAS: 287202-73-7
• 化学式: C₂₂H₂₉NO₇S
• 分子量: 451.541
• InChiKey: HICXWXFHAGYGKY-UHFFFAOYSA-N

物化性质

• 沸点：
  652.1±55.0 °C(Predicted)
• 密度：
  1.256±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  119
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-(4-but-2-ynyloxy-benzenesulfonylmethyl)-piperidine-1,4-dicarboxylic acid mono-tert-butyl ester 在 2,6-二甲基吡啶 、 三氟甲磺酸三甲基硅酯 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 N-(tert-butoxy)-4-({[4-(2-butynyloxy)phenyl]sulfonyl}methyl)-4-piperidinecarboxamide
  参考文献：
  名称：

  Design and synthesis of butynyloxyphenyl β-sulfone piperidine hydroxamates as TACE inhibitors

  摘要：

  A series of butynyloxyphenyl P-sulfone piperidine hydroxamate TACE inhibitors was designed and synthesized. The resulting structure-activity relationship and MMP selectivity of the series were examined. Of the compounds investigated, 17s has excellent in vitro potency against isolated TACE enzyme, shows good selectivity over MMP-1, -2, -7, -8, -9, -13, and -14, and oral activity in an in vivo mouse model of TNF-alpha production. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.05.026
• 作为产物：
  描述：

  N-Boc-4-哌啶甲酸乙酯 在 lithium hydroxide 、 potassium carbonate 、 caesium carbonate 、 间氯过氧苯甲酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 58.08h， 生成 4-(4-but-2-ynyloxy-benzenesulfonylmethyl)-piperidine-1,4-dicarboxylic acid mono-tert-butyl 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

• Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/TACE inhibitors
  申请人：WYETH

  公开号：US20040229924A1

  公开（公告）日：2004-11-18

  Compounds of the formula: 1 useful in the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.

  该式的化合物：1在治疗关节炎、肿瘤转移、组织溃疡、异常伤口愈合、牙周病、骨病、糖尿病（胰岛素抵抗）和HIV感染方面有用。
• Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors
  申请人：American Cyanamid Company

  公开号：US20020086890A1

  公开（公告）日：2002-07-04

  Compounds of the formula: 1 useful in the treatment of arthritis, tumor metastasis, tissue ulceration, abnormal wound healing, periodontal disease, bone disease, diabetes (insulin resistance) and HIV infection.

  以下公式化合物：1，对于治疗关节炎、肿瘤转移、组织溃疡、异常伤口愈合、牙周疾病、骨疾病、糖尿病（胰岛素抵抗）和HIV感染非常有用。
• ALKYNYL CONTAINING HYDROXAMIC ACID DERIVATIVES, THEIR PREPARATION AND THEIR USE AS MATRIX METALLOPROTEINASE (MMP) INHIBITORS / TNF-ALPHA CONVERTING ENZYME (TACE) INHIBITORS
  申请人：Wyeth Holdings Corporation

  公开号：EP1147085B1

  公开（公告）日：2005-11-16
• Identification of potent and selective TACE inhibitors via the S1 pocket
  作者：Jeffrey S. Condon、Diane Joseph-McCarthy、Jeremy I. Levin、Henry-Georges Lombart、Frank E. Lovering、Linhong Sun、Weiheng Wang、Weixin Xu、Yuhua Zhang

  DOI：10.1016/j.bmcl.2006.10.004

  日期：2007.1

  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.
• US6358980B1
  申请人：——

  公开号：US6358980B1

  公开（公告）日：2002-03-19