(2R,3S)-2-(4-Hydroxy-benzenesulfonylmethyl)-piperidine-1,3-dicarboxylic acid di-tert-butyl ester | 441298-09-5

• 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: (2R,3S)-2-(4-Hydroxy-benzenesulfonylmethyl)-piperidine-1,3-dicarboxylic acid di-tert-butyl ester
• CAS: 441298-09-5
• 化学式: C₂₂H₃₃NO₇S
• 分子量: 455.573
• InChiKey: XLDVDVNFTOUNAK-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  31.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 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：

  (2R,3S)-2-(4-Hydroxy-benzenesulfonylmethyl)-piperidine-1,3-dicarboxylic acid di-tert-butyl ester 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3S)-2-[4-(2-Methyl-quinolin-4-ylmethoxy)-benzenesulfonylmethyl]-piperidine-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and structure–activity relationship of a novel sulfone series of TNF-α converting enzyme inhibitors

  摘要：

  Replacement of the amide functionality in IM491 (N-hydroxy-(5S,6S)-1-methyl-6-{[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl}-5-piperidinecarboxamide) with a sulfonyl group led to a new series of alpha,beta-cyclic and beta,beta-cyclic gamma-sulfonyl hydroxamic acids, which were potent TNF-alpha converting enzyme (TACE) inhibitors. Among them, inhibitor 4b (N-hydroxy(4S,5S)-1-methyl-5-1[4-(2-methyl-4-quinolinylmethoxy)phenyl]sulfonylmethyl -4-pyrrolidinecarboxamide) exhibited IC50 values of <1 nM and 180 nM in porcine TACE (pTACE) and cell assays, respectively, with excellent selectivity over MMP- 1, -2, -9 and - 13 and was orally bioavailable with an F value of 46% in mice. (C) 2004 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2004.06.049
• 作为产物：
  描述：

  Cbz-D-天冬氨酸 4-叔丁酯一水物 在 palladium on activated charcoal Oxone 、 重铬酸吡啶 、 9-borabicyclo[3.3.1]nonane dimer 、 TEA 、 硼烷 、 氢气 、 sodium hydride 、 potassium carbonate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2R,3S)-2-(4-Hydroxy-benzenesulfonylmethyl)-piperidine-1,3-dicarboxylic acid di-tert-butyl ester
  参考文献：
  名称：

  Synthesis and structure–activity relationship of a novel sulfone series of TNF-α converting enzyme inhibitors

  摘要：

  Replacement of the amide functionality in IM491 (N-hydroxy-(5S,6S)-1-methyl-6-{[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl}-5-piperidinecarboxamide) with a sulfonyl group led to a new series of alpha,beta-cyclic and beta,beta-cyclic gamma-sulfonyl hydroxamic acids, which were potent TNF-alpha converting enzyme (TACE) inhibitors. Among them, inhibitor 4b (N-hydroxy(4S,5S)-1-methyl-5-1[4-(2-methyl-4-quinolinylmethoxy)phenyl]sulfonylmethyl -4-pyrrolidinecarboxamide) exhibited IC50 values of <1 nM and 180 nM in porcine TACE (pTACE) and cell assays, respectively, with excellent selectivity over MMP- 1, -2, -9 and - 13 and was orally bioavailable with an F value of 46% in mice. (C) 2004 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2004.06.049

文献信息

• Synthesis and structure–activity relationship of a novel sulfone series of TNF-α converting enzyme inhibitors
  作者：Chu-Biao Xue、Xiao-Tao Chen、Xiaohua He、John Roderick、Ronald L. Corbett、Bahman Ghavimi、Rui-Qin Liu、Maryanne B. Covington、Mingxin Qian、Maria D. Ribadeneira、Krishna Vaddi、James Trzaskos、Robert C. Newton、James J.-W. Duan、Carl P. Decicco

  DOI：10.1016/j.bmcl.2004.06.049

  日期：2004.9

  Replacement of the amide functionality in IM491 (N-hydroxy-(5S,6S)-1-methyl-6-[4-(2-methyl-4-quinolinylmethoxy)anilinyl]carbonyl}-5-piperidinecarboxamide) with a sulfonyl group led to a new series of alpha,beta-cyclic and beta,beta-cyclic gamma-sulfonyl hydroxamic acids, which were potent TNF-alpha converting enzyme (TACE) inhibitors. Among them, inhibitor 4b (N-hydroxy(4S,5S)-1-methyl-5-1[4-(2-methyl-4-quinolinylmethoxy)phenyl]sulfonylmethyl -4-pyrrolidinecarboxamide) exhibited IC50 values of <1 nM and 180 nM in porcine TACE (pTACE) and cell assays, respectively, with excellent selectivity over MMP- 1, -2, -9 and - 13 and was orally bioavailable with an F value of 46% in mice. (C) 2004 Published by Elsevier Ltd.