(±)-(3aS,7aS)-tert-butyl 1-oxohexahydrofuro[3,4-c]pyridine-5(3H)-carboxylate

• 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: (±)-(3aS,7aS)-tert-butyl 1-oxohexahydrofuro[3,4-c]pyridine-5(3H)-carboxylate
• 英文别名: tert-butyl (3aS,7aS)-1-oxo-3,3a,4,6,7,7a-hexahydrofuro[3,4-c]pyridine-5-carboxylate
• 化学式: C₁₂H₁₉NO₄
• 分子量: 241.287
• InChiKey: GOGIONPWBODBEY-IUCAKERBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (±)-(3aS,7aS)-tert-butyl 1-oxohexahydrofuro[3,4-c]pyridine-5(3H)-carboxylate 在 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (3S,4S)-3-[4-(2-Methyl-quinolin-4-ylmethoxy)-phenylsulfanylmethyl]-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-methyl 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
• 作为产物：
  描述：

  3,4-吡啶二羧酸 在 platinum(IV) oxide 盐酸 、 sodium hydroxide 、 sodium tetrahydroborate 、 氢气 、 乙酸酐 作用下， 以 四氢呋喃 为溶剂， 生成 (±)-(3aS,7aS)-tert-butyl 1-oxohexahydrofuro[3,4-c]pyridine-5(3H)-carboxylate
  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 of Fused Bicyclic Piperidines: Potential Bioactive Templates for Medicinal Chemistry
  作者：Jinglan Zhou、Erica L. Campbell-Conroy、Alina Silina、Johnny Uy、Fabrice Pierre、Dennis J. Hurley、Nicole Hilgraf、Bryan A. Frieman、Michael P. DeNinno

  DOI：10.1021/jo501967m

  日期：2015.1.2

  An array of six pyridyl-substituted fused bicyclic piperidines was prepared as novel cores for medicinal chemistry. For maximum diversity, the size of the fused ring varied from three to six atoms and contained up to two oxygen atoms. The pyridine ring was incorporated to improve physicochemical properties and to challenge the robustness of the chemistry. The presence of the pyridine did interfere with our initial approaches to these molecules, and in several instances, a blocking strategy had to be employed. These new scaffolds possess high sp3 character and may prove useful in multiple medicinal chemistry applications.