(R)-3-Benzyloxycarbonylamino-4-(4-hydroxy-phenylsulfanyl)-butyric acid tert-butyl ester | 761435-45-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (R)-3-Benzyloxycarbonylamino-4-(4-hydroxy-phenylsulfanyl)-butyric acid tert-butyl ester
• CAS: 761435-45-4
• 化学式: C₂₂H₂₇NO₅S
• 分子量: 417.526
• InChiKey: PEWHIAHXFZSAPG-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.51
• 重原子数：
  29.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  84.86
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (R)-3-Benzyloxycarbonylamino-4-(4-hydroxy-phenylsulfanyl)-butyric acid tert-butyl ester 在 palladium on activated charcoal N-甲基吗啉 、 Oxone 、 重铬酸吡啶 、 9-borabicyclo[3.3.1]nonane dimer 、 氢气 、 羟胺 、 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三氟乙酸 、 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)-N-hydroxy-2-[({4-[(2-methyl-4-quinolinyl)methoxy]phenyl}sulfonyl)methyl]-3-piperidinecarboxamide
  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：

  (R)-4-hydroxy-2-{[(phenylmethoxy)carbonyl]amino}butanoic acid 1,1-dimethylethyl ester 在 TEA 、 sodium hydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-3-Benzyloxycarbonylamino-4-(4-hydroxy-phenylsulfanyl)-butyric acid 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