(S)-2-[(R)-1-Benzyloxycarbonylamino-2-(4-benzyloxy-phenylsulfanyl)-ethyl]-pent-4-enoic acid tert-butyl ester | 761435-49-8

• 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: (S)-2-[(R)-1-Benzyloxycarbonylamino-2-(4-benzyloxy-phenylsulfanyl)-ethyl]-pent-4-enoic acid tert-butyl ester
• CAS: 761435-49-8
• 化学式: C₃₂H₃₇NO₅S
• 分子量: 547.715
• InChiKey: KMRGHDAKXCRLSW-VMPREFPWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.19
• 重原子数：
  39.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  73.86
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (S)-2-[(R)-1-Benzyloxycarbonylamino-2-(4-benzyloxy-phenylsulfanyl)-ethyl]-pent-4-enoic acid tert-butyl ester 在 palladium on activated charcoal Oxone 、 重铬酸吡啶 、 9-borabicyclo[3.3.1]nonane dimer 、 氢气 、 potassium carbonate 、 三氟乙酸 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-(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：

  (R)-4-hydroxy-2-{[(phenylmethoxy)carbonyl]amino}butanoic acid 1,1-dimethylethyl ester 在 TEA 、 sodium hydride 、 potassium carbonate 、 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， 生成 (S)-2-[(R)-1-Benzyloxycarbonylamino-2-(4-benzyloxy-phenylsulfanyl)-ethyl]-pent-4-enoic 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