[(4-Benzyloxy-benzenesulfonyl)-(4-oxo-octyl)-amino]-acetic acid tert-butyl ester | 950888-15-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [(4-Benzyloxy-benzenesulfonyl)-(4-oxo-octyl)-amino]-acetic acid tert-butyl ester
• CAS: 950888-15-0
• 化学式: C₂₇H₃₇NO₆S
• 分子量: 503.66
• InChiKey: APHAHNBVSRUWME-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.14
• 重原子数：
  35.0
• 可旋转键数：
  14.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  89.98
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  [(4-Benzyloxy-benzenesulfonyl)-(4-oxo-octyl)-amino]-acetic acid tert-butyl ester 在 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 (2S,3S)-1-(4-Benzyloxy-benzenesulfonyl)-3-butyl-3-hydroxy-piperidine-2-carboxylic acid tert-butyl ester 、 (2S,3R)-1-(4-Benzyloxy-benzenesulfonyl)-3-butyl-3-hydroxy-piperidine-2-carboxylic acid tert-butyl ester 、 (2R,3S)-1-(4-Benzyloxy-benzenesulfonyl)-3-butyl-3-hydroxy-piperidine-2-carboxylic acid tert-butyl ester 、 (2R,3R)-1-(4-Benzyloxy-benzenesulfonyl)-3-butyl-3-hydroxy-piperidine-2-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of 3-OH-3-methylpipecolic hydroxamates: Potent orally active inhibitors of aggrecanase and MMP-13

  摘要：

  A series of 3-hydroxy-3-methylpipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was designed based on the observation of increased aggrecanase activity with substitution at the 3-position of the piperidine ring. Potency versus aggrecanase was optimized by modification of the benzyloxyarylsulfonamide group that binds in the S1' pocket. These compounds also possess markedly improved bioavailability and lower metabolic clearance compared to analogous 3,3-dimethyl-5-hydroxypipecolic hydroxamates. These improvements are attributed to lowered lipophilicity proximal to the metabolically labile hydroxamic acid. Synthesis, structure activity relationships, and in vivo efficacy data are described. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.037
• 作为产物：
  描述：

  甘氨酸叔丁酯 在 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 [(4-Benzyloxy-benzenesulfonyl)-(4-oxo-octyl)-amino]-acetic acid tert-butyl ester
  参考文献：
  名称：

  Discovery of 3-OH-3-methylpipecolic hydroxamates: Potent orally active inhibitors of aggrecanase and MMP-13

  摘要：

  A series of 3-hydroxy-3-methylpipecolic hydroxamate inhibitors of MMP-13 and aggrecanase was designed based on the observation of increased aggrecanase activity with substitution at the 3-position of the piperidine ring. Potency versus aggrecanase was optimized by modification of the benzyloxyarylsulfonamide group that binds in the S1' pocket. These compounds also possess markedly improved bioavailability and lower metabolic clearance compared to analogous 3,3-dimethyl-5-hydroxypipecolic hydroxamates. These improvements are attributed to lowered lipophilicity proximal to the metabolically labile hydroxamic acid. Synthesis, structure activity relationships, and in vivo efficacy data are described. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.05.037