tert-butyl (3R)-6-cyclohexyl-3-(3-{4-[(methylsulfonyl)amino]phenyl}-1,2,4-oxadiazol-5-yl)hexanoate | 468068-96-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: tert-butyl (3R)-6-cyclohexyl-3-(3-{4-[(methylsulfonyl)amino]phenyl}-1,2,4-oxadiazol-5-yl)hexanoate
• 英文别名: tert-butyl (3R)-6-cyclohexyl-3-[3-[4-(methanesulfonamido)phenyl]-1,2,4-oxadiazol-5-yl]hexanoate
• CAS: 468068-96-4
• 化学式: C₂₅H₃₇N₃O₅S
• 分子量: 491.652
• InChiKey: BNSWECVUUNPTIC-HXUWFJFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  34
• 可旋转键数：
  12
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  120
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (3R)-6-cyclohexyl-3-(3-{4-[(methylsulfonyl)amino]phenyl}-1,2,4-oxadiazol-5-yl)hexanoate 在 三乙胺 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 (3R)-6-CYCLOHEXYL-N-HYDROXY-3-(3-{4-[(METHYLSULFONYL)AMINO]PHENYL}-1,2,4-OXADIAZOL-5-YL)HEXANAMIDE
  参考文献：
  名称：

  Potent and Selective Nonpeptidic Inhibitors of Procollagen C-Proteinase

  摘要：

  6-Cyclohexyl-N-hydroxy-3-(1,2,4-oxadiazol-5-yl)hexanamides were previously disclosed as inhibitors of procollagen C-proteinase (PCP) culminating in the identification of amide 1. Our objective was to discover a second inhibitor that would have improved affinity for PCP and to optimize properties for transepidermal delivery (TED) to intact skin. Further investigation of this template identified a number of potent PCP inhibitors (IC50 values of 2-6 nM) with improved TED flux. Sulfonamide 56 had excellent PCP enzyme activity when measured with a peptide substrate (K-i 8.7 nM) or with the endogenous substrate procollagen (IC50 3.4 nM) and demonstrates excellent selectivity over MMPs involved in wound healing (> 10 000-fold). In the fibroplasia model, 56 inhibited deposition of insoluble collagen by 76 +/- 2% at 10 mu M and was very effective at penetrating human skin in vitro with a TED flux of 1.5 mu g/cm(2)/h, which compares favorably with values for agents that are known to penetrate skin well in vivo. Based on this profile, 56 (UK-421,045) was selected as a candidate for further preclinical evaluation as a topically applied, dermal anti-scarring agent.

  DOI：

  10.1021/jm061010z
• 作为产物：
  描述：

  tert-butyl (3R)-6-cyclohexyl-3-[3-(4-nitrophenyl)-1,2,4-oxadiazol-5-yl]hexanoate 在 吡啶 、 tin(ll) chloride 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.0h， 生成 tert-butyl (3R)-6-cyclohexyl-3-(3-{4-[(methylsulfonyl)amino]phenyl}-1,2,4-oxadiazol-5-yl)hexanoate
  参考文献：
  名称：

  Potent and Selective Nonpeptidic Inhibitors of Procollagen C-Proteinase

  摘要：

  6-Cyclohexyl-N-hydroxy-3-(1,2,4-oxadiazol-5-yl)hexanamides were previously disclosed as inhibitors of procollagen C-proteinase (PCP) culminating in the identification of amide 1. Our objective was to discover a second inhibitor that would have improved affinity for PCP and to optimize properties for transepidermal delivery (TED) to intact skin. Further investigation of this template identified a number of potent PCP inhibitors (IC50 values of 2-6 nM) with improved TED flux. Sulfonamide 56 had excellent PCP enzyme activity when measured with a peptide substrate (K-i 8.7 nM) or with the endogenous substrate procollagen (IC50 3.4 nM) and demonstrates excellent selectivity over MMPs involved in wound healing (> 10 000-fold). In the fibroplasia model, 56 inhibited deposition of insoluble collagen by 76 +/- 2% at 10 mu M and was very effective at penetrating human skin in vitro with a TED flux of 1.5 mu g/cm(2)/h, which compares favorably with values for agents that are known to penetrate skin well in vivo. Based on this profile, 56 (UK-421,045) was selected as a candidate for further preclinical evaluation as a topically applied, dermal anti-scarring agent.

  DOI：

  10.1021/jm061010z