ethyl 3-(5-{(1R)-4-cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-1,2,4-oxadiazol-3-yl)benzoate | 468067-57-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 3-(5-{(1R)-4-cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-1,2,4-oxadiazol-3-yl)benzoate
• 英文别名: ethyl 3-[5-[(3R)-6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl]-1,2,4-oxadiazol-3-yl]benzoate
• CAS: 468067-57-4
• 化学式: C₂₃H₃₁N₃O₅
• 分子量: 429.516
• InChiKey: UIJRLXLOQCHECQ-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 3-(5-{(1R)-4-cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-1,2,4-oxadiazol-3-yl)benzoate 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 以0.05 g的产率得到3-(5-{(1R)-4-CYCLOHEXYL-1-[2-(HYDROXYAMINO)-2-OXOETHYL]BUTYL}-1,2,4-OXADIAZOL-3-YL)BENZOIC ACID
  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：

  (2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid 在 三乙胺 、 N,N'-羰基二咪唑 、 三氟乙酸 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 二氯甲烷 、 xylene 为溶剂， 反应 4.5h， 生成 ethyl 3-(5-{(1R)-4-cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-1,2,4-oxadiazol-3-yl)benzoate
  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

文献信息

• 3-HETEROCYCLYLPROPANOHYDROXAMIC ACID AS PROCOLLAGEN C-PROTEINASE INHIBITORS
  申请人：Pfizer Limited

  公开号：EP1373264A1

  公开（公告）日：2004-01-02
• [EN] 3-HETEROCYCLYLPROPANOHYDROXAMIC ACID AS PROCOLLAGEN C-PROTEINASE INHIBITORS<br/>[FR] ACIDE 3-HETEROCYCLYLPROPANOHYDROXAMIQUE EN TANT QU'INHIBITEUR DE PROCOLLAGENE C-PROTEINASE
  申请人：PFIZER LTD

  公开号：WO2002079200A1

  公开（公告）日：2002-10-10

  Compounds of compounds of formula (I) and their salts, solvates and prodrugs, wherein the substituents are as defined herein, are Procollagen C-proteinase inhibitors for the treatment of scars.