(3R)-6-cyclohexyl-3-[3-(2-pyrazinyl)-1,2,4-oxadiazol-5-yl]hexanoic acid | 468068-63-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (3R)-6-cyclohexyl-3-[3-(2-pyrazinyl)-1,2,4-oxadiazol-5-yl]hexanoic acid
• 英文别名: (3R)-6-cyclohexyl-3-(3-pyrazin-2-yl-1,2,4-oxadiazol-5-yl)hexanoic acid
• CAS: 468068-63-5
• 化学式: C₁₈H₂₄N₄O₃
• 分子量: 344.414
• InChiKey: AJWCDPUNHNOQRX-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (3R)-6-cyclohexyl-3-[3-(2-pyrazinyl)-1,2,4-oxadiazol-5-yl]hexanoic acid 在 三乙胺 、 氯甲酸异丁酯 、 O-(三甲基硅)羟胺 、 甲醇 作用下， 以 四氢呋喃 为溶剂， 反应 2.5h， 以0.76 g的产率得到(3R)-6-cyclohexyl-N-hydroxy-3-[3-(2-pyrazinyl)-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-(2-pyrazinyl)-1,2,4-oxadiazol-5-yl]hexanoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以0.56 g的产率得到(3R)-6-cyclohexyl-3-[3-(2-pyrazinyl)-1,2,4-oxadiazol-5-yl]hexanoic 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

文献信息

• 3-heterocyclylpropanohydroxamic acid PCP inhibitors
  申请人：——

  公开号：US20030069291A1

  公开（公告）日：2003-04-10

  Compounds of formula (I): 1 and their salts, solvates, hydrates and prodrugs are useful PCP inhibitors, processes for making the same, compositions comprising the same, and methods of treating a PCP-mediated condition or disease using the same.

  式(I)的化合物及其盐、溶剂合物、水合物和前药是有用的PCP抑制剂，制备这些化合物的方法，包含这些化合物的组合物，以及使用这些化合物治疗PCP介导的疾病或病症的方法。
• 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
• US6821972B2
  申请人：——

  公开号：US6821972B2

  公开（公告）日：2004-11-23
• [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.