N'-hydroxy-1-(methylsulfonyl)-4-piperidinecarboximidamide | 438630-75-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: N'-hydroxy-1-(methylsulfonyl)-4-piperidinecarboximidamide
• 英文别名: N'-hydroxy-1-methylsulfonylpiperidine-4-carboximidamide
• CAS: 438630-75-2
• 化学式: C₇H₁₅N₃O₃S
• 分子量: 221.28
• InChiKey: KNQNPFFQXUYXDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N'-hydroxy-1-(methylsulfonyl)-4-piperidinecarboximidamide 、 (2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid 在 N,N'-羰基二咪唑 作用下， 以 二氯甲烷 为溶剂， 以1.20 g的产率得到tert-butyl (3R)-3-{[({(Z)-amino[1-(methylsulfonyl)-4-piperidinyl]methylidene}amino)oxy]carbonyl}-6-cyclohexylhexanoate
  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：

  1-(methylsulfonyl)-4-piperidinecarbonitrile 在 盐酸羟胺 、 三乙胺 作用下， 以 甲醇 为溶剂， 生成 N'-hydroxy-1-(methylsulfonyl)-4-piperidinecarboximidamide
  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-ox(adi) azolylpropanohydroxamic acids useful as procollagen C- Proteinase inhibitors
  申请人：——

  公开号：US20020151535A1

  公开（公告）日：2002-10-17

  Compounds of formula (I): 1 wherein the substituents are as defined herein, and their salt, solvates, and prodrugs are procollagen C-proteinase (PCP) inhibitors useful in treating conditions mediated by PCP.

  式（I）的化合物： 其中取代基如本文所定义，并且它们的盐、溶剂合物和前药是用于治疗由PCP介导的疾病的前胶原C蛋白酶（PCP）抑制剂。
• 3-ox(adi)azolylpropanohydroxamic acids useful as procollagen C-proteinase inhibitors
  申请人：——

  公开号：US20040142986A1

  公开（公告）日：2004-07-22

  Compounds of formula (I): 1 wherein the substituents are as defined herein, and their salt, solvates, and prodrugs are procollagen C-proteinase (PCP) inhibitors useful in treating conditions mediated by PCP.

  式(I)的化合物：其中取代基如此处所定义，以及它们的盐、溶剂合物和前药是前胶原C蛋白酶（PCP）抑制剂，可用于治疗由PCP介导的疾病。
• 3-OX(ADI)AZOLYLPROPANOHYDROXAMIC ACIDS USEFUL AS PROCOLLAGEN C-PROTEINASE INHIBITORS
  申请人：Pfizer Limited

  公开号：EP1343771A1

  公开（公告）日：2003-09-17
• US6716861B2
  申请人：——

  公开号：US6716861B2

  公开（公告）日：2004-04-06
• US7214694B2
  申请人：——

  公开号：US7214694B2

  公开（公告）日：2007-05-08