tert-butyl (6Z,10R)-6-amino-10-(3-cyclohexylpropyl)-9-oxo-8-oxa-2-thia-3,7-diazadodec-6-en-12-oate 2,2-dioxide | 944731-39-9

• 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: tert-butyl (6Z,10R)-6-amino-10-(3-cyclohexylpropyl)-9-oxo-8-oxa-2-thia-3,7-diazadodec-6-en-12-oate 2,2-dioxide
• 英文别名: 1-O-[[1-amino-3-(methanesulfonamido)propylidene]amino] 4-O-tert-butyl (2R)-2-(3-cyclohexylpropyl)butanedioate
• CAS: 944731-39-9
• 化学式: C₂₁H₃₉N₃O₆S
• 分子量: 461.623
• InChiKey: OOFFUKGOBVPCOB-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl (6Z,10R)-6-amino-10-(3-cyclohexylpropyl)-9-oxo-8-oxa-2-thia-3,7-diazadodec-6-en-12-oate 2,2-dioxide 在 三氟乙酸 作用下， 以 二氯甲烷 、 xylene 为溶剂， 反应 2.0h， 生成 (3R)-6-cyclohexyl-3-(3-{2-[(methylsulfonyl)amino]ethyl}-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
• 作为产物：
  描述：

  (1Z)-N'-hydroxy-3-[(methylsulfonyl)amino]propanimidamide 、 (2R)-2-[2-(tert-butoxy)-2-oxoethyl]-5-cyclohexylpentanoic acid 生成 tert-butyl (6Z,10R)-6-amino-10-(3-cyclohexylpropyl)-9-oxo-8-oxa-2-thia-3,7-diazadodec-6-en-12-oate 2,2-dioxide
  参考文献：
  名称：

  3-ox(adi) azolylpropanohydroxamic acids useful as procollagen C- Proteinase inhibitors

  摘要：

  化合物的式子为(I):1，其中代替基的定义如此，它们的盐、溶剂化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。

  公开号：

  US20020151535A1

文献信息

• 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。
• US7214694B2
  申请人：——

  公开号：US7214694B2

  公开（公告）日：2007-05-08