methyl (2S,3R)-2-(cyclohexylmethyl)-3-hydroxyhexanoate | 212610-23-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: methyl (2S,3R)-2-(cyclohexylmethyl)-3-hydroxyhexanoate
• 英文别名: methyl (2R,3R)-2-cyclohexylmethyl-3-hydroxyhexanoate；methyl (2R,3R)-2-(cyclohexylmethyl)-3-hydroxyhexanoate
• CAS: 212610-23-6
• 化学式: C₁₄H₂₆O₃
• 分子量: 242.359
• InChiKey: GROYLPOUVWCNMO-CHWSQXEVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (2S,3R)-2-(cyclohexylmethyl)-3-hydroxyhexanoate 在 lithium hydroxide monohydrate 作用下， 以 THF-MeOH-H₂O 为溶剂， 以96%的产率得到(2R,3R)-2-cyclohexylmethyl-3-hydroxyhexanoic acid
  参考文献：
  名称：

  Formamide compounds as therapeutic agents

  摘要：

  具有一般结构式的化合物家族，其中W是一个反向羟肟酸基团，而R1、R2、R3、R4、R5和R6如规范中所述，或其药学上可接受的盐、溶剂化合物、生物水解酯、生物水解酰胺、亲和试剂或其前药。

  公开号：

  US06191150B1
• 作为产物：
  描述：

  methyl (2R,3R)-2-benzyl-3-hydroxyhexanoate 在 铑 氩 、 氢气 、 氮 作用下， 以 甲醇 为溶剂， 反应 8.0h， 以giving methyl (2R,3R)-2-cyclohexylmethyl-3-hydroxyhexanoate as an oil (3.44 g, 99% yield)的产率得到methyl (2S,3R)-2-(cyclohexylmethyl)-3-hydroxyhexanoate
  参考文献：
  名称：

  Formamide compounds as therapeutic agents

  摘要：

  一类化合物具有一般结构式，其中W为反式羟肟酸基团，R1、R2、R3、R4、R5和R6如说明书中所述，或其药学上可接受的盐、溶剂化物、生物可水解酯、生物可水解酰胺、亲和试剂或其前药。

  公开号：

  US06191150B1

文献信息

• Design of Selective and Soluble Inhibitors of Tumor Necrosis Factor-α Converting Enzyme (TACE)
  作者：Michael H. Rabinowitz、Robert C. Andrews、J. David Becherer、D. Mark Bickett、Dulce G. Bubacz、James G. Conway、David J. Cowan、Micheal Gaul、Kimberly Glennon、Millard H. Lambert、M. Anthony Leesnitzer、Darryl L. McDougald、Marcia L. Moss、David L. Musso、Michele C. Rizzolio

  DOI：10.1021/jm0102654

  日期：2001.11.1

  A program to improve upon the in vitro, in vivo, and physicochemical properties of N-hydroxyformamide TACE inhibitor GW 3333 (1) is described. Using the primary structure of pro-TNF-alpha, along with a homology model of the catalytic domain of TACE based on the X-ray diffraction coordinates of adamalysin, we synthesized N-hydroxyformamide TACE inhibitors containing a P2' arginine side chain. Introduction of nitro and sulfonyl electron-withdrawing groups covalently bound to the P2' guanidine moiety rendered the inhibitors electronically neutral at cellular pH and led to potent inhibition of TNF-alpha release from stimulated macrophages. Inhibitors containing these arginine mimetics were found to have increased solubility in simulated gastric fluid (SGF) relative to 1, allowing for the incorporation of lipophilic P1' side chains which had the effect of retaining potent TACE inhibition, but reducing potency against matrix metalloproteases (MMPs) thus increasing overall selectivity against MMP1, MMP3, and MMP9. Selected compounds showed good to excellent in vivo TNF inhibition when administered via subcutaneous injection. One inhibitor, 28a, with roughly 10x selectivity over MMPI and MMP3 and high solubility in SGF, was evaluated in the rat zymosan-induced pleuisy model of inflammation and found to inhibit zymosan-stimulated pleural TNF-alpha elevation by 30%.