(2R,3R)-2-(2-methyl-1-propyl)-3-hydroxyhexanoic acid | 212609-88-6

• 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: (2R,3R)-2-(2-methyl-1-propyl)-3-hydroxyhexanoic acid
• 英文别名: (2R,3R)-3-hydroxy-2-(2-methylpropyl)hexanoic acid
• CAS: 212609-88-6
• 化学式: C₁₀H₂₀O₃
• 分子量: 188.267
• InChiKey: JKFSMVHGMOREKI-RKDXNWHRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,3R)-2-(2-methyl-1-propyl)-3-hydroxyhexanoic acid 在 吡啶 、 sodium hydroxide 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 、 丙酮 为溶剂， 反应 38.0h， 生成 (2R,3R)-3-[formyl(tetrahydro-2H-pyran-2-yloxy)amino]-2-isobutylhexanoic acid
  参考文献：
  名称：

  Design of Selective and Soluble Inhibitors of Tumor Necrosis Factor-α Converting Enzyme (TACE)

  摘要：

  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%.

  DOI：

  10.1021/jm0102654
• 作为产物：
  描述：

  (R)-methyl 3-hydroxyhexanoate 在 palladium on activated charcoal N,N-二甲基丙烯基脲 、 lithium hydroxide 、 氢气 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 24.0h， 生成 (2R,3R)-2-(2-methyl-1-propyl)-3-hydroxyhexanoic acid
  参考文献：
  名称：

  Design of Selective and Soluble Inhibitors of Tumor Necrosis Factor-α Converting Enzyme (TACE)

  摘要：

  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%.

  DOI：

  10.1021/jm0102654

文献信息

• [EN] FORMAMIDE COMPOUNDS AS THERAPEUTIC AGENTS<br/>[FR] AGENTS THERAPEUTIQUES A BASE DE COMPOSES DE FORMAMIDES
  申请人：GLAXO GROUP LTD

  公开号：WO2000012466A1

  公开（公告）日：2000-03-09

  A family of compounds having general structural formula (I), where W is a reverse hydroxamic acid group, and R1, R2, R3, R4, R5 and R6 are as described in the specification, or a pharmaceutically acceptable salt, solvate, biohydrolyzable ester, biohydrolyzable amide, affinity reagent, or prodrug thereof. Also described are methods for their preparation, pharmaceutical compositions including such compounds and their use in medicine.

  一类化合物的一般结构式（I），其中W为反向羟肟酸基团，R1，R2，R3，R4，R5和R6如规范所述，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。还描述了它们的制备方法，包括这些化合物的制药组合物以及它们在医学中的使用。
• Formamide compounds as therapeutic agents
  申请人：Glaxo Wellcome Inc.

  公开号：US06191150B1

  公开（公告）日：2001-02-20

  A family of compounds having the general structural formula where W is a reverse hydroxamic acid group, and R1, R2, R3, R4, R5 and R6 are as described in the specification, or a pharmaceutically acceptable salt, solvate, biohydrolyzable ester, biohydrolyzable amide, affinity reagent, or prodrug thereof.

  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。
• Composition for low-specific gravity urethane-base plastic lens
  申请人：MITSUI CHEMICALS, INC.

  公开号：EP0676428B1

  公开（公告）日：1999-02-03
• Composition for optical materials and use thereof
  申请人：MITSUI CHEMICALS, INC.

  公开号：EP0713105B1

  公开（公告）日：2002-03-13
• US5756766A
  申请人：——

  公开号：US5756766A

  公开（公告）日：1998-05-26