(3aR,4R,7R,7aR)-5-(4'-but-2'-ynyloxybenzenesulfonyl)-7-hydroxy-2,2-dimethylhexahydro[1,3]dioxolo[4,5-c]-4-carboxylic acid hydroxy amide | 683210-73-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (3aR,4R,7R,7aR)-5-(4'-but-2'-ynyloxybenzenesulfonyl)-7-hydroxy-2,2-dimethylhexahydro[1,3]dioxolo[4,5-c]-4-carboxylic acid hydroxy amide
• 英文别名: (3aR,4R,7R,7aR)-5-(4-but-2-ynoxyphenyl)sulfonyl-N,7-dihydroxy-2,2-dimethyl-4,6,7,7a-tetrahydro-3aH-[1,3]dioxolo[4,5-c]pyridine-4-carboxamide
• CAS: 683210-73-3
• 化学式: C₁₉H₂₄N₂O₈S
• 分子量: 440.474
• InChiKey: RFJSQAZBRWXDMS-QBPKDAKJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  143
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (3aR,4R,7R,7aR)-5-(4'-but-2'-ynyloxybenzenesulfonyl)-7-hydroxy-2,2-dimethylhexahydro[1,3]dioxolo[4,5-c]-4-carboxylic acid hydroxy amide 在 Muromac(R) 作用下， 以 甲醇 为溶剂， 生成 (2R,3R,4R,5R)-1-(4-but-2-ynoxyphenyl)sulfonyl-N,3,4,5-tetrahydroxypiperidine-2-carboxamide
  参考文献：
  名称：

  选择性的基于氮杂糖的TACE抑制剂的合成和生物活性。

  摘要：

  描述了一系列具有2R，3R，4R，5R构型的基于氮杂糖的异羟肟酸衍生物。具有4，5-O-丙酮化物基团的化合物4c对TACE显示出优异的体外效力，对MMP-1具有高选择性，对MMP-3和MMP-9具有中等选择性。

  DOI：

  10.1016/j.bmcl.2003.12.091
• 作为产物：
  描述：

  4-(苄氧基)苯-1-磺酰氯 在 palladium on activated charcoal 4-二甲氨基吡啶 、 sodium cyanide 、 cerium(III) chloride 、 氢气 、 羟胺 、 草酸 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， -40.0~90.0 ℃ 、303.98 kPa 条件下， 反应 5.84h， 生成 (3aR,4R,7R,7aR)-5-(4'-but-2'-ynyloxybenzenesulfonyl)-7-hydroxy-2,2-dimethylhexahydro[1,3]dioxolo[4,5-c]-4-carboxylic acid hydroxy amide
  参考文献：
  名称：

  Azasugar-Based MMP/ADAM Inhibitors as Antipsoriatic Agents

  摘要：

  As a part of synthetic studies on MMP (matrix metalloproteinase)/ADAM (a disintegrin and metalloproteinase) inhibitors, we have preliminarily communicated that azasugar-based compound la exhibited a potential inhibitory activity on some metalloprotease-catalyzed proteolytic reactions. To find promising candidates for the topical treatment of psoriasis, we investigated stability in aqueous solution of compound la and its derivative 1b and then optimized the P1' substuent (2-5). In the present study, we synthesized novel derivatives of compound-la and evaluated their inhibitory activity toward MMP-1, -3, and -9, TACE, and HB-EGF shedding, from a viewpoint of versatility of azasugars as a functional scaffold. As a result, it was found that compound 1b demonstrated desirable inhibitory activity as an antipsoriatic agent, and some of the derivatives showed selective inhibitory activity. In addition, it was found that compound 1b exhibited a significant therapeutic effect on a mouse TPA-induced epidermal hyperplasia. model. Therefore, compound 1b could become a promising candidate as a practical antipsoriatic agent.

  DOI：

  10.1021/jm0304313

文献信息

• Synthesis and biological activity of selective azasugar-based TACE inhibitors
  作者：Takahiro Tsukida、Hideki Moriyama、Yoshimasa Inoue、Hirosato Kondo、Kohichiro Yoshino、Shin-Ichiro Nishimura

  DOI：10.1016/j.bmcl.2003.12.091

  日期：2004.3

  A series of azasugar-based hydroxamic acid derivatives bearing 2R,3R,4R,5R-configuration is described. Compound 4c with 4,5-O-acetonide group showed excellent in vitro potency against TACE, with high selectivity over MMP-1 and moderate selectivity over MMP-3 and MMP-9.

  描述了一系列具有2R，3R，4R，5R构型的基于氮杂糖的异羟肟酸衍生物。具有4，5-O-丙酮化物基团的化合物4c对TACE显示出优异的体外效力，对MMP-1具有高选择性，对MMP-3和MMP-9具有中等选择性。
• Azasugar-Based MMP/ADAM Inhibitors as Antipsoriatic Agents
  作者：Hideki Moriyama、Takahiro Tsukida、Yoshimasa Inoue、Kohichi Yokota、Kohichiro Yoshino、Hirosato Kondo、Nobuaki Miura、Shin-Ichiro Nishimura

  DOI：10.1021/jm0304313

  日期：2004.4.1

  As a part of synthetic studies on MMP (matrix metalloproteinase)/ADAM (a disintegrin and metalloproteinase) inhibitors, we have preliminarily communicated that azasugar-based compound la exhibited a potential inhibitory activity on some metalloprotease-catalyzed proteolytic reactions. To find promising candidates for the topical treatment of psoriasis, we investigated stability in aqueous solution of compound la and its derivative 1b and then optimized the P1' substuent (2-5). In the present study, we synthesized novel derivatives of compound-la and evaluated their inhibitory activity toward MMP-1, -3, and -9, TACE, and HB-EGF shedding, from a viewpoint of versatility of azasugars as a functional scaffold. As a result, it was found that compound 1b demonstrated desirable inhibitory activity as an antipsoriatic agent, and some of the derivatives showed selective inhibitory activity. In addition, it was found that compound 1b exhibited a significant therapeutic effect on a mouse TPA-induced epidermal hyperplasia. model. Therefore, compound 1b could become a promising candidate as a practical antipsoriatic agent.