N-hydroxy-5-[2-[N-[2-(isopropenylcarbonyloxy)ethyl]carbamoyl]ethylcarbonyloxy]-2(S)-methyl-4(S)-(4-phenoxybenzoyl)aminopentanamide | 588717-92-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-hydroxy-5-[2-[N-[2-(isopropenylcarbonyloxy)ethyl]carbamoyl]ethylcarbonyloxy]-2(S)-methyl-4(S)-(4-phenoxybenzoyl)aminopentanamide
• 英文别名: [(2S,4S)-5-(hydroxyamino)-4-methyl-5-oxo-2-[(4-phenoxybenzoyl)amino]pentyl] 4-[2-(2-methylprop-2-enoyloxy)ethylamino]-4-oxobutanoate
• CAS: 588717-92-4
• 化学式: C₂₉H₃₅N₃O₉
• 分子量: 569.612
• InChiKey: UNCMUYUQJLRMBR-UNMCSNQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  41
• 可旋转键数：
  18
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  169
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  ONO-M11-335 在 吡啶 、 1-羟基苯并三唑 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-hydroxy-5-[2-[N-[2-(isopropenylcarbonyloxy)ethyl]carbamoyl]ethylcarbonyloxy]-2(S)-methyl-4(S)-(4-phenoxybenzoyl)aminopentanamide
  参考文献：
  名称：

  Development of a Water-Soluble Matrix Metalloproteinase Inhibitor as an Intra-arterial Infusion Drug for Prevention of Restenosis after Angioplasty

  摘要：

  To prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA) and/or stenting of atherosclerotic stenosed arteries, we designed and developed two water-soluble matrix metalloproteinases (MMPs) inhibitors. The first inhibitor was monomeric in type and was chemically synthesized by succinylation of the synthetic MMP inhibitor, N-hydroxy-5-hydroxy-2(S)-methyl-4(S)-(4-phenoxybenzoyl)aminopentanamide (ONO-M11-335). The second inhibitor was polymeric and was a radical copolymer of the vinyl derivative of ONO-M11-335 and a water-soluble monomer, N,N-dimethylacrylamide (DMAAm). For the second inhibitor, NMR analyses and UV-vis spectra measurements showed that the content of the ONO-M11-335 unit in the copolymers (M-n; ca. 10 000 and 20 000 by GPC measurements) was about 8 per molecule. The MMP inhibitors were all highly soluble in water, even under neutral pH. The succinylated derivative markedly inhibited MMP-2, MMP-9, and MMP-12 in vitro, as did ONO-M11-335. In contrast the copolymers, which can maintain effective plasma levels for extended periods by prevention of hepatic uptake, showed a ca. 100-fold reduced inhibition activity. Such water-soluble MMP inhibitors, developed in this study, may potentially be useful as an intra-arterial infusion drug for vascular injury.

  DOI：

  10.1021/jm020356g

文献信息

• Development of a Water-Soluble Matrix Metalloproteinase Inhibitor as an Intra-arterial Infusion Drug for Prevention of Restenosis after Angioplasty
  作者：Takeshi Masuda、Yasuhide Nakayama

  DOI：10.1021/jm020356g

  日期：2003.7.1

  To prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA) and/or stenting of atherosclerotic stenosed arteries, we designed and developed two water-soluble matrix metalloproteinases (MMPs) inhibitors. The first inhibitor was monomeric in type and was chemically synthesized by succinylation of the synthetic MMP inhibitor, N-hydroxy-5-hydroxy-2(S)-methyl-4(S)-(4-phenoxybenzoyl)aminopentanamide (ONO-M11-335). The second inhibitor was polymeric and was a radical copolymer of the vinyl derivative of ONO-M11-335 and a water-soluble monomer, N,N-dimethylacrylamide (DMAAm). For the second inhibitor, NMR analyses and UV-vis spectra measurements showed that the content of the ONO-M11-335 unit in the copolymers (M-n; ca. 10 000 and 20 000 by GPC measurements) was about 8 per molecule. The MMP inhibitors were all highly soluble in water, even under neutral pH. The succinylated derivative markedly inhibited MMP-2, MMP-9, and MMP-12 in vitro, as did ONO-M11-335. In contrast the copolymers, which can maintain effective plasma levels for extended periods by prevention of hepatic uptake, showed a ca. 100-fold reduced inhibition activity. Such water-soluble MMP inhibitors, developed in this study, may potentially be useful as an intra-arterial infusion drug for vascular injury.