4-(S)-benzyl-3-{5-(3-methyl-4-phenylphenyl)pentanoyl}oxazolidin-2-one | 230962-34-2

• 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: 4-(S)-benzyl-3-{5-(3-methyl-4-phenylphenyl)pentanoyl}oxazolidin-2-one
• 英文别名: (4S)-4-benzyl-3-[5-(3-methyl-4-phenylphenyl)pentanoyl]-1,3-oxazolidin-2-one
• CAS: 230962-34-2
• 化学式: C₂₈H₂₉NO₃
• 分子量: 427.543
• InChiKey: PJDAHXMWLZIUJT-VWLOTQADSA-N

物化性质

• 沸点：
  612.4±44.0 °C(Predicted)
• 密度：
  1.159±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(S)-benzyl-3-{5-(3-methyl-4-phenylphenyl)pentanoyl}oxazolidin-2-one 在 lithium hydroxide 、 双氧水 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 25.33h， 生成 tert-butyl (3R)-3-({[(1S)-2,2-dimethyl-1-({[(1S)-2-methoxy-1-phenylethyl]amino}carbonyl)propyl]amino}carbonyl)-6-(3-methyl-4-phenylphenyl)hexanoate
  参考文献：
  名称：

  Matrix metalloprotease inhibitors

  摘要：

  化合物的化学式（I）：或其药用可接受的盐，或两者的溶剂化合物，其中取代基具有此处描述的值，可用作基质金属蛋白酶（MMP）抑制剂。

  公开号：

  US06350907B1
• 作为产物：
  描述：

  5-溴-2-碘甲苯 在 palladium diacetate 、 三苯基膦 三乙基硅烷 、 草酰氯 、 碘 、 sodium carbonate 、 magnesium 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 水 、 丙酮 、 三氟乙酸 为溶剂， 反应 28.75h， 生成 4-(S)-benzyl-3-{5-(3-methyl-4-phenylphenyl)pentanoyl}oxazolidin-2-one
  参考文献：
  名称：

  Matrix metalloprotease inhibitors

  摘要：

  化合物的化学式（I）：或其药用可接受的盐，或两者的溶剂化合物，其中取代基具有此处描述的值，可用作基质金属蛋白酶（MMP）抑制剂。

  公开号：

  US06350907B1

文献信息

• Matrix metalloprotease inhibitors
  申请人：Pfizer Inc

  公开号：US06350907B1

  公开（公告）日：2002-02-26

  Compounds of formula (I): or pharmaceutically acceptable salts thereof, or solvates of either entity, wherein the substituents have the values described herein, are useful as matrix metalloprotease (MMP) inhibitors

  化合物的化学式（I）：或其药用可接受的盐，或两者的溶剂化合物，其中取代基具有此处描述的值，可用作基质金属蛋白酶（MMP）抑制剂。
• MATRIX METALLOPROTEASE INHIBITORS
  申请人：Pfizer Limited

  公开号：EP1047665B1

  公开（公告）日：2003-10-22
• US6350907B1
  申请人：——

  公开号：US6350907B1

  公开（公告）日：2002-02-26
• A Potent, Selective Inhibitor of Matrix Metalloproteinase-3 for the Topical Treatment of Chronic Dermal Ulcers
  作者：M. Jonathan Fray、Roger P. Dickinson、John P. Huggins、Nicholas L. Occleston

  DOI：10.1021/jm0308038

  日期：2003.7.1

  The pathology of chronic dermal ulcers is characterized by excessive proteolytic activity which degrades extracellular matrix (required for cell migration) and growth factors and their receptors. The overexpression of MMP-3 (stromelysin-1) and MMP-13 (collagenase-3) is associated with nonhealing wounds, whereas active MMPs-1, -2, -9, and -14 are required for normal wound healing to occur. We describe the synthesis and enzyme inhibition profile of (3R)-3-([(1S)-2,2-dimethyl-1-([(1S)-2-methoxy-1-phenylethyl]amino}carbonyl)propyl]amino}-carbonyl)-6-(3-methyl-4-phenylphenyl)hexanoic acid (UK-370,106, 7), which is a potent inhibitor of MMP-3 (IC50 = 23 nM) with > 1200-fold weaker potency vs MMP-1, -2, -9, and -14. MMP-13, which may also contribute to the pathology of chronic wounds, was inhibited about 100-fold less potently by compound 7. Compound 7 potently inhibited cleavage of [H-3]-fibronectin by MMP-3 (IC50 = 320 nM) but not cleavage of [H-3]-gelatin by either MMP-2 or -9 (up to 100 muM). Compound 7 had little effect, at MMP-3 selective concentrations, on keratinocyte migration over a collagen matrix in vitro, which is a model of the re-epithelialization process. Following iv (rat) or topical administration to dermal wounds (rabbit), compound 7 was cleared rapidly (t(1/2) = 23 min) from plasma, but slowly (t(1/2) similar to 3 days) from dermal tissue. In a model of chronic dermal ulcers, topical administration of compound 7 for 6 days substantially inhibited MMP-3 ex vivo. These data suggest compound 7 is sufficiently potent to inhibit MMP-3-mediated matrix degradation while leaving unaffected cellular migration mediated by MMPs 1, 2, and 9. These properties make compound 7 a suitable candidate for progression to clinical trials in human chronic dermal wounds, such as venous ulcers.