methyl (2R)-(4'-iodophenylsulfonyl)amino-(3R)-methoxy-5-phenylpent-4-ynoate | 332865-74-4

• 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: methyl (2R)-(4'-iodophenylsulfonyl)amino-(3R)-methoxy-5-phenylpent-4-ynoate
• 英文别名: methyl (2R,3R)-2-[(4-iodophenyl)sulfonylamino]-3-methoxy-5-phenylpent-4-ynoate
• CAS: 332865-74-4
• 化学式: C₁₉H₁₈INO₅S
• 分子量: 499.326
• InChiKey: UDGTZHKPPCIXEX-QZTJIDSGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  90.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (2R)-(4'-iodophenylsulfonyl)amino-(3R)-methoxy-5-phenylpent-4-ynoate 在 lithium hydroxide 、 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 苯 为溶剂， 反应 18.0h， 生成 (2R)-{[4'-methoxy(1,1'-biphenyl)-4-yl]sulfonyl}amino-(3R)-methoxy-5-phenylpent-4-ynoic acid
  参考文献：
  名称：

  Development of New Carboxylic Acid-Based MMP Inhibitors Derived from Functionalized Propargylglycines

  摘要：

  A series of carboxylic acids were prepared from a propargylglycine scaffold and tested for efficacy as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for four enzymes within the MMP family. The inhibitors were typically potent against collagenase-3 (MMP-13) and gelatinase A (MMP-2), while they spared collagenase-1 (MMP-1) and only moderately inhibited stromelysin (MMP-3). Compound 40 represents a typical inhibition profile of a compound with reasonable potency. Introduction of polar groups was required in order to generate inhibitors with acceptable water solubility, and this often resulted in a loss of potency as in compound 63. High serum protein binding proved to be a difficult hurdle with many compounds such as 48 showing > 99% binding. Some compounds such as 64 displayed similar to 90% binding, but no reliable method was discovered for designing molecules with low protein binding. Finally, selected data regarding the pharmacokinetic behavior of these compounds is presented.

  DOI：

  10.1021/jm000477l
• 作为产物：
  描述：

  tert-butyl (1S,2R)-N-[2-methoxy-1-(hydroxymethyl)-4-phenylbut-3-ynyl]carbamate 在 chromium(VI) oxide 、 盐酸 、 硫酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 乙醚 、 水 、 丙酮 为溶剂， 反应 18.0h， 生成 methyl (2R)-(4'-iodophenylsulfonyl)amino-(3R)-methoxy-5-phenylpent-4-ynoate
  参考文献：
  名称：

  Development of New Carboxylic Acid-Based MMP Inhibitors Derived from Functionalized Propargylglycines

  摘要：

  A series of carboxylic acids were prepared from a propargylglycine scaffold and tested for efficacy as matrix metalloproteinase (MMP) inhibitors. Detailed SAR for the series is reported for four enzymes within the MMP family. The inhibitors were typically potent against collagenase-3 (MMP-13) and gelatinase A (MMP-2), while they spared collagenase-1 (MMP-1) and only moderately inhibited stromelysin (MMP-3). Compound 40 represents a typical inhibition profile of a compound with reasonable potency. Introduction of polar groups was required in order to generate inhibitors with acceptable water solubility, and this often resulted in a loss of potency as in compound 63. High serum protein binding proved to be a difficult hurdle with many compounds such as 48 showing > 99% binding. Some compounds such as 64 displayed similar to 90% binding, but no reliable method was discovered for designing molecules with low protein binding. Finally, selected data regarding the pharmacokinetic behavior of these compounds is presented.

  DOI：

  10.1021/jm000477l