N-{4-[(benzyloxy)amino]-4-oxobutyl}-4-methylbenzamide | 861819-79-6

• 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: N-{4-[(benzyloxy)amino]-4-oxobutyl}-4-methylbenzamide
• 英文别名: N-[4-(benzyloxyamino)-4-oxobutyl]-4-methylbenzamide
• CAS: 861819-79-6
• 化学式: C₁₉H₂₂N₂O₃
• 分子量: 326.395
• InChiKey: GHAHEVLDVRGTMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.75
• 重原子数：
  24.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  67.43
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  N-{4-[(benzyloxy)amino]-4-oxobutyl}-4-methylbenzamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以85%的产率得到N-Hydroxy-4-(N-(4-methylphenylcarbonyl)amino)butyramide
  参考文献：
  名称：

  新型金属蛋白酶抑制剂的设计与合成。

  摘要：

  合成了一系列的N-苯甲酰基4-氨基丁酸异羟肟酸酯类似物，并将其评估为基质金属蛋白酶抑制剂。合成工作的重点是使用容易获得的起始原料对4-氨基丁酸部分进行化学修饰。这样，使用可商购的起始原料例如4-氨基丁酸，（+）-和（-）-苹果酸以及D-和L-谷氨酸衍生物进行化学修饰。在测试的化合物中，衍生自L-谷氨酸的N- [4-（苯并呋喃-2-基）苯甲酰基] 4-氨基-4S-羟甲基丁酸异羟肟酸酯与MMP-2和MMP-9相比，对MMP-2和MMP-9的抑制作用更强。分别衍生自（-）-苹果酸的相应2S-羟基类似物或3S-羟基类似物。提出了构效关系研究。

  DOI：

  10.1016/j.bmc.2006.03.032
• 作为产物：
  描述：

  对甲基苯甲酰氯 在 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 N-{4-[(benzyloxy)amino]-4-oxobutyl}-4-methylbenzamide
  参考文献：
  名称：

  Novel matrix metalloproteinase inhibitors: Generation of lead compounds by the in silico fragment-based approach

  摘要：

  Generation of structurally new matrix metalloproteinase inhibitors was successfully carried out using an in silico technique. In order to identify the small fragment interacting with residues in the S1' pocket of MMP-1 through hydrogen bonds, we performed in silico screening using the LUDI program. As a result, acetyl-L-alanyl-(N-methyl)amide (AC-L-Ala-NHMe) was selected to link with another fragment, hydroxamic acid that interacted with catalytic zinc. By this approach, the L-glutamic acid derivative 2b was discovered to be a new type of matrix metalloproteinase inhibitor. Further transformation to reduce its peptidic nature and improve activity yielded nonpeptidic lead compounds as inhibitors of MMP-1, -2, -3, and -9. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.051

文献信息

• Discovery of a new chemical lead for a matrix metalloproteinase inhibitor
  作者：Masahiro Ikura、Shingo Nakatani、Shingo Yamamoto、Hiromu Habashita、Tsuneyuki Sugiura、Kanji Takahashi、Koji Ogawa、Hiroyuki Ohno、Hisao Nakai、Masaaki Toda

  DOI：10.1016/j.bmc.2006.01.059

  日期：2006.6

  A series of N-benzoyl gamma-aminobutyric hydroxamic acids were synthesized and evaluated as matrix metalloproteinase inhibitors. First, we focused on chemical modification of the N-benzoyl residue. Introduction of electron-rich para-substituents was effective to increase the inhibitory activity. Especially, some of the analogs with relatively more planar N-acyl residues, such as 10 and 11, demonstrated more potent activity. Second, chemical modification of the gamma-aminobutyric hydroxamic acid moiety was carried out to optimize the three-dimensional arrangement of the two pharmacophores (hydroxamic acid and N-acyl residues). Among the tested, the gamma-aminobutyric hydroxamic acid moiety was found to be the best spacer for connecting the above-mentioned two pharmacophores. Synthesis and structure-activity relationships are discussed. (c) 2006 Elsevier Ltd. All rights reserved.