N²-[5-chloro-2-(4-chlorophenoxy)phenyl]-N²-{2-[methyl(piperidin-4-yl)amino]-2-oxoethyl}-N¹-(2-pyrrolidin-1-ylethyl)glycinamide

• 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: N²-[5-chloro-2-(4-chlorophenoxy)phenyl]-N²-{2-[methyl(piperidin-4-yl)amino]-2-oxoethyl}-N¹-(2-pyrrolidin-1-ylethyl)glycinamide
• 英文别名: 2-[5-chloro-2-(4-chlorophenoxy)-N-[2-[methyl(piperidin-4-yl)amino]-2-oxoethyl]anilino]-N-(2-pyrrolidin-1-ylethyl)acetamide
• 化学式: C₂₈H₃₇Cl₂N₅O₃
• 分子量: 562.539
• InChiKey: MFOWLJWVPYWSIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  38
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  77.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N²-[5-chloro-2-(4-chlorophenoxy)phenyl]-N²-{2-[methyl(piperidin-4-yl)amino]-2-oxoethyl}-N¹-(2-pyrrolidin-1-ylethyl)glycinamide 、 氯甲酸甲酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以94%的产率得到N²-[5-chloro-2-(4-chlorophenoxy)phenyl]-N²-{2-{[1-(methoxycarbonyl)piperidin-4-yl](methyl)amino}-2-oxoethyl}-N¹-(2-pyrrolidin-1-ylethyl)glycinamide
  参考文献：
  名称：

  Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs

  摘要：

  Optimization of a new series of S-adenosyl-L-homocysteine hydrolase (AdoHcyase) inhibitors based on non-adenosine analogs led to very potent compounds 14n, 18a, and 18b with IC50 values of 13 +/- 3, 5.0 +/- 2.0, and 8.5 +/- 3.1 nM, respectively. An X-ray crystal structure of AdoHcyase with NAD(+) and 18a showed a novel open form co-crystal structure. 18a in the co-crystals formed intramolecular eight membered ring hydrogen bond formations. A single crystal X-ray structure of 14n also showed an intramolecular eight-membered ring hydrogen bond interaction. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.018
• 作为产物：
  描述：

  2,5-二氯硝基苯 在 iron(III) chloride 、 水 、 sodium hydride 、 甲烷 、 1-羟基苯并三唑 、 一水合肼 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 N²-[5-chloro-2-(4-chlorophenoxy)phenyl]-N²-{2-[methyl(piperidin-4-yl)amino]-2-oxoethyl}-N¹-(2-pyrrolidin-1-ylethyl)glycinamide
  参考文献：
  名称：

  Discovery of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs

  摘要：

  High throughput screening using Automated Ligand Identification System (ALIS) resulted in the discovery of a new series of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs. The optimization campaign led to very potent and competitive compound 39 with a Ki value of 1.5 nM. Compound 39 could be a promising lead compound for research to reduce elevated homocysteine levels.

  DOI：

  10.1016/j.bmcl.2014.06.008

文献信息

• Discovery of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs
  作者：Akira Nakao、Hiroko Suzuki、Hiroaki Ueno、Hiroshi Iwasaki、Tomofumi Setsuta

  DOI：10.1016/j.bmcl.2014.06.008

  日期：2014.9

  High throughput screening using Automated Ligand Identification System (ALIS) resulted in the discovery of a new series of S-adenosyl-L-homocysteine hydrolase inhibitors based on non-adenosine analogs. The optimization campaign led to very potent and competitive compound 39 with a Ki value of 1.5 nM. Compound 39 could be a promising lead compound for research to reduce elevated homocysteine levels.
• Discovery and structural analyses of S-adenosyl-l-homocysteine hydrolase inhibitors based on non-adenosine analogs
  作者：Akira Nakao、Hiroko Suzuki、Hiroaki Ueno、Hiroshi Iwasaki、Tomofumi Setsuta、Akiko Kashima、Shinji Sunada

  DOI：10.1016/j.bmc.2015.05.018

  日期：2015.8

  Optimization of a new series of S-adenosyl-L-homocysteine hydrolase (AdoHcyase) inhibitors based on non-adenosine analogs led to very potent compounds 14n, 18a, and 18b with IC50 values of 13 +/- 3, 5.0 +/- 2.0, and 8.5 +/- 3.1 nM, respectively. An X-ray crystal structure of AdoHcyase with NAD(+) and 18a showed a novel open form co-crystal structure. 18a in the co-crystals formed intramolecular eight membered ring hydrogen bond formations. A single crystal X-ray structure of 14n also showed an intramolecular eight-membered ring hydrogen bond interaction. (C) 2015 Elsevier Ltd. All rights reserved.