(3,4-dichlorobenzyl)-bis(2-chloroethyl)amine hydrochloride | 60855-83-6

• 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: (3,4-dichlorobenzyl)-bis(2-chloroethyl)amine hydrochloride
• 英文别名: 2-chloro-N-(2-chloroethyl)-N-[(3,4-dichlorophenyl)methyl]ethanamine；2-chloro-N-(2-chloroethyl)-N-[(3,4-dichlorophenyl)methyl]ethanamine;hydrochloride
• CAS: 60855-83-6
• 化学式: C₁₁H₁₃Cl₄N*ClH
• 分子量: 337.504
• InChiKey: JLLCUHPDAUXTTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.69
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  3.2
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (3,4-dichlorobenzyl)-bis(2-chloroethyl)amine hydrochloride 在 sodium hydroxide 、 18-冠醚-6 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 丙酮 为溶剂， 反应 88.0h， 生成 1-(3,4-dichloro-benzyl)-4-(4-methoxy-benzenesulfonyl)-piperidine-4-carboxylic acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of N-Substituted 4-Arylsulfonylpiperidine-4-hydroxamic Acids as Novel, Orally Active Matrix Metalloproteinase Inhibitors for the Treatment of Osteoarthritis

  摘要：

  The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue degradation. In our preceding paper, we have reported on a series of novel and orally active N-hydroxy-alpha-phenylsulfonylacetamide derivatives. However, these compounds had two drawbacks (moderate selectivity and chirality issues). To circumvent these two problems, a series of novel and orally active N-substituted 4-benzenesulfonylpiperidine-4-carboxylic acid hydroxyamide derivatives have been synthesized. The present paper deals with the synthesis and SAR of these compounds. Among the several compounds synthesized, derivative 55 turned out to be a potent, selective, and an orally active MMP inhibitor in the clinically relevant advanced rabbit osteoarthritis model. Detailed pharmacokinetics and metabolism data are described.

  DOI：

  10.1021/jm0205550
• 作为产物：
  描述：

  2-[(2-hydroxyethyl)(3,4-dichlorobenzyl)amino]ethanol hydrochloride 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以99%的产率得到(3,4-dichlorobenzyl)-bis(2-chloroethyl)amine hydrochloride
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship of N-Substituted 4-Arylsulfonylpiperidine-4-hydroxamic Acids as Novel, Orally Active Matrix Metalloproteinase Inhibitors for the Treatment of Osteoarthritis

  摘要：

  The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue degradation. In our preceding paper, we have reported on a series of novel and orally active N-hydroxy-alpha-phenylsulfonylacetamide derivatives. However, these compounds had two drawbacks (moderate selectivity and chirality issues). To circumvent these two problems, a series of novel and orally active N-substituted 4-benzenesulfonylpiperidine-4-carboxylic acid hydroxyamide derivatives have been synthesized. The present paper deals with the synthesis and SAR of these compounds. Among the several compounds synthesized, derivative 55 turned out to be a potent, selective, and an orally active MMP inhibitor in the clinically relevant advanced rabbit osteoarthritis model. Detailed pharmacokinetics and metabolism data are described.

  DOI：

  10.1021/jm0205550

文献信息

• Synthesis and Structure−Activity Relationship of N-Substituted 4-Arylsulfonylpiperidine-4-hydroxamic Acids as Novel, Orally Active Matrix Metalloproteinase Inhibitors for the Treatment of Osteoarthritis
  作者：Venkatesan Aranapakam、Jamie M. Davis、George T. Grosu、Baker、John Ellingboe、Arie Zask、Jeremy I. Levin、Vincent P. Sandanayaka、Mila Du、Jerauld S. Skotnicki、John F. DiJoseph、Amy Sung、Michele A. Sharr、Loran M. Killar、Thomas Walter、Guixian Jin、Rebecca Cowling、Jeff Tillett、Weiguang Zhao、Joseph McDevitt、Zhang Bao Xu

  DOI：10.1021/jm0205550

  日期：2003.6.1

  The matrix metalloproteinases (MMPs) are a family of zinc-containing endopeptidases that play a key role in both physiological and pathological tissue degradation. In our preceding paper, we have reported on a series of novel and orally active N-hydroxy-alpha-phenylsulfonylacetamide derivatives. However, these compounds had two drawbacks (moderate selectivity and chirality issues). To circumvent these two problems, a series of novel and orally active N-substituted 4-benzenesulfonylpiperidine-4-carboxylic acid hydroxyamide derivatives have been synthesized. The present paper deals with the synthesis and SAR of these compounds. Among the several compounds synthesized, derivative 55 turned out to be a potent, selective, and an orally active MMP inhibitor in the clinically relevant advanced rabbit osteoarthritis model. Detailed pharmacokinetics and metabolism data are described.