2-chloro-N-(2-chloroethyl)-N-(4-methoxybenzyl)ethan-1-amine hydrochloride | 91562-00-4

• 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: 2-chloro-N-(2-chloroethyl)-N-(4-methoxybenzyl)ethan-1-amine hydrochloride
• 英文别名: 4-methoxybenzyl-bis(2-chloroethyl)amine hydrochloride；bis-(2-chloro-ethyl)-(4-methoxy-benzyl)-amine; hydrochloride；Bis-(2-chlor-aethyl)-(4-methoxy-benzyl)-amin; Hydrochlorid；2-chloro-N-(2-chloroethyl)-N-[(4-methoxyphenyl)methyl]ethanamine;hydrochloride
• CAS: 91562-00-4
• 化学式: C₁₂H₁₇Cl₂NO*ClH
• 分子量: 298.64
• InChiKey: IMAWAQZFZIMQBL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  12.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(2-chloroethyl)-N-(4-methoxybenzyl)ethan-1-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 4-(4-n-butoxy-benzenesulfonyl)-1-(4-methoxy-benzyl)-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)(4-methoxybenzyl)amino]ethanol hydrochloride 在 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以75%的产率得到2-chloro-N-(2-chloroethyl)-N-(4-methoxybenzyl)ethan-1-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

• Identification of spirooxindole and dibenzoxazepine motifs as potent mineralocorticoid receptor antagonists
  作者：Stephen D. Lotesta、Andrew P. Marcus、Yajun Zheng、Katerina Leftheris、Paul B. Noto、Shi Meng、Geeta Kandpal、Guozhou Chen、Jing Zhou、Brian McKeever、Yuri Bukhtiyarov、Yi Zhao、Deepak S. Lala、Suresh B. Singh、Gerard M. McGeehan

  DOI：10.1016/j.bmc.2016.02.014

  日期：2016.3

  Mineralocorticoid receptor (MR) antagonists continue to be a prevalent area of research in the pharmaceutical industry. Herein we report the discovery of various spirooxindole and dibenzoxazepine constructs as potent MR antagonists. SAR analysis of our spirooxindole hit led to highly potent compounds containing polar solubilizing groups, which interact with the helix-11 region of the MR ligand binding

  盐皮质激素受体（MR）拮抗剂继续是制药行业研究的主要领域。在本文中，我们报道了作为有效的MR拮抗剂的各种螺氧杂吲哚和二苯并x庚因构建物的发现。SAR分析我们的螺氧杂吲哚导致了含有极性增溶基团的高效化合物，这些基团与MR配体结合域（LBD）的11螺旋区域相互作用。为了替代已知的与MR LBD的疏水区相互作用的二苯并庚烷体系，还制备了各种二苯并x庚因部分。另外，从高效化合物获得了X射线晶体结构，该化合物显示出针对MR的部分激动剂和拮抗剂作用模式。
• 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.