N-[3-azido-2-(3,4-dimethylbenzyl)propyl]-2,2-dimethylpropanamide | 735331-57-4

• 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: N-[3-azido-2-(3,4-dimethylbenzyl)propyl]-2,2-dimethylpropanamide
• 英文别名: JYL-1581；N-[2-(azidomethyl)-3-(3,4-dimethylphenyl)propyl]-2,2-dimethylpropanamide
• CAS: 735331-57-4
• 化学式: C₁₇H₂₆N₄O
• 分子量: 302.42
• InChiKey: XZVZBOFUQBPCFV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  43.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[3-azido-2-(3,4-dimethylbenzyl)propyl]-2,2-dimethylpropanamide 在 Lindlar's catalyst 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-{3-(3,4-Dimethyl-phenyl)-2-[3-(4-methanesulfonylamino-benzyl)-thioureidomethyl]-propyl}-2,2-dimethyl-propionamide
  参考文献：
  名称：

  Analysis of structure–activity relationships with the N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea template for vanilloid receptor 1 antagonism

  摘要：

  In a continuing effort to elucidate the structure-activity relationships of the lead antagonist N-[2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl]-N'-[4-(methylsulfonylamino)benzyl]thiourea (1), the distances between the proposed four pharmacophores in 1 have been varied by insertion or deletion of one carbon to optimize their fit to the receptor. In addition, the acyloxy group of the C region was replaced with amide and N-hydroxy amide to identify the pharmacophoric importance of the ester group in the C2 region. The results indicated that the pharmacophoric arrangement of 1 was optimal for receptor binding affinity and antagonism, and the ester of the C2 region was significant for receptor binding. Among the derivatives, compound 19 showed distinct behavior with a 2-fold improvement in antagonism but a 13-fold reduction in binding affinity compared to 1. The partial separation of pharmacophoric requirements of these two assays has been noted before and compound 19 is thus selective for the calcium entry-linked receptor population. The conformational analysis of 1 generated three distinct conformers having different types of hydrophobic interactions, which will be utilized for exploring the active conformation of the VR1 ligand. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.04.040
• 作为产物：
  描述：

  2-(3,4-dimethylbenzyl)-3-hydroxypropyl azide 在 一水合肼 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 37.0h， 生成 N-[3-azido-2-(3,4-dimethylbenzyl)propyl]-2,2-dimethylpropanamide
  参考文献：
  名称：

  Analysis of structure–activity relationships with the N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea template for vanilloid receptor 1 antagonism

  摘要：

  In a continuing effort to elucidate the structure-activity relationships of the lead antagonist N-[2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl]-N'-[4-(methylsulfonylamino)benzyl]thiourea (1), the distances between the proposed four pharmacophores in 1 have been varied by insertion or deletion of one carbon to optimize their fit to the receptor. In addition, the acyloxy group of the C region was replaced with amide and N-hydroxy amide to identify the pharmacophoric importance of the ester group in the C2 region. The results indicated that the pharmacophoric arrangement of 1 was optimal for receptor binding affinity and antagonism, and the ester of the C2 region was significant for receptor binding. Among the derivatives, compound 19 showed distinct behavior with a 2-fold improvement in antagonism but a 13-fold reduction in binding affinity compared to 1. The partial separation of pharmacophoric requirements of these two assays has been noted before and compound 19 is thus selective for the calcium entry-linked receptor population. The conformational analysis of 1 generated three distinct conformers having different types of hydrophobic interactions, which will be utilized for exploring the active conformation of the VR1 ligand. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.04.040

文献信息

• [EN] PHARMACOLOGICAL TREATMENTS FOR SLEEP DISORDERS<br/>[FR] TRAITEMENTS PHARMACOLOGIQUES CONTRE DES TROUBLES DU SOMMEIL
  申请人：UNIV ILLINOIS

  公开号：WO2007047575A2

  公开（公告）日：2007-04-26

  [EN] This invention is directed to methods for preventing or ameliorating sleep-related breathing disorders. The method comprises administration to a patient in need thereof an effective dose of one or a combination of vanilloid receptor ligands. The vanilloid receptor ligand or combination of vanilloid receptor ligands can be administered in conjunction with one or more serotonin receptor agonists, one or more cannabimimetic agents, one or more serotonin reuptake inhibitors, one or more noradrenalin reuptake inhibitors, a combination of reuptake inhibitors, one or more inhibitors of vanilloid synthesis or vanilloid release, or any combination of the foregoing.
  [FR] L'invention concerne des méthodes pour prévenir ou améliorer des troubles de la respiration associés au sommeil. La méthode consiste à administrer à un patient une dose efficace d'un ligand ou d'une combinaison de ligands du récepteur vanilloïde. Le ligand ou la combinaison de ligands du récepteur vanilloïde peuvent être administrés en conjonction avec un ou plusieurs agonistes du récepteur de sérotonine, un ou plusieurs agents cannabimimétiques, un ou plusieurs inhibiteurs de recaptage de sérotonine, un ou plusieurs inhibiteurs de recaptage de noradrénaline, une combinaison d'inhibiteurs de recaptage, un ou plusieurs inhibiteurs de synthèse ou de libération de vanilloïde ou une combinaison quelconque de ces substances.
• Analysis of structure–activity relationships with the N-(3-acyloxy-2-benzylpropyl)-N′-[4-(methylsulfonylamino)benzyl]thiourea template for vanilloid receptor 1 antagonism
  作者：Jeewoo Lee、Su Yeon Kim、Jiyoun Lee、Myungsim Kang、Min-Jung Kil、Hyun-Kyung Choi、Mi-Kyung Jin、Yun Wang、Attila Toth、Larry V Pearce、Daniel J Lundberg、Richard Tran、Peter M Blumberg

  DOI：10.1016/j.bmc.2004.04.040

  日期：2004.7

  In a continuing effort to elucidate the structure-activity relationships of the lead antagonist N-[2-(3,4-dimethylbenzyl)-3-pivaloyloxypropyl]-N'-[4-(methylsulfonylamino)benzyl]thiourea (1), the distances between the proposed four pharmacophores in 1 have been varied by insertion or deletion of one carbon to optimize their fit to the receptor. In addition, the acyloxy group of the C region was replaced with amide and N-hydroxy amide to identify the pharmacophoric importance of the ester group in the C2 region. The results indicated that the pharmacophoric arrangement of 1 was optimal for receptor binding affinity and antagonism, and the ester of the C2 region was significant for receptor binding. Among the derivatives, compound 19 showed distinct behavior with a 2-fold improvement in antagonism but a 13-fold reduction in binding affinity compared to 1. The partial separation of pharmacophoric requirements of these two assays has been noted before and compound 19 is thus selective for the calcium entry-linked receptor population. The conformational analysis of 1 generated three distinct conformers having different types of hydrophobic interactions, which will be utilized for exploring the active conformation of the VR1 ligand. (C) 2004 Elsevier Ltd. All rights reserved.