4-[[4-[7-[(3-Methylphenyl)methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxypiperidin-1-yl]methyl]-1,3-thiazole | 1365626-78-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并嘧啶类
• 英文名称: 4-[[4-[7-[(3-Methylphenyl)methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxypiperidin-1-yl]methyl]-1,3-thiazole
• CAS: 1365626-78-3
• 化学式: C₂₃H₂₅N₅OS
• 分子量: 419.55
• InChiKey: BJWJWHANJDRZGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  84.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氯吡咯并嘧啶 在 sodium hydride 、 potassium carbonate 作用下， 以 二甲基亚砜 、 乙腈 为溶剂， 反应 16.0h， 生成 4-[[4-[7-[(3-Methylphenyl)methyl]pyrrolo[2,3-d]pyrimidin-4-yl]oxypiperidin-1-yl]methyl]-1,3-thiazole
  参考文献：
  名称：

  Discovery and hit-to-lead optimization of pyrrolopyrimidines as potent, state-dependent Nav1.7 antagonists

  摘要：

  Herein we describe the discovery, optimization, and structure-activity relationships of novel potent pyrrolopyrimidine Na(v)1.7 antagonists. Hit-to-lead SAR studies of the pyrrolopyrimidine core, head, and tail groups of the molecule led to the identification of pyrrolopyrimidine 48 as exceptionally potent Na(v)1.7 blocker with good selectivity over hERG and improved microsomal stability relative to our hit molecule and pyrazolopyrimidine 8 as a promising starting point for future optimization efforts. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2012.01.015

文献信息

• SYSTEMS AND METHODS OF SELECTING COMPOUNDS WITH REDUCED RISK OF CARDIOTOXICITY USING CARDIAC SODIUM ION CHANNEL MODELS
  申请人：THE GOVERNORS OF THE UNIVERSITY OF ALBERTA

  公开号：US20180068053A1

  公开（公告）日：2018-03-08

  Provided herein are systems and methods for selecting compounds that have reduced risk of cardiotoxicity or which are not likely to be cardiotoxic. As an example, a system and method can include a computational dynamic model combined with a high throughput screening in silico that mimics an important ion channels associated with cardiotoxicity, namely the human cardiac sodium ion (hNa v 1.5) channel). In certain embodiments, steered molecular dynamics simulations are used to identify key residues of the channel's permeation pathways that are then used in the high throughput screening. Also provided herein are systems and methods for redesigning compounds that are predicted to be cardiotoxic based on the model and the high throughput screening.