(2R)-N-[4-(4-甲氧基苯基)-2-噻唑基]-1-[(4-甲基苯基)磺酰基]-2-哌啶甲酰胺 | 1401242-74-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (2R)-N-[4-(4-甲氧基苯基)-2-噻唑基]-1-[(4-甲基苯基)磺酰基]-2-哌啶甲酰胺
• 英文名称: ML277
• 英文别名: (2R)-N-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]-1-(4-methylphenyl)sulfonylpiperidine-2-carboxamide
• CAS: 1401242-74-7
• 化学式: C₂₃H₂₅N₃O₄S₂
• 分子量: 471.601
• InChiKey: OXQNLLVUVDAEHC-OAQYLSRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-Boc-D-哌啶-2-羧酸 在 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (2R)-N-[4-(4-甲氧基苯基)-2-噻唑基]-1-[(4-甲基苯基)磺酰基]-2-哌啶甲酰胺
  参考文献：
  名称：

  Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective Kv7.1 (KCNQ1) potassium channel activator

  摘要：

  A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC50 = 260 nM). ML277 was shown to be highly selective against other KCNQ channels (> 100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.07.060

文献信息

• METHODS OF TREATING NEUROPSYCHIATRIC DISORDERS
  申请人：University of Rochester

  公开号：EP3621434A2

  公开（公告）日：2020-03-18
• [EN] METHODS OF TREATING NEUROPSYCHIATRIC DISORDERS<br/>[FR] MÉTHODES DE TRAITEMENT DE TROUBLES NEUROPSYCHIATRIQUES
  申请人：UNIV ROCHESTER

  公开号：WO2018209022A2

  公开（公告）日：2018-11-15

  The present disclosure is directed to a method of treating a neuropsychiatric disorder. This method involves selecting a subject having the neuropsychiatric disorder and administering to the selected subject a preparation of glial progenitor cells at a dosage effective to treat the neuropsychiatric disorder in the subject. Another aspect of the disclosure is directed to a method of treating a neuropsychiatric disorder that includes selecting a subject having the neuropsychiatric disorder and administering, to the selected subject, a potassium (K+) channel activator at a dosage effective to restore normal brain interstitial glial K+ levels in the selected subject and treat the neuropsychiatric disorder is also disclosed.
• [EN] COMPOSITIONS AND METHODS FOR TARGETED PROTEIN STABILIZATION BY REDIRECTING ENDOGENOUS DEUBIQUITINASES<br/>[FR] COMPOSITIONS ET MÉTHODES DE STABILISATION DE PROTÉINES CIBLÉES PAR RÉORIENTATION DE DÉSUBIQUITINASES ENDOGÈNES
  申请人：UNIV COLUMBIA

  公开号：WO2021146390A1

  公开（公告）日：2021-07-22

  The present disclosure provides, inter alia, bivalent nanobody molecules and methods for treating or ameliorating the effects of a disease, such as long QT syndrome, or cystic fibrosis, in a subject, using the bivalent nanobody molecules disclosed herein. Also provided are methods of identifying and preparing nanobody binders that target proteins of interest.
• WO2022272133A2
  申请人：——

  公开号：WO2022272133A2

  公开（公告）日：2022-12-29
• Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective Kv7.1 (KCNQ1) potassium channel activator
  作者：Margrith E. Mattmann、Haibo Yu、Zhihong Lin、Kaiping Xu、Xiaofang Huang、Shunyou Long、Meng Wu、Owen B. McManus、Darren W. Engers、Uyen M. Le、Min Li、Craig W. Lindsley、Corey R. Hopkins

  DOI：10.1016/j.bmcl.2012.07.060

  日期：2012.9

  A high-throughput screen utilizing a depolarization-triggered thallium influx through KCNQ1 channels was developed and used to screen the MLSMR collection of over 300,000 compounds. An iterative medicinal chemistry approach was initiated and from this effort, ML277 was identified as a potent activator of KCNQ1 channels (EC50 = 260 nM). ML277 was shown to be highly selective against other KCNQ channels (> 100-fold selectivity versus KCNQ2 and KCNQ4) as well as against the distantly related hERG potassium channel. (C) 2012 Elsevier Ltd. All rights reserved.