ML253 | 1417616-42-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并吡啶类
• 英文名称: ML253
• 英文别名: 3-amino-5-chloro-4,6-dimethyl-N-(pyridin-4-ylmethyl)thieno[2,3-b]pyridine-2-carboxamide
• CAS: 1417616-42-2
• 化学式: C₁₆H₁₅ClN₄OS
• 分子量: 346.84
• InChiKey: XNCQMFVABACABG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-甲氨基吡啶 、 sodium 3-amino-5-chloro-4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate 在 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.17h， 以51%的产率得到ML253
  参考文献：
  名称：

  Discovery of a selective M4 positive allosteric modulator based on the 3-amino-thieno[2,3-b]pyridine-2-carboxamide scaffold: Development of ML253, a potent and brain penetrant compound that is active in a preclinical model of schizophrenia

  摘要：

  Herein we report a next generation muscarinic receptor 4 (M-4) positive allosteric modulator (PAM), ML253 which exhibits nanomolar activity at both the human (EC50 = 56 nM) and rat (EC50 = 176 nM) receptors and excellent efficacy by the left-ward shift of the ACh concentration response curve (fold shift, human = 106; rat = 50). In addition, ML253 is selective against the four other muscarinic subtypes, displays excellent CNS exposure and is active in an amphetamine-induced hyperlocomotion assay. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.10.073

文献信息

• Discovery of a selective M4 positive allosteric modulator based on the 3-amino-thieno[2,3-b]pyridine-2-carboxamide scaffold: Development of ML253, a potent and brain penetrant compound that is active in a preclinical model of schizophrenia
  作者：Uyen Le、Bruce J. Melancon、Thomas M. Bridges、Paige N. Vinson、Thomas J. Utley、Atin Lamsal、Alice L. Rodriguez、Daryl Venable、Douglas J. Sheffler、Carrie K. Jones、Anna L. Blobaum、Michael R. Wood、J. Scott Daniels、P. Jeffrey Conn、Colleen M. Niswender、Craig W. Lindsley、Corey R. Hopkins

  DOI：10.1016/j.bmcl.2012.10.073

  日期：2013.1

  Herein we report a next generation muscarinic receptor 4 (M-4) positive allosteric modulator (PAM), ML253 which exhibits nanomolar activity at both the human (EC50 = 56 nM) and rat (EC50 = 176 nM) receptors and excellent efficacy by the left-ward shift of the ACh concentration response curve (fold shift, human = 106; rat = 50). In addition, ML253 is selective against the four other muscarinic subtypes, displays excellent CNS exposure and is active in an amphetamine-induced hyperlocomotion assay. (C) 2012 Elsevier Ltd. All rights reserved.