4,6-dimethylthieno[2,3-b]pyridine-2-carboxylic acid | 885461-14-3

• 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: 4,6-dimethylthieno[2,3-b]pyridine-2-carboxylic acid
• CAS: 885461-14-3
• 化学式: C₁₀H₉NO₂S
• mdl: MFCD06660771
• 分子量: 207.253
• InChiKey: OKPHGWXJQSOYAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  78.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4,6-dimethylthieno[2,3-b]pyridine-2-carboxylic acid 、 1-(3-pyridyl)azetidin-3-amine 在 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-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.33h， 生成 4,6-dimethyl-N-[1-(3-pyridyl)azetidin-3-yl]thieno[2,3-b]pyridine-2-carboxamide
  参考文献：
  名称：

  [EN] SUBSTITUTED THIENO[2,3-B]PYRIDINE-2-CARBOXAMIDE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4
  [FR] ANALOGUES DE THIÉNO[2,3-B]PYRIDINE-2-CARBOXAMIDE SUBSTITUÉS À UTILISER EN TANT QUE MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR MUSCARINIQUE DE L'ACÉTYLCHOLINE M4

  摘要：

  在一个方面，该发明涉及替代噻吩[2,3-b]吡啶-2-羧酰胺类似物，其衍生物和相关化合物，这些化合物可用作肌胆碱受体M4（mAChR M4）的正向别构调节剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与肌胆碱受体功能障碍相关的神经系统和精神疾病的方法。本摘要旨在作为在特定领域进行搜索的扫描工具，并不限制本发明。

  公开号：

  WO2015027204A1
• 作为产物：
  描述：

  Ethyl 4,6-dimethylthieno[2,3-b]pyridine-2-carboxylate 在 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 生成 4,6-dimethylthieno[2,3-b]pyridine-2-carboxylic acid
  参考文献：
  名称：

  Novel M4 positive allosteric modulators derived from questioning the role and impact of a presumed intramolecular hydrogen-bonding motif in β-amino carboxamide-harboring ligands

  摘要：

  This letter describes a focused exercise to explore the role of the beta-amino carboxamide moiety found in all of the first generation M-4 PAMs and question if the NH2 group served solely to stabilize an intramolecular hydrogen bond (IMHB) and enforce planarity. To address this issue (and to potentially find a substitute for the beta-amino carboxamide that engendered P-gp and contributed to solubility liabilities), we removed the NH2, generating des-amino congeners and surveyed other functional groups in the beta-position. These modifications led to weak M-4 PAMs with poor DMPK properties. Cyclization of the beta-amino carboxamide moiety by virtue of a pyrazole ring re-enforced the IMHB, led to potent (and patented) M-4 PAMs, many as potent as the classical bicyclic beta-amino carboxamide analogs, but with significant CYP1A2 inhibition. Overall, this exercise indicated that the beta-amino carboxamide moiety most likely facilitates an IMHB, and is essential for M(4)PAM activity within classical bicyclic M-4 PAM scaffolds.

  DOI：

  10.1016/j.bmcl.2018.12.039

文献信息

• SUBSTITUTED THIENO[2,3-B]PYRIDINE-2-CARBOXAMIDE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC ACETYLCHOLINE RECEPTOR M4
  申请人：Vanderbilt University

  公开号：US20160200733A1

  公开（公告）日：2016-07-14

  In one aspect, the invention relates to substituted thieno[2,3-b]pyridine-2-carboxamide analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M 4 (mAChR M 4 ); synthesis methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating neurological and psychiatric disorders associated with muscarinic acetylcholine receptor dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  本发明涉及替代噻吩[2,3-b]吡啶-2-羧酰胺类似物、其衍生物和相关化合物，其作为肌动蛋白乙酰胆碱受体M4（mAChR M4）的正向变构调节剂具有用途；制备这些化合物的合成方法；包含这些化合物的制药组合物；以及使用这些化合物和组合物治疗与肌动蛋白乙酰胆碱受体功能障碍相关的神经和精神障碍的方法。本摘要旨在作为搜索特定技术领域的扫描工具，不限制本发明。