VU0405652 | 1222878-02-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: VU0405652
• 英文别名: ML169；2-[1-(5-bromo-2-fluoro-benzyl)indol-3-yl]sulfonyl-N-(5-methylisoxazol-3-yl)acetamide；2-[1-[(5-bromo-2-fluorophenyl)methyl]indol-3-yl]sulfonyl-N-(5-methyl-1,2-oxazol-3-yl)acetamide
• CAS: 1222878-02-5
• 化学式: C₂₁H₁₇BrFN₃O₄S
• 分子量: 506.352
• InChiKey: RUYRNYRGPSAXTK-UHFFFAOYSA-N

物化性质

• 沸点：
  784.2±60.0 °C(Predicted)
• 密度：
  1.60±0.1 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>5mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-((1H-indol-3-yl)thio)-N-(5-methylisoxazol-3-yl)acetamide 在 Oxone 、 sodium hydride 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 3.25h， 生成 VU0405652
  参考文献：
  名称：

  Discovery and optimization of a novel, selective and brain penetrant M1 positive allosteric modulator (PAM): The development of ML169, an MLPCN probe

  摘要：

  This Letter describes a chemical lead optimization campaign directed at VU0108370, a weak M-1 PAM hit with a novel chemical scaffold from a functional HTS screen within the MLPCN. An iterative parallel synthesis approach rapidly established SAR for this series and afforded VU0405652 (ML169), a potent, selective and brain penetrant M-1 PAM with an in vitro profile comparable to the prototypical M-1 PAM, BQCA, but with an improved brain to plasma ratio. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.12.015

文献信息

• [EN] INDOLE COMPOUNDS AS POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC RECEPTOR<br/>[FR] COMPOSÉS INDOLE COMME MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR MUSCARINIQUE
  申请人：UNIV VANDERBILT

  公开号：WO2011163280A1

  公开（公告）日：2011-12-29

  In one aspect, the invention relates to indole compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M1 (mAChR M1); synthetic 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.

  在一个方面，该发明涉及吲哚化合物、其衍生物和相关化合物，这些化合物可作为肌胆碱受体M1（mAChR M1）的阳性变构调节剂；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，并不意味着对本发明的限制。
• INDOLE COMPOUNDS AS POSITIVE ALLOSTERIC MODULATORS OF THE MUSCARINIC RECEPTOR
  申请人：Lindsley Craig W.

  公开号：US20130210773A1

  公开（公告）日：2013-08-15

  In one aspect, the invention relates to indole compounds, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M 1 (mAChR M 1 ); synthetic 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.

  本发明涉及吲哚化合物、其衍生物和相关化合物，它们可用作肌动蛋白乙酰胆碱受体M1（mAChR M1）的正向变构调节剂；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。本摘要旨在作为在特定领域进行搜索的扫描工具，不限制本发明。
• SUBSTITUTED 4-BENZYL-3,4-DIHYDRO-2H-BENZO[B][1,4]OXAZINE-2CARBOXAMIDE ANALOGS AS POSITIVE ALLOSTERIC MODULATORS OF MUSCARINIC ACETYCHOLINE RECEPTOR M1
  申请人：Vanderbilt University

  公开号：US20170022173A1

  公开（公告）日：2017-01-26

  In one aspect, the invention relates to N-substituted 3,4-dihydro-benzo[£][1,4]oxazine-2-carboxamide analogs, derivatives thereof, and related compounds, which are useful as positive allosteric modulators of the muscarinic acetylcholine receptor M 1 (mAChR M 1 ); 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.
• US8772509B2
  申请人：——

  公开号：US8772509B2

  公开（公告）日：2014-07-08
• US9708278B2
  申请人：——

  公开号：US9708278B2

  公开（公告）日：2017-07-18