methyl 1-nitro-2-naphthoate | 78508-71-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: methyl 1-nitro-2-naphthoate
• 英文别名: 1-nitro-[2]naphthoic acid methyl ester；1-Nitro-[2]naphthoesaeure-methylester；1-Nitro-naphthoesaeure-2-methylester；methyl 1-nitronaphthalene-2-carboxylate
• CAS: 78508-71-1
• 化学式: C₁₂H₉NO₄
• mdl: MFCD06203942
• 分子量: 231.208
• InChiKey: JOBULQXHDUJYCX-UHFFFAOYSA-N

物化性质

• 熔点：
  149-150 °C(Solv: ethanol (64-17-5))
• 沸点：
  366.1±17.0 °C(Predicted)
• 密度：
  1.334±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.083
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-nitro-2-naphthoate 在 二(三叔丁基膦)钯 、 palladium on activated charcoal 、 氢气 、 溴 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 四氯化碳 、 水 为溶剂， 90.0 ℃ 、101.33 kPa 条件下， 反应 59.75h， 生成 3-[(1S,2S)-2-羟基环己基]-6-[(6-甲基-3-吡啶基)甲基]苯并[h]喹唑啉-4(3H)-酮
  参考文献：
  名称：

  MK-7622: A First-in-Class M₁ Positive Allosteric Modulator Development Candidate

  摘要：

  Identification of ligands that selectively activate the M-1 muscarinic signaling pathway has been sought for decades to treat a range of neurological and cognitive disorders. Herein, we describe the optimization efforts focused on addressing key physicochemical and safety properties, ultimately leading to the clinical candidate MK-7622, a highly selective positive allosteric modulator of the M-1 muscarinic receptor that has entered Phase II studies in patients with Alzheimer's disease.

  DOI：

  10.1021/acsmedchemlett.8b00095
• 作为产物：
  描述：

  2-<β-trans-(N,N-dimethylamino)ethenyl>-1-nitronaphthalene 在 potassium permanganate 、 草酰氯 、 potassium carbonate 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 、 水 、 叔丁醇 为溶剂， 反应 20.33h， 生成 methyl 1-nitro-2-naphthoate
  参考文献：
  名称：

  [EN] M1 RECEPTOR POSITIVE ALLOSTERIC MODULATOR COMPOUNDS AND METHODS OF USE THEREOF
  [FR] COMPOSÉS MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 ET LEURS MÉTHODES D'UTILISATION

  摘要：

  本发明涉及式(I)的化合物及其药学上可接受的盐，其中Q、X、Y、Z、R1、R7和n在此处被定义。式(I)的化合物是M1受体正向变构调节剂，在治疗涉及M1受体的疾病中具有用途，包括阿尔茨海默病、精神分裂症、疼痛和睡眠障碍。该发明还涉及包括式(I)化合物和药学上可接受的载体的药物组合物，以及使用式(I)化合物治疗由M1受体介导的疾病的方法。

  公开号：

  WO2017151449A1

文献信息

• [EN] ARYL METHYL BENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 D'ARYLMÉTHYLBENZOQUINAZOLINONE
  申请人：MERCK SHARP & DOHME

  公开号：WO2010059773A1

  公开（公告）日：2010-05-27

  The present invention is directed to benzoquinazilinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的苯并喹噁唑啉酮化合物，这些化合物是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。
• [EN] AMINOBENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 À BASE D'AMINOBENZOQUINAZOLINONE
  申请人：MERCK SHARP & DOHME

  公开号：WO2011084371A1

  公开（公告）日：2011-07-14

  The present invention is directed to aminobenzoquinazolinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的氨基苯并喹唑醌酮化合物，其为M1受体阳性变构调节剂，并且在治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍等方面有用。该发明还涉及包含这些化合物的药物组合物，以及在治疗M1受体介导的疾病中使用这些化合物和组合物。
• [EN] PYRANYL ARYL METHYL BENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DE RÉCEPTEUR M1 DE TYPE PYRANYL-ARYL-MÉTHYL-BENZOQUINAZOLINONE
  申请人：MERCK SHARP & DOHME

  公开号：WO2011025851A1

  公开（公告）日：2011-03-03

  The present invention is directed to pyranyl aryl methyl benzoquinazolinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式（I）的吡喃基芳基甲基苯并喹唑啉酮化合物，这些化合物是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在治疗由M1受体介导的疾病中的用途。
• [EN] DIHYDROBENZOQUINAZOLINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 DE DIHYDROBENZOQUINAZOLINONE
  申请人：MERCK SHARP & DOHME

  公开号：WO2012047702A1

  公开（公告）日：2012-04-12

  The present invention is directed to dihydrobenzoquinazilinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及式(I)的二氢苯并喹唑啉酮化合物，它们是M1受体阳性变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。该发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在治疗由M1受体介导的疾病中的用途。
• Chemistry of a meisenheimer-type σ-adduct derived from a troponoid
  作者：Marino Cavazza、Gioia Morganti、Francesco Pietra

  DOI：10.1016/s0040-4039(01)90350-8

  日期：1981.1

  The gem-dimethoxy σ-adduct of methoxide addition to 2-methoxy-3-nitro-4,5-benzotropone reacts with either (C2H5)3OBF4, to change the nitronate into an oxime function, or (CH3)3SiCl, to give 2-carbomethoxy-1-nitronaphthalene and the nitronic acid corresponding to the starting adduct.

  除2-甲氧基-3-硝基-4,​​5-二苯甲酮外，甲醇盐的二甲氧基二甲氧基σ加合物与（C 2 H 5）3 OBF 4反应，将亚硝酸盐转变为肟官能团，或（CH 3）3 SiCl，得到2-羰基甲氧基-1-硝基萘和对应于起始加合物的硝酸。