7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-5-carboxaldehyde | 855776-96-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-5-carboxaldehyde
• 英文别名: 7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-5-carbaldehyde；2-((2-(trimethylsilyl)ethoxy)methyl)-7-methyl-2H-indazole-5-carbaldehyde；7-methyl-2-(2-trimethylsilylethoxymethyl)indazole-5-carbaldehyde
• CAS: 855776-96-4
• 化学式: C₁₅H₂₂N₂O₂Si
• 分子量: 290.437
• InChiKey: QZWDTMWKBCAAGD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.47
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-5-carboxaldehyde 在 盐酸 、 sodium tetrahydroborate 、 偶氮二甲酸二异丙酯 、 caesium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 丙醇 、 二氯甲烷 、 水 为溶剂， 生成 (+/-)-2-(1-(6-bromopyridin-2-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Calcitonin gene-related peptide (CGRP) receptor antagonists: Pyridine as a replacement for a core amide group

  摘要：

  In our continuing efforts to identify CGRP receptor antagonists that can be dosed orally for the treatment of migraine headache, we have investigated a pyridine bioisosteric replacement of a polar amide portion of a previous lead compound, BMS-694153. Pyridine derivatives were discovered and their SAR was studied. Some of them showed excellent binding potency. However, oral bioavailability was low, even for compounds with good Caco-2 cell permeability. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.065
• 作为产物：
  描述：

  5-溴-7-甲基-1H-吲唑 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 17.25h， 生成 7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazole-5-carboxaldehyde
  参考文献：
  名称：

  吲唑在N -2处的区域选择性保护和在C -3处的衍生化

  摘要：

  在新条件下，吲唑在N -2处被2-（三甲基甲硅烷基）乙氧基甲基（SEM）基团区域选择性保护。SEM组可以有效地指导区域选择性C -3锂化，并且所得亲核试剂可以与各种亲电试剂反应生成新的吲唑衍生物。可以通过在THF中的TBAF或在EtOH中的HCl水溶液处理来除去SEM组。

  DOI：

  10.1021/jo060607j

文献信息

• Substituted Heterocyclic Ethers and Their Use in CNS Disorders
  申请人：Degnan Andrew P.

  公开号：US20090018132A1

  公开（公告）日：2009-01-15

  The invention encompasses compounds of Formula I, including pharmaceutically acceptable salts, their pharmaceutical compositions, and their use in treating CNS disorders.

  这项发明涵盖了公式I的化合物，包括药用盐、它们的药物组合物以及它们在治疗中枢神经系统疾病中的用途。
• Novel therapeutic agents for the treatment of migraine
  申请人：Degnan P. Andrew

  公开号：US20050215576A1

  公开（公告）日：2005-09-29

  The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.

  本发明涉及式(I)化合物作为降钙素基因相关肽受体（“CGRP受体”）拮抗剂，包括它们的药物组合物，用于识别它们的方法，使用它们的治疗方法以及它们在治疗神经源性血管舒张、神经源性炎症、偏头痛和其他头痛、热损伤、循环休克、与绝经期潮红相关的潮红、气道炎症性疾病（如哮喘和慢性阻塞性肺病（COPD））以及其他可以通过CGRP受体拮抗作用来治疗的疾病的治疗中的用途。
• [EN] TETRAHYDROIMDIDAZOPYRAZINE DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS DE TÉTRAHYDROIMDIDAZOPYRAZINE À UTILISER EN TANT QU'ANTAGONISTES DU RÉCEPTEUR CGRP
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2014062548A1

  公开（公告）日：2014-04-24

  The disclosure generally relates to the novel compounds of formula I, including pharmaceutically acceptable salts, which are CGRP receptor antagonists. The disclosure also relates to pharmaceutical compositions and methods for using the compounds in the treatment of CGRP related disorders including migraine and other headaches, neurogenic vasodilation, neurogenic inflammation, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases such as asthma, and chronic obstructive pulmonary disease (COPD). [INSERT CHEMICAL STRUCTURE HERE] I

  该公开涉及公式I的新化合物，包括药用盐，这些化合物是CGRP受体拮抗剂。该公开还涉及制药组合物和使用这些化合物治疗与CGRP相关疾病的方法，包括偏头痛和其他头痛、神经源性血管扩张、神经源性炎症、热损伤、循环休克、与绝经期相关的潮红、哮喘等气道炎症疾病，以及慢性阻塞性肺病（COPD）。
• Heterocyclic anti-migraine agents
  申请人：Luo Guanglin

  公开号：US20050153959A1

  公开（公告）日：2005-07-14

  The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.

  本发明涉及公式(I)的化合物作为降钙素基因相关肽受体（“CGRP受体”）拮抗剂，包括它们的制药组合物、鉴定它们的方法、使用它们的治疗方法以及它们在治疗神经源性血管扩张、神经源性炎症、偏头痛和其他头痛、热损伤、循环性休克、与绝经期相关的潮红、气道炎症性疾病（如哮喘和慢性阻塞性肺疾病（COPD））以及其他可以通过CGRP受体拮抗来治疗的病症的治疗中的应用。
• Therapeutic agents for the treatment of migraine
  申请人：Bristol-Myers Squibb Company

  公开号：US07772244B2

  公开（公告）日：2010-08-10

  The present invention relates to compounds of Formula (I) as antagonists of calcitonin gene-related peptide receptors (“CGRP-receptor”), pharmaceutical compositions comprising them, methods for identifying them, methods of treatment using them and their use in therapy for treatment of neurogenic vasodilation, neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock, flushing associated with menopause, airway inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD), and other conditions the treatment of which can be effected by the antagonism of CGRP-receptors.

  本发明涉及公式（I）化合物作为降钙素基因相关肽受体（“CGRP受体”）拮抗剂，包括它们的制药组合物，鉴定它们的方法，使用它们进行治疗的方法以及它们在治疗神经源性血管扩张、神经源性炎症、偏头痛和其他头痛、热伤害、循环性休克、与更年期相关的潮热、气道炎症性疾病，如哮喘和慢性阻塞性肺疾病（COPD）以及其他可以通过拮抗CGRP受体来治疗的疾病的使用。