2-benzyloxycarbonylamino-3-(7-methyl-1H-indazole-5-yl)-propenoic acid methyl ester | 635712-41-3

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 2-benzyloxycarbonylamino-3-(7-methyl-1H-indazole-5-yl)-propenoic acid methyl ester
• 英文别名: 2-benzyloxycarbonylamino-3-(7-methyl-1H-indazol-5-yl)-propenoic acid methyl ester；2-benzyloxycarbonylamino-3-(7-methyl-1H-indazol-5-yl)-acrylic acid methyl ester；benzyloxycarbonylamino-3-(7-methyl-1H-indazol-5-yl)acrylic acid methyl ester；methyl 3-(7-methyl-1H-indazol-5-yl)-2-(phenylmethoxycarbonylamino)prop-2-enoate
• CAS: 635712-41-3
• 化学式: C₂₀H₁₉N₃O₄
• 分子量: 365.389
• InChiKey: BMWIRDFPIYOOPI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  27
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  93.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-benzyloxycarbonylamino-3-(7-methyl-1H-indazole-5-yl)-propenoic acid methyl ester 在 氮气 、 钯 作用下， 以 甲醇 为溶剂， 反应 16.5h， 以to give the product as a colorless foam (3.62 g, quant.)的产率得到(+/-)-2-amino-3-(7-methyl-1H-indazol-5-yl)-propionic acid methyl ester
  参考文献：
  名称：

  Heterocyclic anti-migraine agents

  摘要：

  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”）的拮抗剂，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、更年期潮红、气道炎症性疾病（如哮喘和慢性阻塞性肺疾病（COPD））以及其他可以通过拮抗CGRP受体来治疗的疾病的治疗中的应用。

  公开号：

  US07569578B2
• 作为产物：
  描述：

  4-溴-2,6-二甲基苯胺 在 盐酸 、 potassium tert-butylate 、 叔丁基锂 、 sodium hydride 、 sodium nitrite 作用下， 以 二甲基亚砜 为溶剂， 生成 2-benzyloxycarbonylamino-3-(7-methyl-1H-indazole-5-yl)-propenoic acid methyl ester
  参考文献：
  名称：

  The synthesis and SAR of calcitonin gene-related peptide (CGRP) receptor antagonists derived from tyrosine surrogates. Part 2

  摘要：

  Various substituted indazole and benzoxazolone amino acids were investigated as D-tyrosine surrogates in highly potent CGRP receptor antagonists. Compound 3, derived from the 7-methylindazole core, afforded a 30-fold increase in CGRP binding potency compared with its unsubstituted indazole analog 1. When dosed at 0.03 mg/kg SC, compound 2 (a racemic mixture of 3 and its (S)-enantiomer) demonstrated robust inhibition of CGRP-induced increases in mamoset facial blood flow up to 105 min. The compound possesses a favorable predictive in vitro toxicology profile, and good aqueous solubility. When dosed as a nasal spray in rabbits, 3 was rapidly absorbed and showed good intranasal bioavailability (42%). (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.01.011

文献信息

• Calcitonin gene related peptide receptor antagonists
  申请人：——

  公开号：US20040204397A1

  公开（公告）日：2004-10-14

  The present invention relates to compounds of Formula (I) 1 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）1的化合物，作为降钙素基因相关肽受体（“CGRP受体”）的拮抗剂，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、热损伤、循环性休克、更年期潮热、气道炎症性疾病（如哮喘和慢性阻塞性肺疾病（COPD））和其他可以通过CGRP受体拮抗治疗的疾病的治疗中的用途。
• ANTI-MIGRAINE TREATMENTS
  申请人：Chen Ling

  公开号：US20070232600A1

  公开（公告）日：2007-10-04

  The present invention relates to methods of treating 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 using pharmaceutical compositions comprising compounds of Formula (I)

  本发明涉及使用含有式(I)化合物的制药组合物来拮抗CGRP受体，从而治疗神经原性血管扩张、神经原性炎症、偏头痛和其他头痛、热损伤、循环休克、与绝经期潮红有关的潮红、气道炎症性疾病（如哮喘和慢性阻塞性肺疾病（COPD））以及其他可通过拮抗CGRP受体治疗的疾病。
• ANTI-MIGRAINE SPIROCYCLES
  申请人：CHATURVEDULA V. PRASAD

  公开号：US20070149503A1

  公开（公告）日：2007-06-28

  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、循环休克、绝经期潮红、气道炎症性疾病（如哮喘和慢性阻塞性肺疾病（COPD））以及其他可通过CGRP受体拮抗剂治疗的疾病的治疗中的应用。
• Non-terminal method of identifying anti-migraine compounds
  申请人：Conway Mark Charles

  公开号：US20070148093A1

  公开（公告）日：2007-06-28

  The present invention relates to in vivo non-terminal method of identifying anti-migraine compounds.

  本发明涉及一种非末期体内鉴定抗偏头痛化合物的方法。
• SPIROCYCLIC ANTI-MIGRAINE COMPOUNDS
  申请人：Chaturvedula V. Prasad

  公开号：US20070149502A1

  公开（公告）日：2007-06-28

  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，包括它们的药物组成物，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原性血管扩张、神经原性炎症、偏头痛和其他头痛、热损伤、循环性休克、与绝经期潮红相关的面部潮红、气道炎症性疾病，如哮喘和慢性阻塞性肺疾病（COPD），以及其他可以通过拮抗CGRP受体来治疗的疾病的治疗中的应用。