(+/-)-2-(7-Methyl-1H-indazol-5-ylmethyl)-succinic acid 1-methyl ester | 855776-47-5

• 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: (+/-)-2-(7-Methyl-1H-indazol-5-ylmethyl)-succinic acid 1-methyl ester
• 英文别名: 2-(7-methyl-1H-indazol-5-ylmethyl)-succinic acid 1-methyl ester；2-(7-methyl-1H-indazol-5-ylmethyl)succinic acid 1-methyl ester；methyl 2-(7-methyl-1H-indazol-5-ylmethyl)-succinate；4-methoxy-3-((7-methyl-1H-indazol-5-yl)methyl)-4-oxobutanoic acid；4-methoxy-3-[(7-methyl-1H-indazol-5-yl)methyl]-4-oxobutanoic acid
• CAS: 855776-47-5
• 化学式: C₁₄H₁₆N₂O₄
• 分子量: 276.292
• InChiKey: XNBGCSBABKFOIK-UHFFFAOYSA-N

物化性质

• 沸点：
  505.0±50.0 °C(Predicted)
• 密度：
  1.323±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  92.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (+/-)-2-(7-Methyl-1H-indazol-5-ylmethyl)-succinic acid 1-methyl ester 在 三乙胺 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 2-[(7-methyl-1H-indazol-5-yl)methyl]-4-oxo-4-[4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidin-1-yl]butanoic acid
  参考文献：
  名称：

  Calcitonin gene-related peptide (CGRP) receptor antagonists: Novel aspartates and succinates

  摘要：

  Novel aspartate and succinate CGRP full antagonists were identified through core modification of a potent lead CGRP antagonist, BMS-694153. While aspartates were much less active and had a flat SAR, some of the succinates were very potent CGRP full antagonists and matched the potency of BMS-694153. The most potency resides in the S enantiomer as demonstrated through an asymmetric synthesis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.066
• 作为产物：
  描述：

  丁二酸二甲酯 在 palladium on activated charcoal 、 potassium tert-butylate 、 氢气 作用下， 以 甲醇 、 乙酸乙酯 、 叔丁醇 为溶剂， 生成 (+/-)-2-(7-Methyl-1H-indazol-5-ylmethyl)-succinic acid 1-methyl ester
  参考文献：
  名称：

  Calcitonin gene-related peptide (CGRP) receptor antagonists: Novel aspartates and succinates

  摘要：

  Novel aspartate and succinate CGRP full antagonists were identified through core modification of a potent lead CGRP antagonist, BMS-694153. While aspartates were much less active and had a flat SAR, some of the succinates were very potent CGRP full antagonists and matched the potency of BMS-694153. The most potency resides in the S enantiomer as demonstrated through an asymmetric synthesis. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.02.066

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，包括它们的药物组合物，用于识别它们的方法，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））以及其他可以通过拮抗CGRP受体来治疗的疾病的治疗中的用途。
• [EN] CALCITONIN GENE RELATED PEPTIDE RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DES RECEPTEURS DU PEPTIDE RELIE AU GENE DE LA CALCITONINE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2003104236A1

  公开（公告）日：2003-12-18

  The presnt 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.

  本发明涉及化合物的公式（I），作为降钙素基因相关肽受体（“CGRP受体”）的拮抗剂，包括它们的药物组合物，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、循环性休克、与绝经相关的潮红、气道炎症性疾病（如哮喘和慢性阻塞性肺病（COPD））以及其他可以通过拮抗CGRP受体来治疗的疾病的用途。
• Selected CGRP-antagonists process for preparing them and their use as pharmaceutical compositions
  申请人：Lustenberger Philipp

  公开号：US20050227968A1

  公开（公告）日：2005-10-13

  The present invention relates to substituted piperidines of general formula wherein A, B, D, E, X, R 1 and R 2 are defined as in claim 1, the tautomers, the diastereomers, the enantiomers, the hydrates thereof, the mixtures thereof and the salts thereof and the hydrates of the salts, particularly the physiologically acceptable salts thereof with inorganic or organic acids, pharmaceutical compositions containing these compounds, the use thereof and processes for the preparation thereof.

  本发明涉及通式所示的取代哌啶，其中A，B，D，E，X，R1和R2如权利要求书1所定义的那样，其互变异构体，对映异构体，立体异构体，其水合物，其混合物和其盐及其盐的水合物，特别是其与无机或有机酸的生理上可接受的盐，以及含有这些化合物的制药组合物，其使用和其制备方法。
• 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）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，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扩张、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），以及其他可以通过抗CGRP受体治疗的疾病的治疗中的应用。
• 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)

  本发明涉及使用公式（I）化合物的制药组合物，用于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。