(±)-1-(7-benzyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazin-3-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate | 1458062-06-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (±)-1-(7-benzyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazin-3-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate
• 英文别名: (+/-)-1-(7-Benzyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazin-3-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate；[1-(7-benzyl-6,8-dihydro-5H-imidazo[1,5-a]pyrazin-3-yl)-2-[7-methyl-2-(2-trimethylsilylethoxymethyl)indazol-5-yl]ethyl] 4-(2-oxo-1H-quinolin-3-yl)piperidine-1-carboxylate
• CAS: 1458062-06-0
• 化学式: C₄₄H₅₃N₇O₄Si
• 分子量: 772.035
• InChiKey: RXWNJSXTWPSHIN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.01
• 重原子数：
  56
• 可旋转键数：
  13
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  107
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (±)-1-(7-benzyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazin-3-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.5h， 以40%的产率得到(±)-1-(7-benzyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazin-3-yl)-2-(7-methyl-1H-indazol-5-yl)ethyl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  [EN] TETRAHYDROIMDIDAZOPYRAZINE DERIVATIVES AS CGRP RECEPTOR ANTAGONISTS
  [FR] DÉRIVÉS DE TÉTRAHYDROIMDIDAZOPYRAZINE À UTILISER EN TANT QU'ANTAGONISTES DU RÉCEPTEUR CGRP

  摘要：

  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）。

  公开号：

  WO2014062548A1
• 作为产物：
  描述：

  7-Benzyl-5,6,7,8-tetrahydroimidazo[1,5-A]pyrazine-3-carbaldehyde 在 sodium tetrahydroborate 、 caesium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 生成 (±)-1-(7-benzyl-5,6,7,8-tetrahydroimidazo[1,5-a]pyrazin-3-yl)-2-(7-methyl-2-((2-(trimethylsilyl)ethoxy)methyl)-2H-indazol-5-yl)ethyl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate
  参考文献：
  名称：

  Preparation of imidazoles as potent calcitonin gene-related peptide (CGRP) antagonists

  摘要：

  Several new potent CGRP receptor antagonists have been prepared in which the amide bond of lead compound 1 has been replaced by bioisosteric imidazole moieties. Substitution at N-1 of the imidazole was optimized to afford compounds with comparable potency to that of lead 1. Conformational restraint of the imidazole to form tetrahydroimidazo[1,5-a] pyrazine 43 gave substantially improved permeability. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.08.031

文献信息

• CGRP RECEPTOR ANTAGONISTS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20150274734A1

  公开（公告）日：2015-10-01

  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]

  本公开涉及一般与公式I有关的新化合物，包括药学上可接受的盐，这些化合物是CGRP受体拮抗剂。本公开还涉及制药组合物和使用这些化合物治疗CGRP相关疾病的方法，包括偏头痛和其他头痛、神经原性血管扩张、神经原性炎症、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，以及慢性阻塞性肺疾病（COPD）。[插入化学结构]
• [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）。
• Preparation of imidazoles as potent calcitonin gene-related peptide (CGRP) antagonists
  作者：George Tora、Andrew P. Degnan、Charles M. Conway、Walter A. Kostich、Carl D. Davis、Sokhom S. Pin、Richard Schartman、Cen Xu、Kimberly A. Widmann、John E. Macor、Gene M. Dubowchik

  DOI：10.1016/j.bmcl.2013.08.031

  日期：2013.10

  Several new potent CGRP receptor antagonists have been prepared in which the amide bond of lead compound 1 has been replaced by bioisosteric imidazole moieties. Substitution at N-1 of the imidazole was optimized to afford compounds with comparable potency to that of lead 1. Conformational restraint of the imidazole to form tetrahydroimidazo[1,5-a] pyrazine 43 gave substantially improved permeability. (C) 2013 Elsevier Ltd. All rights reserved.