5-bromonicotinoyl-1H-imidazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-bromonicotinoyl-1H-imidazole
• 英文别名: (5-Bromopyridin-3-yl)-imidazol-1-ylmethanone；(5-bromopyridin-3-yl)-imidazol-1-ylmethanone
• 化学式: C₉H₆BrN₃O
• 分子量: 252.07
• InChiKey: PGUAWVYSMRNAGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  47.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-bromonicotinoyl-1H-imidazole 在 氨 、 三乙胺 、 三氟乙酸酐 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 5-溴烟腈
  参考文献：
  名称：

  Selective Cyclooxygenase-2 Inhibitors:  Heteroaryl Modified 1,2-Diarylimidazoles Are Potent, Orally Active Antiinflammatory Agents

  摘要：

  A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and found to be potent and highly selective (1000-9000-fold) inhibitors of the human COX-2. 3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent activity in acute (carrageenan induced paw edema, ED50 = 5.4 mg/kg) and chronic (adjuvant induced arthritis, ED50 = 0.25 mg/kg) models of inflammation. The relatively long half-life of 25 in rat and dog prompted investigation of the pyridyl and other heteroaromatic systems containing potential metabolic functionalities. A number of substituted pyridyl and thiazole containing compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in every efficacy model evaluated. Several orally active diarylimidazoles exhibited desirable pharmacokinetics profiles and showed no CI toxicity in the rat up to 100 mg/kg in both acute and chronic models. The paper describes facile and practical syntheses of the targeted diarylimidazoles. The structure-activity relationships and antiinflammatory properties of a series of diarylimidazoles are discussed.

  DOI：

  10.1021/jm0000719
• 作为产物：
  描述：

  5-溴烟酸 、 N,N'-羰基二咪唑 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 5-bromonicotinoyl-1H-imidazole
  参考文献：
  名称：

  一种尼麦角林的新制备方法

  摘要：

  本发明涉及一种尼麦角林的新制备方法，该方法包括以下步骤：(1)在极性非质子溶剂中，加入无机碱，使麦角醇(II)与甲基化试剂进行甲基化反应，生成1‑甲基麦角醇(III)；(2)1‑甲基麦角醇(III)与甲醇在浓硫酸的催化下进行光反应，制得1‑甲基‑10α‑甲氧基光麦角醇(IV)；(3)在极性非质子有机溶剂中，以N,N’‑羰基二咪唑为缩合剂，将5‑溴烟酸(V)与N,N’‑羰基二咪唑先反应制得5‑溴烟酰咪唑(VI)中间体，再将5‑溴烟酰咪唑(VI)中间体与1‑甲基‑10α‑甲氧基光麦角醇(IV)进行缩合反应，制得尼麦角林(I)。与现有技术相比，本发明无需惰性气体保护、酸用量小、产品质量好、收率高、反应副产物易回收利用，适合工业化生产。

  公开号：

  CN111004233A

文献信息

• 一种尼麦角林的新制备方法
  申请人：上海应用技术大学

  公开号：CN111004233A

  公开（公告）日：2020-04-14

  本发明涉及一种尼麦角林的新制备方法，该方法包括以下步骤：(1)在极性非质子溶剂中，加入无机碱，使麦角醇(II)与甲基化试剂进行甲基化反应，生成1‑甲基麦角醇(III)；(2)1‑甲基麦角醇(III)与甲醇在浓硫酸的催化下进行光反应，制得1‑甲基‑10α‑甲氧基光麦角醇(IV)；(3)在极性非质子有机溶剂中，以N,N’‑羰基二咪唑为缩合剂，将5‑溴烟酸(V)与N,N’‑羰基二咪唑先反应制得5‑溴烟酰咪唑(VI)中间体，再将5‑溴烟酰咪唑(VI)中间体与1‑甲基‑10α‑甲氧基光麦角醇(IV)进行缩合反应，制得尼麦角林(I)。与现有技术相比，本发明无需惰性气体保护、酸用量小、产品质量好、收率高、反应副产物易回收利用，适合工业化生产。
• Selective Cyclooxygenase-2 Inhibitors:  Heteroaryl Modified 1,2-Diarylimidazoles Are Potent, Orally Active Antiinflammatory Agents
  作者：Ish K. Khanna、Yi Yu、Renee M. Huff、Richard M. Weier、Xiangdong Xu、Francis J. Koszyk、Paul W. Collins、J. Nita Cogburn、Peter C. Isakson、Carol M. Koboldt、Jaime L. Masferrer、William E. Perkins、Karen Seibert、Amy W. Veenhuizen、Jinhua Yuan、Dai-Chang Yang、Yan Y. Zhang

  DOI：10.1021/jm0000719

  日期：2000.8.1

  A series of heteroaryl modified 1,2-diarylimidazoles has been synthesized and found to be potent and highly selective (1000-9000-fold) inhibitors of the human COX-2. 3-Pyridyl derived COX-2 selective inhibitor (25) exhibited excellent activity in acute (carrageenan induced paw edema, ED50 = 5.4 mg/kg) and chronic (adjuvant induced arthritis, ED50 = 0.25 mg/kg) models of inflammation. The relatively long half-life of 25 in rat and dog prompted investigation of the pyridyl and other heteroaromatic systems containing potential metabolic functionalities. A number of substituted pyridyl and thiazole containing compounds (e.g., 44, 46, 54, 76, and 78) demonstrated excellent oral activity in every efficacy model evaluated. Several orally active diarylimidazoles exhibited desirable pharmacokinetics profiles and showed no CI toxicity in the rat up to 100 mg/kg in both acute and chronic models. The paper describes facile and practical syntheses of the targeted diarylimidazoles. The structure-activity relationships and antiinflammatory properties of a series of diarylimidazoles are discussed.