benzyl 4-chloronicotinate | 1618131-28-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzyl 4-chloronicotinate
• 英文别名: Benzyl 4-chloropyridine-3-carboxylate
• CAS: 1618131-28-4
• 化学式: C₁₃H₁₀ClNO₂
• 分子量: 247.681
• InChiKey: AKSYYJYHKYNVDW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  benzyl 4-chloronicotinate 在 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 三乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 ethyl 6-chloro-5-(3-(4-cyclopropyl-1,2,3,4-tetrahydroquinoxaline-1-carbonyl)pyridin-4-yloxy)-3-methylbenzofuran-2-carboxylate
  参考文献：
  名称：

  4-Benzofuranyloxynicotinamide derivatives are novel potent and orally available TGR5 agonists

  摘要：

  A series of 4-benzofuranyloxynicotinamide derivatives were identified to be novel, potent, and orally available TGR5 agonists. Among them, compound 9r had the highest potency in vitro (hTGR5 EC50 = 0.28 nM, mTGR5 EC50 = 0.92 nM). Further in vivo studies disclosed that 9r could effectively lower the blood glucose, but meantime caused an increase in the gallbladder volume of mice. Subsequent research toward eliminating the gallbladder toxicity resulted in compound 19 with low permeability. Although the EC50 of mTGR5 of 19 was larger one order than that of 9r, it still had good glucose-lowing activity. Nevertheless, 19 also caused the adverse effects to the gallbladder. The drug levels detection disclosed that the concentration of 19 was only lower than that of 9r in plasma but was higher in bile and gallbladder tissue. This result indicated that low exposure in plasma could not guarantee low exposure in bile and gallbladder tissue, and thus resulting in the gallbladder toxicity of 19. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.031
• 作为产物：
  描述：

  4-氯烟酸 、 苯甲醇 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 benzyl 4-chloronicotinate
  参考文献：
  名称：

  4-Benzofuranyloxynicotinamide derivatives are novel potent and orally available TGR5 agonists

  摘要：

  A series of 4-benzofuranyloxynicotinamide derivatives were identified to be novel, potent, and orally available TGR5 agonists. Among them, compound 9r had the highest potency in vitro (hTGR5 EC50 = 0.28 nM, mTGR5 EC50 = 0.92 nM). Further in vivo studies disclosed that 9r could effectively lower the blood glucose, but meantime caused an increase in the gallbladder volume of mice. Subsequent research toward eliminating the gallbladder toxicity resulted in compound 19 with low permeability. Although the EC50 of mTGR5 of 19 was larger one order than that of 9r, it still had good glucose-lowing activity. Nevertheless, 19 also caused the adverse effects to the gallbladder. The drug levels detection disclosed that the concentration of 19 was only lower than that of 9r in plasma but was higher in bile and gallbladder tissue. This result indicated that low exposure in plasma could not guarantee low exposure in bile and gallbladder tissue, and thus resulting in the gallbladder toxicity of 19. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.031

文献信息

• Design of G-protein-coupled bile acid receptor 1 (GPBAR1, TGR5) soft drugs with reduced gallbladder-filling effects
  作者：Fanghui Han、Mengmeng Ning、Hua Cao、Yangliang Ye、Ying Feng、Ying Leng、Jianhua Shen

  DOI：10.1016/j.ejmech.2020.112619

  日期：2020.10

  The G-protein-coupled bile acid receptor TGR5 agonists were widely developed in type 2 diabetes and gastrointestinal disorders, but were also full of challenges, due to the systemic on-targeted side effects, especially the gallbladder-filling effects. Here, to circumvent these risks, several TGR5 agonists with soft-drug designation had been designed and synthesized with the properties of rapid metabolized

  G蛋白偶联的胆汁酸受体TGR5激动剂在2型糖尿病和胃肠道疾病中得到了广泛开发，但由于全身靶向副作用，特别是胆囊充盈作用，也充满了挑战。在这里，为了规避这些风险，已经设计并合成了几种具有软性药物标记的TGR5激动剂，它们具有药物作用后快速代谢的特性。其中，化合物19在3天连续给药中表现出可忽略的全身暴露和良好的胆囊安全性，为开发TGR5激动剂提供了新的策略。
• 酯类化合物及其制备方法和应用、酯类软药
  申请人：中国科学院上海药物研究所

  公开号：CN112794844B

  公开（公告）日：2023-03-21

  本发明涉及酯类化合物及其制备方法和应用、酯类软药，其中酯类化合物具有式(I)所示通式：
• [EN] THIAZOLOPYRIDYL AMIDE DERIVATIVES AS DNA POLYMERASE THETA INHIBITORS<br/>[FR] DÉRIVÉS DE THIAZOLOPYRIDYL AMIDE EN TANT QU'INHIBITEURS D'ADN POLYMÉRASE THÊTA
  申请人：[en]BEIGENE , LTD.

  公开号：WO2023134708A1

  公开（公告）日：2023-07-20

  Provided are compounds containing thiazolopyridyl amide structure, the process for their synthesis, as well as the use of such compounds for inhibiting DNA Polymerase Theta (Pol Theta), and in the treatment of various diseases including cancers.