4-(1-甲基-1H-吲唑-3-基)苯甲酸乙酯 | 1018788-87-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-(1-甲基-1H-吲唑-3-基)苯甲酸乙酯
• 英文名称: ethyl 4-(1-Methyl-1H-indazol-3-yl)benzoate
• 英文别名: Ethyl 4-(1-methylindazol-3-yl)benzoate
• CAS: 1018788-87-8
• 化学式: C₁₇H₁₆N₂O₂
• 分子量: 280.326
• InChiKey: RXIHCJWVGJKFSL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  吲唑 在 1,10-菲罗啉 、 palladium diacetate 、 potassium carbonate 、 potassium hydroxide 作用下， 以 N,N-二甲基乙酰胺 、 丙酮 为溶剂， 反应 48.0h， 生成 4-(1-甲基-1H-吲唑-3-基)苯甲酸乙酯
  参考文献：
  名称：

  1H-吲唑的直接C-3-芳基化

  摘要：

  报道了取代的 1H-吲唑的分子间 C-H 芳基化的第一个例子。各种 1-取代的吲唑被用作原料，（杂）芳基溴化物和碘化物作为偶联伙伴进行了研究。研究了不同的反应条件。使用 Pd(OAc)2 作为催化剂，1,10-菲咯啉作为配体，K2CO3 作为碱，DMA 作为溶剂获得了最好的结果。配体对取代的 1H-吲唑的 C-H 芳基化的关键作用得到强调。

  DOI：

  10.1002/ejoc.201200860

文献信息

• A robust protocol for Pd(ii)-catalyzed C-3 arylation of (1H) indazoles and pyrazoles: total synthesis of nigellidine hydrobromide
  作者：Mengchun Ye、Andrew J. F. Edmunds、James A. Morris、David Sale、Yejia Zhang、Jin-Quan Yu

  DOI：10.1039/c3sc50184a

  日期：——

  indazole and pyrazoles are privileged structural motifs in agrochemicals and pharmaceuticals. C-3 C-H arylation of (1H) indazole and pyrazole has been a significant challenge due to the poor reactivity of the C-3 position. Herein, we report a practical Pd(II)/Phen catalyst and conditions for direct C-3 arylation of indazole and pyrazole with ArI or ArBr without using Ag additives as halide scavengers. The

  C3-芳基吲唑和吡唑是农用化学品和药物中的优先结构基序。由于C-3位置的反应性较差，（1H）吲唑和吡唑的C-3 CH芳基化已成为一项重大挑战。在这里，我们报告了一种实用的Pd（II）/ Phen催化剂，以及吲哚和吡唑与ArI或ArBr进行直接C-3芳基化而不使用Ag添加剂作为卤化物清除剂的条件。发现使用甲苯，氯苯，三氟甲基苯和均三甲苯作为溶剂对于选择性和反应性至关重要。我们通过首次氢溴酸尼古丁的全合成以及与农药和药物分子结构相关的杂环的简便制备，进一步证明了该方案的稳健性。
• Synthesis and antiplatelet activity of ethyl 4-(1-benzyl-1H-indazol-3-yl)benzoate (YD-3) derivatives
  作者：Hua-Sin Chen、Sheng-Chu Kuo、Che-Ming Teng、Fang-Yu Lee、Jih-Pyang Wang、Yu-Chun Lee、Chiung-Wen Kuo、Ching-Che Huang、Chin-Chung Wu、Li-Jiau Huang

  DOI：10.1016/j.bmc.2007.10.070

  日期：2008.2.1

  Previously, ethyl 4-(1-benzyl-1H-indazol-3-yl)benzoate (YD-3) was identified by us as the first non-peptide protease-activated receptor 4 (PAR4) antagonist. To continue on our development of novel anti-PAR4 agents, YD-3 was used as a lead compound and a series of its derivatives were synthesized and evaluated for their selective anti-PAR4 activity. Through structure-activity relationship (SAR) study, we identified the important functional groups contributing to anti-PAR4 activity, and these functional groups were kept intact during subsequent structural modification. Several new compounds with anti-PAR4 activity comparable to YD-3 were identified. Among them, ethyl 4-[1-(3-chlorobenzyl)-1H-indazol-3-yl]benzoate (33) showed the most potent inhibitory effect on PAR4-mediated platelet aggregation, ATP release, and P-selectin expression. On the other hand, ethyl 4-(1-phenyl-1H-indazol-3-yl)benzoate (83) exhibited dual inhibitory effects on PAR4 and thromboxane formation from arachidonic acid. The above findings can be used as guidelines for development of novel antiplatelet drug candidates. (c) 2008 Published by Elsevier Ltd.
• TRICYCLIC HETEROARYL-SUBSTITUTED QUINOLINE AND AZAQUINOLINE COMPOUNDS AS PAR4 INHIBITORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20210188877A1

  公开（公告）日：2021-06-24

  Disclosed are compounds of Formula (I) to (VIII): or a stereoisomer, tautomer, pharmaceutically acceptable salt, solvate or prodrug thereof, wherein R 3 is a tricyclic heteroaryl group substituted with R 3a and zero to 2 R 3b ; and R 1 , R 2 , R 3a , R 3b , R 4 , and n are defined herein. Also disclosed are methods of using such compounds as PAR4 inhibitors, and pharmaceutical compositions comprising such compounds. These compounds are useful in inhibiting or preventing platelet aggregation, and are useful for the treatment of a thromboembolic disorder or the primary prophylaxis of a thromboembolic disorder.