3-(2-mesityl)-2-mercapto-3H-imidazo[4,5-b]pyridine | 1383787-15-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(2-mesityl)-2-mercapto-3H-imidazo[4,5-b]pyridine
• 英文别名: 3-mesityl-3H-imidazo[4,5-b]pyridine-2-thiol；3-(2,4,6-trimethylphenyl)-1H-imidazo[4,5-b]pyridine-2-thione
• CAS: 1383787-15-2
• 化学式: C₁₅H₁₅N₃S
• 分子量: 269.37
• InChiKey: YAFQMBWCHUTVAT-UHFFFAOYSA-N

物化性质

• 沸点：
  437.0±55.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  60.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-(2-mesityl)-2-mercapto-3H-imidazo[4,5-b]pyridine 、 N-(2-溴-4-甲基苯基)-2-氯乙酰胺 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 2.0h， 以67.6%的产率得到N-(2-bromo-4-methyl-phenyl)-2-[3-(2,4,6-trimethylphenyl)imidazo[4,5-b]pyridin-2-yl]sulfanyl-acetamide
  参考文献：
  名称：

  Arylazolyl(azinyl)thioacetanilides. Part 10: Design, synthesis and biological evaluation of novel substituted imidazopyridinylthioacetanilides as potent HIV-1 inhibitors

  摘要：

  In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with novel structures, we have employed a scaffold hopping strategy to explore the chemically diversed space of bioactive compounds. The original arylazolylthioacetanilide platform was replaced with different imidazopyridinylthioacetanilide scaffolds to yield the optimal pharmacophore moieties in order to generate novel NNRTIs with desirable potency. Some of the new compounds proved able to inhibit HIV-1 replication in the low micromolar range. In particular, compound 5b16 displayed the most potent anti-HIV-1 activity (EC50 = 0.21 +/- 0.06 mu M), inhibiting HIV-1 IIIB replication in MT-4 cells more effectively than dideoxycytidine (EC50 = 1.4 +/- 0.1 mu M) and similarly with nevirapine (EC50 = 0.20 +/- 0.10 mu M). Preliminary structure-activity relationship (SAR) of the newly synthesized congeners is discussed, and molecular modeling study is performed to rationalize the SAR conclusions. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.07.026
• 作为产物：
  描述：

  2-氯-3-硝基吡啶 在 potassium fluoride 、 palladium on activated charcoal 、 氢气 、 碳酸氢钠 作用下， 以 乙醇 、 水 为溶剂， 反应 32.0h， 生成 3-(2-mesityl)-2-mercapto-3H-imidazo[4,5-b]pyridine
  参考文献：
  名称：

  发现和表征新型咪唑并吡啶衍生物CHEQ-2作为有效的CDC25抑制剂和有希望的抗癌药物候选物

  摘要：

  细胞分裂周期（CDC）25蛋白是通过与CDK /细胞周期蛋白复合物相互作用调节细胞周期过渡和增殖的关键磷酸酶。CDC25蛋白的过表达在癌症中经常被观察到，并且与侵略性，高级别肿瘤和不良预后有关。因此，在癌症治疗中抑制CDC25活性似乎是一种很好的治疗策略。在本文中，通过合成和筛选聚焦的化合物文库对最初命中的XDW-1进行了优化，从而鉴定出一套新的咪唑并吡啶衍生物作为有效的CDC25抑制剂。其中最有效的分子是CHEQ-2，它可以在体外有效抑制CDC25A / B酶的活性以及各种不同类型癌细胞的增殖。分析。此外，CHEQ-2触发了MCF-7，HepG2和HT-29细胞系的S期细胞周期停滞，并伴有ROS的产生，线粒体功能障碍和凋亡。此外，口服CHEQ-2（10 mg / kg）可显着抑制裸鼠体内异种移植的人肝肿瘤的生长，同时显示出极低的毒性（LD 50  > 2000 mg / kg）。这些发现

  DOI：

  10.1016/j.ejmech.2014.05.063

文献信息

• 一种咪唑并吡啶巯乙酸类衍生物及其制备方 法与应用
  申请人：山东大学

  公开号：CN106083847B

  公开（公告）日：2018-10-30

  本发明涉及一种咪唑并吡啶巯乙酸类衍生物及其制备方法和应用。所述化合物具有式I、II、III所示的结构。本发明还涉及含有式I、II、III结构化合物的制备方法以及药物组合物。本发明还提供上述化合物在制备抗痛风的药物中的应用。
• IMIDAZOPYRIDINE THIOGLYCOLIC ACID DERIVATIVE, PREPARATION METHOD THEREFOR AND APPLICATION THEREOF
  申请人：Shandong University

  公开号：EP3495362A1

  公开（公告）日：2019-06-12

  Provided are an imidazopyridine thioglycolic acid derivative, a preparation method therefor and an application thereof. Said compound has the structure as shown in formula I, II and III. Also provided are a preparation method for the compound having the structure as shown in formula I, II and III, and a pharmaceutical composition thereof. Also provided is an application of the above compound in the preparation of anti-gout drugs.

  本发明提供了一种咪唑吡啶硫代乙醇酸衍生物、其制备方法及其应用。所述化合物具有如式 I、II 和 III 所示的结构。还提供了具有式 I、II 和 III 所示结构的化合物的制备方法及其药物组合物。还提供了上述化合物在制备抗痛风药物中的应用。
• Imidazopyridine thioglycolic acid derivatives as potent inhibitors of human urate transporter 1
  申请人：SHANDONG UNIVERSITY

  公开号：US10399978B2

  公开（公告）日：2019-09-03

  It relates to the imidazopyridine thioglycolic acid derivatives, the preparation, and use thereof. The invention contained imidazopyridine thioglycolic acid derivatives with the formula I or II or III. Also described here are preparation of imidazopyridine thioglycolic acid derivatives, pharmaceutical compositions comprising these compounds as therapy and prevention for gout.

  本发明涉及咪唑吡啶硫代乙醇酸衍生物、其制备方法和用途。本发明包含式 I 或 II 或 III 的咪唑吡啶硫代乙醇酸衍生物。这里还描述了咪唑吡啶硫代乙醇酸衍生物的制备、包含这些化合物的药物组合物作为痛风的治疗和预防。
• Novel Human Urate Transporter 1 Inhibitors as Hypouricemic Drug Candidates with Favorable Druggability
  作者：Tong Zhao、Qing Meng、Zhuosen Sun、Yanyu Chen、Wei Ai、Zean Zhao、Dongwei Kang、Yue Dong、Ruipeng Liang、Ting Wu、Jianxin Pang、Xinyong Liu、Peng Zhan

  DOI：10.1021/acs.jmedchem.0c00223

  日期：2020.10.8

  Lesinurad, a human urate transporter 1 (URAT1) inhibitor approved as a medication for the treatment of hyperuricemia associated with gout in 2015, can cause liver and renal toxicity. Here, we modified all three structural components of lesinurad by applying scaffold hopping, bioisosterism, and substituent-decorating strategies. In a mouse model of acute hyperuricemia, 21 of the synthesized compounds showed increased serum uric acid (SUA)-reducing activity; SUA was about 4-fold lower in animals treated with 44, 54, and 83 compared with lesinurad or benzbromarone. In the URAT1 inhibition assay, 44 was over 8-fold more potent than lesinurad (IC50: 1.57 mu M vs 13.21 mu M). Notably, 83 also displayed potent inhibitory activity (IC50 = 31.73 mu M) against GLUT9. Furthermore, we also preliminarily explored the effect of chirality on the potency of the promising derivatives 44 and 54. Compounds 44, 54, and 83 showed favorable drug-like pharmacokinetics and appear to be promising candidates for the treatment of hyperuricemia and gout.
• Novel Imidazopyridine Thioglycolic Acid Derivatives as Potent Inhibitors of Human Urate Transporter 1
  申请人：SHANDONG UNIVERSITY

  公开号：US20190225606A1

  公开（公告）日：2019-07-25

  It relates to the imidazopyridine thioglycolic acid derivatives, the preparation, and use thereof. The invention contained imidazopyridine thioglycolic acid derivatives with the formula I or II or III. Also described here are preparation of imidazopyridine thioglycolic acid derivatives, pharmaceutical compositions comprising these compounds as therapy and prevention for gout.