3-fluoroisonicotinohydrazide | 364-82-9

• 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: 3-fluoroisonicotinohydrazide
• 英文别名: 3-Fluoropyridine-4-carbohydrazide
• CAS: 364-82-9
• 化学式: C₆H₆FN₃O
• mdl: MFCD21114912
• 分子量: 155.132
• InChiKey: BGDVMASDBPPEBX-UHFFFAOYSA-N

物化性质

• 密度：
  1.356±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  68
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险性防范说明：
  P261,P264,P270,P271,P280,P301+P312,P302+P352,P304+P340,P305+P351+P338,P330,P332+P313,P337+P313,P362,P403+P233,P405,P501
• 危险性描述：
  H302,H312,H315,H319,H332,H335

反应信息

• 作为反应物：
  描述：

  3-fluoroisonicotinohydrazide 在 4-二甲氨基吡啶 、 四丁基溴化铵 、 一水合肼 、 potassium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 水 为溶剂， 生成 6-((4-bromophenoxy)methyl)-3-(3-fluoropyridin-4-yl)[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole
  参考文献：
  名称：

  SAR studies on 1,2,4-triazolo[3,4-b][1,3,4]thiadiazoles as inhibitors of Mtb shikimate dehydrogenase for the development of novel antitubercular agents

  摘要：

  三唑噻二唑是一种具有较强抗结核活性的药物，对MtSD有适度的抑制作用，并且没有明显的细胞毒性。

  DOI：

  10.1039/c5ra19334f
• 作为产物：
  描述：

  3-氟吡啶-4-甲酸 在 三乙胺 、 fluoro-N,N,N',N'-tetramethylformamidinium hexafluorophosphate 、 hydrazine hydrate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.33h， 以73%的产率得到3-fluoroisonicotinohydrazide
  参考文献：
  名称：

  异烟肼构效关系的再研究

  摘要：

  异烟肼 (INH) 仍然是治疗药物敏感结核病 (TB) 的基石，但文献中尚未详细记录 INH 的定量构效关系。在本文中，我们评估了一系列 INH 类似物对来自不同谱系的当代结核分枝杆菌菌株和一些非结核分枝杆菌 (NTM) 的系统性影响。吡啶基氮原子的缺失、吡啶氮异构化到其他位置、用等排杂环取代吡啶环以及修饰INH的酰肼部分会消除抗结核活性。类似地，吡啶环在3位上的取代是不能容忍的，而在2位上的取代允许用2-甲基-INH 9进行，其抗分枝杆菌活性与INH相当。为了评估这一系列 INH 类似物针对分枝杆菌的比活性，我们对一组革兰氏阳性和革兰氏阴性细菌以及一些真菌进行了测定。正如预期的那样，INH 及其类似物显示出较窄的活性谱，并且对所评估的所有非分枝杆菌菌株均无活性，但4 菌株除外，该菌株对新型隐球菌具有适度的抑制活性。我们的研究结果提供了对 INH 结构-活性关系的最新分析，我们希望这能为社区提供有用的资源。

  DOI：

  10.1016/j.tube.2021.102100

文献信息

• 3,6-二取代[1,2,4]三唑[3,4-b][1,3,4]噻二 唑化合物及其用途
  申请人：中国科学院上海药物研究所

  公开号：CN104892639B

  公开（公告）日：2018-10-30

  本发明公开了具有如下通式(I)所示的3,6‑二取代[1,2,4]三唑[3,4‑b][1,3,4]噻二唑类化合物及其药学上可以接受的盐或药学上可以接受的溶剂合物，其可以作为包括金黄色葡萄球菌、酿脓杆菌、炭疽杆菌和肺炎链球菌在内的革兰氏阳性菌转肽酶SrtA抑制剂，可以应用于制备治疗以革兰氏阳性菌例如金黄色葡萄球菌、酿脓杆菌、炭疽杆菌和肺炎链球菌等转肽酶SrtA为靶点的病原菌感染性疾病的药物。本发明在一定程度上避免了病原菌由于选择压力而产生耐药性，减轻了持续出现的耐药病原菌对人类健康的威胁。
• Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drug-resistant Mtb strains
  作者：Ziqiang Li、Xiaoguang Bai、Qi Deng、Guoning Zhang、Lei Zhou、Yishuang Liu、Juxian Wang、Yucheng Wang

  DOI：10.1016/j.bmc.2016.10.027

  日期：2017.1

  Following up the SAR study of triazolothiadiazoles for their antitubercular activities targeting Mt SD in our previous study, on the principle of scaffold hopping, the C3 and C6 positions of triazolothiadiazine were examined systematically to define a preliminary structure-activity relationship (SAR) with respect to biological activity. This study herein highlights the potential of two highly potent advanced leads 6c-3, 6g-3 and several other compounds with comparable potencies as promising new candidates for the treatment of TB (6c-3, MIC-H37Rv = 0.25 mu g/mL; MIC-MDRTB = 2.0 mu g/mL; MIC-RDRTB = 0.25 mu g/mL; Mt SD-IC50 = 86.39 mu g/mL; and 6g-3, MIC-H37Rv = 1.0 mu g/mL; MIC-MDRTB = 4.0 mu g/mL; MICRDRTB = 2.0 mu g/mL; Mt SD-IC50 = 73.57 mu g/mL). Compounds 6c-3 and 6g-3 possessed a para-nitro phenyl at the 6 position showed low Vero and HepG2 cells toxicity, turning out to be two excellent lead candidates for preclinical trials. In addition, in vitro Mt SD inhibitory assay indicates that Mt SD is at least one of the targets for their antitubercular activity. Thus, they may turn out to be promising multidrug-resistance- reversing agents. (C) 2016 Elsevier Ltd. All rights reserved.
• Narrow SAR in odorant sensing Orco receptor agonists
  作者：Ian M. Romaine、Robert W. Taylor、Samsudeen P. Saidu、Kwangho Kim、Gary A. Sulikowski、Laurence J. Zwiebel、Alex G. Waterson

  DOI：10.1016/j.bmcl.2014.04.081

  日期：2014.6

  The systematic exploration of a series of triazole-based agonists of the cation channel insect odorant receptor is reported. The structure-activity relationships of independent sections of the molecules are examined. Very small changes to the compound structure were found to exert a large impact on compound activity. Optimal substitutions were combined using a 'mix-and-match' strategy to produce best-in-class compounds that are capable of potently agonizing odorant receptor activity and may form the basis for the identification of a new mode of insect behavior modification. (C) 2014 Elsevier Ltd. All rights reserved.
• Highly selective c-Jun N-terminal kinase (JNK) 3 inhibitors with in vitro CNS-like pharmacokinetic properties II. Central core replacement
  作者：R. Jeffrey Neitz、Andrei W. Konradi、Hing L. Sham、Wes Zmolek、Karina Wong、Ann Qin、Colin Lorentzen、David Nakamura、Kevin P. Quinn、John-Michael Sauer、Kyle Powell、Lany Ruslim、David Chereau、Zhao Ren、John Anderson、Frédérique Bard、Ted A. Yednock、Irene Griswold-Prenner

  DOI：10.1016/j.bmcl.2011.04.074

  日期：2011.6

  In this Letter, we describe the evolution of selective JNK3 inhibitors from 1, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs. Strong SAR was found for substitution of the naphthalene ring, as well as for inhibitors adopting different central scaffolds. Significant potency gains were appreciated by inverting the polarity of the thione of the parent triazolothione 1, resulting in potent compounds with attractive pharmacokinetic profiles. (C) 2011 Elsevier Ltd. All rights reserved.
• THE PREPARATION OF 3-FLUOROISONICOTINIC ACID AND RELATED COMPOUNDS
  作者：ARTHUR ROE、ROBERT B. SELIGMAN

  DOI：10.1021/jo01364a020

  日期：1955.12