4-isothiocyanato-1-methyl-1H-pyrazole | 1001500-53-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-isothiocyanato-1-methyl-1H-pyrazole
• 英文别名: 4-isothiocyanato-1-methylpyrazole
• CAS: 1001500-53-3
• 化学式: C₅H₅N₃S
• 分子量: 139.181
• InChiKey: MTXQEKCAXHBISK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  62.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-isothiocyanato-1-methyl-1H-pyrazole 、 2-hydroxy-2-(4-methylthiazol-2-yl)propanehydrazide 以 四氢呋喃 为溶剂， 生成 2-(2-hydroxy-2-(4-methylthiazol-2-yl)propanoyl)-N-(1-methyl-1H-pyrazol-4-yl)hydrazine-1-carbothioamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of New Thiadiazole-Based Direct Inhibitors of Enoyl Acyl Carrier Protein Reductase (InhA) for the Treatment of Tuberculosis

  摘要：

  Mycobacterial enoyl acyl carrier protein reductase (InhA) is a clinically validated target for the treatment of tuberculosis infections, a disease that still causes the death of at least a million people annually. A known class of potent, direct, and competitive InhA inhibitors based on a tetracyclic thiadiazole structure has been shown to have in vivo activity in murine models of tuberculosis infection. On the basis of this template, we have here explored the medicinal chemistry of truncated analogues that have only three aromatic rings. In particular, compounds 8b, 8d, 8f, 8l, and 8n show interesting features, including low nanomolar InhA IC50, submicromolar antimycobacterial potency, and improved physicochemical profiles in comparison with the tetracyclic analogues. From this series, 8d is identified as having the best balance of potency and properties, whereby the resolved 8d S-enatiomer shows encouraging in vivo efficacy.

  DOI：

  10.1021/jm501029r
• 作为产物：
  描述：

  硫光气 、 1-甲基-1H-吡唑-4-胺 在 吡啶 作用下， 生成 4-isothiocyanato-1-methyl-1H-pyrazole
  参考文献：
  名称：

  [EN] AMINOPYRAZOLE TRIAZOLOTHIADIAZOLE INHIBITORS OF C-MET PROTIEN KINASE
  [FR] INHIBITEURS À BASE DE TRIAZOLOPYRAZOLE, TRIAZOLOTHIADIAZOLE DE LA PROTÉINE KINASE C-MET

  摘要：

  本发明涉及公式（I）的化合物，该化合物在抑制c-Met蛋白激酶方面具有用途。该发明还提供了包含公式（I）化合物的药学上可接受的组合物，并提供了使用这些组合物治疗增生性疾病的方法。

  公开号：

  WO2010138665A1

文献信息

• [EN] THIOPHENE DERIVATIVES FOR THE TREATMENT OF DISORDERS CAUSED BY IGE<br/>[FR] DÉRIVÉS DE THIOPHÈNE POUR LE TRAITEMENT DE TROUBLES PROVOQUÉS PAR IGE
  申请人：UCB BIOPHARMA SRL

  公开号：WO2019243550A1

  公开（公告）日：2019-12-26

  Thiophene derivatives of formula (I) and a pharmaceutically acceptable salt thereof are provided. These compounds have utility for the treatment or prevention of disorders caused by IgE, such as allergy, type 1 hypersensitivity or familiar sinus inflammation.

  提供了公式（I）的噻吩衍生物及其药用可接受的盐。这些化合物对于治疗或预防由IgE引起的疾病具有用途，如过敏、1型超敏反应或家族性鼻窦炎。
• [EN] AMINOPYRAZOLE TRIAZOLOTHIADIAZOLE INHIBITORS OF C-MET PROTIEN KINASE<br/>[FR] INHIBITEURS À BASE DE TRIAZOLOPYRAZOLE, TRIAZOLOTHIADIAZOLE DE LA PROTÉINE KINASE C-MET
  申请人：VERTEX PHARMA

  公开号：WO2010138665A1

  公开（公告）日：2010-12-02

  The present invention relates to compounds of formula (I), which is useful in the inhibition of c-Met protein kinase. The invention also provides pharmaceutically acceptable compositions comprising compounds of formula (I) and methods of using the compositions in the treatment of proliferative disorders.

  本发明涉及公式（I）的化合物，该化合物在抑制c-Met蛋白激酶方面具有用途。该发明还提供了包含公式（I）化合物的药学上可接受的组合物，并提供了使用这些组合物治疗增生性疾病的方法。
• Discovery of Potent, Selective Triazolothiadiazole-Containing c-Met Inhibitors
  作者：Qing Tang、Alex M. Aronov、David D. Deininger、Simon Giroux、David J. Lauffer、Pan Li、Jianglin Liang、Kira McGinty、Steven Ronkin、Rebecca Swett、Nathan Waal、Diane Boucher、Pamella J. Ford、Cameron S. Moody

  DOI：10.1021/acsmedchemlett.1c00094

  日期：2021.6.10

  Herein, we report a novel series of highly potent and selective triazolothiadiazole c-Met inhibitors. Starting with molecule 5, we have applied structure-based drug design principles to identify the triazolothiadiazole ring system. We successfully replaced the metabolically unstable phenolic moiety with a quinoline group. Further optimization around the 5,6 bicyclic moiety led to the identification

  在此，我们报告了一系列新的高效和选择性三唑并噻二唑 c-Met 抑制剂。从分子5开始，我们应用了基于结构的药物设计原则来识别三唑并噻二唑环系统。我们成功地用喹啉基团取代了代谢不稳定的酚类部分。围绕 5,6 双环部分的进一步优化导致了21的鉴定。化合物21存在 PDE3 选择性问题，随后的结构知情设计导致化合物23的发现。化合物23具有精细的激酶选择性、优异的效力、良好的 ADME 谱，并在 SNU-5 胃癌异种移植模型中显示出剂量依赖性的抗肿瘤功效。
• Design, Synthesis, and Evaluation of New Thiadiazole-Based Direct Inhibitors of Enoyl Acyl Carrier Protein Reductase (InhA) for the Treatment of Tuberculosis
  作者：Roman Šink、Izidor Sosič、Matej Živec、Raquel Fernandez-Menendez、Samo Turk、Stane Pajk、Daniel Alvarez-Gomez、Eva Maria Lopez-Roman、Carolina Gonzales-Cortez、Joaquin Rullas-Triconado、Inigo Angulo-Barturen、David Barros、Lluís Ballell-Pages、Robert J. Young、Lourdes Encinas、Stanislav Gobec

  DOI：10.1021/jm501029r

  日期：2015.1.22

  Mycobacterial enoyl acyl carrier protein reductase (InhA) is a clinically validated target for the treatment of tuberculosis infections, a disease that still causes the death of at least a million people annually. A known class of potent, direct, and competitive InhA inhibitors based on a tetracyclic thiadiazole structure has been shown to have in vivo activity in murine models of tuberculosis infection. On the basis of this template, we have here explored the medicinal chemistry of truncated analogues that have only three aromatic rings. In particular, compounds 8b, 8d, 8f, 8l, and 8n show interesting features, including low nanomolar InhA IC50, submicromolar antimycobacterial potency, and improved physicochemical profiles in comparison with the tetracyclic analogues. From this series, 8d is identified as having the best balance of potency and properties, whereby the resolved 8d S-enatiomer shows encouraging in vivo efficacy.