3-((3,5-二甲基-1H-吡唑-1-基)甲基)苯甲酸 | 376359-05-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-((3,5-二甲基-1H-吡唑-1-基)甲基)苯甲酸
• 中文别名: 3-[(3,5-二甲基-1H-吡唑-1-基)甲基]苯甲酸
• 英文名称: 3-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzoic acid
• 英文别名: 3-[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]benzoic acid；3-[(3,5-dimethylpyrazol-1-yl)methyl]benzoic acid
• CAS: 376359-05-6
• 化学式: C₁₃H₁₄N₂O₂
• mdl: MFCD01114897
• 分子量: 230.266
• InChiKey: WWFUQDPIXVPKQB-UHFFFAOYSA-N

物化性质

• 沸点：
  433.2±45.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933199090

反应信息

• 作为反应物：
  描述：

  3-((3,5-二甲基-1H-吡唑-1-基)甲基)苯甲酸 在 氯化铵 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.16h， 生成 4-(3-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)benzamido)-1-ethyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of 1-ethylpyrazole-3-carboxamide compounds as novel hypoxia-inducible factor (HIF)-1 inhibitors

  摘要：

  Hypoxia-inducible factor (HIF)-1 is well known as a promising target for cancer chemotherapy. By screening an in-house chemical library using a hypoxia-responsive luciferase reporter gene assay, we identified CLB-016 (1) containing 1-ethylpyrazole-3-carboxamide as a HIF-1 inhibitor (IC50 = 19.1 mu M). In a subsequent extensive structure-activity relationship (SAR) study, we developed compound 11Ae with an IC50 value of 8.1 mu M against HIF-1-driven luciferase activity. Compounds 1 and 11Ae were shown to significantly suppress the HIF-1-mediated hypoxia response, including carbonic anhydrase IX (CAIX) gene expression and migration of human sarcoma HT1080 cells. These results revealed 1-ethylpyrazole-3-carboxamide as a novel scaffold to develop promising anti-cancer drugs targeting the HIF-1 signaling pathway. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.02.038
• 作为产物：
  描述：

  3-氯甲基苯甲酸甲酯 在 potassium tert-butylate 、 四丁基碘化铵 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 48.0h， 生成 3-((3,5-二甲基-1H-吡唑-1-基)甲基)苯甲酸
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of 1-ethylpyrazole-3-carboxamide compounds as novel hypoxia-inducible factor (HIF)-1 inhibitors

  摘要：

  Hypoxia-inducible factor (HIF)-1 is well known as a promising target for cancer chemotherapy. By screening an in-house chemical library using a hypoxia-responsive luciferase reporter gene assay, we identified CLB-016 (1) containing 1-ethylpyrazole-3-carboxamide as a HIF-1 inhibitor (IC50 = 19.1 mu M). In a subsequent extensive structure-activity relationship (SAR) study, we developed compound 11Ae with an IC50 value of 8.1 mu M against HIF-1-driven luciferase activity. Compounds 1 and 11Ae were shown to significantly suppress the HIF-1-mediated hypoxia response, including carbonic anhydrase IX (CAIX) gene expression and migration of human sarcoma HT1080 cells. These results revealed 1-ethylpyrazole-3-carboxamide as a novel scaffold to develop promising anti-cancer drugs targeting the HIF-1 signaling pathway. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.02.038

文献信息

• <i>N</i>-Benzyl-4-((heteroaryl)methyl)benzamides: A New Class of Direct NADH-Dependent 2-<i>trans</i>Enoyl-Acyl Carrier Protein Reductase (InhA) Inhibitors with Antitubercular Activity
  作者：Ana Guardia、Gulcin Gulten、Raquel Fernandez、Jesus Gómez、Feng Wang、Maire Convery、Delia Blanco、María Martínez、Esther Pérez-Herrán、Marta Alonso、Fátima Ortega、Joaquín Rullás、David Calvo、Lydia Mata、Robert Young、James C. Sacchettini、Alfonso Mendoza-Losana、Modesto Remuiñán、Lluís Ballell Pages、Julia Castro-Pichel

  DOI：10.1002/cmdc.201600020

  日期：2016.4.5

  carrier protein reductase (InhA) inhibitors based on an N‐benzyl‐4‐((heteroaryl)methyl)benzamide template; unlike INH, these do not require prior activation by KatG. Given their direct InhA target engagement, these compounds should be able to circumvent KatG‐related resistance in the clinic. The lead molecules were shown to be potent inhibitors of InhA and showed activity against M. tuberculosis bacteria

  异烟肼（INH）仍然是结核分枝杆菌药物敏感菌株抗结核化疗的基石之一。然而，在KatG酶中含有突变的多药耐药（MDR）和广泛耐药（XDR）菌株的流行正在增加，这导致INH活化为其抗结核形式，这使这种药物很少或根本没有使用在许多耐药结核病例中。本文介绍的是基于N的抗结核性直接依赖NADH的2-反式烯酰-酰基载体蛋白还原酶（InhA）抑制剂的新家族-苄基-4-（（杂芳基）甲基）苯甲酰胺模板; 与INH不同，这些不需要KatG预先激活。鉴于它们直接参与了InhA靶标的结合，因此这些化合物应能够在临床中规避与KatG相关的耐药性。铅分子被证明是InhA的有效抑制剂，并表现出抗结核分枝杆菌的活性。发现这种新的抑制剂家族具有化学易处理性，例如类似物的简便合成和构效关系的建立就是例证。此外，还揭示了该酶最初命中的共晶体结构，为设计用于治疗MDR / XDR结核病的新型InhA抑制剂提供了有价值的信息。
• 10.1080/14756366.2024.2353711
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  DOI：10.1080/14756366.2024.2353711

  日期：——

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• Design, synthesis, and structure–activity relationships of 1-ethylpyrazole-3-carboxamide compounds as novel hypoxia-inducible factor (HIF)-1 inhibitors
  作者：Yorinobu Yasuda、Takeaki Arakawa、Yumi Nawata、Sayaka Shimada、Shinya Oishi、Nobutaka Fujii、Shinichi Nishimura、Akira Hattori、Hideaki Kakeya

  DOI：10.1016/j.bmc.2015.02.038

  日期：2015.4

  Hypoxia-inducible factor (HIF)-1 is well known as a promising target for cancer chemotherapy. By screening an in-house chemical library using a hypoxia-responsive luciferase reporter gene assay, we identified CLB-016 (1) containing 1-ethylpyrazole-3-carboxamide as a HIF-1 inhibitor (IC50 = 19.1 mu M). In a subsequent extensive structure-activity relationship (SAR) study, we developed compound 11Ae with an IC50 value of 8.1 mu M against HIF-1-driven luciferase activity. Compounds 1 and 11Ae were shown to significantly suppress the HIF-1-mediated hypoxia response, including carbonic anhydrase IX (CAIX) gene expression and migration of human sarcoma HT1080 cells. These results revealed 1-ethylpyrazole-3-carboxamide as a novel scaffold to develop promising anti-cancer drugs targeting the HIF-1 signaling pathway. (C) 2015 Elsevier Ltd. All rights reserved.