ethyl 4-amino-1-ethyl-1H-pyrazole-3-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 4-amino-1-ethyl-1H-pyrazole-3-carboxylate
• 英文别名: ethyl 4-amino-1-ethylpyrazole-3-carboxylate
• 化学式: C₈H₁₃N₃O₂
• mdl: MFCD04971146
• 分子量: 183.21
• InChiKey: JOKFTFRNYGOITH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  70.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-amino-1-ethyl-1H-pyrazole-3-carboxylate 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 22.08h， 生成 4-(5-((3,5-dimethyl-1H-pyrazol-1-yl)methyl)thiophene-2-carboxamido)-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：

  ethyl 1-ethyl-4-nitro-1H-pyrazole-3-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 反应 22.0h， 以76.8%的产率得到ethyl 4-amino-1-ethyl-1H-pyrazole-3-carboxylate
  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

• Collaborative Virtual Screening Identifies a 2-Aryl-4-aminoquinazoline Series with Efficacy in an <i>In Vivo</i> Model of <i>Trypanosoma cruzi</i> Infection
  作者：Taisuke Tawaraishi、Atsuko Ochida、Yuichiro Akao、Sachiko Itono、Masahiro Kamaura、Thamina Akther、Mitsuyuki Shimada、Stacie Canan、Sanjoy Chowdhury、Yafeng Cao、Kevin Condroski、Ola Engkvist、Amanda Francisco、Sunil Ghosh、Rina Kaki、John M. Kelly、Chiaki Kimura、Thierry Kogej、Kazuya Nagaoka、Akira Naito、Garry Pairaudeau、Constantin Radu、Ieuan Roberts、David Shum、Nao-aki Watanabe、Huanxu Xie、Shuji Yonezawa、Osamu Yoshida、Ryu Yoshida、Charles Mowbray、Benjamin Perry

  DOI：10.1021/acs.jmedchem.2c00775

  日期：2023.1.26