(1-乙基-5-甲基-1H-吡唑-4-基)甲醇 | 494214-31-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: (1-乙基-5-甲基-1H-吡唑-4-基)甲醇
• 英文名称: (1-ethyl-5-methyl-1H-pyrazol-4-yl)methanol
• 英文别名: (1-ethyl-5-methylpyrazol-4-yl)methanol
• CAS: 494214-31-2
• 化学式: C₇H₁₂N₂O
• mdl: MFCD02253732
• 分子量: 140.18
• InChiKey: FGYVPWYZXQJMNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  10
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  38
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2933199090

反应信息

• 作为反应物：
  描述：

  (S)-1-((S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl)piperidine-2-carboxylic acid 、 (1-乙基-5-甲基-1H-吡唑-4-基)甲醇 在 4-吡咯烷基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲苯 为溶剂， 以57 %的产率得到(1-ethyl-5-methyl-1H-pyrazol-4-yl)methyl (S)-1-((S)-2-cyclohexyl-2-(3,4,5-trimethoxyphenyl)acetyl)piperidine-2-carboxylate
  参考文献：
  名称：

  10.1002/cmdc.202400264

  摘要：

  The FK506 binding protein 51 (FKBP51) is an appealing drug target due to its role in several diseases such as depression, anxiety, chronic pain and obesity. Towards this, selectivity versus the close homolog FKBP52 is essential. However, currently available FKBP51‐selective ligands such as SAFit2 are too large and lack drug‐like properties. Here, we present a structure activity relationship (SAR) analysis of the pipecolic ester moiety of SAFit1 and SAFit2, which culminated in the discovery of the 1,4‐pyrazolyl derivative 23d, displaying a binding affinity of 0.077 µM for FKBP51, reduced molecular weight (541.7 g/mol), lower hydrophobicity (cLogP = 3.72) and higher ligand efficiency (LE = 0.25). Cocrystal structures revealed the importance of the 1,4‐ and 1,3,4‐ substitution patterns of the pyrazole ring versus the 1,4,5 arrangement.

  DOI：

  10.1002/cmdc.202400264
• 作为产物：
  描述：

  ethyl 2-[(dimethylamino)methylene]-3-oxobutanoate 在 盐酸 、 lithium aluminium tetrahydride 、 sodium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.0h， 生成 (1-乙基-5-甲基-1H-吡唑-4-基)甲醇
  参考文献：
  名称：

  10.1002/cmdc.202400264

  摘要：

  The FK506 binding protein 51 (FKBP51) is an appealing drug target due to its role in several diseases such as depression, anxiety, chronic pain and obesity. Towards this, selectivity versus the close homolog FKBP52 is essential. However, currently available FKBP51‐selective ligands such as SAFit2 are too large and lack drug‐like properties. Here, we present a structure activity relationship (SAR) analysis of the pipecolic ester moiety of SAFit1 and SAFit2, which culminated in the discovery of the 1,4‐pyrazolyl derivative 23d, displaying a binding affinity of 0.077 µM for FKBP51, reduced molecular weight (541.7 g/mol), lower hydrophobicity (cLogP = 3.72) and higher ligand efficiency (LE = 0.25). Cocrystal structures revealed the importance of the 1,4‐ and 1,3,4‐ substitution patterns of the pyrazole ring versus the 1,4,5 arrangement.

  DOI：

  10.1002/cmdc.202400264

文献信息

• 10.1002/cmdc.202400264
  作者：Buffa, Vanessa、Meyners, Christian、Sugiarto, Wisely Oki、Bauder, Michael、Gaali, Steffen、Hausch, Felix

  DOI：10.1002/cmdc.202400264

  日期：——

  The FK506 binding protein 51 (FKBP51) is an appealing drug target due to its role in several diseases such as depression, anxiety, chronic pain and obesity. Towards this, selectivity versus the close homolog FKBP52 is essential. However, currently available FKBP51‐selective ligands such as SAFit2 are too large and lack drug‐like properties. Here, we present a structure activity relationship (SAR) analysis of the pipecolic ester moiety of SAFit1 and SAFit2, which culminated in the discovery of the 1,4‐pyrazolyl derivative 23d, displaying a binding affinity of 0.077 µM for FKBP51, reduced molecular weight (541.7 g/mol), lower hydrophobicity (cLogP = 3.72) and higher ligand efficiency (LE = 0.25). Cocrystal structures revealed the importance of the 1,4‐ and 1,3,4‐ substitution patterns of the pyrazole ring versus the 1,4,5 arrangement.