3-chloromethyl-5-boc-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine | 1305336-27-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-chloromethyl-5-boc-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine
• 英文别名: tert-butyl 3-(chloromethyl)-6,7-dihydro-4H-triazolo[1,5-a]pyrazine-5-carboxylate
• CAS: 1305336-27-9
• 化学式: C₁₁H₁₇ClN₄O₂
• 分子量: 272.735
• InChiKey: BSGSXOCUUPQMPJ-UHFFFAOYSA-N

物化性质

• 沸点：
  420.8±55.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  60.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-chloromethyl-5-boc-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine 在 盐酸 、 palladium on activated charcoal 、 氢气 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 6.0h， 生成 3-methyl-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationship Studies of Novel Fused Heterocycles-Linked Triazoles with Good Activity and Water Solubility

  摘要：

  Triazoles with fused-heterocycle nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SAR of antifungal triazoles. Tetrahydro-[1,2,4]-triazolo[1,5-a]pyrazine and tetrahydro-thiazolo[5,4-c]pyridine nuclei were preferable to the other four fused-heterocycle nuclei investigated. Potent in vitro activity, broad spectrum and better water solubility were attained when triazoles containing nitrogen aromatic heterocycles were attached to these two nuclei. The most potent compounds 27aa and 45x, with low hERG inhibition and hepatocyte toxicity, both exhibited excellent activity against Candida, Cryptococcus, and Aspergillus spp., as well as selected fluconazole-resistant strains. A high water-soluble compound 58 (the disulfate salt of 45x) displayed unsatisfactory in vivo activity because of its poor PK profiles. Mice infected with C.alb. SC5314 and C.alb. 103 (fluconazole-resistant strain) and administered with 27aa displayed significantly improved survival rates. 27aa also showed favorable pharmacokinetic (PK) profiles.

  DOI：

  10.1021/jm4016284
• 作为产物：
  描述：

  (4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazin-3-yl)methyl acetate 在 吡啶 、 氯化亚砜 、 lithium hydroxide monohydrate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 10.0h， 生成 3-chloromethyl-5-boc-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationship Studies of Novel Fused Heterocycles-Linked Triazoles with Good Activity and Water Solubility

  摘要：

  Triazoles with fused-heterocycle nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SAR of antifungal triazoles. Tetrahydro-[1,2,4]-triazolo[1,5-a]pyrazine and tetrahydro-thiazolo[5,4-c]pyridine nuclei were preferable to the other four fused-heterocycle nuclei investigated. Potent in vitro activity, broad spectrum and better water solubility were attained when triazoles containing nitrogen aromatic heterocycles were attached to these two nuclei. The most potent compounds 27aa and 45x, with low hERG inhibition and hepatocyte toxicity, both exhibited excellent activity against Candida, Cryptococcus, and Aspergillus spp., as well as selected fluconazole-resistant strains. A high water-soluble compound 58 (the disulfate salt of 45x) displayed unsatisfactory in vivo activity because of its poor PK profiles. Mice infected with C.alb. SC5314 and C.alb. 103 (fluconazole-resistant strain) and administered with 27aa displayed significantly improved survival rates. 27aa also showed favorable pharmacokinetic (PK) profiles.

  DOI：

  10.1021/jm4016284

文献信息

• Design, Synthesis, and Structure–Activity Relationship Studies of Novel Fused Heterocycles-Linked Triazoles with Good Activity and Water Solubility
  作者：Xufeng Cao、Zhaoshuan Sun、Yongbing Cao、Ruilian Wang、Tongkai Cai、Wenjing Chu、Wenhao Hu、Yushe Yang

  DOI：10.1021/jm4016284

  日期：2014.5.8

  Triazoles with fused-heterocycle nuclei were designed and evaluated for their in vitro activity on the basis of the binding mode of albaconazole using molecular docking, along with SAR of antifungal triazoles. Tetrahydro-[1,2,4]-triazolo[1,5-a]pyrazine and tetrahydro-thiazolo[5,4-c]pyridine nuclei were preferable to the other four fused-heterocycle nuclei investigated. Potent in vitro activity, broad spectrum and better water solubility were attained when triazoles containing nitrogen aromatic heterocycles were attached to these two nuclei. The most potent compounds 27aa and 45x, with low hERG inhibition and hepatocyte toxicity, both exhibited excellent activity against Candida, Cryptococcus, and Aspergillus spp., as well as selected fluconazole-resistant strains. A high water-soluble compound 58 (the disulfate salt of 45x) displayed unsatisfactory in vivo activity because of its poor PK profiles. Mice infected with C.alb. SC5314 and C.alb. 103 (fluconazole-resistant strain) and administered with 27aa displayed significantly improved survival rates. 27aa also showed favorable pharmacokinetic (PK) profiles.