3-methyl-5-boc-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine | 1293995-81-9

• 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-methyl-5-boc-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine
• 英文别名: tert-butyl 3-methyl-6,7-dihydro-4H-triazolo[1,5-a]pyrazine-5-carboxylate
• CAS: 1293995-81-9
• 化学式: C₁₁H₁₈N₄O₂
• 分子量: 238.29
• InChiKey: UPTGNMNEHORZKN-UHFFFAOYSA-N

物化性质

• 沸点：
  384.5±52.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.34
• 重原子数：
  17.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  60.25
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3-methyl-5-boc-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine 在 盐酸 、 lithium perchlorate 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 30.0h， 生成 (2R, 3R)-3-(3-methyl-6,7-dihydro-[1,2,3]triazolo[1,5-a]pyrazin-5(4H)-yl)-2-(2,4-difluorophenyl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
  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 、 palladium on activated charcoal 、 氢气 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 10.0h， 生成 3-methyl-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

• Discovery of potent dipeptidyl peptidase IV inhibitors derived from β-aminoamides bearing substituted [1,2,3]-triazolopiperidines for the treatment of type 2 diabetes
  作者：Zhenwei Shan、Min Peng、Houxing Fan、Qingtao Lu、Peng Lu、Chuansheng Zhao、Yilang Chen

  DOI：10.1016/j.bmcl.2011.01.086

  日期：2011.3

  A series of novel [1,2,3]-triazolopiperidine derivatives 5a–5y were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes, most of the compounds exhibited excellent in vitro potency (IC50 <50 nM) against DPP-4. Among these, compound 5d with potent in vitro activity against DPP-4 and good pharmacokinetic profiles exhibited pronounced in vivo

  合成了一系列新颖的[1,2,3]-三唑并哌啶衍生物5a-5y，并作为二肽基肽酶IV（DPP-4）的抑制剂进行了评估，用于治疗2型糖尿病，大多数化合物具有出色的体外药效（ 针对DPP-4的IC 50 <50 nM）。在这些化合物中，对DPP-4具有强大的体外活性和良好的药代动力学特征的化合物5d在ICR小鼠的口服葡萄糖耐量试验（OGTT）中表现出明显的体内功效。基于这些特性，选择化合物5d作为治疗2型糖尿病的潜在新候选药物。