3-methyl-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine | 1293996-10-7

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3-methyl-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine
• 英文别名: 3-methyl-4,5,6,7-tetrahydrotriazolo[1,5-a]pyrazine；3-Methyl-4,5,6,7-tetrahydrotriaZolo[1,5-a]pyraZine
• CAS: 1293996-10-7
• 化学式: C₆H₁₀N₄
• 分子量: 138.172
• InChiKey: BYQUGLSPIPRJQI-UHFFFAOYSA-N

物化性质

• 沸点：
  308.7±44.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  42.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-methyl-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (R)-3-amino-4-(2,4,5-trifluorophenyl)-1-(6,7-dihydro-3-methyl-[1,2,3]triazolo[1,5-a]pyrazin-5(4H)-yl)butan-1-one hydrochloride
  参考文献：
  名称：

  发现有效的衍生自带有取代的[1,2,3]-三唑并哌啶的β-氨基酰胺的二肽基肽酶IV抑制剂，用于治疗2型糖尿病

  摘要：

  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。

  DOI：

  10.1016/j.bmcl.2011.01.086
• 作为产物：
  描述：

  在 三氟乙酸 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 生成 3-methyl-4,5,6,7-tetrahydro-[1,2,3]triazolo[1,5-a]pyrazine
  参考文献：
  名称：

  发现有效的衍生自带有取代的[1,2,3]-三唑并哌啶的β-氨基酰胺的二肽基肽酶IV抑制剂，用于治疗2型糖尿病

  摘要：

  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。

  DOI：

  10.1016/j.bmcl.2011.01.086

文献信息

• [EN] SUBSTITUTED 1,5-NAPHTHYRIDINES OR QUINOLINES AS ALK5 INHIBITORS<br/>[FR] 1,5-NAPHTYRIDINES OU QUINOLÉINES SUBSTITUÉES EN TANT QU'INHIBITEURS D'ALK5
  申请人：THERAVANCE BIOPHARMA R&D IP LLC

  公开号：WO2021102468A1

  公开（公告）日：2021-05-27

  The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.

  本公开提供了激活素受体样激酶5（ALK5）的抑制剂。还公开了调节ALK5活性的方法和通过ALK5介导的疾病的治疗方法。
• 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.
• ALK5 INHIBITORS
  申请人：THERAVANCE BIOPHARMA R&D IP, LLC

  公开号：US20210154178A1

  公开（公告）日：2021-05-27

  The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.
• [EN] ALK5 INHIBITORS<br/>[FR] INHIBITEURS D'ALK5
  申请人：THERAVANCE BIOPHARMA R&D IP LLC

  公开号：WO2020123453A2

  公开（公告）日：2020-06-18

  The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.
• 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。