(1Z)-2,2,2-三氟-N-羟基-N'-(2-吡嗪基)乙脒 | 681249-55-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: (1Z)-2,2,2-三氟-N-羟基-N'-(2-吡嗪基)乙脒
• 英文名称: 2,2,2-trifluoro-N’-hydroxy-N-pyrazin-2-ylacetimidamide
• 英文别名: (E)-2,2,2-trifluoro-N'-hydroxy-N-(pyrazin-2-yl)acetimidamide；2,2,2-trifluoro-N'-hydroxy-N-pyrazin-2-ylethanimidamide；2,2,2-trifluoro-N-hydroxy-N'-pyrazin-2-ylethanimidamide
• CAS: 681249-55-8
• 化学式: C₆H₅F₃N₄O
• 分子量: 206.127
• InChiKey: FSMJPGPBUMVVNE-UHFFFAOYSA-N

物化性质

• 沸点：
  257.8±50.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  70.4
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (1Z)-2,2,2-三氟-N-羟基-N'-(2-吡嗪基)乙脒 在 palladium on activated charcoal 、 氢气 作用下， 以 甲醇 为溶剂， 20.0~100.0 ℃ 、101.33 kPa 条件下， 反应 2.0h， 以50.8%的产率得到2-(三氟甲基)-5,6,7,8-四氢-[1,2,4]三唑并[1,5-a]吡嗪
  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：

  2,2,2-三氟-N-2-吡嗪乙酰胺 在 五氯化磷 、 三氯氧磷 、 盐酸羟胺 、 羟胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 7.0h， 以72.8%的产率得到(1Z)-2,2,2-三氟-N-羟基-N'-(2-吡嗪基)乙脒
  参考文献：
  名称：

  一种PARP抑制剂氟唑帕利中间体的合成工 艺

  摘要：

  本发明公开了适合放大制备2‑三氟甲基[1,2,4]三唑并[1,5‑a]吡嗪的工艺方法，属于药物中间体合成领域。以2‑氨基吡嗪和三氟乙酸乙酯为原料，经过氨酯交换反应、取代反应和脱水反应得到2‑三氟甲基[1,2,4]三唑并[1,5‑a]吡嗪，本发明工艺选用便宜的三氟乙酸乙酯代替昂贵的三氟乙酸酐，其他有机溶剂代替一类溶剂二氯乙烷，TFFA代替很难后处理的PPA，大幅降低了现有生物、医药、化学中间体的生产成本，该工艺在公斤级规模进行了放大验证，收率和产品纯度与克级规模基本相当，有望作为工业化规模生产的工艺。

  公开号：

  CN111635407B

文献信息

• [EN] AMINOCYCLOHEXANES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES<br/>[FR] AMINOCYCLOHEXANES EN TANT QU'INHIBITEURS DE DIPEPTIDYL PEPTIDASE-IV POUR LE TRAITEMENT OU LA PRÉVENTION DE DIABÈTES
  申请人：MERCK & CO INC

  公开号：WO2006009886A1

  公开（公告）日：2006-01-26

  The present invention is directed to novel substituted aminocyclohexanes which are inhibitors of the dipeptidyl peptidase-IV enzyme ('DPP-IV inhibitors') and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及一种新型的取代氨基环己烷，它们是二肽基肽酶-IV酶（'DPP-IV抑制剂'）的抑制剂，并且在治疗或预防涉及二肽基肽酶-IV酶的疾病中具有用处，如糖尿病，特别是2型糖尿病。该发明还涉及包含这些化合物的药物组合物以及在预防或治疗涉及二肽基肽酶-IV酶的这类疾病中使用这些化合物和组合物。
• Beta-amino heterocyclic dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
  申请人：Kim Dooseop

  公开号：US20060014953A1

  公开（公告）日：2006-01-19

  The present invention is directed to compounds which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及抑制二肽基肽酶-IV酶（“DP-IV抑制剂”）的化合物，该化合物在治疗或预防二肽基肽酶-IV酶参与的疾病中，如糖尿病和特别是2型糖尿病中有用。本发明还涉及含有这些化合物的药物组合物以及使用这些化合物和组合物在预防或治疗二肽基肽酶-IV酶参与的这些疾病中的应用。
• Aminocyclohexanes as Dipeptidyl Peptidase-Iv Inhibitors for the Treatment or Prevention of Diabetes
  申请人：Biftu Tesfaye

  公开号：US20070254865A1

  公开（公告）日：2007-11-01

  The present invention is directed to novel substituted aminocyclohexanes which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DPP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly Type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及新型的取代氨基环己烷，其为二肽基肽酶-IV酶（“DPP-IV抑制剂”）的抑制剂，并且对于二肽基肽酶-IV酶参与的疾病，例如糖尿病和特别是2型糖尿病的治疗或预防有用。该发明还涉及包含这些化合物的制药组合物以及在预防或治疗二肽基肽酶-IV酶参与的这些疾病中使用这些化合物和组合物。
• Fused Triazole Derivatives as Dipeptidyl Peptidase-IV Inhibitors for the Treatment or Prevention of Diabetes
  申请人：Weber E. Ann

  公开号：US20070208010A1

  公开（公告）日：2007-09-06

  The present invention is directed to novel fused triazole derivatives which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DPP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved.

  本发明涉及新型融合的三唑衍生物，它们是二肽基肽酶-IV酶（“DPP-IV抑制剂”）的抑制剂，可用于治疗或预防二肽基肽酶-IV酶参与的疾病，如糖尿病，特别是2型糖尿病。本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗二肽基肽酶-IV酶参与的疾病中的使用。
• Beta-amino heterocyclic dipeptidyl peptidase inhibitors for diabetes
  申请人：Merck & Co., Inc.

  公开号：US07390809B2

  公开（公告）日：2008-06-24

  The present invention is directed to compounds of structural formula (I) which are inhibitors of the dipeptidyl peptidase-IV enzyme (“DP-IV inhibitors”) and which are useful in the treatment or prevention of diseases in which the dipeptidyl peptidase-IV enzyme is involved, such as diabetes and particularly type 2 diabetes. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which the dipeptidyl peptidase-IV enzyme is involved

  本发明涉及结构式（I）的化合物，其为二肽基肽酶-IV酶（“DP-IV抑制剂”）的抑制剂，并且在治疗或预防二肽基肽酶-IV酶涉及的疾病，如糖尿病，特别是2型糖尿病中有用。本发明还涉及包含这些化合物的药物组合物以及这些化合物和组合物在预防或治疗二肽基肽酶-IV酶涉及的疾病中的使用。