(2S,5R)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-(2',4',5'-trifluorobenzyl)-pyrazine | 486460-07-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,5R)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-(2',4',5'-trifluorobenzyl)-pyrazine
• 英文别名: (2S,5R)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-(2',4',5'-trifluorobenzyl)pyrazine；(2S,5R)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-(2,4,5-trifluorobenzyl)pyrazine；Pyrazine, 2,5-dihydro-3,6-dimethoxy-2-(1-methylethyl)-5-[(2,4,5-trifluorophenyl)methyl]-, (2S,5R)-；(2S,5R)-3,6-dimethoxy-2-propan-2-yl-5-[(2,4,5-trifluorophenyl)methyl]-2,5-dihydropyrazine
• CAS: 486460-07-5
• 化学式: C₁₆H₁₉F₃N₂O₂
• 分子量: 328.334
• InChiKey: PFDZQKDQCHLUNL-KGLIPLIRSA-N

物化性质

• 沸点：
  372.7±42.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  43.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,5R)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-(2',4',5'-trifluorobenzyl)-pyrazine 在 盐酸 、 lithium hydroxide 、 silver benzoate 、 三乙胺 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 乙腈 为溶剂， 反应 91.25h， 生成 Boc-(R)-3-氨基-4-(2,4,5-三氟苯基)丁酸
  参考文献：
  名称：

  (2R)-4-Oxo-4-[3-(Trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin- 7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine:  A Potent, Orally Active Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes

  摘要：

  A novel series of beta-amino amides incorporating fused heterocycles, i.e., triazolopiperazines, were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-IV) for the treatment of type 2 diabetes. (2R)-4-Oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine (1) is a potent, orally active DPP-IV inhibitor (IC(50) = 18 nM) with excellent selectivity over other proline-selective peptidases, oral bioavailability in preclinical species, and in vivo efficacy in animal models. MK-0431, the phosphate salt of compound 1, was selected for development as a potential new treatment for type 2 diabetes.

  DOI：

  10.1021/jm0493156
• 作为产物：
  描述：

  (S)-2,5-二氢-3,6-二甲氧基-2-异丙基吡嗪 、 2,4,5-三氟苄基溴 生成 (2S,5R)-2,5-dihydro-3,6-dimethoxy-2-isopropyl-5-(2',4',5'-trifluorobenzyl)-pyrazine
  参考文献：
  名称：

  METHOD FOR PREPARING DIPEPTIDYL PEPTIDASE-IV INHIBITOR AND INTERMEDIATE

  摘要：

  本发明涉及一种改进的制备二肽基肽酶-IV抑制剂和中间体的方法。本发明通过在反应中使用低成本试剂，能够降低制备成本，并通过提高产量能够用于大规模生产。

  公开号：

  US20120016125A1

文献信息

• BETA-AMINO HETEROCYCLIC DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
  申请人：Merck Sharp & Dohme Corp.

  公开号：US20150359793A1

  公开（公告）日：2015-12-17

  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.

  本发明涉及一种抑制二肽基肽酶-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酶参与的疾病中具有用途，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，以及在预防或治疗二肽基肽酶-IV酶参与的这类疾病中使用这些化合物和组合物。
• [EN] 3-AMINO-4-PHENYLBUTANOIC ACID DERIVATIVES AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES<br/>[FR] DERIVES DE 3-AMINO-4-PHENYLBUTANOIQUE ACIDE UTILISES EN TANT QU'INHIBITEURS DE DIPEPTIDYL PEPTIDASE POUR LE TRAITEMENT OU LA PREVENTION DU DIABETE
  申请人：MERCK & CO INC

  公开号：WO2004058266A1

  公开（公告）日：2004-07-15

  The present invention is directed to 3-amino-4-phenylbutanoic acid derivatives 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3-氨基-4-苯基丁酸衍生物，这些衍生物是二肽基肽酶-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酶参与的疾病中有用，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二肽基肽酶-IV酶参与的这类疾病中使用这些化合物和组合物。
• [EN] PIPERIDINO PYRIMIDINE DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OF DIABETES<br/>[FR] INHIBITEURS DE PIPERIDINO PYRIMIDINE DIPEPTIDYL PEPTIDASE UTILISES DANS LE TRAITEMENT DU DIABETE
  申请人：MERCK & CO INC

  公开号：WO2004007468A1

  公开（公告）日：2004-01-22

  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.

  本发明涉及一种抑制二肽基肽酶IV酶（'DP-IV抑制剂'）的化合物，该化合物在治疗或预防涉及二肽基肽酶IV酶的疾病中具有用途，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，以及利用这些化合物和组合物在预防或治疗涉及二肽基肽酶IV酶的疾病中的用途。
• PROCESS FOR THE PREPARATION OF R-SITAGLIPTIN AND ITS PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF
  申请人：ARJUNAN SANKAR

  公开号：US20100317856A1

  公开（公告）日：2010-12-16

  The present invention provides processes for the preparation of R-sitagliptin and its pharmaceutically acceptable salts thereof.

  本发明提供了用于制备R-西他列汀及其药用可接受的盐的工艺。
• [EN] NOVEL PROCESS FOR THE PREPARATION OF DIPEPTIDYL PEPTIDASE-4 (DPP-4) ENZYME INHIBITOR<br/>[FR] NOUVEAU PROCÉDÉ POUR LA PRÉPARATION D'INHIBITEUR DE L'ENZYME DIPEPTIDYL PEPTIDASE-4 (DPP-4)
  申请人：LEE PHARMA LTD

  公开号：WO2016110750A1

  公开（公告）日：2016-07-14

  The present invention relates to a novel and improved process for the preparation of Sitagliptin of Formula (I) and its pharmaceutically acceptable salts. The present invention also relates to novel intermediates and process for the preparation of intermediates used in the preparation of Sitagliptin.

  本发明涉及一种用于制备化学式（I）的西他列汀及其药用可接受盐的新型改进工艺。本发明还涉及用于制备西他列汀中所用的新型中间体和制备中间体的工艺。