(3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-[2-fluoro-4-(trifluoromethyl)phenyl]butanoic acid | 486459-99-8

• 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: (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-[2-fluoro-4-(trifluoromethyl)phenyl]butanoic acid
• 英文别名: (3R)-3-[(tert-butoxycarbonyl)amino]-4-(2-fluoro-4-(trifluoromethyl)phenyl)butanoic acid；(R)-3[(1,1-dimethylethoxycarbonyl)amino]-4-[2-fluoro-4-(trifluoromethyl)phenyl]butanoic acid；(3R)-3-[(tert-Butoxycarbonyl)amino]-4-[2-fluoro-4-(trifluoromethyl)phenyl]-butanoic acid；(3R)-4-[2-fluoro-4-(trifluoromethyl)phenyl]-3-[(2-methylpropan-2-yl)oxycarbonylamino]butanoic acid
• CAS: 486459-99-8
• 化学式: C₁₆H₁₉F₄NO₄
• 分子量: 365.325
• InChiKey: YZJNBXCYRXNTTQ-LLVKDONJSA-N

物化性质

• 沸点：
  444.6±45.0 °C(Predicted)
• 密度：
  1.291±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-3-Methyl-2-(4-{[((S)-pyrrolidine-2-carbonyl)-amino]-methyl}-phenoxy)-butyric acid ethyl ester 、 (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-[2-fluoro-4-(trifluoromethyl)phenyl]butanoic acid 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  有效和选择性脯氨酸衍生的二肽基肽酶IV抑制剂。

  摘要：

  对Merck样品的内部筛选表明，脯氨酸衍生的高苯丙氨酸3作为DPP-IV抑制剂具有中等效力（DPP-IV IC50 = 1.9 microM）。对3的优化导致化合物37，它是迄今为止发现的最有效和选择性最强的DPP-IV抑制剂之一。

  DOI：

  10.1016/j.bmcl.2004.07.056
• 作为产物：
  描述：

  tert-butyl (R)-(4-diazo-1-(2-fluoro-4-(trifluoromethyl)phenyl)-3-oxobutan-2-yl)carbamate 在 silver benzoate 、 N,N-二异丙基乙胺 、 lithium hydroxide 、 水 作用下， 以 甲醇 、 四氢呋喃 为溶剂， 反应 5.0h， 生成 (3R)-3-[(1,1-dimethylethoxycarbonyl)amino]-4-[2-fluoro-4-(trifluoromethyl)phenyl]butanoic acid
  参考文献：
  名称：

  [EN] PIPERIDINO PYRIMIDINE DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OF DIABETES
  [FR] INHIBITEURS DE PIPERIDINO PYRIMIDINE DIPEPTIDYL PEPTIDASE UTILISES DANS LE TRAITEMENT DU DIABETE

  摘要：

  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。

  公开号：

  WO2004007468A1

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。
• Beta-amino tetrahydroimidazo (1, 2-a) pyrazines and tetrahydrotrioazolo (4,3-a) pyrazines as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
  申请人：——

  公开号：US20040167133A1

  公开（公告）日：2004-08-26

  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，该化合物对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型糖尿病非常有用。本发明还涉及包含这些化合物的制药组合物，以及使用这些化合物和组合物预防或治疗二肽基肽酶-IV酶参与的疾病的方法。
• NOVEL CYCLIC AZABENZIMIDAZOLE DERIVATIVES USEFUL AS ANTI-DIABETIC AGENTS
  申请人：Edmondson Scott D.

  公开号：US20110190308A1

  公开（公告）日：2011-08-04

  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，这些化合物可用于治疗或预防涉及二肽基肽酶-IV酶的疾病，例如糖尿病，特别是2型糖尿病。本发明还涉及包括这些化合物的制药组合物以及在涉及二肽基肽酶-IV酶的这些疾病的预防或治疗中使用这些化合物和组合物。
• [EN] BETA-AMINO TETRAHYDROIMIDAZO (1, 2-A) PYRAZINES AND TETRAHYDROTRIOAZOLO (4, 3-A) PYRAZINES AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES<br/>[FR] PYRAZINES BETA-AMINO TETRAHYDROIMIDAZO (1, 2-A) ET PYRAZINES TETRAHYDROTRIOAZOLO (4, 3-A) UTILISEES EN TANT QU'INHIBITEURS DE LA DIPEPTIDYL PEPTIDASE DANS LE TRAITEMENT OU LA PREVENTION DU DIABETE
  申请人：MERCK & CO INC

  公开号：WO2003004498A1

  公开（公告）日：2003-01-16

  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，该化合物可用于治疗或预防二肽基肽酶-IV酶参与的疾病，例如糖尿病，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。