(3R)-4-[(3R)-3-Amino-4-(2, 4, 5-trifluorophenyl) butanoyl]-3-(2, 2, 2-trifluoroethyl)-1, 4-diazepan-2-one

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (3R)-4-[(3R)-3-Amino-4-(2, 4, 5-trifluorophenyl) butanoyl]-3-(2, 2, 2-trifluoroethyl)-1, 4-diazepan-2-one
• 英文别名: (3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one
• 化学式: C₁₇H₁₉F₆N₃O₂
• 分子量: 411.347
• InChiKey: RMDAPSXWBVPVOG-QMTHXVAHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  Boc-(R)-3-氨基-4-(2,4,5-三氟苯基)丁酸 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (3R)-4-[(3R)-3-Amino-4-(2, 4, 5-trifluorophenyl) butanoyl]-3-(2, 2, 2-trifluoroethyl)-1, 4-diazepan-2-one
  参考文献：
  名称：

  (3R)-4-[(3R)-3-Amino-4-(2,4,5-trifluorophenyl)butanoyl]-3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one, a selective dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes

  摘要：

  Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin.

  DOI：

  10.1016/j.bmcl.2006.09.099

文献信息

• HETEROCYCLIC DERIVATIVES AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Isabel Elise

  公开号：US20110301143A1

  公开（公告）日：2011-12-08

  Heterocyclic compounds of structural formula (I), or a pharmaceutically acceptable salt thereof, wherein W is a R 1 — substituted heteroaryl, R 1 is an heteroaryl ring substituted with an ester or carboxylic acid containing radical, X-T is N—CR 5 R 6 , C═CR 5 or CR 13 —CR 5 R 6 , Y is a bond or —C(O)—, a and b represent an integer selected from 1 to 4, and Ar is an optionally substituted phenyl or naphtyl, are inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD) The heterocyclic compounds are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, atherosclerosis, obesity, diabetes, neurological disease, Metabolic Syndrome, insulin resistance, cancer, liver steatosis, and non-alcoholic steatohepatitis.

  结构式（I）的杂环化合物，或其药学上可接受的盐，其中W是R1-取代的杂芳基，R1是取代有酯基或羧基的杂芳基环，X-T是N—CR5R6，C═CR5或CR13—CR5R6，Y是键或—C(O)—，a和b代表选自1到4的整数，Ar是可选择取代的苯基或萘基，是硬脂酰辅酶A 9-脱饱和酶（SCD）的抑制剂。这些杂环化合物对于预防和治疗与异常脂质合成和代谢有关的疾病非常有用，包括心血管疾病、动脉粥样硬化、肥胖症、糖尿病、神经系统疾病、代谢综合征、胰岛素抵抗、癌症、肝脂肪变性和非酒精性脂肪肝。
• [EN] SUBSTITUTED CYCLOPROPYL COMPOUNDS USEFUL AS GPR119 AGONISTS<br/>[FR] COMPOSÉS CYCLOPROPYLÉS SUBSTITUÉS UTILES COMME AGONISTES DE GPR119
  申请人：MERCK SHARP & DOHME

  公开号：WO2013122821A1

  公开（公告）日：2013-08-22

  Substituted cyclopropyl compounds of the formula I: and pharmaceutically acceptable salts thereof are disclosed as useful for treating or preventing type 2 diabetes and similar conditions. The compounds are useful as agonists of the G-protein coupled receptor GPR-119. Pharmaceutical compositions and methods of treatment are also included.

  公开了公式I的环丙基化合物及其药用盐，用于治疗或预防2型糖尿病和类似疾病。这些化合物可作为G蛋白偶联受体GPR-119的激动剂。还包括药物组合物和治疗方法。
• [EN] ANTIDIABETIC TRICYCLIC COMPOUNDS<br/>[FR] COMPOSÉS TRICYCLIQUES ANTIDIABÉTIQUES
  申请人：MERCK SHARP & DOHME

  公开号：WO2015176267A1

  公开（公告）日：2015-11-26

  Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR 40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds may be useful in the treatment of Type 2 diabetes mellitus and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

  结构式（I）的新化合物及其药学上可接受的盐是G蛋白偶联受体40（GPR 40）的激动剂，可能在治疗、预防和抑制由G蛋白偶联受体40介导的疾病方面有用。这些化合物可能在治疗2型糖尿病以及通常与该疾病相关的疾病，包括肥胖和脂质紊乱，如混合型或糖尿病性脂质代谢异常、高脂血症、高胆固醇血症和高甘油三酯血症方面有用。
• HETEROAROMATIC COMPOUNDS AS INHIBITORS OF STEAROYL-COENZYME A DELTA-9 DESATURASE
  申请人：Leclerc Jean-Philippe

  公开号：US20110152295A1

  公开（公告）日：2011-06-23

  Heteroaromatic compounds of structural formula I are selective inhibitors of stearoyl-coenzyme A delta-9 desaturase (SCD1) relative to other known stearoyl-coenzyme A desaturases. The compounds of the present invention are useful for the prevention and treatment of conditions related to abnormal lipid synthesis and metabolism, including cardiovascular disease, such as atherosclerosis; obesity; diabetes; neurological disease; metabolic syndrome; insulin resistance; and liver steatosis.

  结构式I的杂环芳香化合物相对于其他已知的硬脂酰辅酶A去饱和酶(SCD1)，是选择性抑制剂。本发明的化合物对于预防和治疗与异常脂质合成和代谢相关的疾病非常有用，包括心血管疾病，如动脉粥样硬化；肥胖；糖尿病；神经系统疾病；代谢综合征；胰岛素抵抗；和肝脂肪变性。
• [EN] DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES<br/>[FR] INHIBITEURS DE DIPEPTIDYLE PEPTIDASE-IV POUR LE TRAITEMENT OU LA PRÉVENTION DU DIABÈTE
  申请人：MERCK SHARP & DOHME

  公开号：WO2013122920A1

  公开（公告）日：2013-08-22

  The present invention is directed to novel substituted dihydropyrrolopyrazoles of structural Formula I which are inhibitors of the dipeptidyl peptidase-IV enzyme 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的新型取代二氢吡咯吡嗪，它们是二肽基肽酶IV酶的抑制剂，并且在治疗或预防二肽基肽酶IV酶参与的疾病，如糖尿病和特别是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的用途。