tert-butyl [(1S,2R)-5-oxo-2-(2,4,5-trifluorophenyl)cyclohexyl]carbamate | 874359-92-9

• 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: tert-butyl [(1S,2R)-5-oxo-2-(2,4,5-trifluorophenyl)cyclohexyl]carbamate
• 英文别名: tert-butyl [(1S,2R)5-oxo-2-(2,4,5-trifluorophenyl)cyclohexyl]carbamate；tert-butyl N-[(1S,2R)-5-oxo-2-(2,4,5-trifluorophenyl)cyclohexyl]carbamate
• CAS: 874359-92-9
• 化学式: C₁₇H₂₀F₃NO₃
• 分子量: 343.346
• InChiKey: VXXQYIDEQHGCSU-BMIGLBTASA-N

物化性质

• 沸点：
  416.2±45.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl [(1S,2R)-5-oxo-2-(2,4,5-trifluorophenyl)cyclohexyl]carbamate 在 盐酸 、 decaborane 作用下， 以 1,4-二氧六环 、 甲醇 为溶剂， 生成 (1S,2R,5S)-5-[3-(Trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-A]pyrazin-7(8H)-YL]-2-(2,4,5-trifluorophenyl)cyclohexanamine
  参考文献：
  名称：

  Rational design of a novel, potent, and orally bioavailable cyclohexylamine DPP-4 inhibitor by application of molecular modeling and X-ray crystallography of sitagliptin

  摘要：

  Molecular modeling was used to design a rigid analog of sitagliptin 1. The X-ray crystal structure of sitagliptin bound to DPP-4 suggested that the central beta-amino butyl amide moiety could be replaced with a cyclohexylamine group. This was confirmed by structural analysis and the resulting analog 2a was synthesized and found to be a potent DPP-4 inhibitor (IC50 = 21 nM) with excellent in vivo activity and pharmacokinetic profile. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.095
• 作为产物：
  描述：

  tert-butyl (trans-6-(2,4,5-trifluorophenyl)-3-[(triisopropylsilyl)oxy]cyclohex-2-en-1-yl)carbamate 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 生成 tert-butyl [(1S,2R)-5-oxo-2-(2,4,5-trifluorophenyl)cyclohexyl]carbamate
  参考文献：
  名称：

  WO2008/60488

  摘要：

  公开号：

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。
• The discovery of novel 5,6,5- and 5,5,6-tricyclic pyrrolidines as potent and selective DPP-4 inhibitors
  作者：Jason M. Cox、Hong D. Chu、Jeffrey T. Kuethe、Ying-Duo Gao、Giovanna Scapin、George Eiermann、Huaibing He、Xiaohua Li、Kathryn A. Lyons、Joseph Metzger、Aleksandr Petrov、Joseph K. Wu、Shiyao Xu、Ranabir Sinha-Roy、Ann E. Weber、Tesfaye Biftu

  DOI：10.1016/j.bmcl.2016.04.020

  日期：2016.6

  Novel potent and selective 5,6,5- and 5,5,6-tricyclic pyrrolidine dipeptidyl peptidase IV (DPP-4) inhibitors were identified. Structure–activity relationship (SAR) efforts focused on improving the intrinsic DPP-4 inhibition potency, increasing protease selectivity, and demonstrating clean ion channel and cytochrome P450 profiles while trying to achieve a pharmacokinetic profile suitable for once weekly

  确定了新型有效和选择性的5,6,5-和5,5,6-三环吡咯烷二肽基肽酶IV（DPP-4）抑制剂。结构-活性关系（SAR）的工作重点是提高内在的DPP-4抑制能力，增加蛋白酶的选择性，并展示出清洁的离子通道和细胞色素P450谱，同时力图获得适合于人类每周一次给药的药代动力学谱。
• 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。
• Aminocyclohexanes as Dipeptidyl Peptidase-IV Inhibitors for the Treatment or Prevention of Diabetes
  申请人：Biftu Tesfaye

  公开号：US20090270467A1

  公开（公告）日：2009-10-29

  The present invention is directed to novel substituted aminocyclohexanes 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）的新型取代氨基环己烷，其是二肽基肽酶-IV酶的抑制剂，并且对于涉及二肽基肽酶-IV酶的疾病的治疗或预防，例如糖尿病，特别是2型糖尿病，具有用途。本发明还涉及包含这些化合物的制药组合物以及这些化合物和组合物在预防或治疗涉及二肽基肽酶-IV酶的疾病中的使用。
• TRICYCLIC HETEROAROMATIC COMPOUNDS AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
  申请人：Cox Jason M.

  公开号：US20100056550A1

  公开（公告）日：2010-03-04

  The present invention is directed to novel substituted tricyclic heteroaromatic compounds 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)的新型取代三环杂芳烃化合物，其为二肽基肽酶-IV酶的抑制剂，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制药组合物以及在预防或治疗二肽基肽酶-IV酶参与的此类疾病中使用这些化合物和组合物的方法。