4-{(1S,2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,3-difluoropyrrolidin-1-yl)-1-[(dimethylamino)carbonyl]-3-oxopropyl}cyclohex-1-en-1-yl trifluoromethanesulfonate | 870773-59-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-{(1S,2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,3-difluoropyrrolidin-1-yl)-1-[(dimethylamino)carbonyl]-3-oxopropyl}cyclohex-1-en-1-yl trifluoromethanesulfonate
• 英文别名: 4-{(1s,2s)-2-[(Tert-butoxycarbonyl)amino]-3-(3,3-difluoropyrrolidin-1-yl)-1-[(dimethylamino)carbonyl]-3-oxopropyl}cyclohex-1-en-1-yl trifluoromethanesulfonate；[4-[(2S,3S)-4-(3,3-difluoropyrrolidin-1-yl)-1-(dimethylamino)-3-[(2-methylpropan-2-yl)oxycarbonylamino]-1,4-dioxobutan-2-yl]cyclohexen-1-yl] trifluoromethanesulfonate
• CAS: 870773-59-4
• 化学式: C₂₂H₃₂F₅N₃O₇S
• 分子量: 577.57
• InChiKey: VXGKUYXDNXKVNW-FMYDAXTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  4-{(1S,2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,3-difluoropyrrolidin-1-yl)-1-[(dimethylamino)carbonyl]-3-oxopropyl}cyclohex-1-en-1-yl trifluoromethanesulfonate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 palladium 10% on activated carbon 氢气 、 potassium acetate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 甲醇 、 DMF (N,N-dimethyl-formamide) 为溶剂， 反应 52.0h， 生成 trans-tert-butyl [(1S,2S)-1-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-3-(dimethylamino)-3-oxo-2-(4-[1,2,4]triazolo[1,5-a]pyridin-6-cyclohexyl)propyl]carbamate
  参考文献：
  名称：

  [EN] CYCLOHEXYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
  [FR] DERIVES DE LA CYCLOHEXYLALANINE UTILISES COMME INHIBITEURS DE LA DIPEPTIDYL PEPTIDASE-IV POUR LE TRAITEMENT OU LA PREVENTION DES DIABETES

  摘要：

  本发明涉及新颖的环己基丙氨酸衍生物，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。

  公开号：

  WO2005116029A1
• 作为产物：
  描述：

  tert-butyl [(1S,2S)-3-(dimethylamino)-1-{[3,3-difluoropyrrolidin-1-yl]carbonyl}-2-(4-oxocyclohexyl)-3-oxopropyl]carbamate 、 三氟甲烷磺基苯胺 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 4-{(1S,2S)-2-[(tert-butoxycarbonyl)amino]-3-(3,3-difluoropyrrolidin-1-yl)-1-[(dimethylamino)carbonyl]-3-oxopropyl}cyclohex-1-en-1-yl trifluoromethanesulfonate
  参考文献：
  名称：

  [EN] CYCLOHEXYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
  [FR] DERIVES DE LA CYCLOHEXYLALANINE UTILISES COMME INHIBITEURS DE LA DIPEPTIDYL PEPTIDASE-IV POUR LE TRAITEMENT OU LA PREVENTION DES DIABETES

  摘要：

  本发明涉及新颖的环己基丙氨酸衍生物，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。

  公开号：

  WO2005116029A1

文献信息

• 4-Arylcyclohexylalanine analogs as potent, selective, and orally active inhibitors of dipeptidyl peptidase IV
  作者：David E. Kaelin、Abigail L. Smenton、George J. Eiermann、Huaibing He、Barbara Leiting、Kathryn A. Lyons、Reshma A. Patel、Sangita B. Patel、Alexsandr Petrov、Giovanna Scapin、Joseph K. Wu、Nancy A. Thornberry、Ann E. Weber、Joseph L. Duffy

  DOI：10.1016/j.bmcl.2007.08.049

  日期：2007.11

  A novel series of 4-arylcyclohexylalanine DPP-4 inhibitors was synthesized and tested for inhibitory activity as well as selectivity over the related proline-specific enzymes DPP-8 and DPP-9. Optimization of this series led to 28 (DPP-4 IC(50)=4.8 nM), which showed an excellent pharmacokinetic profile across several preclinical species. Evaluation of 28 in an oral glucose tolerance test demonstrated

  合成了一系列新的4-芳基环己基丙氨酸DPP-4抑制剂，并测试了其对相关脯氨酸特异性酶DPP-8和DPP-9的抑制活性以及选择性。此系列的优化导致了28（DPP-4 IC（50）= 4.8 nM），在多个临床前物种中均显示出优异的药代动力学特征。在口服葡萄糖耐量试验中对28的评估表明，该化合物可有效减少瘦小鼠的葡萄糖偏移。
• Cyclohexylalanine Derivatives as Dipeptidyl Peptidase-IV Inhibitors for the Treatment or Prevention of Diabetes
  申请人：Duffy L. Joseph

  公开号：US20080027093A1

  公开（公告）日：2008-01-31

  The present invention is directed to novel cyclohexylalanine 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.

  本发明涉及新型环己基丙氨酸衍生物，其为二肽酶-IV酶（“DP-IV抑制剂”）的抑制剂，用于治疗或预防二肽酶-IV酶参与的疾病，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这些化合物和组合物在预防或治疗二肽酶-IV酶参与的这些疾病中的使用。
• Cyclohexylalanine derivatives as dipeptidyl peptidase-IV inhibitors for the treatment or prevention of diabetes
  申请人：Merck Sharp & Dohme Corp.

  公开号：US07671073B2

  公开（公告）日：2010-03-02

  The present invention is directed to novel cyclohexylalanine 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.

  本发明涉及一种新型的环己基丙氨酸衍生物，其是二肽基肽酶-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，例如糖尿病和特别是2型糖尿病方面有用。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酶参与的这种疾病中使用这些化合物和组合物。
• US7671073B2
  申请人：——

  公开号：US7671073B2

  公开（公告）日：2010-03-02
• [EN] CYCLOHEXYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE-IV INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES<br/>[FR] DERIVES DE LA CYCLOHEXYLALANINE UTILISES COMME INHIBITEURS DE LA DIPEPTIDYL PEPTIDASE-IV POUR LE TRAITEMENT OU LA PREVENTION DES DIABETES
  申请人：MERCK & CO INC

  公开号：WO2005116029A1

  公开（公告）日：2005-12-08

  The present invention is directed to novel cyclohexylalanine 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.

  本发明涉及新颖的环己基丙氨酸衍生物，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。