(3S)-1-[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-oxobutanyl]-3-fluoropyrrolidine | 690257-93-3

• 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: (3S)-1-[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-oxobutanyl]-3-fluoropyrrolidine
• 英文别名: tert-butyl {(1S,2S)-1-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propyl}carbamate；Tert-butyl{(1s,2s)-1-{[(3s)-3-fluoropyrrolidin-1-yl]carbonyl}-2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propyl}carbamate；tert-butyl N-[(2S,3S)-1-[(3S)-3-fluoropyrrolidin-1-yl]-1-oxo-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]butan-2-yl]carbamate
• CAS: 690257-93-3
• 化学式: C₂₅H₃₈BFN₂O₅
• 分子量: 476.397
• InChiKey: UGUYIENFGQSMIK-VDGAXYAQSA-N

物化性质

• 沸点：
  609.7±55.0 °C(Predicted)
• 密度：
  1.14±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.55
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.68
• 拓扑面积：
  77.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (3S)-1-[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-oxobutanyl]-3-fluoropyrrolidine 在 Rh/Al₂O₃ sodium hydroxide 、 水 、 氢气 、 双氧水 作用下， 以 甲醇 为溶剂， 反应 26.0h， 生成
  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：

  (4R)-3-[(3R)-3-(4-bromophenyl)butanoyl]-4-phenyl-1,3-oxazolidin-2-one 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride lithium hydroxide 、 三氟甲磺酸二丁硼 、 双氧水 、 potassium acetate 、 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 、 tetramethylguanidinum azide 作用下， 以 四氢呋喃 、 DMF (N,N-dimethyl-formamide) 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 57.75h， 生成 (3S)-1-[(2S,3S)-2-[(tert-butoxycarbonyl)amino]-3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-oxobutanyl]-3-fluoropyrrolidine
  参考文献：
  名称：

  [EN] PHENYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES
  [FR] DERIVES DE PHENYLALANINE UTILISES COMME INHIBITEURS DE LA DIPEPTIDYL PEPTIDASE DANS LE TRAITEMENT OU LA PREVENTION DU DIABETE

  摘要：

  本发明涉及苯丙氨酸衍生物，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：

  WO2004043940A1

文献信息

• Discovery of potent, selective, and orally bioavailable pyridone-based dipeptidyl peptidase-4 inhibitors
  作者：Jinyou Xu、Lan Wei、Robert Mathvink、Scott D. Edmondson、Anthony Mastracchio、George J. Eiermann、Huaibing He、Joseph F. Leone、Barbara Leiting、Kathryn A. Lyons、Frank Marsilio、Reshma A. Patel、Aleksandr Petrov、Joseph K. Wu、Nancy A. Thornberry、Ann E. Weber

  DOI：10.1016/j.bmcl.2005.11.052

  日期：2006.3

  anti-Substituted beta-methylphenylalanine derived amides have been shown to be potent DPP-IV inhibitors exhibiting excellent selectivity over both DPP8 and DPP9. The optimized compound exhibited good pharmacokinetic profiles in three preclinical species.

  抗取代的β-甲基苯基丙氨酸衍生的酰胺已被证明是有效的DPP-IV抑制剂，对DPP8和DPP9均表现出优异的选择性。优化的化合物在三个临床前物种中表现出良好的药代动力学特征。
• 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。
• Phenylalanine derivatives as depeptidyl peptidase inhibitors for the treatment or prevention of diabetes
  申请人：Colandrea J. Vincent

  公开号：US20050222140A1

  公开（公告）日：2005-10-06

  The present invention is directed to phenylalanine 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.

  本发明涉及苯丙氨酸衍生物，它们是二肽酶-IV酶（“DP-IV抑制剂”）的抑制剂，可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。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二肽酶-IV酶参与的疾病中的使用。
• Phenylalanine derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
  申请人：Merck & Co., Inc.

  公开号：US07157490B2

  公开（公告）日：2007-01-02

  The present invention is directed to phenylalanine 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.

  本发明涉及苯丙氨酸衍生物，它们是二肽基肽酶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酶涉及的疾病，如糖尿病，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酶涉及的这些疾病中使用这些化合物和组合物。
• 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。