(βS)-4-bromo-N-(tert-butoxycarbonyl)-β-[(1E)-prop-1-en-1-yl]-L-phenylalanine | 690258-03-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (βS)-4-bromo-N-(tert-butoxycarbonyl)-β-[(1E)-prop-1-en-1-yl]-L-phenylalanine
• 英文别名: (βS)-4-bromo-N-(tert-butoxycarbonyl)-β-[(1E)-prop-1-enyl]-L-phenylalanine；(betaS)-4-Bromo-N-(tert-butoxycarbonyl)-beta-[(1E)-prop-1-enyl]-L-phenylalanine；(E,2S,3S)-3-(4-bromophenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]hex-4-enoic acid
• CAS: 690258-03-8
• 化学式: C₁₇H₂₂BrNO₄
• 分子量: 384.27
• InChiKey: IRYDRWBDZGDXAW-BEVHLOIGSA-N

物化性质

• 沸点：
  510.3±50.0 °C(Predicted)
• 密度：
  1.330±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (βS)-4-bromo-N-(tert-butoxycarbonyl)-β-[(1E)-prop-1-en-1-yl]-L-phenylalanine 在 potassium permanganate 、 sodium periodate 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 DMF (N,N-dimethyl-formamide) 、 水 、 叔丁醇 为溶剂， 反应 32.0h， 生成 (2S,3S)-3-N-(tert-butoxycarbonyl)amino-2-(4-bromophenyl)-4-[(3S)-3-fluoropyrrolidin-1-yl]-N,N-dimethyl-4-oxobutanamide
  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：

  (E)-3-(4-bromophenyl)-N-methoxy-N-methylacrylamide 在 甲醇 、 sodium hydroxide 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 zinc(II) chloride 、 lithium hexamethyldisilazane 、 (R)-2-甲基-CBS-恶唑硼烷 、 儿萘酚硼烷 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 甲苯 为溶剂， 反应 32.5h， 生成 (βS)-4-bromo-N-(tert-butoxycarbonyl)-β-[(1E)-prop-1-en-1-yl]-L-phenylalanine
  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

• [EN] PHENYLALANINE DERIVATIVES AS DIPEPTIDYL PEPTIDASE INHIBITORS FOR THE TREATMENT OR PREVENTION OF DIABETES<br/>[FR] DERIVES DE PHENYLALANINE UTILISES COMME INHIBITEURS DE LA DIPEPTIDYL PEPTIDASE DANS LE TRAITEMENT OU LA PREVENTION DU DIABETE
  申请人：MERCK & CO INC

  公开号：WO2004043940A1

  公开（公告）日：2004-05-27

  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，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。
• Discovery of potent and selective orally bioavailable β-substituted phenylalanine derived dipeptidyl peptidase IV inhibitors
  作者：Scott D. Edmondson、Anthony Mastracchio、Joseph L. Duffy、George J. Eiermann、Huaibing He、Ida Ita、Barbara Leiting、Joseph F. Leone、Kathryn A. Lyons、Amanda M. Makarewicz、Reshma A. Patel、Aleksandr Petrov、Joseph K. Wu、Nancy A. Thornberry、Ann E. Weber

  DOI：10.1016/j.bmcl.2005.04.028

  日期：2005.6

  nine derived amides have been shown to be potent DPP-IV inhibitors that suffer from suboptimal selectivity and pharmacokinetics. This letter describes the substitution of the beta-methyl substituent with beta-polar substituents, culminating in the discovery of a beta-dimethylamide substituted phenylalanine derivative with an excellent potency, selectivity, and pharmacokinetic profile.

  抗取代的联芳基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，其选择性和药物动力学都不理想。这封信描述了用β-极性取代基取代β-甲基取代基，最终发现了具有出色效价，选择性和药代动力学特征的β-二甲基酰胺取代的苯丙氨酸衍生物。
• Phenylalanine derivatives as dipeptidyl peptidase inhibitors for the treatment or prevention of diabetes
  申请人：Duffy L. Joseph

  公开号：US20060111336A1

  公开（公告）日：2006-05-25

  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酶”）的抑制剂，可用于治疗或预防DP-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，以及使用这些化合物和组合物预防或治疗DP-IV酶参与的这些疾病。
• 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。
• (2<i>S</i>,3<i>S</i>)-3-Amino-4-(3,3-difluoropyrrolidin-1-yl)-<i>N,N</i>-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-<i>a</i>]- pyridin-6-ylphenyl)butanamide:  A Selective α-Amino Amide Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes
  作者：Scott D. Edmondson、Anthony Mastracchio、Robert J. Mathvink、Jiafang He、Bart Harper、You-Jung Park、Maria Beconi、Jerry Di Salvo、George J. Eiermann、Huaibing He、Barbara Leiting、Joseph F. Leone、Dorothy A. Levorse、Kathryn Lyons、Reshma A. Patel、Sangita B. Patel、Aleksandr Petrov、Giovanna Scapin、Jackie Shang、Ranabir Sinha Roy、Aaron Smith、Joseph K. Wu、Shiyao Xu、Bing Zhu、Nancy A. Thornberry、Ann E. Weber

  DOI：10.1021/jm060015t

  日期：2006.6.1

  A series of beta-substituted biarylphenylalanine amides were synthesized and evaluated as inhibitors of dipeptidyl peptidase IV (DPP-4) for the treatment of type 2 diabetes. Optimization of the metabolic profile of early analogues led to the discovery of (2S,3S)-3-amino-4-(3,3-difluoropyrrolidin-1-yl)-N,N-dimethyl-4-oxo-2(4-[1,2,4] triazolo[1,5-a]pyridin-6-ylphenyl)butanamide (6), a potent, orally active DPP-4 inhibitor (IC50 = 6.3 nM) with excellent selectivity, oral bioavailability in preclinical species, and in vivo efficacy in animal models. Compound 6 was selected for further characterization as a potential new treatment for type 2 diabetes.