(2S,3S)-3-N-(tert-butoxycarbonyl)amino-2-(4-bromophenyl)-4-(3-fluoroazetidin-1-yl)-N,N-dimethyl-4-oxobutanamide | 899429-07-3

• 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: (2S,3S)-3-N-(tert-butoxycarbonyl)amino-2-(4-bromophenyl)-4-(3-fluoroazetidin-1-yl)-N,N-dimethyl-4-oxobutanamide
• 英文别名: tert-butyl N-[(2S,3S)-3-(4-bromophenyl)-4-(dimethylamino)-1-(3-fluoroazetidin-1-yl)-1,4-dioxobutan-2-yl]carbamate
• CAS: 899429-07-3
• 化学式: C₂₀H₂₇BrFN₃O₄
• 分子量: 472.354
• InChiKey: PTYVDDSXLCFEOP-HOTGVXAUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  79
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-N-(tert-butoxycarbonyl)amino-2-(4-bromophenyl)-4-(3-fluoroazetidin-1-yl)-N,N-dimethyl-4-oxobutanamide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 sodium carbonate 作用下， 以 乙醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 生成 (2S,3S)-3-Amino-4-(3-fluoro-azetidin-1-yl)-N,N-dimethyl-4-oxo-2-(4-[1,2,4]triazolo[1,5-a]pyridin-6-yl-phenyl)-butyramide; compound with trifluoro-acetic acid
  参考文献：
  名称：

  (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:  A Selective α-Amino Amide Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes

  摘要：

  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.

  DOI：

  10.1021/jm060015t
• 作为产物：
  描述：

  (2S,3S)-2-(4-Bromo-phenyl)-3-tert-butoxycarbonylamino-4-(3-fluoro-azetidin-1-yl)-4-oxo-butyric acid 、 二甲胺 在 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 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S,3S)-3-N-(tert-butoxycarbonyl)amino-2-(4-bromophenyl)-4-(3-fluoroazetidin-1-yl)-N,N-dimethyl-4-oxobutanamide
  参考文献：
  名称：

  (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:  A Selective α-Amino Amide Dipeptidyl Peptidase IV Inhibitor for the Treatment of Type 2 Diabetes

  摘要：

  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.

  DOI：

  10.1021/jm060015t

文献信息

• (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.