tert-butyl (S)-(1-(benzyl(methyl)amino)-1-oxo-3-(4-(trifluoromethyl)phenyl)propan-2-yl)carbamate | 142995-32-2

• 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: tert-butyl (S)-(1-(benzyl(methyl)amino)-1-oxo-3-(4-(trifluoromethyl)phenyl)propan-2-yl)carbamate
• 英文别名: Boc-Phe(4-CF3)-NMeBzl
• CAS: 142995-32-2
• 化学式: C₂₃H₂₇F₃N₂O₃
• 分子量: 436.474
• InChiKey: CNKHHLUPMZHJRD-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  31.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  58.64
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl (S)-(1-(benzyl(methyl)amino)-1-oxo-3-(4-(trifluoromethyl)phenyl)propan-2-yl)carbamate 在 盐酸 、 1-羟基苯并三唑 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 <(1-methyl-1H-indol-3-yl)carbonyl>-(2S,4R)Hyp-Phe(4-CF3)-NMeBzl
  参考文献：
  名称：

  Studies on Neurokinin Antagonists. 4. Synthesis and Structure-Activity Relationships of Novel Dipeptide Substance P Antagonists: N2-[(4R)-4-Hydroxy-1-[(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl]-N-methyl-N-(phenylmethyl)-3-(2-naphthyl)-L-alaninamide and Its Related Compounds

  摘要：

  As an extension of our studies on discovering a novel substance P (SP) antagonist, we modified the previously reported dipeptide, N-2-[N-2-(1H-indol-3-ylcarbonyl)-L-lysyl]-N-methyl-N-(phenylmethyl)-L-phenylalaninamide (2b). The lysine part in 2b was first optimized to a (2S,4R)hydroxyproline derivative (3h),which is 2-fold more potent than 2b in [H-3]SP binding assay using guinea pig lung membranes. Next we modified the 1H-indol-3-ylcarbonyl part in 3h. Introduction; of a methyl group at the indole nitrogen enhanced the oral activity, while retaining the binding activity. Finally, we modified the phenylalanine part to culminate in the most potent compound 7k (FK888), which is a potent SP antagonist with NK1 selectivity as well as oral activity.

  DOI：

  10.1021/jm00039a022
• 作为产物：
  描述：

  4-(trifluoromethyl)-L-phenylalanine 在 WSCD*HCl 、 1-羟基苯并三唑 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 生成 tert-butyl (S)-(1-(benzyl(methyl)amino)-1-oxo-3-(4-(trifluoromethyl)phenyl)propan-2-yl)carbamate
  参考文献：
  名称：

  Studies on Neurokinin Antagonists. 4. Synthesis and Structure-Activity Relationships of Novel Dipeptide Substance P Antagonists: N2-[(4R)-4-Hydroxy-1-[(1-methyl-1H-indol-3-yl)carbonyl]-L-prolyl]-N-methyl-N-(phenylmethyl)-3-(2-naphthyl)-L-alaninamide and Its Related Compounds

  摘要：

  As an extension of our studies on discovering a novel substance P (SP) antagonist, we modified the previously reported dipeptide, N-2-[N-2-(1H-indol-3-ylcarbonyl)-L-lysyl]-N-methyl-N-(phenylmethyl)-L-phenylalaninamide (2b). The lysine part in 2b was first optimized to a (2S,4R)hydroxyproline derivative (3h),which is 2-fold more potent than 2b in [H-3]SP binding assay using guinea pig lung membranes. Next we modified the 1H-indol-3-ylcarbonyl part in 3h. Introduction; of a methyl group at the indole nitrogen enhanced the oral activity, while retaining the binding activity. Finally, we modified the phenylalanine part to culminate in the most potent compound 7k (FK888), which is a potent SP antagonist with NK1 selectivity as well as oral activity.

  DOI：

  10.1021/jm00039a022

文献信息

• Design and Combinatorial Development of Shield-1 Peptide Mimetics Binding to Destabilized FKBP12
  作者：Daniel Madsen、Frederik P. Jørgensen、Daniel Palmer、Milena E. Roux、Jakob V. Olsen、Mikael Bols、Sanne Schoffelen、Frederik Diness、Morten Meldal

  DOI：10.1021/acscombsci.9b00197

  日期：2020.3.9

  rapid structure evaluation prior to off-bead resynthesis. Subsequently, a series of 19 compounds were prepared and tested using a competitive fluorescence polarization assay, which led to the discovery of peptide ligands with low micromolar binding affinity towards the DD. The methodology represents a rapid approach for identification of a novel structure scaffold, where the screening and initial structure

  在计算设计的基础上，已针对由小三肽和三唑封端的N末端组成的微粒编码的PEGA1900珠制备了聚焦的单珠单化合物文库。针对人FKBP12蛋白的双点突变版本（称为去稳定结构域（DD））筛选了该文库。受解码的文库命中率的启发，在新颖的珠上检测方法中筛选了非天然肽结构，这对于在离珠重新合成之前进行快速结构评估很有用。随后，制备了19种化合物，并使用竞争荧光偏振分析法进行了测试，这导致发现了对DD具有低微摩尔结合亲和力的肽配体。该方法代表了一种鉴定新型结构支架的快速方法，