(Ph)2C=DL-Phg(αMe)-OMe | 169390-25-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (Ph)2C=DL-Phg(αMe)-OMe
• 英文别名: Methyl 2-(benzhydrylideneamino)-2-phenylpropanoate
• CAS: 169390-25-4
• 化学式: C₂₃H₂₁NO₂
• 分子量: 343.425
• InChiKey: RGZCIUYFMPABBB-UHFFFAOYSA-N

物化性质

• 沸点：
  444.1±45.0 °C(Predicted)
• 密度：
  1.04±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  38.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (Ph)2C=DL-Phg(αMe)-OMe 在 盐酸 作用下， 反应 24.0h， 以63%的产率得到DL-2-氨基-2-苯基丙酸
  参考文献：
  名称：

  Structure-Activity Study of Tripeptide Thrombin Inhibitors Using .alpha.-Alkyl Amino Acids and Other Conformationally Constrained Amino Acid Substitutions

  摘要：

  In our continuing effort to design novel thrombin inhibitors, a series of conformationally constrained amino acids (e.g. alpha-alkyl, N-alkyl cyclic, etc.) were utilized in a systematic structure-activity study of the P3, P2, and P1 positions of tripeptide arginal thrombin inhibitors. Early examples of this effort include: D-MePhe-Pro-Arg-H (15), Boc-D-Phg-Pro-Arg-H (18), D-1-Tiq-Pro-Arg-H (23, D-1-Tiq D-1,2,3,4-tetrahydroisoquinolin-1-ylcarbonyl), and Boc-D-Phe-Pro-Arg-H (25).(10a,20) The current work clarifies the contribution of each residue of the tripeptide arginals toward the potent and selective inhibition of thrombin relative to that of t-PA and plasmin. The alpha-methylarginal modification in the P1 residue resulted in analogs 30 (D-MePhe at P3) and 32 (D-1-Tiq at P3) which had lower potency toward thrombin while exhibiting improved selectivity. Analogs modified at the P2 site were found to be very sensitive to the conformational changes induced by variations in side chain ring size with the flexible pipecolinic acid 31 being 2 orders of magnitude less potent at thrombin inhibition than the conformationally constrained azetidine analog 20. Examination of the P3 binding region indicated that alpha-alkylphenylglycine residues resulted in a tendency to exhibit substantial improvements in selectivity over the nonalkylated residues. Combinations of optimal P3 and P2 changes led to compounds TFA-D-Phg(alpha Et)-Azt-Arg-H (16), TFA-D-Phg(alpha Me)-Azt-Arg-H (17), Ac-D-Phg(alpha Me)-Azt-Arg-H (21), TFA-D-Phg(alpha Me)-Pro-Arg-H (27), 30, and 32, which are clearly more selective for thrombin versus plasmin than the nonconformationally constrained compounds.

  DOI：

  10.1021/jm00022a009
• 作为产物：
  描述：

  methyl 2-((diphenylmethylene)amino)-2-phenylacetate 、 碘甲烷 在 18-冠醚-6 、 potassium hydride 作用下， 生成 (Ph)2C=DL-Phg(αMe)-OMe
  参考文献：
  名称：

  Structure-Activity Study of Tripeptide Thrombin Inhibitors Using .alpha.-Alkyl Amino Acids and Other Conformationally Constrained Amino Acid Substitutions

  摘要：

  In our continuing effort to design novel thrombin inhibitors, a series of conformationally constrained amino acids (e.g. alpha-alkyl, N-alkyl cyclic, etc.) were utilized in a systematic structure-activity study of the P3, P2, and P1 positions of tripeptide arginal thrombin inhibitors. Early examples of this effort include: D-MePhe-Pro-Arg-H (15), Boc-D-Phg-Pro-Arg-H (18), D-1-Tiq-Pro-Arg-H (23, D-1-Tiq D-1,2,3,4-tetrahydroisoquinolin-1-ylcarbonyl), and Boc-D-Phe-Pro-Arg-H (25).(10a,20) The current work clarifies the contribution of each residue of the tripeptide arginals toward the potent and selective inhibition of thrombin relative to that of t-PA and plasmin. The alpha-methylarginal modification in the P1 residue resulted in analogs 30 (D-MePhe at P3) and 32 (D-1-Tiq at P3) which had lower potency toward thrombin while exhibiting improved selectivity. Analogs modified at the P2 site were found to be very sensitive to the conformational changes induced by variations in side chain ring size with the flexible pipecolinic acid 31 being 2 orders of magnitude less potent at thrombin inhibition than the conformationally constrained azetidine analog 20. Examination of the P3 binding region indicated that alpha-alkylphenylglycine residues resulted in a tendency to exhibit substantial improvements in selectivity over the nonalkylated residues. Combinations of optimal P3 and P2 changes led to compounds TFA-D-Phg(alpha Et)-Azt-Arg-H (16), TFA-D-Phg(alpha Me)-Azt-Arg-H (17), Ac-D-Phg(alpha Me)-Azt-Arg-H (21), TFA-D-Phg(alpha Me)-Pro-Arg-H (27), 30, and 32, which are clearly more selective for thrombin versus plasmin than the nonconformationally constrained compounds.

  DOI：

  10.1021/jm00022a009

文献信息

• α‐Amination of Carbonyl Compounds by Using Hypervalent Iodine‐Based Aminating Reagents Containing a Transferable (Diarylmethylene)amino Group
  作者：Daichi Okumatsu、Kazuki Kawanaka、Shunpei Kainuma、Kensuke Kiyokawa、Satoshi Minakata

  DOI：10.1002/chem.202203722

  日期：2023.2.16

  Primary resource: Hypervalent iodine-based aminating reagents containing a transferable (diarylmethylene)amino group can be used for the α-amination of simple carbonyl compounds such as esters, amides, and ketones in the presence of a lithium base. The (diarylmethylene)amino groups of the products can be readily modified, thus providing access to primary amines and diarylmethylamines.

  主要资源: 含有可转移（二芳基亚甲基）氨基的高价碘基胺化试剂可用于在锂碱存在下对简单的羰基化合物（如酯、酰胺和酮）进行 α-胺化。产品的（二芳基亚甲基）氨基可以很容易地进行修饰，从而提供获得伯胺和二芳基甲基胺的途径。
• Structure-Activity Study of Tripeptide Thrombin Inhibitors Using .alpha.-Alkyl Amino Acids and Other Conformationally Constrained Amino Acid Substitutions
  作者：Robert T. Shuman、Robert B. Rothenberger、Charles S. Campbell、Gerald F. Smith、Donetta S. Gifford-Moore、Jonathan W. Paschal、Paul D. Gesellchen

  DOI：10.1021/jm00022a009

  日期：1995.10

  In our continuing effort to design novel thrombin inhibitors, a series of conformationally constrained amino acids (e.g. alpha-alkyl, N-alkyl cyclic, etc.) were utilized in a systematic structure-activity study of the P3, P2, and P1 positions of tripeptide arginal thrombin inhibitors. Early examples of this effort include: D-MePhe-Pro-Arg-H (15), Boc-D-Phg-Pro-Arg-H (18), D-1-Tiq-Pro-Arg-H (23, D-1-Tiq D-1,2,3,4-tetrahydroisoquinolin-1-ylcarbonyl), and Boc-D-Phe-Pro-Arg-H (25).(10a,20) The current work clarifies the contribution of each residue of the tripeptide arginals toward the potent and selective inhibition of thrombin relative to that of t-PA and plasmin. The alpha-methylarginal modification in the P1 residue resulted in analogs 30 (D-MePhe at P3) and 32 (D-1-Tiq at P3) which had lower potency toward thrombin while exhibiting improved selectivity. Analogs modified at the P2 site were found to be very sensitive to the conformational changes induced by variations in side chain ring size with the flexible pipecolinic acid 31 being 2 orders of magnitude less potent at thrombin inhibition than the conformationally constrained azetidine analog 20. Examination of the P3 binding region indicated that alpha-alkylphenylglycine residues resulted in a tendency to exhibit substantial improvements in selectivity over the nonalkylated residues. Combinations of optimal P3 and P2 changes led to compounds TFA-D-Phg(alpha Et)-Azt-Arg-H (16), TFA-D-Phg(alpha Me)-Azt-Arg-H (17), Ac-D-Phg(alpha Me)-Azt-Arg-H (21), TFA-D-Phg(alpha Me)-Pro-Arg-H (27), 30, and 32, which are clearly more selective for thrombin versus plasmin than the nonconformationally constrained compounds.