(2S)-2-amino-3-phenyl-N-(3-phenylpropyl)propanamide | 35373-99-0

• 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)-2-amino-3-phenyl-N-(3-phenylpropyl)propanamide
• CAS: 35373-99-0
• 化学式: C₁₈H₂₂N₂O
• 分子量: 282.385
• InChiKey: BAXHJXRNYOWQJE-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2S)-2-amino-3-phenyl-N-(3-phenylpropyl)propanamide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 (R)-2-Amino-4-methyl-pentanoic acid [(S)-2-phenyl-1-(3-phenyl-propylcarbamoyl)-ethyl]-amide; hydrochloride
  参考文献：
  名称：

  Chymotrypsin inhibitory conformation induced by amino acid side chain–side chain intramolecular CH/π interaction

  摘要：

  Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/pi interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2](n)-C6H5 (n = 0-4) have been assayed for chymotrypsin, They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (K-1 3.6 x 10(-6) M), The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition, The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically, The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active, When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (K-1 = 6.1 x 10(-7) M; this dipeptide is one of the most potent chymotrypsin inhibitors to date), H-1 NMR conformational analyses of these dipeptide amide derivatives show the CH/pi: interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition, These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S-1 site, while the hydrophobic core constructed by D-Leu-Phe CH/pi interaction fits the chymotrypsin S-2 or S-1' site.

  DOI：

  10.1039/p19960002479
• 作为产物：
  描述：

  Boc-Phe-NH-PPA 在 三氟乙酸 作用下， 生成 (2S)-2-amino-3-phenyl-N-(3-phenylpropyl)propanamide
  参考文献：
  名称：

  Structure−Activity Relationships on Phenylalanine-Containing Inhibitors of Histone Deacetylase:  In Vitro Enzyme Inhibition, Induction of Differentiation, and Inhibition of Proliferation in Friend Leukemic Cells

  摘要：

  Inhibitors of histone deacetylases (HDACs) are a new class of anticancer agents that affect gene regulation. We had previously reported the first simple synthetic HDAC inhibitors with in vitro activity at submicromolar concentrations. Here, we present structure-activity data on modifications of a phenylalanine-containing lead compound including amino acid amides as well as variations of the amino acid part. The compounds were tested for inhibition of maize HD-2, rat liver HDAC, and for the induction of terminal cell differentiation and inhibition of proliferation in Friend leukemic cells. In the amide series, in vitro inhibition was potentiated up to 15-fold, but the potential to induce cell differentiation decreased. Interestingly, an HDAC class selectivity was indicated among some of these amides. In the amino acid methyl ester series, a biphenylalanine derivative was identified as a good enzyme inhibitor, which blocks proliferation in the submicromolar range and is also a potent inducer of terminal cell differentiation.

  DOI：

  10.1021/jm0208119

文献信息

• Hexylsilane-mediated direct amidation of amino acids with a catalytic amount of 1,2,4-triazole
  作者：Tomoya Nobuta、Nozomi Tsuchiya、Yutaka Suto、Noriyuki Yamagiwa

  DOI：10.1039/d3ob01722b

  日期：——

  In this study, we report amino acid amidation using hexylsilane and a catalytic amount of 1,2,4-triazole. The conventional protection/deprotection method for the α-amino group of amino acids is not required. The corresponding α-amino amides were obtained in moderate to good yields with low to no racemization.

  在这项研究中，我们报道了使用己基硅烷和催化量的 1,2,4-三唑进行氨基酸酰胺化。不需要常规的氨基酸α-氨基保护/脱保护方法。相应的 α-氨基酰胺以中等至良好的产率获得，且外消旋作用低或无外消旋作用。
• SUZUKI, KENJI;FUJITA, HIROKI;SASAKI, YUSUKE;SHIRATORI, MIKI;SAKURADA, SHI+, CHEM. AND PHARM. BULL., 36,(1988) N2, C. 4834-4840
  作者：SUZUKI, KENJI、FUJITA, HIROKI、SASAKI, YUSUKE、SHIRATORI, MIKI、SAKURADA, SHI+

  DOI：——

  日期：——
• Structure−Activity Relationships on Phenylalanine-Containing Inhibitors of Histone Deacetylase:  In Vitro Enzyme Inhibition, Induction of Differentiation, and Inhibition of Proliferation in Friend Leukemic Cells
  作者：Sybille Wittich、Hans Scherf、Changping Xie、Gerald Brosch、Peter Loidl、Clarissa Gerhäuser、Manfred Jung

  DOI：10.1021/jm0208119

  日期：2002.7.1

  Inhibitors of histone deacetylases (HDACs) are a new class of anticancer agents that affect gene regulation. We had previously reported the first simple synthetic HDAC inhibitors with in vitro activity at submicromolar concentrations. Here, we present structure-activity data on modifications of a phenylalanine-containing lead compound including amino acid amides as well as variations of the amino acid part. The compounds were tested for inhibition of maize HD-2, rat liver HDAC, and for the induction of terminal cell differentiation and inhibition of proliferation in Friend leukemic cells. In the amide series, in vitro inhibition was potentiated up to 15-fold, but the potential to induce cell differentiation decreased. Interestingly, an HDAC class selectivity was indicated among some of these amides. In the amino acid methyl ester series, a biphenylalanine derivative was identified as a good enzyme inhibitor, which blocks proliferation in the submicromolar range and is also a potent inducer of terminal cell differentiation.
• Chymotrypsin inhibitory conformation induced by amino acid side chain–side chain intramolecular CH/π interaction
  作者：Yasuyuki Shimohigashi、Iori Maeda、Takeru Nose、Koichi Ikesue、Hiroshi Sakamoto、Tomohisa Ogawa、Yuzuru Ide、Megumi Kawahara、Takashi Nezu、Yoshihiro Terada、Keiichi Kawano、Motonori Ohno

  DOI：10.1039/p19960002479

  日期：——

  Dipeptide amides H-D-Leu-Phe-NH-R have been found to assume a conformation induced by the CH/pi interaction and to inhibit chymotrypsin strongly. A series of benzyl amide derivatives H-D-Leu-Phe-NH-[CH2](n)-C6H5 (n = 0-4) have been assayed for chymotrypsin, They inhibit the enzyme in a competitive manner and the highest inhibition is achieved by the amide of n = 1 (K-1 3.6 x 10(-6) M), The activity enhancement is dependent upon the length of methylene chain, not upon the increase in molecular hydrophobicity, indicating the presence of an optimal distance between dipeptide backbone and C-terminal phenyl group for chymotrypsin inhibition, The C-terminal phenyl group has been found to interact with chymotrypsin stereospecifically, The R-isomer of H-D-Leu-Phe-NH-CH(CH3)-C6H5 is as active as the benzyl amide, while the S-isomer is about twenty-fold less active, When the fluorine atom is introduced at a para-position of the C-terminal phenyl group, the resulting dipeptide H-D-Leu-Phe-NH-CH2-C6H4F-p exhibits about six-times increased inhibitory activity (K-1 = 6.1 x 10(-7) M; this dipeptide is one of the most potent chymotrypsin inhibitors to date), H-1 NMR conformational analyses of these dipeptide amide derivatives show the CH/pi: interaction between D-Leu-isobutyl and Phe-phenyl as a key structural element for chymotrypsin inhibition, These structural examinations strongly suggest that in the inhibitory conformation the C-terminal phenyl group fits the chymotrypsin S-1 site, while the hydrophobic core constructed by D-Leu-Phe CH/pi interaction fits the chymotrypsin S-2 or S-1' site.