(S)-2-amino-N-(4-fluorophenyl)-3-phenylpropanamide | 52084-06-7

• 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: (S)-2-amino-N-(4-fluorophenyl)-3-phenylpropanamide
• 英文别名: (2S)-2-amino-N-(p-fluorophenyl)-3-phenylpropionamide；(2S)-2-amino-N-(4-fluorophenyl)-3-phenylpropanamide
• CAS: 52084-06-7
• 化学式: C₁₅H₁₅FN₂O
• 分子量: 258.295
• InChiKey: ZYZNWJNPTMMUHO-AWEZNQCLSA-N

物化性质

• 沸点：
  462.4±45.0 °C(Predicted)
• 密度：
  1.241±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-N-(4-fluorophenyl)-3-phenylpropanamide 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成
  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：

  phthaloyl-L-phenylalanyl chloride 在 hydrazine hydrate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 (S)-2-amino-N-(4-fluorophenyl)-3-phenylpropanamide
  参考文献：
  名称：

  双功能萘醌芳香酰胺-肟衍生物通过同时靶向吲哚胺-2,3-双加氧酶和信号转导器和转录激活剂发挥联合免疫治疗和抗肿瘤作用。

  摘要：

  Indoleamine-2,3-dioxygenase 1 (IDO1) 和信号转导和转录激活因子 3 (STAT3) 是肿瘤微环境中用于癌症治疗的重要靶点。在本研究中，设计了一组萘醌芳香酰胺肟衍生物，它们通过抑制 IDO1 来刺激免疫反应，同时通过抑制 STAT3 信号传导对三种选定的癌细胞系显示出强大的抗肿瘤活性。代表性化合物8u与IDO1有效结合，相对于商业IDO1抑制剂4-氨基-N-(3-氯-4-氟苯基)-N'-羟基-1,2,5-恶二唑-3-具有更大的抑制活性羧酰亚胺酰胺 (IDO5L) 除了有效抑制 STAT3 的核易位。一贯地，体内试验证明化合物 8u 在野生型 B16-F10 同种移植肿瘤和无胸腺 HepG2 异种移植模型中相对于 1-甲基-1-色氨酸 (1-MT) 和多柔比星 (DOX) 具有更高的抗增殖活性。这种具有双重免疫治疗和抗癌功效的双功能化合物可能代表新一代高效的癌症治疗候选药物。

  DOI：

  10.1021/acs.jmedchem.9b01386

文献信息

• Design and synthesis of thiol containing inhibitors of matrix metalloproteinases
  作者：Cynthia A. Fink、J.Eric Carlson、Charles Boehm、Patricia McTaggart、Ying Qiao、John Doughty、Vishwas Ganu、Richard Melton、Ronald Goldberg

  DOI：10.1016/s0960-894x(98)00716-1

  日期：1999.1

  A series of thiol containing derivatives was prepared. Several of these compounds were found to inhibit matrix metalloproteinases 1, 3, and 9 with selectivity towards 3 and 9. Compounds 15, 20, and 22 were administered to rats orally at 75 mumol/kg. Drug levels of compounds 20 and 22 in the plasma were found to exceed the IC50 values for MMP 3 and 9 four hours after administration.

  制备了一系列含硫醇的衍生物。发现这些化合物中的几种抑制基质金属蛋白酶1、3和9，对3和9具有选择性。将化合物15、20和22以75μmol/ kg口服给予大鼠。发现给药后四小时血浆中化合物20和22的药物水平超过MMP 3和9的IC50值。
• Synthesis and antitumor activities of novel dipeptide derivatives derived from dehydroabietic acid
  作者：Xiao-Chao Huang、Meng Wang、Heng-Shan Wang、Zhen-Feng Chen、Ye Zhang、Ying-Ming Pan

  DOI：10.1016/j.bmcl.2014.02.001

  日期：2014.3

  series of dipeptide derivatives from dehydroabietic acid were designed and synthesized as novel antitumor agents. The antitumor activities screening indicated that many compounds showed moderate to high levels of inhibition activities against NCI-H460, HepG2, SK-OV-3, BEL-7404, HeLa and HCT-116 cancer cell lines and that some displayed more potent inhibitory activities than commercial anticancer drug

  设计并合成了一系列来自脱氢松香酸的二肽衍生物，作为新型抗肿瘤剂。抗肿瘤活性筛选表明，许多化合物显示出对NCI-H460，HepG2，SK-OV-3，BEL-7404，HeLa和HCT-116癌细胞的中等至高水平的抑制活性，并且某些化合物比商业抗癌药物5-氟尿嘧啶。通过AO / EB染色，Hoechst 33258染色，JC-1线粒体膜电位染色，TUNEL法，DNA阶梯法和流式细胞术研究了代表性化合物7b的机制，表明该化合物可诱导HeLa细胞凋亡。进一步研究表明，化合物7b 通过线粒体途径诱导HeLa细胞凋亡。
• 己酰胺衍生物、其制备方法、中间体和应用
  申请人：上海医药工业研究院

  公开号：CN103319367B

  公开（公告）日：2016-05-04

  本发明公开了一种如式A所示的己酰胺衍生物或其药学上可接受的盐，其中，R1为H或卤素；R2为卤素、C1～C4的烷基、C1～C4的烷氧基、或C3～C7的杂环，杂环中的杂原子数为1～3个，杂原子为氮和/或氧；R0为苄基、取代苄基或C4的烷基，取代苄基中的取代基为C1～C3的烷基。本发明还公开了上述己酰胺衍生物的制备方法，中间体以及应用。本发明的己酰胺衍生物具有有效且较佳的抗菌作用，在医药领域有较高的应用价值。
• Synthesis of Chiral Amino Acid Anilides by Ligand-Free Copper-Catalyzed Selective<i>N</i>-Arylation of Amino Acid Amides
  作者：Junyu Dong、Yan Wang、Qinjie Xiang、Xirui Lv、Wen Weng、Qingle Zeng

  DOI：10.1002/adsc.201200752

  日期：2013.3.11

  atom‐economic, practical and cost‐effective protocol for synthesis of chiral amino acid anilides via ligand‐free copper‐catalyzed selective CN cross coupling of chiral amino acid amides and aryl halides, hetereoaryl halides and a vinyl bromide has been developed. No racemization occurred during the CN coupling. A plausible mechanism is proposed.

  为手性氨基酰苯胺的合成中的原子经济性，实用性和成本效益的协议经由无配体的铜-催化的选择性Ç  Ñ手性氨基酸酰胺和芳基卤化物，杂芳卤化物与乙烯基溴化镁的交叉偶联已经研制成功。CN偶联过程中未发生外消旋作用。提出了一个合理的机制。
• GASTRIN AND CCK RECEPTOR LIGANDS
  申请人：JAMES BLACK FOUNDATION LIMITED

  公开号：EP0720601A1

  公开（公告）日：1996-07-10