<(tert-butyloxycarbonyl)amino>-N-(4-methoxyphenyl)propanamide | 220903-51-5

• 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-butyloxycarbonyl)amino>-N-(4-methoxyphenyl)propanamide
• 英文别名: tert-butyl N-[1-(4-methoxyanilino)-1-oxopropan-2-yl]carbamate
• CAS: 220903-51-5
• 化学式: C₁₅H₂₂N₂O₄
• 分子量: 294.351
• InChiKey: JDALLHFGWLOPEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  <(tert-butyloxycarbonyl)amino>-N-(4-methoxyphenyl)propanamide 在 N-甲基咪唑 、 氰基磷酸二乙酯 、 N,N-二异丙基乙胺 、 丙酮 、 三氟乙酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 14.5h， 生成 氨基-N-(4-甲氧基苯基)乙酰胺
  参考文献：
  名称：

  N-Substituted 2-(2,6-Dinitrophenylamino)propanamides:  Novel Prodrugs That Release a Primary Amine via Nitroreduction and Intramolecular Cyclization

  摘要：

  A series of N-dinitrophenylamino acid amides [(4-CONHZ-2,6-diNO(2)Ph)N(R)C(X,Y)CONHPhOMe] were prepared as potential bioreductive prodrugs and reduced radiolytically to study their rates of subsequent intramolecular cyclization. Compounds bearing a free NH group (R = H) underwent rapid cyclization in neutral aqueous buffers (t(1/2) < 1 min) following 4-electron reduction, with the generation of a N-hydroxydihydroquinoxalinone and concomitant release of 4-methoxyaniline. Amine release from analogous N-methyl analogues (R = Me) was relatively slow. These results are consistent-with intramolecular cyclization of a monohydroxylamine intermediate. The high rates of cyclization/extrusion by these very electron-deficient hydroxylamines suggest that the process is greatly accelerated by the presence of an H-bonding "conformational lock" between the anilino NH group and the adjacent o-nitro group (Kirk and Cohen, 1972). Changes in the phenylcarboxamide side chain or in C-methylation in the linking chain had little effect-on the rate of cyclization. The model compounds had 1-electron reduction potentials in the range appropriate for cellular reduction (-373 mV for a measured example) and appeared suitable for development as prodrugs that release amine-based effecters following enzymic or radiolytic reduction. Prodrug examples containing 4-aminoaniline mustard and 5-amino-1-(chloromethyl)benz[e]indoline alkylating units were evaluated but were not activated efficiently by cellular nitroreductases. However, cell killing by the radiation-induced reduction of the latter prodrug was demonstrated.

  DOI：

  10.1021/jm960783s
• 作为产物：
  描述：

  BOC-甘氨酸 、 N-t-butyloxycarbonyl-DL-alanine 在 N-甲基咪唑 、 氰基磷酸二乙酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以77%的产率得到<(tert-butyloxycarbonyl)amino>-N-(4-methoxyphenyl)propanamide
  参考文献：
  名称：

  N-Substituted 2-(2,6-Dinitrophenylamino)propanamides:  Novel Prodrugs That Release a Primary Amine via Nitroreduction and Intramolecular Cyclization

  摘要：

  A series of N-dinitrophenylamino acid amides [(4-CONHZ-2,6-diNO(2)Ph)N(R)C(X,Y)CONHPhOMe] were prepared as potential bioreductive prodrugs and reduced radiolytically to study their rates of subsequent intramolecular cyclization. Compounds bearing a free NH group (R = H) underwent rapid cyclization in neutral aqueous buffers (t(1/2) < 1 min) following 4-electron reduction, with the generation of a N-hydroxydihydroquinoxalinone and concomitant release of 4-methoxyaniline. Amine release from analogous N-methyl analogues (R = Me) was relatively slow. These results are consistent-with intramolecular cyclization of a monohydroxylamine intermediate. The high rates of cyclization/extrusion by these very electron-deficient hydroxylamines suggest that the process is greatly accelerated by the presence of an H-bonding "conformational lock" between the anilino NH group and the adjacent o-nitro group (Kirk and Cohen, 1972). Changes in the phenylcarboxamide side chain or in C-methylation in the linking chain had little effect-on the rate of cyclization. The model compounds had 1-electron reduction potentials in the range appropriate for cellular reduction (-373 mV for a measured example) and appeared suitable for development as prodrugs that release amine-based effecters following enzymic or radiolytic reduction. Prodrug examples containing 4-aminoaniline mustard and 5-amino-1-(chloromethyl)benz[e]indoline alkylating units were evaluated but were not activated efficiently by cellular nitroreductases. However, cell killing by the radiation-induced reduction of the latter prodrug was demonstrated.

  DOI：

  10.1021/jm960783s

文献信息

• New sulphonamide pyrolidine carboxamide derivatives: Synthesis, molecular docking, antiplasmodial and antioxidant activities
  作者：Efeturi A. Onoabedje、Akachukwu Ibezim、Uchechukwu C. Okoro、Sanjay Batra

  DOI：10.1371/journal.pone.0243305

  日期：——

  Here we report the synthesis of thirty-two new drug-like sulphonamide pyrolidine carboxamide derivatives and their antiplasmodial and antioxidant capabilities. In addition, molecular docking was used to check their binding affinities for homology modelled P. falciparum N-myristoyltransferase, a confirmed drug target in the pathogen. Results revealed that sixteen new derivatives killed the parasite

  带有磺酰胺功能的羧酰胺已显示出对人类疟疾的病原体恶性疟原虫具有显着的致死作用。在这里，我们报告了三十二种新的药物样磺酰胺吡咯烷羧酰胺衍生物的合成及其抗血浆和抗氧化能力。此外，分子对接用于检查它们与恶性疟原虫N-肉豆蔻酰基转移酶（病原体中已确认的药物靶标）同源性的结合亲和力。结果显示，有16种新衍生物以单位微摩尔浓度（IC50 = 2.40-8.30μM）杀死了该寄生虫，化合物10b，10c，10d，10j和10o在IC50处清除了DPPH自由基（6.48、8.49、3.02、6.44和4.32μg） / mL）与抗坏血酸的1.06μg/ mL相当。与理论配体吡唑-磺酰胺（Ki = 0.01μM）相比，化合物10o以与理论配体抑制常数（Ki = 0.09μM）结合PfNMT的活性最高。这项研究确定了化合物10o（通常是该系列化合物）是具有抗氧化活性的潜在抗疟疾候选药物，需要进一步关注以优化其活性。
• Visible Light Induced Copper‐Catalyzed Enantioselective Deaminative Arylation of Amino Acid Derivatives Assisted by Phenol
  作者：Yue Jia、Zhihan Zhang、Guo‐Ming Yu、Xuan Jiang、Liang‐Qiu Lu、Wen‐Jing Xiao

  DOI：10.1002/anie.202312102

  日期：2023.12.18

  A visible light induced enantioselective deaminative arylation of amino acid derivatives by bifunctional copper catalysis is disclosed. A variety of α-aryl-N-phenylamides are prepared with good efficiency and high enantioselectivity. A possible reaction mechanism and an asymmetric induction mode have been proposed based on experimental and computational evidence.

  公开了通过双功能铜催化的可见光诱导的氨基酸衍生物的对映选择性脱氨芳基化。多种α-芳基-N-苯基酰胺的制备具有良好的效率和高对映选择性。基于实验和计算证据，提出了一种可能的反应机制和不对称诱导模式。
• Structure-Based Discovery of Highly Selective Phosphodiesterase-9A Inhibitors and Implications for Inhibitor Design
  作者：Fei Meng、Jing Hou、Yong-Xian Shao、Pei-Ying Wu、Manna Huang、Xinhai Zhu、Yonghong Cai、Zhe Li、Jie Xu、Peiqing Liu、Hai-Bin Luo、Yiqian Wan、Hengming Ke

  DOI：10.1021/jm301189c

  日期：2012.10.11

  A new series of phosphodiesterase-9 (PDE9) inhibitors that contain a scaffold of 6-amino-pyrazolopyrimidinone have been discovered by a combination of structure-based design and computational docking. This procedure significantly saved the load of chemical synthesis and is an effective method for the discovery of inhibitors. The best compound 28 has an IC50 of 21 nM and 3.3 mu M, respectively, for PDE9 and PDE5 and about 3 orders of magnitude of selectivity against other PDE families. The crystal structure of the PDE9 catalytic domain in complex with 28 has been determined and shows a hydrogen bond between 28 and Tyr424. This hydrogen bond may account for the 860-fold selectivity of 28 against PDE1B, in comparison with about 30-fold selectivity of BAY73-6691. Thus, our studies suggest that Tyr424, a unique residue of PDE8 and PDE9, is a potential target for improvement of selectivity of PDE9 inhibitors.
• New sulphonamide-peptide hybrid molecules as potential PBP 2a ligands and methicillin resistant <i>Staphylococcus aureus</i> actives
  作者：Akachukwu Ibezim、Raphael Onuku、Chidalu Ottih、Ifeoma Ezeonu、Efeturi Onoabedje、Karuppasamy Ramanathan、Ngozi Nwodo

  DOI：10.1080/07391102.2022.2111359

  日期：——
• <i>N</i>-Substituted 2-(2,6-Dinitrophenylamino)propanamides:  Novel Prodrugs That Release a Primary Amine via Nitroreduction and Intramolecular Cyclization
  作者：Bridget M. Sykes、Graham J. Atwell、Alison Hogg、William R. Wilson、Charmian J. O'Connor、William A. Denny

  DOI：10.1021/jm960783s

  日期：1999.2.1

  A series of N-dinitrophenylamino acid amides [(4-CONHZ-2,6-diNO(2)Ph)N(R)C(X,Y)CONHPhOMe] were prepared as potential bioreductive prodrugs and reduced radiolytically to study their rates of subsequent intramolecular cyclization. Compounds bearing a free NH group (R = H) underwent rapid cyclization in neutral aqueous buffers (t(1/2) < 1 min) following 4-electron reduction, with the generation of a N-hydroxydihydroquinoxalinone and concomitant release of 4-methoxyaniline. Amine release from analogous N-methyl analogues (R = Me) was relatively slow. These results are consistent-with intramolecular cyclization of a monohydroxylamine intermediate. The high rates of cyclization/extrusion by these very electron-deficient hydroxylamines suggest that the process is greatly accelerated by the presence of an H-bonding "conformational lock" between the anilino NH group and the adjacent o-nitro group (Kirk and Cohen, 1972). Changes in the phenylcarboxamide side chain or in C-methylation in the linking chain had little effect-on the rate of cyclization. The model compounds had 1-electron reduction potentials in the range appropriate for cellular reduction (-373 mV for a measured example) and appeared suitable for development as prodrugs that release amine-based effecters following enzymic or radiolytic reduction. Prodrug examples containing 4-aminoaniline mustard and 5-amino-1-(chloromethyl)benz[e]indoline alkylating units were evaluated but were not activated efficiently by cellular nitroreductases. However, cell killing by the radiation-induced reduction of the latter prodrug was demonstrated.