4-氨基-N-苯乙基苯甲酰胺 | 61251-99-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氨基-N-苯乙基苯甲酰胺
• 英文名称: 4-amino-N-phenethylbenzamide
• 英文别名: 4-amino-N-(2-phenylethyl)benzamide
• CAS: 61251-99-8
• 化学式: C₁₅H₁₆N₂O
• mdl: MFCD00578787
• 分子量: 240.305
• InChiKey: MIHLCBDTDZSJDS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.133
• 拓扑面积：
  55.1
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2924299090

反应信息

• 作为反应物：
  描述：

  4-氨基-N-苯乙基苯甲酰胺 在 sodium cyanoborohydride 作用下， 以 甲醇 、 苯 为溶剂， 反应 26.5h， 生成 4-(2,5-dihydroxybenzylamino)-N-phenethylbenzamide
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Series of Lavendustin A Analogues That Inhibit EGFR and Syk Tyrosine Kinases, as Well as Tubulin Polymerization

  摘要：

  A series of N-alkylamide analogues of the lavendustin A pharmacophore were synthesized and tested for inhibition of the epidermal growth factor receptor (EGFR) protein tyrosine kinase and the nonreceptor protein tyrosine kinase Syk. Although several compounds in the series were effective inhibitors of both kinases, it seemed questionable whether their inhibitory effects on these kinases were responsible for the cytotoxic properties observed in a variety of human cancer cell cultures. Accordingly, a COMPARE analysis of the cytotoxicity profile of the most cytotoxic member of the series was performed, and the results indicated that its cytotoxicity profile was similar to that of antitubulin agents. This mechanism of action was supported by demonstrating that most compounds in the series were moderately effective as inhibitors of tubulin polymerization. This suggests that the lavendustin A analogues reported here, as well as some of the previously reported lavendustin A analogues, may be acting as cytotoxic agents by a mechanism involving the inhibition of tubulin polymerization.

  DOI：

  10.1021/jm000387g
• 作为产物：
  描述：

  4-[(tert-butoxycarbonyl)amino]-N-(β-phenethyl)benzamide 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以98.6%的产率得到4-氨基-N-苯乙基苯甲酰胺
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of a Series of Lavendustin A Analogues That Inhibit EGFR and Syk Tyrosine Kinases, as Well as Tubulin Polymerization

  摘要：

  A series of N-alkylamide analogues of the lavendustin A pharmacophore were synthesized and tested for inhibition of the epidermal growth factor receptor (EGFR) protein tyrosine kinase and the nonreceptor protein tyrosine kinase Syk. Although several compounds in the series were effective inhibitors of both kinases, it seemed questionable whether their inhibitory effects on these kinases were responsible for the cytotoxic properties observed in a variety of human cancer cell cultures. Accordingly, a COMPARE analysis of the cytotoxicity profile of the most cytotoxic member of the series was performed, and the results indicated that its cytotoxicity profile was similar to that of antitubulin agents. This mechanism of action was supported by demonstrating that most compounds in the series were moderately effective as inhibitors of tubulin polymerization. This suggests that the lavendustin A analogues reported here, as well as some of the previously reported lavendustin A analogues, may be acting as cytotoxic agents by a mechanism involving the inhibition of tubulin polymerization.

  DOI：

  10.1021/jm000387g

文献信息

• Base-Mediated Anti-Markovnikov Hydroamidation of Vinyl Arenes with Arylamides
  作者：Ayushee、Monika Patel、Priyanka Meena、Kousar Jahan、Prasad V. Bharatam、Akhilesh K. Verma

  DOI：10.1021/acs.orglett.0c04084

  日期：2021.1.15

  anti-Markovnikov hydroamidation of vinyl arenes with arylamides to furnish the arylethylbenzamides with excellent chemo- and regioselectivity. The reaction tolerates an extensive variety of functional groups and has been successfully extended with electronically varied handles, aminobenzamides, electron-rich/electron-deficient heterocyclic amides, and vinyl arenes to afford the hydroamidated products.

  我们研究了乙烯基芳烃与芳基酰胺的分子间抗Markovnikov加氢酰胺化的碱促进方案，以提供具有优异的化学和区域选择性的芳基乙基苯甲酰胺。该反应可耐受多种官能团，并已成功地扩展了电子形式的手柄，氨基苯甲酰胺，富电子/缺电子的杂环酰胺和乙烯基芳烃，以提供加氢酰胺化产物。观察到酰胺基优于胺具有出色的化学选择性。氘标记研究和对照实验充分支持了所提出的溶剂机理和重要作用。
• Synthesis and anticonvulsant activity of analogs of 4-amino-N-(1-phenylethyl)benzamide
  作者：C. Randall Clark、Timothy W. Davenport

  DOI：10.1021/jm00390a016

  日期：1987.7

  to 4-amino-N-(1-phenylethyl)benzamide, 1, were prepared in a study on the relationship of structure to anticonvulsant activity in this compound. Acylation and alkylation of the amino group of 1 resulted in almost total loss of anticonvulsant activity. Insertion of a methylene between the 4-amino group and the aromatic ring of 1 produced a slight increase in anticonvulsant potency and a significant increase

  为了研究该化合物的结构与抗惊厥活性之间的关系，制备了一组与4-氨基-N-（1-苯基乙基）苯甲酰胺有关的酰胺和胺。1氨基的酰化和烷基化导致抗惊厥活性几乎完全丧失。在4-氨基和1的芳环之间插入亚甲基会导致抗惊厥药力的轻微增加和毒性的显着增加。1中酰胺羰基的氢化物还原还产生具有抗电击引起的惊厥的ED50稍低的化合物，而在转子法中的TD50则低得多。1-苯基乙基1的修饰也降低了抗惊厥药的效力。
• Anticonvulsant activity of some 4-aminobenzamides
  作者：C. Randall Clark、Martha J. M. Wells、Ricky T. Sansom、George N. Norris、Randy C. Dockens、William R. Ravis

  DOI：10.1021/jm00372a013

  日期：1984.6

  A series of 4- aminobenzamides of some simple primary and secondary amines were prepared and evaluated for anticonvulsant effects. The compounds were tested in mice against seizures induced by electroshock and pentylenetetrazole ( metrazole ) and in the rotorod assay for neurologic deficit. For those N-alkyl amides tested, 4-amino-N- amylbenzamide (6) was the most potent against maximal electroshock

  制备了一系列一些简单的伯胺和仲胺的4-氨基苯甲酰胺，并评估了其抗惊厥作用。在小鼠中对化合物进行了抗电击和戊四氮（甲唑）诱发的癫痫发作的测试，并在转子法中测试了神经功能缺损。对于所测试的那些N-烷基酰胺，4-氨基-N-戊基苯甲酰胺（6）对最大电击发作（MES）的抑制作用最强：ED50 = 42.98 mg / kg； ED50 = 42.98 mg / kg。然而，N-环己基苯甲酰胺（8）显示出最大的保护指数（PI = TD50 / ED50），为2.8。第二芳环的引入产生更有效的化合物，其中d，1-4-4-氨基-N-（α-甲基苄基）-苯甲酰胺（12）显示出最高的活性水平。腹膜内（ip）给药时，该化合物在小鼠中的抗MES ED50为18.02 mg / kg，TD50为170.78 mg / kg（PI = 9）。5）在相同的物种。这些数据与苯巴比妥和苯妥英在相同试验中的数据相比非常有利。
• Comparative study of dG affinity vs. DNA methylation modulating properties of side chain derivatives of procainamide: insight into its DNA hypomethylating effect
  作者：R. L. Gawade、D. K. Chakravarty、J. Debgupta、E. Sangtani、S. Narwade、R. G. Gonnade、V. G. Puranik、D. D. Deobagkar

  DOI：10.1039/c5ra20012a

  日期：——

  MCF-7 cancer cell line compared to other derivatives and procainamide. A docking study has also illustrated the plausible structural basis of DNA methylation modulating a property of procainamide. Strong association of procainamide with dG bases of partially denatured CpG rich DNA via H-bonding and other non-covalent interactions may alter the active topology of DNA required by the DNA-binding regulatory

  已合成普鲁卡因酰胺衍生物，以研究侧链在调节癌细胞中DNA甲基化水平中的作用，并深入了解其作用机理。合成的衍生物包括柔性的（二甲基），受约束的（吡咯烷，哌啶，吗啉）和平面芳香族（吡啶，苯基）侧链基序。普鲁卡因酰胺及其衍生物对中性形式的脱氧鸟苷（dG）碱的亲和力已通过在生理条件下进行差动脉冲伏安法（DPV）进行了评估。此外，分子与从活性mDNMT-1-DNA（PDB ID-4DA4）晶体结构获得的富含半甲基化CpG的DNA分子对接，揭示了它们在小沟的插层腔中与dG核碱基的优先非共价相互作用。在亚致死浓度下，衍生物对dG碱基的中性和结合形式（DNA）的差异亲和力与其DNA甲基化调节特性有关。在所有衍生物中，具有芳族苯基侧链的化合物（1）对中性形式的dG核碱基以及部分变性的富含CpG的DNA表现出最高的结合亲和力，这归因于N–H⋯O氢与嘧啶环的氢键结合，还形成了π⋯π堆积相互作用。 dG基础。与其
• Multitarget, Selective Compound Design Yields Potent Inhibitors of a Kinetoplastid Pteridine Reductase 1
  作者：Ina Pöhner、Antonio Quotadamo、Joanna Panecka-Hofman、Rosaria Luciani、Matteo Santucci、Pasquale Linciano、Giacomo Landi、Flavio Di Pisa、Lucia Dello Iacono、Cecilia Pozzi、Stefano Mangani、Sheraz Gul、Gesa Witt、Bernhard Ellinger、Maria Kuzikov、Nuno Santarem、Anabela Cordeiro-da-Silva、Maria P. Costi、Alberto Venturelli、Rebecca C. Wade

  DOI：10.1021/acs.jmedchem.2c00232

  日期：2022.7.14

  antiparasitic compounds. Computational fragment-based design of novel pteridine derivatives along with iterations of crystallographic structure determination allowed for the derivation of a structure–activity relationship for multitarget inhibition. The approach yielded compounds showing apparent picomolar inhibition of T. brucei pteridine reductase 1 (PTR1), nanomolar inhibition of L. major PTR1, and selective

  具有多个目标的化合物的优化是药物发现周期中一个困难的多维问题。在这里，我们提出了一种系统的、多学科的方法来开发选择性抗寄生虫化合物。新型蝶啶衍生物的基于计算片段的设计以及晶体结构确定的迭代允许推导多靶点抑制的结构-活性关系。该方法产生的化合物显示出对布氏蝶啶还原酶 1 (PTR1) 的明显皮摩尔抑制，对L. major的纳摩尔抑制PTR1，以及对寄生虫二氢叶酸还原酶 (DHFR) 与人类 DHFR 的选择性亚微摩尔抑制。此外，通过将多药理学设计与基于特性的寄生虫优化相结合，我们发现三种化合物对布氏布氏锥虫表现出微摩尔 EC 50值，同时保持其目标抑制作用。我们的结果为进一步开发基于蝶啶的化合物提供了基础，我们希望我们的多靶点方法普遍适用于抗感染药物的设计和优化。