3-anilino-2-<4-(benzyloxy)benzyl>acrylonitrile | 30077-74-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-anilino-2-<4-(benzyloxy)benzyl>acrylonitrile
• 英文别名: β-anilino-α-(p-benzyloxybenzyl) acrylonitrile；beta-Anilino-alpha-(p-benzyloxybenzyl) acrylonitrile；3-anilino-2-[(4-phenylmethoxyphenyl)methyl]prop-2-enenitrile
• CAS: 30077-74-8
• 化学式: C₂₃H₂₀N₂O
• 分子量: 340.425
• InChiKey: HJYHYIDVIAZOHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  45
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-anilino-2-<4-(benzyloxy)benzyl>acrylonitrile 在 palladium on activated charcoal 氢气 、 sodium methylate 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 90.0~100.0 ℃ 、310.27 kPa 条件下， 反应 2.0h， 生成 2,4-diamino-5-(4-hydroxybenzyl)pyrimidine
  参考文献：
  名称：

  2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 7. Analysis of the effect of 3,5-dialkyl substituent size and shape on binding to four different dihydrofolate reductase enzymes

  摘要：

  A group of trimethoprim (TMP) analogues containing 3,5-dialkyl(or halo)-4-alkoxy, -hydroxy, or -amino substitution were analyzed in terms of their inhibitory activities against four dihydrofolate reductase (DHFR) isozymes. Although selectivities were lower than with TMP, the activities against vertebrate DHFR were usually at least 2 orders of magnitude less than against enzymes from microbial sources. However, the profiles of activity were remarkably similar for rat, Neisseria gonorrhoeae, and Plasmodium berghei enzymes in all three series, although somewhat different for Escherichia coli DHFR, leading to the conclusion that the hydrophobic pockets are similar for the first three isozymes. Optimal substitution was reached with 3,5-di-n-propyl or 3-ethyl-5-n-propyl groups. Branching of chains at the alpha-carbon, which resulted in increased substituent thickness, was detrimental to E. coli DHFR inhibition in particular. MR is an inadequate parameter for use in correlating such substituent effects. Conformational changes of the more bulky inhibitors can be invoked to explain some differences in inhibitory pattern. Although log P explains simple substituent effects with the vertebrate DHFRs very well, it is insufficient in the more complex cases described here, where shape is clearly involved as well. Solvent-accessible surface areas were measured for TMP in E. coli and chicken DHFRs, where the coordinates are now known. The environment is more hydrophobic in the latter case; this can also be postulated for rat DHFR, which has a very similar activity profile. As with the mammalian isozymes, N. gonorrhoeae DHFR contains an active site phenylalanine replacing Leu-28 of E. coli DHFR, thus creating a more hydrophobic pocket. A similar replacement may also occur in the P.berghei isozyme. Selectivity for bacterial DHFR is dependent on the nature of the 4-substituent, being low for polar 4-hydroxy compounds but high for polar 4-amino analogues, possibly as a result of solvation differences. With complex substituents, the environment of each atom in the active site must be taken into account to adequately explain structure-activity relationships.

  DOI：

  10.1021/jm00385a017
• 作为产物：
  描述：

  4-苄氧基苯甲醛 在 盐酸 、 sodium methylate 作用下， 以 二甲基亚砜 、 异丙醇 为溶剂， 反应 1.5h， 生成 3-anilino-2-<4-(benzyloxy)benzyl>acrylonitrile
  参考文献：
  名称：

  Hachtel; Haller; Seydel, Arzneimittel-Forschung/Drug Research, 1988, vol. 38, # 12, p. 1778 - 1783

  摘要：

  DOI：

文献信息

• Preparation of .beta.-anilino-.alpha.-benzylacrylonitriles
  申请人：Burroughs Wellcome Co.

  公开号：US03950378A1

  公开（公告）日：1976-04-13

  Compounds comprising selected N-substituted .beta.-amino-.alpha.-benzyl-acrylonitriles and methods of preparing said compounds substantially free from the corresponding bensalacrylonitrile. The compounds are useful as intermediates in the preparation of antibacterial and antimalerial agents.

  由选定的N-取代β-氨基-α-苄基丙烯腈组成的化合物，以及制备这些化合物的方法，基本上不含相应的苯乙烯腈。这些化合物在制备抗菌和抗疟疾药物中作为中间体是有用的。
• Method of preparing 2,4-diamino-5-benzyl pyrimidines
  申请人：Burroughs Wellcome Co.

  公开号：US03956327A1

  公开（公告）日：1976-05-11

  The method of preparing 2,4-diamino benzyl pyrimidines which comprises the step of reacting an N-aryl (substituted or unsubstituted)-.beta.-amino-.alpha.-benzylacrylonitrile with guanidine.

  制备2,4-二氨基苄基嘧啶的方法包括将N-芳基（取代或未取代）-β-氨基-α-苄基丙烯腈与脲反应的步骤。
• Process for preparing .beta.-amino-.alpha.-benzylacrylonitriles
  申请人：Burroughs Wellcome Co.

  公开号：US03998814A1

  公开（公告）日：1976-12-21

  Compounds comprising selected N-substituted .beta.-amino-.alpha.-benzyl-acrylonitriles and methods of preparing said compounds substantially free from the corresponding benzalacrylonitrile. The compounds are useful as intermediates in the preparation of antibacterial and antimalarial agents.

  所述化合物包括选择的N-取代.beta.-氨基-.alpha.-苯甲基-丙烯腈化合物，并且制备所述化合物的方法基本上不含相应的苯甲基丙烯腈。这些化合物可用作制备抗菌和抗疟疾药物的中间体。
• Preparation of .beta.-Amino-.alpha.-benzylacrylonitriles
  申请人：Burroughs Wellcome Co.

  公开号：US03991050A1

  公开（公告）日：1976-11-09

  Compounds and methods of making compounds of the formula ##SPC1## Where X is a diloweralkylsulphone or diloweralkyl sulphoxide group and R.sup.1 -R.sup.4 is hydrogen, loweralkyl, loweralkoxyl, halogen, benzyloxy or methylenedioxy provided that one of R.sup.1 -R.sup.4 is a substituent other than hydrogen, and where R.sup.7 and R.sup.8 are hydrogen atoms or together represent an additional bond between the carbon and oxygen atoms. The compounds are useful as intermediates in the method of preparing other valuable intermediates which are useful in preparing antibacterial agents.

  该文献介绍的是一种化合物及其制备方法，化合物的化学式为##SPC1##其中X为二甲基亚磺酰基或二甲基亚磺醇基，R.sup.1-R.sup.4为氢、低碳基、低碳氧基、卤素、苄氧基或甲烯二氧基，其中至少一个R.sup.1-R.sup.4为氢以外的取代基，而R.sup.7和R.sup.8为氢原子或共同代表碳和氧原子之间的额外键。这些化合物可用作制备其他有用中间体的中间体，并可用于制备抗菌剂。
• 5-Benzyl pyrimidines intermediates therefore, and method
  申请人：Burroughs Wellcome Co.

  公开号：US04052553A1

  公开（公告）日：1977-10-04

  Compounds comprising selected N-substituted .beta.-amino-.alpha.-benzyl-acrylonitriles and methods of preparing said compounds substantially free from the corresponding benzalacrylonitrile. The compounds are useful as intermediates in the preparation of antibacterial and antimalarial agents.

  本发明涉及选定的N-取代β-氨基-α-苄基丙烯腈化合物及其制备方法，该方法可使所得化合物中相应的苯甲酰丙烯腈含量大大降低。该化合物可用作制备抗菌和抗疟疾药物的中间体。