2-Benzyl-3-morpholinoacrylonitrile | 76651-70-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: 2-Benzyl-3-morpholinoacrylonitrile
• 英文别名: 2-benzyl-3-morpholin-4-ylprop-2-enenitrile
• CAS: 76651-70-2
• 化学式: C₁₄H₁₆N₂O
• 分子量: 228.294
• InChiKey: IAHHSFVWNZFBFX-UHFFFAOYSA-N

物化性质

• 沸点：
  411.5±45.0 °C(Predicted)
• 密度：
  1.171±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  36.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-Benzyl-3-morpholinoacrylonitrile 在 盐酸 、 sodium methylate 作用下， 以 乙醇 、 异丙醇 为溶剂， 反应 36.0h， 生成 5-苄基-2,4-二氨基嘧啶
  参考文献：
  名称：

  Folate-Synthesizing Enzyme System as Target for Development of Inhibitors and Inhibitor Combinations against Candida albicansSynthesis and Biological Activity of New 2,4-Diaminopyrimidines and 4‘-Substituted 4-Aminodiphenyl Sulfones

  摘要：

  The paper describes the design, synthesis, and testing of inhibitors of folate-synthesizing enzymes and of whole cell cultures of Candida albicans. The target enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested as inhibitors of DHFR and compared with their activity against DHFR derived from mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory activity against SYN and the I-50 values compared to those obtained previously against Plasmodium berghei- and E. coli-derived SYN. Surprisingly, QSAR equations show very similar structural dependencies. To find an explanation for the large difference in the I-50 values observed for enzyme inhibition (SYN, DHFR) and for inhibition of cell cultures of Candida, mutant strains with overexpressed efflux pumps and strains in which such pumps are deleted were included in the study and the MICs compared. Efflux pumps were responsible for the low activity of some of the tested derivatives, others showed no increase in activity after pumps were knocked out. In this case it may be speculated that these derivatives are not able to enter the cells.

  DOI：

  10.1021/jm030931w
• 作为产物：
  描述：

  3-(4-吗啉基)丙腈 、 苯甲醛 在 sodium methylate 作用下， 以 二甲基亚砜 为溶剂， 生成 2-Benzyl-3-morpholinoacrylonitrile
  参考文献：
  名称：

  Folate-Synthesizing Enzyme System as Target for Development of Inhibitors and Inhibitor Combinations against Candida albicansSynthesis and Biological Activity of New 2,4-Diaminopyrimidines and 4‘-Substituted 4-Aminodiphenyl Sulfones

  摘要：

  The paper describes the design, synthesis, and testing of inhibitors of folate-synthesizing enzymes and of whole cell cultures of Candida albicans. The target enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested as inhibitors of DHFR and compared with their activity against DHFR derived from mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory activity against SYN and the I-50 values compared to those obtained previously against Plasmodium berghei- and E. coli-derived SYN. Surprisingly, QSAR equations show very similar structural dependencies. To find an explanation for the large difference in the I-50 values observed for enzyme inhibition (SYN, DHFR) and for inhibition of cell cultures of Candida, mutant strains with overexpressed efflux pumps and strains in which such pumps are deleted were included in the study and the MICs compared. Efflux pumps were responsible for the low activity of some of the tested derivatives, others showed no increase in activity after pumps were knocked out. In this case it may be speculated that these derivatives are not able to enter the cells.

  DOI：

  10.1021/jm030931w

文献信息

• Method of preparing .beta.-alkoxyacrlonitriles
  申请人：Dynamit Nobel Aktiengesellschaft

  公开号：US04319024A1

  公开（公告）日：1982-03-09

  A process for the preparation of a .beta.-alkoxyacrylonitrile of the formula R'O--CH.dbd.CR--CN (C) where R is hydrogen or an alkyl moiety, among others, by contacting a compound of the formula (1/.alpha.Me) O--CH.dbd.CR--CN (A) where Me is an alkali metal or alkaline earth metal and .alpha. is 1 or 2 respectively, an elevated temperature with a halogen compound of the formula R'Hal (B) where R' is among others a straight or branched alkyl or alkenyl moiety and Hal represents chlorine, bromine, or iodine. Also disclosed is a process for preparing a 3-amino-acrylonitrile of the formula ##STR1## where R.sup.5 and R.sup.6 represent, among others, hydrogen, alkyl or alkenyl by contacting a 3-alkoxyacrylonitrile or a metal salt of 3-hydroxyacrylonitrile with ammonia and/or amine. Also disclosed is a process for the preparation of such 3-aminoacrylonitrile by contacting a 3-alkoxyacrylonitrile of the formula ##STR2## where R' has the meaning given above and R.sup.7 has the same meaning as R stated above with an amine of the formula ##STR3## wherein R.sup.5 and R.sup.6 represent among others hydrogen, alkyl or alkenyl. The application further discloses a process for preparing a 3-amino-acrylonitrile of the formula ##STR4## where R.sup.5, R.sup.6 and R.sup.7 have the above meanings by contacting a compound of the formula ##EQU1## with an amine. The Application also discloses the preparation of two-cyanovinyl esters by reaction of a cyanovinyl compound of the formula ##EQU2## with an acid halide or an acid anhydride.

  一种制备式R'O-CH=CR-CN（C）的β-烷氧基丙烯腈的方法，其中R是氢或烷基基团，通过将式（1/α.Me）O-CH=CR-CN（A）的化合物与卤素化合物式R'Hal（B）接触，在高温下进行，其中Me是碱金属或碱土金属，α分别为1或2。还揭示了一种通过将3-烷氧基丙烯腈或3-羟基丙烯腈的金属盐与氨和/或胺接触，制备式##STR1##其中R5和R6表示氢，烷基或烯基等。还揭示了一种通过将式##STR2##其中R'具有上述给定的含义，R7与上述R具有相同的含义，与式##STR3##其中R5和R6表示氢，烷基或烯基等的胺接触，制备这种3-氨基丙烯腈的方法。该申请还揭示了一种通过将式##EQU1##与胺接触，制备式##STR4##其中R5，R6和R7具有上述含义的方法。该申请还揭示了通过将式##EQU2##的氰基化合物与酸卤或酸酐反应，制备两种氰基乙烯酯的方法。
• Folate-Synthesizing Enzyme System as Target for Development of Inhibitors and Inhibitor Combinations against <i>Candida </i><i>a</i><i>lbicans</i>Synthesis and Biological Activity of New 2,4-Diaminopyrimidines and 4‘-Substituted 4-Aminodiphenyl Sulfones
  作者：Thomas Otzen、Ellen G. Wempe、Brigitte Kunz、Rainer Bartels、Gudrun Lehwark-Yvetot、Wolfram Hänsel、Klaus-Jürgen Schaper、Joachim K. Seydel

  DOI：10.1021/jm030931w

  日期：2004.1.1

  The paper describes the design, synthesis, and testing of inhibitors of folate-synthesizing enzymes and of whole cell cultures of Candida albicans. The target enzymes used were dihydropteroic acid synthase (SYN) and dihydrofolate reductase (DHFR). Several series of new 2,4-diaminopyrimidines were synthesized and tested as inhibitors of DHFR and compared with their activity against DHFR derived from mycobacteria and Escherichia coli. To test for selectivity, also rat DHFR was used. A series of substituted 4-aminodiphenyl sulfones was tested for inhibitory activity against SYN and the I-50 values compared to those obtained previously against Plasmodium berghei- and E. coli-derived SYN. Surprisingly, QSAR equations show very similar structural dependencies. To find an explanation for the large difference in the I-50 values observed for enzyme inhibition (SYN, DHFR) and for inhibition of cell cultures of Candida, mutant strains with overexpressed efflux pumps and strains in which such pumps are deleted were included in the study and the MICs compared. Efflux pumps were responsible for the low activity of some of the tested derivatives, others showed no increase in activity after pumps were knocked out. In this case it may be speculated that these derivatives are not able to enter the cells.