N-phthaloyl-(S)-phenylalanine morpholineamide | 232923-93-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: N-phthaloyl-(S)-phenylalanine morpholineamide
• 英文别名: (S)-2-(1-morpholino-1-oxo-3-phenylpropan-2-yl)isoindoline-1,3-dione；2-[(2S)-1-morpholin-4-yl-1-oxo-3-phenylpropan-2-yl]isoindole-1,3-dione
• CAS: 232923-93-2
• 化学式: C₂₁H₂₀N₂O₄
• 分子量: 364.401
• InChiKey: UUCVKLWHONNUJM-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  N-邻苯二甲酰基-L-苯丙氨酸 在 氯化亚砜 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 为溶剂， 反应 4.0h， 生成 N-phthaloyl-(S)-phenylalanine morpholineamide
  参考文献：
  名称：

  Design, synthesis and biological evaluation of functionalized phthalimides: A new class of antimalarials and inhibitors of falcipain-2, a major hemoglobinase of malaria parasite

  摘要：

  Phthalimides functionalized with cyclic amines were synthesized, characterized and screened for their in vitro antimalarial efficacy against Plasmodium falciparum (Pf3D7). Of all the listed phthalimides evaluated, 14 and 24 were identified as potent antimalarial agents as advocated by assessment of their ability to inhibit [H-3] hypoxanthine incorporation in the nucleic acid of parasites. In addition, phthalimides 14 and 24 were incubated for 60 and 90 h and an enhanced antimalarial effect was noticed with increase in time to great extent. A reduction in IC50 values was observed with increase in exposure time of the parasite to the compounds. A symmetric phthalimide, 24 possessing piperazine as linker unit was identified as the most potent antimalarial agent with IC50 values of 5.97 +/- 0.78, 2.0 +/- 1.09 and 1.1 +/- 0.75 mu M on incubation period of 42, 60 and 90 h, respectively. The abnormal morphologies such as delay in developmental stages, growth arrest and condensed nuclei of parasite were observed with the aid of microscopic studies upon exposure with 14 and 24. The evaluation of 14 and 24 against chloroquine resistant strain, (Pf7GB) of P. falciparum afforded IC50 values, 13.29 +/- 1.20 and 7.21 +/- 0.98 mu M, respectively. The combination of 24 with artemisinin (ART) showed enhanced killing of parasite against Pf3D7. Further, all phthalimides were evaluated for their activity against falcipain-2 (FP2), a major hemoglobinase of malarial parasite. The enzymatic assay afforded 6 as most active member against FP2. To the best of our knowledge this is the initial study represents phthalimide protected amino acids functionalized with cyclic amines as potent antimalarial agents. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.02.029

文献信息

• Process Development in the Synthesis of the ACE Intermediate MDL 28,726
  作者：Stephen W. Horgan、David W. Burkhouse、Robert J. Cregge、David W. Freund、Michael LeTourneau、Alexey Margolin、Mark E. Webster、Daniel R. Henton、Kathy P. Barton、Robert C. Clouse、Michael A. DesJardin、Richard E. Donaldson、Neal J. Fetner、Christian T. Goralski、Gerald P. Heinrich、John F. Hoops、Robert T. Keaten、J. Russell McConnell、Mark A. Nitz、Sandra K. Stolz-Dunn

  DOI：10.1021/op970125x

  日期：1999.7.1

  MDL 28,726 is a key intermediate in the synthesis of the ACE inhibitors MDL 27,210A and MDL 100,240, An efficient nine-step synthesis of this tricyclic acid, which has three chiral centers, was developed beginning with 3,4-dihydro-2H-pyran. A key step in the synthesis features an enzyme-catalyzed resolution of the lithium salt of the N-trifluoroacetamide of (R,S)-6-hydroxynorleucine. All of the steps were optimized and completed in reactor equipment using environmentally acceptable processes. Process development of this route is described.
• Design, synthesis and biological evaluation of functionalized phthalimides: A new class of antimalarials and inhibitors of falcipain-2, a major hemoglobinase of malaria parasite
  作者：Anil K. Singh、Vinoth Rajendran、Akansha Pant、Prahlad C. Ghosh、Neelu Singh、N. Latha、Sandeep Garg、Kailash C. Pandey、Brajendra K. Singh、Brijesh Rathi

  DOI：10.1016/j.bmc.2015.02.029

  日期：2015.4

  Phthalimides functionalized with cyclic amines were synthesized, characterized and screened for their in vitro antimalarial efficacy against Plasmodium falciparum (Pf3D7). Of all the listed phthalimides evaluated, 14 and 24 were identified as potent antimalarial agents as advocated by assessment of their ability to inhibit [H-3] hypoxanthine incorporation in the nucleic acid of parasites. In addition, phthalimides 14 and 24 were incubated for 60 and 90 h and an enhanced antimalarial effect was noticed with increase in time to great extent. A reduction in IC50 values was observed with increase in exposure time of the parasite to the compounds. A symmetric phthalimide, 24 possessing piperazine as linker unit was identified as the most potent antimalarial agent with IC50 values of 5.97 +/- 0.78, 2.0 +/- 1.09 and 1.1 +/- 0.75 mu M on incubation period of 42, 60 and 90 h, respectively. The abnormal morphologies such as delay in developmental stages, growth arrest and condensed nuclei of parasite were observed with the aid of microscopic studies upon exposure with 14 and 24. The evaluation of 14 and 24 against chloroquine resistant strain, (Pf7GB) of P. falciparum afforded IC50 values, 13.29 +/- 1.20 and 7.21 +/- 0.98 mu M, respectively. The combination of 24 with artemisinin (ART) showed enhanced killing of parasite against Pf3D7. Further, all phthalimides were evaluated for their activity against falcipain-2 (FP2), a major hemoglobinase of malarial parasite. The enzymatic assay afforded 6 as most active member against FP2. To the best of our knowledge this is the initial study represents phthalimide protected amino acids functionalized with cyclic amines as potent antimalarial agents. (C) 2015 Elsevier Ltd. All rights reserved.