Hydroxyethylamine-based inhibitor 11f | 500767-38-4

• 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: Hydroxyethylamine-based inhibitor 11f
• 英文别名: N-[(2S)-1-[[(2S,3S)-4-[[(2S)-1-amino-3-(4-bromophenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-phenylbutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]pyridine-2-carboxamide
• CAS: 500767-38-4
• 化学式: C₃₀H₃₆BrN₅O₄
• 分子量: 610.551
• InChiKey: IZXMGPHRTJQLGQ-FWEHEUNISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  40
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  146
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Hydroxyethylamine-based inhibitor 11f 在 bis-triphenylphosphine-palladium(II) chloride caesium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.33h， 生成 Pyridine-2-carboxylic acid ((S)-1-{(1S,2S)-1-benzyl-3-[benzyl-((S)-2-biphenyl-4-yl-1-carbamoyl-ethyl)-amino]-2-hydroxy-propylcarbamoyl}-2-methyl-propyl)-amide
  参考文献：
  名称：

  合成物，生物学评估和模型研究，针对疟疾蛋白酶-纤溶酶I和II的抑制剂。

  摘要：

  疟原虫对抗疟药的抗药性增加是该病重新出现的主要原因，并增加了对新药靶标的需求。最近已经出现了来自恶性疟原虫的两种天冬氨酸蛋白酶，纤溶酶I和II，作为潜在的靶标。为了抑制这些血红蛋白酶，制备了一系列以碱性羟乙基胺过渡态等排体为中心片段的抑制剂。合成的化合物在P1'位置变化，并表现出31至> 2000 nM的生物活性。为了使结果合理化，使用了分子对接和3D-QSAR分析。

  DOI：

  10.1016/j.bmc.2005.06.048
• 作为产物：
  描述：

  L-对溴苯丙氨酸甲酯 在 盐酸 、 三氟甲磺酸 、 氨 、 sodium carbonate 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 苯甲醚 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 2.83h， 生成 Hydroxyethylamine-based inhibitor 11f
  参考文献：
  名称：

  Design and Synthesis of Plasmepsin I and Plasmepsin II Inhibitors with Activity in Plasmodium falciparum-Infected Cultured Human Erythrocytes

  摘要：

  A series of protease inhibitors targeted at the malarial enzymes plasmepsin I and II, and encompassing a basic hydroxyethylamine transition state isostere scaffold, was prepared. The substituents in the P1' position were varied and the biological activities expressed in K-i-values ranged from 60 to > 2000 nM. A more than 4-fold selectivity for either of the plasmepsins could be achieved. All of the active compounds exhibited high preference for the plasmepsins over cathepsin D, the most closely related human protease. A few active compounds were shown to inhibit parasite growth in cultured infected human erythrocytes. An ED50 value as low as 1.6 muM was observed for one of the inhibitors despite K-i values of 115 nM (Plm I) and 121 nM (Plm II).

  DOI：

  10.1021/jm020951i

文献信息

• Design and Synthesis of Plasmepsin I and Plasmepsin II Inhibitors with Activity in <i>Plasmodium </i><i>f</i><i>alciparum</i>-Infected Cultured Human Erythrocytes
  作者：Daniel Nöteberg、Elizabeth Hamelink、Johan Hultén、Mats Wahlgren、Lotta Vrang、Bertil Samuelsson、Anders Hallberg

  DOI：10.1021/jm020951i

  日期：2003.2.1

  A series of protease inhibitors targeted at the malarial enzymes plasmepsin I and II, and encompassing a basic hydroxyethylamine transition state isostere scaffold, was prepared. The substituents in the P1' position were varied and the biological activities expressed in K-i-values ranged from 60 to > 2000 nM. A more than 4-fold selectivity for either of the plasmepsins could be achieved. All of the active compounds exhibited high preference for the plasmepsins over cathepsin D, the most closely related human protease. A few active compounds were shown to inhibit parasite growth in cultured infected human erythrocytes. An ED50 value as low as 1.6 muM was observed for one of the inhibitors despite K-i values of 115 nM (Plm I) and 121 nM (Plm II).
• Synthesis, biological evaluation, and modeling studies of inhibitors aimed at the malarial proteases plasmepsins I and II
  作者：Daniel Muthas、Daniel Nöteberg、Yogesh A. Sabnis、Elizabeth Hamelink、Lotta Vrang、Bertil Samuelsson、Anders Karlén、Anders Hallberg

  DOI：10.1016/j.bmc.2005.06.048

  日期：2005.9

  The increasing resistance of the malarial parasite to antimalarial drugs is a major contributor to the reemergence of the disease and increases the need for new drug targets. The two aspartic proteases, plasmepsins I and II, from Plasmodium falciparum have recently emerged as potential targets. In an effort to inhibit these hemoglobinases, a series of inhibitors encompassing a basic hydroxyethylamine

  疟原虫对抗疟药的抗药性增加是该病重新出现的主要原因，并增加了对新药靶标的需求。最近已经出现了来自恶性疟原虫的两种天冬氨酸蛋白酶，纤溶酶I和II，作为潜在的靶标。为了抑制这些血红蛋白酶，制备了一系列以碱性羟乙基胺过渡态等排体为中心片段的抑制剂。合成的化合物在P1'位置变化，并表现出31至> 2000 nM的生物活性。为了使结果合理化，使用了分子对接和3D-QSAR分析。