JAB75 | 908075-25-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: JAB75
• 英文别名: methyl 6-benzyl-4-naphthalen-2-yl-2-oxo-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 908075-25-2
• 化学式: C₂₃H₂₀N₂O₃
• 分子量: 372.423
• InChiKey: KORAVFADPQXWNG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3-氧代-4-苯基丁酸甲酯 、 2-萘甲醛 、 尿素 在 polyphosphate ester 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 以44%的产率得到JAB75
  参考文献：
  名称：

  Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum

  摘要：

  Plasmodium falciparum, the Apicomplexan parasite that is responsible for the most lethal forms of human malaria, is exposed to radically different environments and stress factors during its complex lifecycle. In any organism, Hsp70 chaperones are typically associated with tolerance to stress. We therefore reasoned that inhibition of P. falciparum Hsp70 chaperones would adversely affect parasite homeostasis. To test this hypothesis, we measured whether pyrimidinone-amides, a new class of Hsp70 modulators, could inhibit the replication of the pathogenic P. falciparum stages in human red blood cells. Nine compounds with IC50 values from 30 nM to 1.6 mu M were identified. Each compound also altered the ATPase activity of purified P. falciparum Hsp70 in single-turnover assays, although higher concentrations of agents were required than was necessary to inhibit P. falciparum replication. Varying effects of these compounds on Hsp70s from other organisms were also observed. Together, our data indicate that pyrimidinone-amides constitute a novel class of anti-malarial agents. (c) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.01.024

文献信息

• Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum
  作者：Annette N. Chiang、Juan-Carlos Valderramos、Raghavan Balachandran、Raj J. Chovatiya、Brian P. Mead、Corinne Schneider、Samantha L. Bell、Michael G. Klein、Donna M. Huryn、Xiaojiang S. Chen、Billy W. Day、David A. Fidock、Peter Wipf、Jeffrey L. Brodsky

  DOI：10.1016/j.bmc.2009.01.024

  日期：2009.2

  Plasmodium falciparum, the Apicomplexan parasite that is responsible for the most lethal forms of human malaria, is exposed to radically different environments and stress factors during its complex lifecycle. In any organism, Hsp70 chaperones are typically associated with tolerance to stress. We therefore reasoned that inhibition of P. falciparum Hsp70 chaperones would adversely affect parasite homeostasis. To test this hypothesis, we measured whether pyrimidinone-amides, a new class of Hsp70 modulators, could inhibit the replication of the pathogenic P. falciparum stages in human red blood cells. Nine compounds with IC50 values from 30 nM to 1.6 mu M were identified. Each compound also altered the ATPase activity of purified P. falciparum Hsp70 in single-turnover assays, although higher concentrations of agents were required than was necessary to inhibit P. falciparum replication. Varying effects of these compounds on Hsp70s from other organisms were also observed. Together, our data indicate that pyrimidinone-amides constitute a novel class of anti-malarial agents. (c) 2009 Elsevier Ltd. All rights reserved.