5-(吡啶-2-基氨基甲酰)-3H-咪唑-4-羧酸 | 436088-75-4

• 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
• 中文名称: 5-(吡啶-2-基氨基甲酰)-3H-咪唑-4-羧酸
• 英文名称: 4-(pyridine-2-ylcarbamoyl)-1H-imidazole-5-carboxylic acid
• 英文别名: 5-(Pyridin-2-ylcarbamoyl)-3H-imidazole-4-carboxylic acid；4-(pyridin-2-ylcarbamoyl)-1H-imidazole-5-carboxylic acid
• CAS: 436088-75-4
• 化学式: C₁₀H₈N₄O₃
• mdl: MFCD01366409
• 分子量: 232.199
• InChiKey: CXVUEKICGYNMBG-UHFFFAOYSA-N

物化性质

• 沸点：
  493.3±35.0 °C(Predicted)
• 密度：
  1.594±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 海关编码：
  2933990090

反应信息

• 作为产物：
  描述：

  2-氨基吡啶 、 diphenyl 5,10-dioxo-5H,10H-diimidazo[1,5-a:1',5'-d]pyrazine-1,6-dicarboxylate 在 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 26.37h， 以67%的产率得到5-(吡啶-2-基氨基甲酰)-3H-咪唑-4-羧酸
  参考文献：
  名称：

  Discovery of a novel 5-carbonyl-1H-imidazole-4-carboxamide class of inhibitors of the HIV-1 integrase–LEDGF/p75 interaction

  摘要：

  Though much progress has been made in the inhibition of HIV-1 integrase catalysis, clinical resistance mutations have limited the promise of long-term drug prescription. Consequently, allosteric inhibition of integrase activity has emerged as a promising approach to antiretroviral discovery and development. Specifically, inhibitors of the interaction between HIV-1 integrase and cellular cofactor LEDGF/p75 have been validated to diminish proviral integration in cells and deliver a potent reduction in viral replicative capacity. Here, we have contributed to the development of novel allosteric integrase inhibitors with a high-throughput AlphaScreen-based random screening approach, with which we have identified novel 5-carbonyl-1H-imidazole-4-carboxamides capable of inhibiting the HIV-1 integrase-LEDGF/p75 interaction in vitro. Following a structure-activity relationship analysis of the initial 1H-imidazole-4,5-dicarbonyl core, we optimized the compound's structure through an industrial database search, and we went further to synthesize a selective and non-cytotoxic panel of inhibitors with enhanced potency. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.07.047

文献信息

• Discovery of a novel 5-carbonyl-1H-imidazole-4-carboxamide class of inhibitors of the HIV-1 integrase–LEDGF/p75 interaction
  作者：Erik Serrao、Zhong-Liang Xu、Bikash Debnath、Frauke Christ、Zeger Debyser、Ya-Qiu Long、Nouri Neamati

  DOI：10.1016/j.bmc.2013.07.047

  日期：2013.10

  Though much progress has been made in the inhibition of HIV-1 integrase catalysis, clinical resistance mutations have limited the promise of long-term drug prescription. Consequently, allosteric inhibition of integrase activity has emerged as a promising approach to antiretroviral discovery and development. Specifically, inhibitors of the interaction between HIV-1 integrase and cellular cofactor LEDGF/p75 have been validated to diminish proviral integration in cells and deliver a potent reduction in viral replicative capacity. Here, we have contributed to the development of novel allosteric integrase inhibitors with a high-throughput AlphaScreen-based random screening approach, with which we have identified novel 5-carbonyl-1H-imidazole-4-carboxamides capable of inhibiting the HIV-1 integrase-LEDGF/p75 interaction in vitro. Following a structure-activity relationship analysis of the initial 1H-imidazole-4,5-dicarbonyl core, we optimized the compound's structure through an industrial database search, and we went further to synthesize a selective and non-cytotoxic panel of inhibitors with enhanced potency. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.