5-(morpholine-4-carbonyl)-N-(pyridin-2-yl)-1H-imidazole-4-carboxamide | 1454887-73-0

• 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: 5-(morpholine-4-carbonyl)-N-(pyridin-2-yl)-1H-imidazole-4-carboxamide
• 英文别名: 5-(morpholine-4-carbonyl)-N-(2-pyridyl)-1H-imidazole-4-carboxamide；5-(morpholine-4-carbonyl)-N-pyridin-2-yl-1H-imidazole-4-carboxamide
• CAS: 1454887-73-0
• 化学式: C₁₄H₁₅N₅O₃
• 分子量: 301.305
• InChiKey: IGCLYQFJRGQXRR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  100
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  吗啉 、 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以81%的产率得到5-(morpholine-4-carbonyl)-N-(pyridin-2-yl)-1H-imidazole-4-carboxamide
  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.