N-(4-fluorobenzyl)-5,6-dihydroxy-2-(pyrrolidin-2-yl)pyrimidine-4-carboxamide | 519030-48-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: N-(4-fluorobenzyl)-5,6-dihydroxy-2-(pyrrolidin-2-yl)pyrimidine-4-carboxamide
• 英文别名: N-(4-fluorobenzyl)-5,6-dihydroxy-2-pyrrolidin-2-ylpyrimidine-4-carboxamide；N-[(4-fluorophenyl)methyl]-5-hydroxy-6-oxo-2-pyrrolidin-2-yl-1H-pyrimidine-4-carboxamide
• CAS: 519030-48-9
• 化学式: C₁₆H₁₇FN₄O₃
• 分子量: 332.334
• InChiKey: ZLOFMAVYNFGKRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  103
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(4-fluorobenzyl)-5,6-dihydroxy-2-(pyrrolidin-2-yl)pyrimidine-4-carboxamide 、 乙酸酐 以 吡啶 为溶剂， 生成 2-(1-acetylpyrrolidin-2-yl)-N-[(4-fluorophenyl)methyl]-5,6-dihydroxy-pyrimidine-4-carboxamide
  参考文献：
  名称：

  Dihydroxy-pyrimidine and N-methylpyrimidone HIV-integrase inhibitors: Improving cell based activity by the quaternarization of a chiral center

  摘要：

  In the context of HIV-integrase, dihydroxypyrimidine and N-methyl pyrimidone inhibitors the cellular activity of this class of compounds has been optimized by the introduction of a simple methyl substituent in the alpha-position of the C-2 side chains. Enhanced passive membrane permeability has been identified as the key factor driving the observed cell-based activity improvement. The rat PK profile of the alpha-methyl derivative 26a was also improved over its des-methyl exact analog. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.091
• 作为产物：
  描述：

  在 1% Pd/C 、 氢气 作用下， 以 甲醇 为溶剂， 生成 N-(4-fluorobenzyl)-5,6-dihydroxy-2-(pyrrolidin-2-yl)pyrimidine-4-carboxamide
  参考文献：
  名称：

  Dihydroxy-pyrimidine and N-methylpyrimidone HIV-integrase inhibitors: Improving cell based activity by the quaternarization of a chiral center

  摘要：

  In the context of HIV-integrase, dihydroxypyrimidine and N-methyl pyrimidone inhibitors the cellular activity of this class of compounds has been optimized by the introduction of a simple methyl substituent in the alpha-position of the C-2 side chains. Enhanced passive membrane permeability has been identified as the key factor driving the observed cell-based activity improvement. The rat PK profile of the alpha-methyl derivative 26a was also improved over its des-methyl exact analog. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.06.091

文献信息

• Dihydroxypyrimidine-4-carboxamides as Novel Potent and Selective HIV Integrase Inhibitors
  作者：Paola Pace、M. Emilia Di Francesco、Cristina Gardelli、Steven Harper、Ester Muraglia、Emanuela Nizi、Federica Orvieto、Alessia Petrocchi、Marco Poma、Michael Rowley、Rita Scarpelli、Ralph Laufer、Odalys Gonzalez Paz、Edith Monteagudo、Fabio Bonelli、Daria Hazuda、Kara A. Stillmock、Vincenzo Summa

  DOI：10.1021/jm070027u

  日期：2007.5.1

  chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clinical setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these molecules were made in order

  人类免疫缺陷病毒1型（HIV-1）整合酶是复制所需的三种组成型病毒酶之一，是化学疗法干预AIDS的合理靶标，最近在临床环境中也得到了证实。我们在这里报告的N-苄基5,6-二羟基嘧啶-4-羧酰胺的设计和合成作为一类药物，对HIV整合酶催化的链转移过程具有有效的抑制作用。在当前的研究中，对这些分子进行了结构修饰，以检查其对HIV整合酶抑制效能的影响。该系列中最有趣的化合物之一是2- [1-（二甲基氨基）-1-甲基乙基] -N-（4-氟苄基）-5,6-二羟基嘧啶-4-羧酰胺38，CIC95为78 nM。在血清蛋白存在下进行基于细胞的测定。
• [EN] DIHYDROXYPYRIMIDINE CARBOXAMIDE INHIBITORS OF HIV INTEGRASE<br/>[FR] INHIBITEURS DE L'INTEGRASE DU VIH A BASE DE DIHYDROXYPYRIMIDINE CARBOXAMIDE
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2003035076A1

  公开（公告）日：2003-05-01

  4,5-Dihydroxypyrimidine-6-carboxamides of formula (I); are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R?1, R2, R3 and R4¿ are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

  公式为（I）的4,5-二羟基嘧啶-6-羧酰胺被描述为HIV整合酶抑制剂和HIV复制抑制剂，其中R?1，R2，R3和R4¿在此定义。这些化合物对于预防和治疗HIV感染以及预防、延迟发病和治疗艾滋病非常有用。这些化合物作为化合物本身或药物可接受的盐的形式用于对抗HIV感染和艾滋病。这些化合物及其盐可作为药物组合中的成分，可选地与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。还描述了预防、治疗或延迟艾滋病发病的方法以及预防或治疗HIV感染的方法。
• Dihydroxypyrimidine carboxamide inhibitors of hiv integrase
  申请人：Di Francesco E. Maria

  公开号：US20050075356A1

  公开（公告）日：2005-04-07

  4,5-Dihydroxypyrimidine-6-carboxamides of formula (I); are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R 1 , R 2 , R 3 and R 4 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

  本文描述了式（I）的4,5-二羟基嘧啶-6-羧酰胺类化合物作为HIV整合酶抑制剂和HIV复制抑制剂，其中R1，R2，R3和R4在此定义。这些化合物在预防和治疗HIV感染以及预防，延迟发病和治疗艾滋病方面非常有用。这些化合物可作为化合物本身或作为药物可接受的盐的形式用于对抗HIV感染和艾滋病。这些化合物及其盐可作为药物组合物中的成分，可选择与其他抗病毒药物，免疫调节剂，抗生素或疫苗组合使用。还描述了预防，治疗或延迟艾滋病发病的方法以及预防或治疗HIV感染的方法。
• Dihydroxypyrimidine carboxamide inhibitors of HIV integrase
  申请人：Di Francesco E. Maria

  公开号：US20070083045A1

  公开（公告）日：2007-04-12

  4,5-Dihydroxypyrimidine-6-carboxamides of formula: are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R 1 , R 2 , R 3 and R 4 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

  本文描述了式子中R1，R2，R3和R4被定义的4,5-二羟基嘧啶-6-羧酰胺化合物，其作为HIV整合酶抑制剂和HIV复制抑制剂。这些化合物对于预防和治疗HIV感染以及预防、延迟AIDS发病和治疗AIDS非常有用。这些化合物可以作为化合物本身或药物可接受的盐形式用于对抗HIV感染和AIDS。这些化合物及其盐可以与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用，作为制药组合物的成分。本文还描述了预防、治疗或延迟AIDS发病以及预防或治疗HIV感染的方法。
• DIHYDROXYPYRIMIDINE CARBOXAMIDE INHIBITORS OF HIV INTEGRASE
  申请人：Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A.

  公开号：EP1441734A1

  公开（公告）日：2004-08-04