N-[(4-fluorophenyl)methyl]-5-hydroxy-2-(2-methylpiperidin-2-yl)-6-oxo-1H-pyrimidine-4-carboxamide | 519031-62-0

• 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-fluorophenyl)methyl]-5-hydroxy-2-(2-methylpiperidin-2-yl)-6-oxo-1H-pyrimidine-4-carboxamide
• CAS: 519031-62-0
• 化学式: C₁₈H₂₁FN₄O₃
• 分子量: 360.388
• InChiKey: AWXUJSKCZCJLCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 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：

  2,4-二甲基-1,3-噻唑-5-羧酸 、 N-[(4-fluorophenyl)methyl]-5-hydroxy-2-(2-methylpiperidin-2-yl)-6-oxo-1H-pyrimidine-4-carboxamide 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 2-[1-(2,4-dimethylthiazole-5-carbonyl)-2-methyl-2-piperidyl]-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-fluorophenyl)methyl]-5-hydroxy-2-(2-methylpiperidin-2-yl)-6-oxo-1H-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 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。
• US7232819B2
  申请人：——

  公开号：US7232819B2

  公开（公告）日：2007-06-19
• US7459452B2
  申请人：——

  公开号：US7459452B2

  公开（公告）日：2008-12-02
• Dihydroxy-pyrimidine and N-methylpyrimidone HIV-integrase inhibitors: Improving cell based activity by the quaternarization of a chiral center
  作者：Emanuela Nizi、Maria Vittoria Orsale、Benedetta Crescenzi、Giovanna Pescatore、Ester Muraglia、Anna Alfieri、Cristina Gardelli、Stéphane A.H. Spieser、Vincenzo Summa

  DOI：10.1016/j.bmcl.2009.06.091

  日期：2009.8

  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.