1-O-benzyl 4-O-tert-butyl 2-(5-benzoyloxy-4-methoxy-6-methoxycarbonylpyrimidin-2-yl)-2-methylpiperazine-1,4-dicarboxylate | 1187846-56-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-O-benzyl 4-O-tert-butyl 2-(5-benzoyloxy-4-methoxy-6-methoxycarbonylpyrimidin-2-yl)-2-methylpiperazine-1,4-dicarboxylate
• CAS: 1187846-56-5
• 化学式: C₃₂H₃₆N₄O₉
• 分子量: 620.659
• InChiKey: HRKOYXNMXHZCMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  45
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  147
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  1-benzyl 4-tert-butyl 2-[5-(benzoyloxy)-4-hydroxy-6-(methoxycarbonyl)pyrimidin-2-yl]-2-methylpiperazine-1,4-dicarboxylate 、 硫酸二甲酯 在 lithium hydride 作用下， 以 1,4-二氧六环 为溶剂， 生成 1-O-benzyl 4-O-tert-butyl 2-(5-benzoyloxy-4-methoxy-6-methoxycarbonylpyrimidin-2-yl)-2-methylpiperazine-1,4-dicarboxylate 、 1-Benzyl 4-tert-butyl 2-[5-(benzoyloxy)-4-(methoxycarbonyl)-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl]-2-methylpiperazine-1,4-dicarboxylate
  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

• N-Substituted hydroxypyrimidinone carboxamide inhibitors of HIV integrase
  申请人：Crescenzi Benedetta

  公开号：US20080275004A1

  公开（公告）日：2008-11-06

  N-substituted 5-hydroxypyrimidin-6-one-4-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.

  本文描述了式子中定义的具有N取代的5-羟基嘧啶-6-酮-4-羧酰胺的化合物，这些化合物是HIV整合酶的抑制剂和HIV复制的抑制剂，其中R1、R2、R3和R4在此处定义。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。这些化合物可以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以作为药物组成部分，与其他抗病毒药物、免疫调节剂、抗生素或疫苗可选地结合使用。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。
• N-substituted hydroxypyrimidinone carboxamide inhibitors of HIV integrase
  申请人：Crescenzi Benedetta

  公开号：US20070123524A1

  公开（公告）日：2007-05-31

  N-substituted 5-hydroxypyrimidin-6-one-4-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.

  本发明涉及一种公式如下的N-取代的5-羟基嘧啶-6-酮-4-羧酰胺，其中R1、R2、R3和R4如下所定义，作为HIV整合酶的抑制剂和HIV复制的抑制剂。这些化合物在预防和治疗HIV感染以及预防、延缓发病和治疗艾滋病方面是有用的。这些化合物作为化合物本身或以药学上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成物中的成分，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。本发明还描述了预防、治疗或延缓艾滋病发病的方法以及预防或治疗HIV感染的方法。
• US7169780B2
  申请人：——

  公开号：US7169780B2

  公开（公告）日：2007-01-30
• US7217713B2
  申请人：——

  公开号：US7217713B2

  公开（公告）日：2007-05-15
• US7435734B2
  申请人：——

  公开号：US7435734B2

  公开（公告）日：2008-10-14