N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide | 518047-37-5

• 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-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide
• 英文别名: N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxo-pyrimidine-4-carboxamide；N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxopyrimidine-4-carboxamide
• CAS: 518047-37-5
• 化学式: C₁₈H₂₁FN₄O₄
• 分子量: 376.388
• InChiKey: MMPZNODECHHWIW-UHFFFAOYSA-N

物化性质

• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  27
• 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：
  94.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide 生成 (-)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide 、 (+)-N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide
  参考文献：
  名称：

  4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species

  摘要：

  The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. The optimization of physicochemical properties, pharmacokinetic profiles, and potency led to the identification of 13 in the dihydroxypyrimidine series and 18 in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclinical species.

  DOI：

  10.1021/jm060854f
• 作为产物：
  描述：

  对氟苄胺 在 sodium acetate 、 sodium cyanoborohydride 、 三乙胺 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 生成 N-(4-fluorobenzyl)-5-hydroxy-1-methyl-2-(4-methylmorpholin-3-yl)-6-oxo-1,6-dihydropyrimidine-4-carboxamide
  参考文献：
  名称：

  4,5-Dihydroxypyrimidine Carboxamides and N-Alkyl-5-hydroxypyrimidinone Carboxamides Are Potent, Selective HIV Integrase Inhibitors with Good Pharmacokinetic Profiles in Preclinical Species

  摘要：

  The dihydroxypyrimidine carboxamide 4a was discovered as a potent and selective HIV integrase strand transfer inhibitor. The optimization of physicochemical properties, pharmacokinetic profiles, and potency led to the identification of 13 in the dihydroxypyrimidine series and 18 in the N-methylpyrimidinone series having low nanomolar activity in the cellular HIV spread assay in the presence of 50% normal human serum and very good pharmacokinetics in preclinical species.

  DOI：

  10.1021/jm060854f

文献信息

• Preparation of 5-hydroxy-6-oxo-1,6-dihydropyrimidine compounds
  申请人：Dreher D. Spencer

  公开号：US20050090668A1

  公开（公告）日：2005-04-28

  5-Hydroxy-6-oxo-1,6-dihydropyrimidine compounds are prepared by the condensation of dihydroxyfumarate derivatives with amidines. The pyrimidine compounds are useful as intermediates in the preparation of pharmacologically active compounds.

  5-羟基-6-氧代-1,6-二氢嘧啶化合物是通过二羟基富马酸酯与胺基甲酸酯的缩合制备的。这些嘧啶化合物在制备药理活性化合物中作为中间体是有用的。
• 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：US20060258860A1

  公开（公告）日：2006-11-16

  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 ASS. 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.

  本文介绍了式子中R1、R2、R3和R4已定义的N-取代的5-羟基嘧啶-6-酮-4-羧酰胺类化合物，其作为HIV整合酶抑制剂和HIV复制抑制剂。这些化合物可用于预防和治疗HIV感染以及预防、延缓ASS的发病和治疗。这些化合物可作为化合物本身或作为药物可接受的盐用于对抗HIV感染和AIDS。这些化合物及其盐可作为药物组合物中的成分，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。本文还介绍了预防、治疗或延缓AIDS以及预防或治疗HIV感染的方法。
• [EN] N-SUBSTITUTED HYDROXYPYRIMIDINONE CARBOXAMIDE INHIBITORS OF HIV INTEGRASE<br/>[FR] INHIBITEURS DE L'INTEGRASE DU VIH A BASE D'HYDROXYPYRIMIDINONE CARBOXAMIDE N-SUBSTITUE
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2003035077A1

  公开（公告）日：2003-05-01

  N-substituted 5-hydroxypyrimidin-6-one-4-carboxamides of formula (I): are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R1, 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.

  描述了式(I)的N-取代的5-羟基嘧啶-6-酮-4-羧酰胺化合物作为HIV整合酶抑制剂和HIV复制抑制剂，其中R1、R2、R3和R4如本文所定义。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。这些化合物可以作为化合物本身或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。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：US20050025774A1

  公开（公告）日：2005-02-03

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

  描述了式(I)的N-取代的5-羟基嘧啶-6-酮-4-羧酰胺化合物作为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AIDS发病和治疗中是有用的。这些化合物可作为化合物本身或药学上可接受的盐的形式用于对抗HIV感染和AIDS。这些化合物及其盐可作为制药组合物的成分，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AIDS发病的方法以及预防或治疗HIV感染的方法。