methyl 4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate | 569353-96-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: methyl 4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate
• 英文别名: methyl 4-hydroxy-2-oxo-1H-1,5-naphthyridine-3-carboxylate
• CAS: 569353-96-4
• 化学式: C₁₀H₈N₂O₄
• 分子量: 220.185
• InChiKey: HPMKRDSMDYYKIY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  88.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate 、 对氟苄胺 在 crude material 、 acetonitrile-water 作用下， 以 乙醇 、 水 为溶剂， 反应 6.0h， 生成 N-(4-fluorobenzyl)4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide
  参考文献：
  名称：

  Hydroxynaphthyridinone carboxamides useful as HIV integrase inhibitors

  摘要：

  本文描述了式子所示的羟基萘啶酮羧酰胺类化合物，其为HIV整合酶的抑制剂和HIV复制的抑制剂，其中L、R1a、R1b、R1c、R2a、R2b、R3、R4和R5在此被定义。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。这些化合物可作为化合物本身或以药用盐的形式用于对抗HIV感染和艾滋病。这些化合物及其盐可以作为药物组合中的成分，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。本文还描述了预防、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。

  公开号：

  US07279487B2
• 作为产物：
  描述：

  Methyl 3-[(3-methoxy-3-oxopropanoyl)amino]pyridine-2-carboxylate 在 甲醇 、 sodium methylate 作用下， 反应 1.0h， 以63%的产率得到methyl 4-hydroxy-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate
  参考文献：
  名称：

  Synthesis and Antiviral Activity of 7-Benzyl-4-hydroxy-1,5-naphthyridin-2(1H)-one HIV Integrase Inhibitors

  摘要：

  The medicinal chemistry and structure-activity relationships for a novel series of 7-benzyl-4-hydroxy-1,5-naphthyridin-2(1H)-one HIV-integrase inhibitors are disclosed. Substituent effects were evaluated at the N-1, C-3, and 7-benzyl positions of the naphthyridinone ring system. Low nanomolar IC50 values were achieved in an HIV-integrase strand transfer assay with both carboxylic ester and carboxamide groups at C-3. More importantly, several carboxamide congeners showed potent antiviral activity in cellular assays. A 7-benzyl substituent was found to be critical for potent enzyme inhibition, and an N-(2-methoxyethyl)-carboxamide moiety at C-3 significantly reduced plasma protein binding effects in vitro. Pharmacokinetic data in rats for one carboxamide analogue demonstrated oral bioavailability and reasonable in vivo clearance.

  DOI：

  10.1021/jm801404b

文献信息

• Hydroxynaphthyridinone carboxamides useful as hiv integrase inhibitors
  申请人：Egbertson Melissa

  公开号：US20050119482A1

  公开（公告）日：2005-06-02

  Hydroxynaphthyridinone carboxamides of formula: are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein L, R 1a , R 1b , R 1c , R 2a , R 2b , R 3 , R 4 , and R 5 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.

  描述了式子为的羟基萘啶酮羧酰胺化合物作为HIV整合酶抑制剂和HIV复制抑制剂，其中L、R1a、R1b、R1c、R2a、R2b、R3、R4和R5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。这些化合物可作为化合物本身或以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成部分，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。
• HYDROXYNAPHTHYRIDINONE CARBOXAMIDES USEFUL AS HIV INTEGRASE INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1467970A1

  公开（公告）日：2004-10-20
• EP1467970A4
  申请人：——

  公开号：EP1467970A4

  公开（公告）日：2005-12-21
• US7279487B2
  申请人：——

  公开号：US7279487B2

  公开（公告）日：2007-10-09
• [EN] HYDROXYNAPHTHYRIDINONE CARBOXAMIDES USEFUL AS HIV INTEGRASE INHIBITORS<br/>[FR] CARBOXAMIDES HYDROXYNAPHTHYRIDINONE UTILES COMME INHIBITEURS DE L'INTEGRASE DU VIH
  申请人：MERCK & CO INC

  公开号：WO2003062204A1

  公开（公告）日：2003-07-31

  Hydroxynaphthyridinone carboxamides of formula (I): are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein L, R1a, R1b, R1c R2a, R2b, R3, R4 and R5 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.