7-(4-Fluorobenzyl)-4-hydroxy-N,1-dimethyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide | 863438-07-7

• 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: 7-(4-Fluorobenzyl)-4-hydroxy-N,1-dimethyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide
• 英文别名: 7-[(4-fluorophenyl)methyl]-4-hydroxy-N,1-dimethyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide；7-[(4-fluorophenyl)methyl]-4-hydroxy-N,1-dimethyl-2-oxo-1,5-naphthyridine-3-carboxamide
• CAS: 863438-07-7
• 化学式: C₁₈H₁₆FN₃O₃
• 分子量: 341.342
• InChiKey: GPUWROATNJMQHS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  82.5
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ethyl 7-[(4-fluorophenyl)methyl]-4-hydroxy-1-methyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxylate 、 甲胺 以 甲醇 、 乙醇 为溶剂， 反应 0.75h， 以32%的产率得到7-(4-Fluorobenzyl)-4-hydroxy-N,1-dimethyl-2-oxo-1,2-dihydro-1,5-naphthyridine-3-carboxamide
  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

• HIV INTEGRASE INHIBITORS
  申请人：ViiV Healthcare Company

  公开号：US20150225399A1

  公开（公告）日：2015-08-13

  The present invention features compounds that are HIV integrase inhibitors and therefore are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.

  本发明具有作为HIV整合酶抑制剂的化合物，因此在抑制HIV复制、预防及/或治疗HIV感染以及治疗艾滋病及/或艾滋病相关综合症方面具有用途。
• Hiv Integrase Inhibitors
  申请人：Johns Alvin Brian

  公开号：US20070124152A1

  公开（公告）日：2007-05-31

  The present invention features compounds that are HIV integrase inhibitors and therefore are useful in the inhibition of HIV replication, the prevention and/or treatment of infection by HIV, and in the treatment of AIDS and/or ARC.

  本发明涉及一种HIV整合酶抑制剂化合物，因此在抑制HIV复制，预防和/或治疗HIV感染以及治疗艾滋病和/或ARC方面具有用途。
• US20140256713A1
  申请人：——

  公开号：US20140256713A1

  公开（公告）日：2014-09-11
• Synthesis and Antiviral Activity of 7-Benzyl-4-hydroxy-1,5-naphthyridin-2(1<i>H</i>)-one HIV Integrase Inhibitors
  作者：Eric E. Boros、Cynthia E. Edwards、Scott A. Foster、Masahiro Fuji、Tamio Fujiwara、Edward P. Garvey、Pamela L. Golden、Richard J. Hazen、Jerry L. Jeffrey、Brian A. Johns、Takashi Kawasuji、Ryuichi Kiyama、Cecilia S. Koble、Noriyuki Kurose、Wayne H. Miller、Angela L. Mote、Hitoshi Murai、Akihiko Sato、James B. Thompson、Mark C. Woodward、Tomokazu Yoshinaga

  DOI：10.1021/jm801404b

  日期：2009.5.14

  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.