5-(1,3-dimethyl-2,6-dioxo-pyrimidin-4-yl)-N-[(4-fluorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide

• 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: 5-(1,3-dimethyl-2,6-dioxo-pyrimidin-4-yl)-N-[(4-fluorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide
• 英文别名: 5-(1,3-dimethyl-2,6-dioxopyrimidin-4-yl)-N-[(4-fluorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide
• 化学式: C₂₂H₁₈FN₅O₄
• 分子量: 435.414
• InChiKey: CNABPYHXXNLSKX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  116
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-(4-fluorobenzyl)-8-hydroxy-5-iodo-1,6-naphthyridine-7-carboxamide 、 6-iodo-1,3-dimethyluracil 在 三甲基氯硅烷 、 1,2-二溴乙烷 、 锌 、 tris-(dibenzylideneacetone)dipalladium(0) 、 三(2-呋喃基)膦 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.0h， 以60%的产率得到5-(1,3-dimethyl-2,6-dioxo-pyrimidin-4-yl)-N-[(4-fluorophenyl)methyl]-8-hydroxy-1,6-naphthyridine-7-carboxamide
  参考文献：
  名称：

  A series of 5-(5,6)-dihydrouracil substituted 8-hydroxy-[1,6]naphthyridine-7-carboxylic acid 4-fluorobenzylamide inhibitors of HIV-1 integrase and viral replication in cells

  摘要：

  Introduction of a 5,6-dihydrouracil functionality in the 5-position of N-(4-fluorobenzyl)-8-hydroxy-[1,6]naphthyridine-7-carboxamide I led to a series of highly active HIV-1 integrase inhibitors. These compounds displayed low nanomolar activity in inhibiting both the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 11 is a 150-fold more potent antiviral agent than 1, with a CIC95 of 40 nM in the presence of human serum. It displays good pharmacokinetics when dosed in rats and dogs. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.06.105

文献信息

• A series of 5-(5,6)-dihydrouracil substituted 8-hydroxy-[1,6]naphthyridine-7-carboxylic acid 4-fluorobenzylamide inhibitors of HIV-1 integrase and viral replication in cells
  作者：Mark W. Embrey、John S. Wai、Timothy W. Funk、Carl F. Homnick、Debbie S. Perlow、Steven D. Young、Joseph P. Vacca、Daria J. Hazuda、Peter J. Felock、Kara A. Stillmock、Marc V. Witmer、Gregory Moyer、William A. Schleif、Lori J. Gabryelski、Lixia Jin、I-Wu Chen、Joan D. Ellis、Bradley K. Wong、Jiunn H. Lin、Yvonne M. Leonard、Nancy N. Tsou、Linghang Zhuang

  DOI：10.1016/j.bmcl.2005.06.105

  日期：2005.10

  Introduction of a 5,6-dihydrouracil functionality in the 5-position of N-(4-fluorobenzyl)-8-hydroxy-[1,6]naphthyridine-7-carboxamide I led to a series of highly active HIV-1 integrase inhibitors. These compounds displayed low nanomolar activity in inhibiting both the strand transfer process of HIV-1 integrase and viral replication in cells. Compound 11 is a 150-fold more potent antiviral agent than 1, with a CIC95 of 40 nM in the presence of human serum. It displays good pharmacokinetics when dosed in rats and dogs. (c) 2005 Elsevier Ltd. All rights reserved.