methyl (2E)-3-(7-{[(4-fluorobenzyl)amino]carbonyl}-8-hydroxy[1,6]-naphthyridin-5-yl)-2-propenoate | 410544-70-6

• 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 (2E)-3-(7-{[(4-fluorobenzyl)amino]carbonyl}-8-hydroxy[1,6]-naphthyridin-5-yl)-2-propenoate
• 英文别名: methyl (E)-3-[7-[(4-fluorophenyl)methylcarbamoyl]-8-hydroxy-1,6-naphthyridin-5-yl]prop-2-enoate
• CAS: 410544-70-6
• 化学式: C₂₀H₁₆FN₃O₄
• 分子量: 381.363
• InChiKey: ISASPXMALWTACB-CMDGGOBGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  101
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl (2E)-3-(7-{[(4-fluorobenzyl)amino]carbonyl}-8-hydroxy[1,6]-naphthyridin-5-yl)-2-propenoate 生成 5-(1,3-dimethyl-2,6-dioxohexahydro-4-pyrimidinyl)-N-(4-fluorobenzyl)-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
• 作为产物：
  描述：

  N-(4-fluorobenzyl)-8-hydroxy-5-bromo-1,6-naphthyridine-7-carboxamide 、 丙烯酸甲酯（MA） 在 二(三叔丁基膦)钯 tris(dibenzylideneacetone)dipalladium (0) 、 三叔丁基膦 、 N-甲基二环己基胺 作用下， 以 1,4-二氧六环 为溶剂， 以55%的产率得到methyl (2E)-3-(7-{[(4-fluorobenzyl)amino]carbonyl}-8-hydroxy[1,6]-naphthyridin-5-yl)-2-propenoate
  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

• Aza- and polyaza-naphthalenyl carboxamides useful as HIV integrase inhibitors
  申请人：——

  公开号：US20030055071A1

  公开（公告）日：2003-03-20

  Aza- and polyaza-naphthalenyl carboxamide derivatives including certain quinoline carboxamide and naphthyridine carboxamide derivatives are described. These compounds are inhibitors of HIV integrase and inhibitors of HIV replication, and are useful in the prevention or treatment of infection by HIV and the treatment of AIDS, as compounds or pharmaceutically acceptable salts, or 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.

  描述了包括某些喹啉羧酰胺和萘啉羧酰胺衍生物在内的氮杂萘基羧酰胺衍生物。这些化合物是HIV整合酶的抑制剂和HIV复制的抑制剂，可用于预防或治疗HIV感染和治疗艾滋病，作为化合物或药学上可接受的盐，或作为药物组合物中的成分，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。还描述了预防、治疗或延缓艾滋病发作的方法，以及预防或治疗HIV感染的方法。
• AZA- AND POLYAZA-NAPHTHALENYL CARBOXAMIDES USEFUL AS HIV INTEGRASE INHIBITORS
  申请人：Merck & Co., Inc.

  公开号：EP1326865B1

  公开（公告）日：2009-05-06
• 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.