Methyl 2-((bis(tert-butoxycarbonyl)amino)methyl)-5-fluorobenzoate | 569354-58-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Methyl 2-((bis(tert-butoxycarbonyl)amino)methyl)-5-fluorobenzoate
• 英文别名: methyl 2-[[bis[(2-methylpropan-2-yl)oxycarbonyl]amino]methyl]-5-fluorobenzoate
• CAS: 569354-58-1
• 化学式: C₁₉H₂₆FNO₆
• 分子量: 383.417
• InChiKey: VBYXTQSCZPEZMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  82.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Methyl 2-((bis(tert-butoxycarbonyl)amino)methyl)-5-fluorobenzoate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 16.0h， 生成 methyl-2-(aminomethyl)-5-fluorobenzoate hydrochloride
  参考文献：
  名称：

  Copper-Catalyzed C–N Coupling in the Synthesis of Integrase Inhibitors of Immunodeficiency Viruses

  摘要：

  This contribution describes the total synthesis of a complex macrocyclic integrase inhibitor, a key enzyme involved in the infection process of various immunodeficiency viruses. The key transformation of the synthetic strategy was the selective C-N coupling of a sulfonamide to a heteroaryl bromide in the presence of potentially competing amide and carbamate functionalities. The transformation was accomplished with CuI catalysis using bypiridine as the ligand in the presence of base and enabled a convergent approach to the target molecule.

  DOI：

  10.1021/op400228z
• 作为产物：
  描述：

  5-氟-2-甲基苯甲酸甲酯 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 生成 Methyl 2-((bis(tert-butoxycarbonyl)amino)methyl)-5-fluorobenzoate
  参考文献：
  名称：

  A potent and orally active HIV-1 integrase inhibitor

  摘要：

  A 1,6-naphthyridine inhibitor of HIV-1 integrase has been discovered with excellent inhibitory activity in cells, good pharmacokinetics, and an excellent ability to inhibit virus with mutant enzyme. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2006.11.080

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。
• N-(substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides useful as hiv integrase inhibitors
  申请人：Egbertson Melissa

  公开号：US20050176955A1

  公开（公告）日：2005-08-11

  N-(Substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides are inhibitors of HIV integrase and inhibitors of HIV replication. The naphthyridine carboxamides are of Formula (I): wherein R 1 ′, R 2 ′ and R 3 ′ are defined herein. The 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 described.

  N-(取代苯基)-8-羟基-1,6-萘啶-7-羧酰胺是HIV整合酶的抑制剂和HIV复制的抑制剂。萘啶羧酰胺的化学式为(I):其中R1'，R2'和R3'在此被定义。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作为药物可接受的盐形式用于对抗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。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：US07279487B2

  公开（公告）日：2007-10-09

  Hydroxynaphthyridinone carboxamides of formula: 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.

  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。
• N-(substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides useful as HIV integrase inhibitors
  申请人：Merck & Co., Inc.

  公开号：US07323460B2

  公开（公告）日：2008-01-29

  N-(Substituted benzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamides are inhibitors of HIV integrase and inhibitors of HIV replication. The naphthyridine carboxamides are of Formula (I): wherein R1′, R2′ and R3′ are defined herein. The 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 described.

  N-(取代苯基)-8-羟基-1,6-萘啶-7-羧酰胺是HIV整合酶的抑制剂和HIV复制的抑制剂。萘啶羧酰胺的化合物为公式（I）：其中R1'，R2'和R3'在此定义。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。这些化合物作为化合物本身或以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。
• A potent and orally active HIV-1 integrase inhibitor
  作者：Melissa S. Egbertson、H. Marie Moritz、Jeffrey Y. Melamed、Wei Han、Debra S. Perlow、Michelle S. Kuo、Mark Embrey、Joseph P. Vacca、Matthew M. Zrada、Amanda R. Cortes、Audrey Wallace、Yvonne Leonard、Daria J. Hazuda、Michael D. Miller、Peter J. Felock、Kara A. Stillmock、Marc V. Witmer、William Schleif、Lori J. Gabryelski、Gregory Moyer、Joan D. Ellis、Lixia Jin、Wei Xu、Matthew P. Braun、Kellem Kassahun、Nancy N. Tsou、Steven D. Young

  DOI：10.1016/j.bmcl.2006.11.080

  日期：2007.3

  A 1,6-naphthyridine inhibitor of HIV-1 integrase has been discovered with excellent inhibitory activity in cells, good pharmacokinetics, and an excellent ability to inhibit virus with mutant enzyme. (c) 2006 Elsevier Ltd. All rights reserved.