2-(4-fluorobenzyl)-10-hydroxy-8-methyl-7,8-dihydropyrazino[1',2':1,5]-pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione | 870004-61-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(4-fluorobenzyl)-10-hydroxy-8-methyl-7,8-dihydropyrazino[1',2':1,5]-pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione
• 英文别名: 5-[(4-fluorophenyl)methyl]-8-hydroxy-11-methyl-1,4,5,11-tetrazatricyclo[7.4.0.02,7]trideca-2(7),3,8-triene-6,10-dione
• CAS: 870004-61-8
• 化学式: C₁₇H₁₅FN₄O₃
• 分子量: 342.33
• InChiKey: MGZQUZOYUZERGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  78.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  苄基-4-甲基-3-氧代-3.(2H)-羧酸酯 在 二(三叔丁基膦)钯 、 10% Pt/activated carbon N-甲基二环己基胺 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 乙醇 为溶剂， 20.0~100.0 ℃ 、1.72 MPa 条件下， 反应 24.0h， 生成 2-(4-fluorobenzyl)-10-hydroxy-8-methyl-7,8-dihydropyrazino[1',2':1,5]-pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-dione
  参考文献：
  名称：

  [EN] HIV INTEGRASE INHIBITORS
  [FR] INHIBITEURS DE L'INTEGRASE DU VIH

  摘要：

  公开号：

  WO2005110414A3

文献信息

• Hiv Integrase Inhibitors
  申请人：Wai John S.

  公开号：US20080287394A1

  公开（公告）日：2008-11-20

  Hydroxy-substituted pyrazinopyrrolopyridazine dione compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dione compounds are of Formula (I) wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 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.

  羟基取代的吡嗪吡咯吡啶二酮化合物是HIV整合酶的抑制剂和HIV复制的抑制剂。在一种实施例中，二酮化合物是公式（I）中的化合物，其中R1，R2，R3，R4，R5，R6和R7在此被定义。这些化合物对于预防和治疗HIV感染以及预防、延缓和治疗艾滋病非常有用。这些化合物作为化合物本身或作为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以作为药物组成部分使用，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。
• HIV integrase inhibitors
  申请人：Merck & Co., Inc.

  公开号：US07538112B2

  公开（公告）日：2009-05-26

  Hydroxy-substituted pyrazinopyrrolopyridazine dione compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dione compounds are of Formula (I) wherein R1, R2, R3, R4, R5, R6 and R7 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.

  羟基取代的吡嗪吡咯吡啶二酮化合物是HIV整合酶的抑制剂和HIV复制的抑制剂。在一种实施方式中，二酮化合物为式(I)的化合物，其中R1、R2、R3、R4、R5、R6和R7如本文所定义。这些化合物可用于预防和治疗HIV感染，并用于预防、延缓发病和治疗艾滋病。这些化合物可作为化合物本身或以药学上可接受的盐的形式用于抗击HIV感染和艾滋病。这些化合物及其盐可作为制药组合物的成分，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。
• 10-Hydroxy-7,8-dihydropyrazino[1′,2′:1,5]pyrrolo[2,3-d]pyridazine-1,9(2H,6H)-diones: Potent, orally bioavailable HIV-1 integrase strand-transfer inhibitors with activity against integrase mutants
  作者：Catherine M. Wiscount、Peter D. Williams、Lekhanh O. Tran、Mark W. Embrey、Thorsten E. Fisher、Vanessa Sherman、Carl F. Homnick、D. Donnette Staas、Terry A. Lyle、John S. Wai、Joseph P. Vacca、ZiQiang Wang、Peter J. Felock、Kara A. Stillmock、Marc V. Witmer、Michael D. Miller、Daria J. Hazuda、Alysha M. Day、Lori J. Gabryelski、Linda T. Ecto、William A. Schleif、Daniel J. DiStefano、Christopher J. Kochansky、M. Reza Anari

  DOI：10.1016/j.bmcl.2008.07.037

  日期：2008.8

  A series of 10-hydroxy-7,8-dihydropyrazino[1',2':1,5]pyrrolo[ 2,3-d]pyridazine-1,9(2H,6H)-diones was synthesized and tested for their inhibition of HIV-1 replication in cell culture. Structure-activity studies indicated that high antiviral potency against wild-type virus as well as viruses containing integrase mutations that confer resistance to three different structural classes of integrase inhibitors could be achieved by incorporation of small aliphatic groups at certain positions on the core template. An optimal compound from this study, 16, inhibits integrase strand-transfer activity with an IC50 value of <= 10 nM, inhibits HIV-1 replication in cell culture with an IC95 value of 35 nM in the presence of 50% normal human serum, and displays modest pharmacokinetic properties in rats (iv t(1/2) = 5.3 h, F = 17%). (C) 2008 Elsevier Ltd. All rights reserved.
• HIV INTEGRASE INHIBITORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP1756114B1

  公开（公告）日：2014-11-19
• US7538112B2
  申请人：——

  公开号：US7538112B2

  公开（公告）日：2009-05-26