methyl (7S)-3-(benzyloxy)-5-methyl-4-oxo-7-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate | 871937-19-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl (7S)-3-(benzyloxy)-5-methyl-4-oxo-7-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate
• 英文别名: Methyl (7S)-3-(benzyloxy)-5-methyl-4-oxo-7-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate；methyl (7S)-5-methyl-4-oxo-7-phenyl-3-phenylmethoxy-6,7-dihydropyrazolo[1,5-a]pyrazine-2-carboxylate
• CAS: 871937-19-8
• 化学式: C₂₂H₂₁N₃O₄
• 分子量: 391.426
• InChiKey: GJDOYSMAZNVMDU-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  73.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (7S)-3-(benzyloxy)-5-methyl-4-oxo-7-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate 在 sodium hydroxide 、 乙醇 、 水 、 盐酸 作用下， 以 甲醇 为溶剂， 生成 (7S)-3-(benzyloxy)-5-methyl-7-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylic acid
  参考文献：
  名称：

  WO2007/50510

  摘要：

  公开号：
• 作为产物：
  描述：

  methyl 4-(benzyloxy)-5-{[[(2R)-2-hydroxy-2-phenylethyl](methyl)amino]carbonyl}-1H-pyrazole-3-carboxylate 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 为溶剂， 反应 2.08h， 生成 methyl (7S)-3-(benzyloxy)-5-methyl-4-oxo-7-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxylate
  参考文献：
  名称：

  WO2007/50510

  摘要：

  公开号：

文献信息

• Hiv Integrase Inhibitors
  申请人：Wai John S

  公开号：US20090312335A1

  公开（公告）日：2009-12-17

  Substituted hydroxytetrahydropyrrolopyrazinone and substituted hydroxytetrahydro-pyrazolopyrazinone compounds of Formula (I) are inhibitors of HIV integrase and inhibitors of HIV replication: (I) wherein R 1 , R 2 , R 3 , R 4 ; R 5 , X, ring A, and Q are as 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.

  公式（I）中的取代羟基四氢吡咯吡嗪酮和取代羟基四氢吡唑吡嗪酮化合物是HIV整合酶的抑制剂和HIV复制的抑制剂，其中R1，R2，R3，R4；R5，X，环A和Q如此定义。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以作为药物组成部分使用，可选配其他抗病毒药物，免疫调节剂，抗生素或疫苗。
• Design and synthesis of substituted 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides, novel HIV-1 integrase inhibitors
  作者：H. Marie Langford、Peter D. Williams、Carl F. Homnick、Joseph P. Vacca、Peter J. Felock、Kara A. Stillmock、Marc V. Witmer、Daria J. Hazuda、Lori J. Gabryelski、William A. Schleif

  DOI：10.1016/j.bmcl.2007.11.049

  日期：2008.1

  A series of 4-oxo-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrazine-2-carboxamides was synthesized and tested for their inhibition of HIV-1 integrase catalytic activity and HIV-1 replication in cells. Structure-activity studies around lead compound 5 indicated that a coplanar relationship of metal-binding heteroatoms provides optimal binding to the integrase active site. Identification of potency-enhancing substituents and adjustments in lipophilicity provided 17b which inhibits integrase-catalyzed strand transfer with an IC50 value of 74 nM and inhibits HIV-1 replication in cell culture in the presence of 50% normal human serum with an IC95 value of 63 nM. (c) 2007 Elsevier Ltd. All rights reserved.