{3-[(4-benzoylpiperazin-1-yl)(oxo)acetyl]-4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-1-yl}methyl dihydrogen phosphate (L)-lysine | 864953-34-4

• 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: {3-[(4-benzoylpiperazin-1-yl)(oxo)acetyl]-4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-1-yl}methyl dihydrogen phosphate (L)-lysine
• 英文别名: {3-[(4-benzoylpiperazin-1-yl)(oxo)acetyl]-4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-1-yl}methyl dihydrogen phosphate, L-lysine salt；1-benzoyl-4-[2-[4,7-dimethoxy-1-[(phosphonooxy)methyl]-1H-pyrrolo[2,3-c]pyridin-3-yl]-1,2-dioxoethyl]piperazine monolysine salt；BMS-663749 lysine；[3-[2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl]-4,7-dimethoxypyrrolo[2,3-c]pyridin-1-yl]methyl dihydrogen phosphate;(2S)-2,6-diaminohexanoic acid
• CAS: 864953-34-4
• 化学式: C₆H₁₄N₂O₂*C₂₃H₂₅N₄O₉P
• 分子量: 678.636
• InChiKey: ZBSWJVQMWMTXIV-ZSCHJXSPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.59
• 重原子数：
  47
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  259
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  (3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-1-yl)methyl di-tert-butyl phosphate 在 三氟乙酸 作用下， 以 水 、 丙酮 为溶剂， 生成 {3-[(4-benzoylpiperazin-1-yl)(oxo)acetyl]-4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-1-yl}methyl dihydrogen phosphate (L)-lysine
  参考文献：
  名称：

  Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Attachment 6. Preclinical and Human Pharmacokinetic Profiling of BMS-663749, a Phosphonooxymethyl Prodrug of the HIV-1 Attachment Inhibitor 2-(4-Benzoyl-1-piperazinyl)-1-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoethanone (BMS-488043)

  摘要：

  BMS-663749, a phosphonooxymethyl prodrug 4 of the HIV-1 attachment inhibitor 2-(4-benzoyl-1-piperazinyl)-1-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-oxoethanone (BMS-488043) (2) was prepared and profiled in a variety of preclinical in vitro and in vivo models designed to assess its ability to deliver parent drug following oral administration. The data showed that prodrug 4 had excellent potential to significantly reduce dissolution rate-limited absorption following oral dosing in humans. Clinical studies in normal healthy subjects confirmed the potential of 4, revealing that the prodrug significantly increased both the AUC and C-max of 2 compared to a solid capsule formulation containing the parent drug upon dose escalation. These data provided guidance for further efforts to obtain an effective HIV-1 attachment inhibitor.

  DOI：

  10.1021/jm201218m

文献信息

• Prodrugs of piperazine and substituted piperidine antiviral agents
  申请人：Ueda Yasutsugu

  公开号：US20050209246A1

  公开（公告）日：2005-09-22

  This invention provides for prodrug Compounds I, pharmaceutical compositions thereof, and their use in treating HIV infection. wherein: X is C or N with the proviso that when X is N, R 1 does not exist; W is C or N with the proviso that when W is N, R 2 does not exist; V is C; E is hydrogen or a pharmaceutically acceptable salt thereof; and Y is selected from the group consisting of Also, this invention provides for intermediate Compounds II useful in making prodrug Compounds I. wherein: L and M are independently selected from the group consisting of C 1 -C 6 alkyl, phenyl, benzyl, trialkylsilyl, -2,2,2-trichloroethoxy and 2-trimethylsilylethoxy.

  这项发明提供了前药化合物I，其药物组成物以及它们在治疗HIV感染中的用途。 其中： X为C或N，但当X为N时，R1不存在； W为C或N，但当W为N时，R2不存在；V为C；E为氢或其药用可接受盐；以及 Y从以下组中选择： 此外，这项发明提供了制备前药化合物I的有用中间体化合物II。 其中： L和M独立地选自C1-C6烷基，苯基，苯甲基，三烷基硅基，-2,2,2-三氯乙氧基和2-三甲基硅基乙氧基的组。
• Crystalline forms of 1-benzoyl-4-[2-[4,7-dimethoxy-1-[(phosphonooxy)methyl]-1H-pyrrolo[2,3-C]pyridin-3-yl]-1,2-dioxoethyl]-piperazine
  申请人：Chen H. Chung-Pin

  公开号：US20060172974A1

  公开（公告）日：2006-08-03

  The instant disclosure provides crystalline forms of 1-benzoyl-4-[2-[4,7-dimethoxy-1-[(phosphonooxy)methyl]-1H-pyrrolo[2,3-c]pyridin-3-yl]-1,2-dioxoethyl]-piperazine, salts and solvates thereof. The present disclosure also generally relates to pharmaceutical compositions comprising the crystalline form(s), as well of methods of using the crystalline form(s) in the treatment of HIV and/or AIDS, and methods for obtaining such crystalline form(s).

  即时披露提供了1-苯甲酰基-4-[2-[4,7-二甲氧基-1-[(磷酸酯基)甲基]-1H-吡咯[2,3-c]吡啶-3-基]-1,2-二氧代乙基]-哌嗪的结晶形式，以及其盐和溶剂合物。本公开还一般涉及包含该结晶形式的药物组合物，以及使用该结晶形式治疗HIV和/或艾滋病的方法，以及获取该结晶形式的方法。
• Preparation of Phosphonooxymethyl Prodrugs of HIV-1 Attachment Inhibitors
  作者：David K. Leahy、Shawn K. Pack

  DOI：10.1021/op400225q

  日期：2013.11.15

  A practical and scalable synthesis of phosphonooxymethyl prodrugs of HIV-1 attachment inhibitors is described. Starting from azaindoles 1 and 2, this two-step sequence features an efficient alkylation using chloromethyl phosphate 5 and an exceptionally mild deprotection for tert-butyl phosphates. After a salt formation, the API is formed in 82% and 70% overall yield for 3a and 4a, respectively. This chemistry was used to prepare multikilogram quantities of API.