1-(4-benzoyl-piperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-ethane-1,2-dione | 619331-12-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: 1-(4-benzoyl-piperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-ethane-1,2-dione
• 英文别名: 1-benzoyl-4-[2-[4-fluoro-7-(1H-1,2,3-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]-1,2-dioxoethyl]-piperazine；1,2-Ethanedione, 1-(4-benzoyl-1-piperazinyl)-2-(4-fluoro-7-(1H-1,2,3-triazol-1-yl)-1H-pyrrolo(2,3-C)pyridin-3-yl)-；1-(4-benzoylpiperazin-1-yl)-2-[4-fluoro-7-(triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]ethane-1,2-dione
• CAS: 619331-12-3
• 化学式: C₂₂H₁₈FN₇O₃
• 分子量: 447.428
• InChiKey: YILIMUKOYIOIAY-UHFFFAOYSA-N

物化性质

• 沸点：
  733.0±70.0 °C(Predicted)
• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  117
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(4-benzoyl-piperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-ethane-1,2-dione 在 水 、 caesium carbonate 、 potassium iodide 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 20.0h， 生成 [3-[(4-benzoylpiperazin-1-yl)(oxo)acetyl]-4-fluoro-7-(1H-1,2,3-triazol-1-yl)-1H-pyrrolo[2,3-c]pyridin-1-yl]methyl dihydrogen phosphate
  参考文献：
  名称：

  Preparation of Phosphonooxymethyl Prodrugs of HIV-1 Attachment Inhibitors

  摘要：

  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.

  DOI：

  10.1021/op400225q
• 作为产物：
  描述：

  7-溴-4-氟-1H-吡咯并[2,3-c]吡啶 在 aluminum (III) chloride 、 铜 、 potassium carbonate 、 氯化 1-乙基-3-甲基咪唑 、 N,N-二异丙基乙胺 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 1-(4-benzoyl-piperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)-ethane-1,2-dione 、 1-(4-benzoylpiperazin-1-yl)-2-[4-fluoro-7-(triazol-2-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl]ethane-1,2-dione
  参考文献：
  名称：

  Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Attachment. 12. Structure–Activity Relationships Associated with 4-Fluoro-6-azaindole Derivatives Leading to the Identification of 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-585248)

  摘要：

  A series of highly potent HIV-1 attachment inhibitors with 4-fluoro-6-azaindole core heterocycles that target the viral envelope protein gp120 has been prepared. Substitution in the 7-position of the azaindole core with amides (12a,b), C-linked heterocycles (12c-I), and N-linked heterocycles (12m-u) provided compounds with subnanomolar potency in a pseudotype infectivity assay and good pharmacokinetic profiles in vivo. A predictive model was developed from the initial SAR in which the potency of the analogues correlated with the ability of the substituent in the 7-position of the azaindole to adopt a coplanar conformation by either forming internal hydrogen bonds or avoiding repulsive substitution patterns. 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-[1,2,3]triazol-1-yl-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-585248, 12m) exhibited much improved in vitro potency and pharmacokinetic properties than the previous clinical candidate BMS-488043 (1). The predicted low clearance in humans, modest protein binding, and good potency in the presence of 40% human serum for 12m led to its selection for human clinical studies.

  DOI：

  10.1021/jm3016377

文献信息

• Composition and antiviral activity of substituted azaindoleoxoacetic piperazine derivatives
  申请人：——

  公开号：US20040110785A1

  公开（公告）日：2004-06-10

  This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.

  这项发明提供了具有药物和生物影响特性的化合物，它们的药物组合物和使用方法。具体而言，该发明涉及吡啶并咪唑酮乙酰基哌嗪衍生物。这些化合物具有独特的抗病毒活性，无论是单独使用还是与其他抗病毒药物、抗感染剂、免疫调节剂或HIV进入抑制剂结合使用。更具体地，本发明涉及治疗HIV和艾滋病。
• 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。
• Process for preparing triazole substituted azaindoleoxoacetic piperazine derivatives and novel salt forms produced therein
  申请人：Soundararajan Nachimuthu

  公开号：US20060293304A1

  公开（公告）日：2006-12-28

  A process is provided for preparing triazole substituted azaindoleoxoacetic piperazine derivative. Novel intermediates produced in the above process, and novel N-1 and amorphous forms of a 1,2,3-triazole substituted azaindoloxoacetic piperazine derivatives and processes for producing such novel forms are also provided.

  提供了一种制备三唑取代的氮杂吲哚氧乙酸哌嗪衍生物的过程。上述过程中产生的新型中间体，以及一种1,2,3-三唑取代的氮杂吲哚氧乙酸哌嗪衍生物的新型N-1和非晶形式，以及生产这种新型形式的过程也提供了。
• Aminium salts of 1,2,3-triazoles as prodrugs of drugs including antiviral agents
  申请人：Kadow F. John

  公开号：US20060142298A1

  公开（公告）日：2006-06-29

  This disclosure provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the disclosure is concerned with new aminium salts of 1,2,3-triazoles which can be used as prodrugs to improve the solubility or pharmaceutical properties of 1,2,3-triazole containing compounds. More particularly, the present disclosure relates to compounds containing N-aminium-1,2,3-triazoles that are useful as antiviral agents and specifically for the treatment of HIV and AIDS.

  本公开提供具有药物和生物影响性质的化合物，它们的药物组合物和使用方法。具体而言，本公开涉及新的1,2,3-三唑的氨盐，可用作前药，以改善含有1,2,3-三唑化合物的溶解性或药物性质。更具体地说，本公开涉及含有N-氨盐基-1,2,3-三唑的化合物，可用作抗病毒剂，特别是用于治疗艾滋病毒（HIV）和艾滋病。
• COMPOSITION AND ANTIVIRAL ACTIVITY OF SUBSTITUTED AZAINDOLEOXOACETIC PIPERAZINE DERIVATIVES
  申请人：Wang Tao

  公开号：US20080119480A1

  公开（公告）日：2008-05-22

  This invention provides compounds having drug and bio-affecting properties, their pharmaceutical compositions and method of use. In particular, the invention is concerned with azaindoleoxoacetyl piperazine derivatives. These compounds possess unique antiviral activity, whether used alone or in combination with other antivirals, antiinfectives, immunomodulators or HIV entry inhibitors. More particularly, the present invention relates to the treatment of HIV and AIDS.

  该发明提供了具有药物和生物影响性质的化合物，它们的制药组合物和使用方法。特别地，该发明涉及氮杂吲哌酮乙酰基哌嗪衍生物。这些化合物具有独特的抗病毒活性，无论是单独使用还是与其他抗病毒药物、抗感染药物、免疫调节剂或HIV进入抑制剂联合使用。更具体地，本发明涉及治疗HIV和艾滋病。