di-tert-butyl (9H-fluorene-2,7-diyl)dicarbamate | 917615-27-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: di-tert-butyl (9H-fluorene-2,7-diyl)dicarbamate
• 英文别名: 2,7-di(Boc-amino)fluorene；tert-butyl N-[7-[(2-methylpropan-2-yl)oxycarbonylamino]-9H-fluoren-2-yl]carbamate
• CAS: 917615-27-1
• 化学式: C₂₃H₂₈N₂O₄
• 分子量: 396.486
• InChiKey: SIESPOFABWAKDJ-UHFFFAOYSA-N

物化性质

• 沸点：
  476.6±38.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  di-tert-butyl (9H-fluorene-2,7-diyl)dicarbamate 在 caesium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 18.0h， 以63%的产率得到di-tert-butyl (9-oxo-9H-fluorene-2,7-diyl)dicarbamate
  参考文献：
  名称：

  Structure-activity relationship (SAR) studies on the mutagenic properties of 2,7-diaminofluorene and 2,7-diaminocarbazole derivatives

  摘要：

  We discovered that 2,7-diaminofluorene or 2,7-diaminocarbazole moiety can be employed as a core structure of highly effective NS5A inhibitors that are connected through amide bonds to proline-valine-carbamate motifs. Amide bonds can be easily cleaved via various metabolic pathways upon administration into the body, and metabolites containing 2,7-diaminofluorene and 2,7-diaminocarbazole core structures have been known to be strong mutagens. To avoid the mutagenesis issue of these core structures, we examined various functional groups at the C9 or N9 position of 2,7-diaminofluorene or 2,7-diaminocarbazole, respectively, through the Ames test in TA98 and TA100 mutants of Salmonella typhimurium LT-2. We discovered that, through proper alkyl substitution at the C9 or N9 position, 2,7-diaminofluorene and 2,7-diaminocarbazole moieties can be successfully employed in drug discovery without necessarily causing mutagenicity problems.

  DOI：

  10.1016/j.bmcl.2020.127662
• 作为产物：
  描述：

  2,7-二硝基芴 在 iron(II,III) oxide 、 一水合肼 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 26.0h， 生成 di-tert-butyl (9H-fluorene-2,7-diyl)dicarbamate
  参考文献：
  名称：

  Structure-activity relationship (SAR) studies on the mutagenic properties of 2,7-diaminofluorene and 2,7-diaminocarbazole derivatives

  摘要：

  We discovered that 2,7-diaminofluorene or 2,7-diaminocarbazole moiety can be employed as a core structure of highly effective NS5A inhibitors that are connected through amide bonds to proline-valine-carbamate motifs. Amide bonds can be easily cleaved via various metabolic pathways upon administration into the body, and metabolites containing 2,7-diaminofluorene and 2,7-diaminocarbazole core structures have been known to be strong mutagens. To avoid the mutagenesis issue of these core structures, we examined various functional groups at the C9 or N9 position of 2,7-diaminofluorene or 2,7-diaminocarbazole, respectively, through the Ames test in TA98 and TA100 mutants of Salmonella typhimurium LT-2. We discovered that, through proper alkyl substitution at the C9 or N9 position, 2,7-diaminofluorene and 2,7-diaminocarbazole moieties can be successfully employed in drug discovery without necessarily causing mutagenicity problems.

  DOI：

  10.1016/j.bmcl.2020.127662

文献信息

• Conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates
  申请人：Bentley D. Michael

  公开号：US20060293499A1

  公开（公告）日：2006-12-28

  The present invention provides conjugates having a degradable linkage and polymeric reagents useful in preparing such conjugates. The conjugates as well as the polymeric reagents used to form the conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods of making polymeric reagents and conjugates, as well as methods for administering conjugates and compositions, are also provided.

  本发明提供具有可降解连接的共轭物和用于制备这种共轭物的高分子试剂。用于形成共轭物的高分子试剂以及共轭物本身包括以下至少一种：包含可离子化氢原子的芳香基团、间隔基团和水溶性聚合物。还提供了制备高分子试剂和共轭物的方法，以及用于给药的共轭物和组合物的方法。
• POLYMER CONJUGATES OF GLP-1
  申请人：Bossard Mary J.

  公开号：US20100210505A1

  公开（公告）日：2010-08-19

  Conjugates of a GLP-I moiety may be covalently attached to one or more water-soluble polymers. For instance, a GLP-I polymer conjugate may include a GLP-I moiety releasably attached at its N-terminus to a water-soluble polymer. The GLP-I polymer conjugate may include a GLP-I moiety covalently attached to a water-soluble polymer, wherein the GLP-I moiety possesses an N-methyl substituent. The GLP-I polymer conjugate may include a GLP-I moiety covalently attached at a polymer attachment site to a water-soluble polymer, wherein the GLP-I moiety is glycosylated at a site separate from the polymer attachment site.

  GLP-I基团的共轭物可以共价地附加在一个或多个水溶性聚合物上。例如，GLP-I聚合物共轭物可以包括一个GLP-I基团可释放地附着在其N-末端到水溶性聚合物上。GLP-I聚合物共轭物可以包括一个GLP-I基团共价附着在水溶性聚合物上，其中GLP-I基团具有一个N-甲基取代基。GLP-I聚合物共轭物可以包括一个GLP-I基团共价附着在聚合物附着位点到水溶性聚合物上，其中GLP-I基团在与聚合物附着位点分离的位点被糖基化。
• PHARMACEUTICAL COMPOSITIONS AND METHODS FOR DELIVERING SUCH COMPOSITIONS
  申请人：Bentley Michael D.

  公开号：US20120258912A1

  公开（公告）日：2012-10-11

  The present invention provides pharmaceutical compositions comprising a pharmaceutically acceptable excipient and a conjugate having a degradable linkage. The conjugates include at least one of each the following: an aromatic moiety comprising an ionizable hydrogen atom, a spacer moiety, and a water-soluble polymer. Methods for delivering such compositions are also provided.

  本发明提供了含有可降解连接的共轭物的制药组合物，其中包括药用可接受的赋形剂和共轭物。共轭物包括以下至少一种：具有可离解氢原子的芳香基团，间隔基团和水溶性聚合物。本发明还提供了传递这种组合物的方法。
• Polymer conjugates of GLP-1
  申请人：Nektar Therapeutics

  公开号：US08293869B2

  公开（公告）日：2012-10-23

  Conjugates of a GLP-I moiety may be covalently attached to one or more water-soluble polymers. For instance, a GLP-I polymer conjugate may include a GLP-I moiety releasably attached at its N-terminus to a water-soluble polymer. The GLP-I polymer conjugate may include a GLP-I moiety covalently attached to a water-soluble polymer, wherein the GLP-I moiety possesses an N-methyl substituent. The GLP-I polymer conjugate may include a GLP-I moiety covalently attached at a polymer attachment site to a water-soluble polymer, wherein the GLP-I moiety is glycosylated at a site separate from the polymer attachment site.

  GLP-I分子的共轭物可以共价地连接到一个或多个水溶性聚合物上。例如，GLP-I聚合物共轭物可以包括一个GLP-I分子，可在其N-末端可释放地连接到水溶性聚合物上。GLP-I聚合物共轭物可以包括一个GLP-I分子，共价地连接到水溶性聚合物上，其中GLP-I分子具有N-甲基取代基。GLP-I聚合物共轭物可以包括一个GLP-I分子，共价地连接到聚合物附着位点上的水溶性聚合物，其中GLP-I分子在与聚合物附着位点分离的位点上被糖基化。
• METHODS FOR PREPARING POLYMERIC REAGENTS
  申请人：Nektar Therapeutics

  公开号：US20150141665A1

  公开（公告）日：2015-05-21

  The present invention provides among other things methods for preparing polymeric reagents, wherein the method comprises (a) providing an aromatic moiety bearing a hydroxy group, a first amino group and a second amino group; (b) reacting a functional group reagent with the hydroxy group to result in a hydroxy group bearing a functional group capable of reacting with an amino group of an active agent and resulting in a hydolyzable carbamate; and (c) reacting a plurality of poly(alkylene glycol) water-soluble polymers bearing a reactive group with the first amino group and second amino group to result in (i) a first amino group bearing a water-soluble polymer through a spacer moiety, and (ii) a second amino group bearing a second water-soluble polymer through a spacer moiety.

  本发明提供了制备聚合试剂的方法，其中该方法包括（a）提供一种带有羟基、第一氨基和第二氨基的芳香基团；（b）将功能性试剂与羟基反应，以得到带有功能性基团的羟基，该功能性基团能够与活性剂的氨基反应，并产生可水解的碳酸酯；以及（c）将带有反应性基团的多种聚（烷基乙二醇）水溶性聚合物与第一氨基和第二氨基反应，以得到（i）通过间隔基团带有第一氨基的水溶性聚合物，以及（ii）通过间隔基团带有第二氨基的第二种水溶性聚合物。