(S)-tert-butyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-(2-(tert-butoxycarbonylamino)ethylamino)-5-oxopentanoate | 910661-24-4

• 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: (S)-tert-butyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-(2-(tert-butoxycarbonylamino)ethylamino)-5-oxopentanoate
• 英文别名: tert-Butyl N2-(((9H-fluoren-9-yl)methoxy)carbonyl)-N5-(2-((tert-butoxycarbonyl)amino)ethyl)-L-glutaminate；tert-butyl (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-5-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethylamino]-5-oxopentanoate
• CAS: 910661-24-4
• 化学式: C₃₁H₄₁N₃O₇
• 分子量: 567.682
• InChiKey: JFRATIPTXUHODE-VWLOTQADSA-N

物化性质

• 沸点：
  772.0±60.0 °C(Predicted)
• 密度：
  1.171±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  41
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  132
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-(2-(tert-butoxycarbonylamino)ethylamino)-5-oxopentanoate 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 二乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 31.0h， 生成 ethylelediamine-folate
  参考文献：
  名称：

  Redirection of Genetically Engineered CAR-T Cells Using Bifunctional Small Molecules

  摘要：

  Chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) provide a potent antitumor response and have become a promising treatment option for cancer. However, despite their efficacy, CAR-T cells are associated with significant safety challenges related to the inability to control their activation and expansion and terminate their response. Herein, we demonstrate that a bifunctional small molecule switch consisting of folate conjugated to fluorescein isothiocyanate (folate-FITC) can redirect and regulate FITC-specific CAR-T cell activity toward folate receptor (FR)-overexpressing tumor cells. This system was shown to be highly cytotoxic to FR-positive cells with no activity against FR-negative cells, demonstrating the specificity of redirection by folate-FITC. Anti-FITC-CAR-T cell activation and proliferation was strictly dependent on the presence of both folate-FITC and FR-positive cells and was dose titratable with folate-FITC switch. This novel treatment paradigm may ultimately lead to increased safety for CAR-T cell immunotherapy.

  DOI：

  10.1021/jacs.5b00106
• 作为产物：
  描述：

  N-叔丁氧羰基-1,2-乙二胺 、 芴甲氧羰基-L-谷氨酸 1-叔丁酯 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以90%的产率得到(S)-tert-butyl 2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-5-(2-(tert-butoxycarbonylamino)ethylamino)-5-oxopentanoate
  参考文献：
  名称：

  Redirection of Genetically Engineered CAR-T Cells Using Bifunctional Small Molecules

  摘要：

  Chimeric antigen receptor (CAR)-engineered T cells (CAR-Ts) provide a potent antitumor response and have become a promising treatment option for cancer. However, despite their efficacy, CAR-T cells are associated with significant safety challenges related to the inability to control their activation and expansion and terminate their response. Herein, we demonstrate that a bifunctional small molecule switch consisting of folate conjugated to fluorescein isothiocyanate (folate-FITC) can redirect and regulate FITC-specific CAR-T cell activity toward folate receptor (FR)-overexpressing tumor cells. This system was shown to be highly cytotoxic to FR-positive cells with no activity against FR-negative cells, demonstrating the specificity of redirection by folate-FITC. Anti-FITC-CAR-T cell activation and proliferation was strictly dependent on the presence of both folate-FITC and FR-positive cells and was dose titratable with folate-FITC switch. This novel treatment paradigm may ultimately lead to increased safety for CAR-T cell immunotherapy.

  DOI：

  10.1021/jacs.5b00106

文献信息

• WO2008/98788
  申请人：——

  公开号：——

  公开（公告）日：——
• USE OF BUFFERS FOR RADIONUCLIDE COMPLEXATION
  申请人：Port Marc

  公开号：US20120009124A1

  公开（公告）日：2012-01-12

  The present invention relates to a method for complexation of a chelate with a radionuclide, advantageously gallium, the complexation being carried out advantageously at ambient temperature without heating, by adding the radionuclide to the chelate in a buffer solution, the buffer of this solution comprising between two and five functions for coordination with the radionuclide, each coordination function being independently chosen from a carboxylic acid function and a hydroxyl function, on the condition that the buffer comprises at least one carboxylic acid function and at most two carboxylic acid functions. It also relates to the injectable solution obtained.
• COMPLEX FOLATE-NOTA-Ga68
  申请人：PORT Marc

  公开号：US20120064003A1

  公开（公告）日：2012-03-15

  The present invention concerns a Ga68 complex of formula FOLATE-(LINKER)i-NOTA-Ga 68 in which: 1) FOLATE is a folate compound or a derivative thereof capable of targeting a folate receptor, 2) NOTA is a chelate capable of complexing Ga68 having a NOTA scaffold or derivatives thereof 3) LINKER is a chemical group linking FOLATE and NOTA 4) i is an integer chosen between 0 and 1 wherein NOTA is complexing Ga68
• US8986650B2
  申请人：——

  公开号：US8986650B2

  公开（公告）日：2015-03-24
• [EN] USE OF BUFFERS FOR RADIONUCLIDE COMPLEXATION<br/>[FR] UTILISATION DE TAMPONS POUR LA COMPLEXATION DE RADIONUCLÉIDES
  申请人：GUERBET SA

  公开号：WO2010092114A1

  公开（公告）日：2010-08-19

  The present invention relates to a method for complexation of a chelate with a radionuclide, advantageously gallium, the complexation being carried out advantageously at ambient temperature without heating, by adding the radionuclide to the chelate in a buffer solution, the buffer of this solution comprising between two and five functions for coordination with the radionuclide, each coordination function being independently chosen from a carboxylic acid function and a hydroxyl function, on the condition that the buffer comprises at least one carboxylic acid function and at most two carboxylic acid functions. It also relates to the injectable solution obtained.