methyl (S)-3-(2-nitro-1H-imidazol-1-yl)-2-(tritylamino)propanoate | 600157-66-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: methyl (S)-3-(2-nitro-1H-imidazol-1-yl)-2-(tritylamino)propanoate
• 英文别名: methyl 3-(2-nitro-1H-imidazol-1-yl)-N-trityl-L-alaninate；methyl (2S)-3-(2-nitroimidazol-1-yl)-2-(tritylamino)propanoate
• CAS: 600157-66-2
• 化学式: C₂₆H₂₄N₄O₄
• 分子量: 456.501
• InChiKey: GPFUZKLMPQGIHH-QHCPKHFHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  34
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl (S)-3-(2-nitro-1H-imidazol-1-yl)-2-(tritylamino)propanoate 在 nitroreductase 、 三氟乙酸 、 还原型辅酶II(NADPH)四钠盐 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成
  参考文献：
  名称：

  用于缺氧反应性肽自组装和荧光的非常规氨基酸

  摘要：

  内源性刺激响应氨基酸的设计允许在生物微环境下精确调节蛋白质或肽，从而调节它们的性能。在这里，我们报告了一种非常规氨基酸 2-nitroimidazol-1-yl 丙氨酸，并探讨了它在创建基于硝基还原酶 (NTR) 响应肽的超分子探针以实现高效缺氧成像中的功能。基于硝基咪唑单元的还原电位，通过2-硝基咪唑与丝氨酸衍生物的Mitsunobu反应合成氨基酸。我们阐明了氨基酸的 NTR 反应性与涉及一系列肽的肽的结构特征之间的关系。这最终通过合理优化序列促进了进行 NTR 响应自组装的芳香肽的开发。由于 2-硝基咪唑在荧光猝灭中的内在作用，我们创建了一种形态可转换的超分子探针，用于基于 NTR 还原对缺氧肿瘤细胞进行成像。我们发现由此产生的超分子探针渗透到实体瘤中，从而可以对缺氧区域的肿瘤细胞进行有效的荧光成像。我们的研究结果证明了一种易于合成且用途广泛的氨基酸的开发，该氨基酸在创建响应生物微环境

  DOI：

  10.1021/jacs.1c06435
• 作为产物：
  描述：

  2-硝基咪唑 、 N-三苯甲基-L-丝氨酸甲酯 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以20%的产率得到methyl (S)-3-(2-nitro-1H-imidazol-1-yl)-2-(tritylamino)propanoate
  参考文献：
  名称：

  用于缺氧反应性肽自组装和荧光的非常规氨基酸

  摘要：

  内源性刺激响应氨基酸的设计允许在生物微环境下精确调节蛋白质或肽，从而调节它们的性能。在这里，我们报告了一种非常规氨基酸 2-nitroimidazol-1-yl 丙氨酸，并探讨了它在创建基于硝基还原酶 (NTR) 响应肽的超分子探针以实现高效缺氧成像中的功能。基于硝基咪唑单元的还原电位，通过2-硝基咪唑与丝氨酸衍生物的Mitsunobu反应合成氨基酸。我们阐明了氨基酸的 NTR 反应性与涉及一系列肽的肽的结构特征之间的关系。这最终通过合理优化序列促进了进行 NTR 响应自组装的芳香肽的开发。由于 2-硝基咪唑在荧光猝灭中的内在作用，我们创建了一种形态可转换的超分子探针，用于基于 NTR 还原对缺氧肿瘤细胞进行成像。我们发现由此产生的超分子探针渗透到实体瘤中，从而可以对缺氧区域的肿瘤细胞进行有效的荧光成像。我们的研究结果证明了一种易于合成且用途广泛的氨基酸的开发，该氨基酸在创建响应生物微环境

  DOI：

  10.1021/jacs.1c06435

文献信息

• [EN] HETEROCYCLIC AMIDE DERIVATIVES AS INHIBITORS OF GLYCOGEN PHOSPHORYLASE<br/>[FR] DERIVES D'AMIDES HETEROCYCLIQUES COMME INHIBITEURS DE LA GLYCOGENE PHOSPHORYLASE
  申请人：ASTRAZENECA AB

  公开号：WO2003074532A1

  公开（公告）日：2003-09-12

  Heterocyclic amides of formula (1) wherein: X is N or CH; R4 and R5 together are either -S-C(R6)=C(R7)- or -C(R7)=C(R6)-S-; R6 and R7 are independently selected from, for example hydrogen, halo and C1-4alkyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; R2 is hydrogen, hydroxy or carboxy; R3 is selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C1-4alkyl (optionally substituted by 1 or 2 R8 groups); R8 is selected from for example hydroxy, -COCOOR9, -C(O)N(R9)(R10), -NHC(O)R9, (R9)(R10)N- and -COOR9; R9 and R10 are selected from for example hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 R13); R13 is selected from hydroxy, halo, trihalomethyl and C1-4alkoxy; or a pharmaceutically acceptable salt or pro-drug thereof; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.

  式（1）的杂环酰胺，其中：X为N或CH；R4和R5一起是-S-C（R6）=C（R7）-或-C（R7）=C（R6）-S-；R6和R7可独立地选择自氢、卤素和C1-4烷基；A为苯基或杂芳基；n为0、1或2；R1可从卤素、硝基、氰基、羟基、羧基中选择；R2为氢、羟基或羧基；R3可从氢、羟基、芳基、杂环烷基和C1-4烷基中选择（可选地由1或2个R8基取代）；R8可从羟基、-COCOOR9、-C（O）N（R9）（R10）、-NHC（O）R9、（R9）（R10）N-和-COOR9中选择；R9和R10可从氢、羟基、C1-4烷基（可选地由1或2个R13取代）中选择；R13可从羟基、卤素、三卤甲基和C1-4烷氧基中选择；或其药学上可接受的盐或前药；具有糖原磷酸化酶抑制活性，因此在治疗与糖原磷酸化酶活性增加相关的疾病状态中具有价值。描述了制备所述杂环酰胺衍生物和含有它们的药物组合物的方法。
• Heterocyclic amide derivatives as inhibitors of glycogen phoshorylase
  申请人：Birch Martin Alan

  公开号：US20050131015A1

  公开（公告）日：2005-06-16

  Heterocyclic amides of formula (1) wherein: X is N or CH; R 4 and R 5 together are either —S—C(R 6 )═C(R 7 )— or —C(R 7 )═C(R 6 )—S—; R 6 and R 7 are independently selected from, for example hydrogen, halo and C l-4 alkyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R 1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; R 2 is hydrogen, hydroxy or carboxy; R 3 is selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C 1-4 alkyl(optionally substituted by 1 or 2 R 8 groups); R 8 is selected from for example hydroxy, —COCOOR 9 , —C(O)N(R 9 )(R 10 ), —NHC(O)R 9 , (R 9 )(R 10 )N— and —COOR 9 ; R 9 and R 10 are selected from for example hydrogen, hydroxy, C 1-4 alkyl (optionally substituted by 1 or 2 R 13 ); R 13 is selected from hydroxy, halo, trihalomethyl and C 1-4 alkoxy; or a pharmaceutically acceptable salt or pro-drug thereof; possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.

  公式（1）的杂环酰胺，其中：X是N或CH；R4和R5一起是—S—C(R6)═C(R7)—或—C(R7)═C(R6)—S—；R6和R7独立选择自氢、卤素和Cl-4烷基；A是苯基或杂环芳基；n为0、1或2；R1选择自卤素、硝基、氰基、羟基、羧基；R2是氢、羟基或羧基；R3选择自氢、羟基、芳基、杂环芳基和C1-4烷基（可选地取代1或2个R8基）；R8选择自羟基、—COCOOR9、—C（O）N（R9）（R10）、—NHC（O）R9、（R9）（R10）N—和—COOR9；R9和R10选择自氢、羟基、C1-4烷基（可选地取代1或2个R13）；R13选择自羟基、卤素、三卤甲基和C1-4烷氧基；或其药学上可接受的盐或前药；具有糖原磷酸化酶抑制活性，因此在治疗与增加的糖原磷酸化酶活性相关的疾病状态中具有价值。还描述了制造该杂环酰胺衍生物的过程以及含有它们的制药组合物。
• Heterocyclic amide derivatives as inhibitors of glycogen phosphorylase
  申请人：AstraZeneca AB

  公开号：US07276517B2

  公开（公告）日：2007-10-02

  Heterocyclic amides of formula (1) wherein: X is N or CH; R4 and R5 together are either —S—C(R6)═C(R7)— or —C(R7)═C(R6)—S—; R6 and R7 are independently selected from, for example hydrogen, halo and C1-4alkyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; R2 is hydrogen, hydroxy or carboxy; R3 is selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C1-4alkyl(optionally substituted by 1 or 2 R8 groups); R8 is selected from for example hydroxy, —COCOOR9, —C(O)N(R9)(R10), —NHC(O)R9, (R9)(R10)N— and —COOR9; R9 and R10 are selected from for example hydrogen, hydroxy, C1-4alkyl (optionally substituted by 1 or 2 R13); R13 is selected from hydroxy, halo, trihalomethyl and C1-4alkoxy; or a pharmaceutically acceptable salt or pro-drug thereof, possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.

  公式（1）中的杂环酰胺，其中： X为N或CH; R4和R5一起是—S—C(R6)═C(R7)—或—C(R7)═C(R6)—S—; R6和R7独立选择自例如氢，卤素和C1-4烷基; A为苯基或杂环芳基; n为0，1或2; R1选择自例如卤素，硝基，氰基，羟基，羧基; R2为氢，羟基或羧基; R3选择自例如氢，羟基，芳基，杂环基和C1-4烷基（可选地取代1或2个R8基团）; R8选择自例如羟基，—COCOOR9，—C（O）N（R9）（R10），—NHC（O）R9，（R9）（R10）N—和—COOR9; R9和R10选择自例如氢，羟基，C1-4烷基（可选地取代1或2个R13）; R13选择自例如羟基，卤素，三卤甲基和C1-4烷氧基; 或其药学上可接受的盐或前药，具有糖原磷酸化酶抑制活性，因此在治疗与糖原磷酸化酶活性增加相关的疾病状态方面具有价值。描述了制造该杂环酰胺衍生物的方法以及含有它们的制药组合物。
• HETEROCYCLIC AMIDE DERIVATIVES AS INHIBITORS OF GLYCOGEN PHOSPHORYLASE
  申请人：Birch Martin Alan

  公开号：US20070043069A1

  公开（公告）日：2007-02-22

  Heterocyclic amides of formula (1) wherein: X is N or CH; R 4 and R 5 together are either —S—C(R 6 )═C(R 7 )— or —C(R 7 )═C(R 6 )—S—; R 6 and R 7 are independently selected from, for example hydrogen, halo and C 1-4 alkyl; A is phenylene or heteroarylene; n is 0, 1 or 2; R 1 is selected from for example halo, nitro, cyano, hydroxy, carboxy; R 2 is hydrogen, hydroxy or carboxy; R 3 is selected from for example hydrogen, hydroxy, aryl, heterocyclyl and C 1-4 alkyl(optionally substituted by 1 or 2 R 8 groups); R 8 is selected from for example hydroxy, —COCOOR 9 , —C(O)N(R 9 )(R 10 ), —NHC(O)R 9 , (R 9 )(R 10 )N— and —COOR 9 ; R 9 and R 10 are selected from for example hydrogen, hydroxy, C 1-4 alkyl (optionally substituted by 1 or 2 R 13 ); R 13 is selected from hydroxy, halo, trihalomethyl and C 1-4 alkoxy; or a pharmaceutically acceptable salt or pro-drug thereof, possess glycogen phosphorylase inhibitory activity and accordingly have value in the treatment of disease states associated with increased glycogen phosphorylase activity. Processes for the manufacture of said heterocyclic amide derivatives and pharmaceutical compositions containing them are described.

  式（1）的杂环酰胺，其中：X为N或CH；R4和R5组合在一起是—S—C(R6)═C(R7)—或—C(R7)═C(R6)—S—；R6和R7独立选择自例如氢、卤素和C1-4烷基；A为苯撑或杂芳撑；n为0、1或2；R1选择自例如卤素、硝基、氰基、羟基、羧基；R2为氢、羟基或羧基；R3选择自例如氢、羟基、芳基、杂环基和C1-4烷基（可以选择性地被1或2个R8基取代）；R8选择自例如羟基、—COCOOR9、—C(O)N(R9)(R10)、—NHC(O)R9、(R9)(R10)N—和—COOR9；R9和R10选择自例如氢、羟基、C1-4烷基（可以选择性地被1或2个R13取代）；R13选择自羟基、卤素、三卤甲基和C1-4烷氧基；或其药学上可接受的盐或前药具有糖原磷酸化酶抑制活性，因此在治疗与增加的糖原磷酸化酶活性相关的疾病状态方面具有价值。描述了制备该杂环酰胺衍生物的方法和含有它们的药物组合物。
• Enhanced tumor specific drug release by hypoxia sensitive dual-prodrugs based on 2-nitroimidazole
  作者：Takashi Tsuji、Honoka Tsunematsu、Masaki Imanishi、Masaya Denda、Koichiro Tsuchiya、Akira Otaka

  DOI：10.1016/j.bmcl.2023.129484

  日期：2023.10