2-(2-methyl-5-nitroimidazol-1-yl)-N-(2,3,3-trifluoroprop-2-enyl)acetamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(2-methyl-5-nitroimidazol-1-yl)-N-(2,3,3-trifluoroprop-2-enyl)acetamide
• 化学式: C9H9F3N4O3
• 分子量: 278.19
• InChiKey: ZNBOZOMHXKVJTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  92.7
• 氢给体数：
  1
• 氢受体数：
  7

文献信息

• [EN] COMPOUNDS AND METHODS FOR SELECTIVE IMAGING AND/OR ABLATION<br/>[FR] COMPOSÉS ET PROCÉDÉS POUR L'IMAGERIE ET/OU L'ABLATION SÉLECTIVES
  申请人：AUCKLAND UNISERVICES LTD

  公开号：WO2014007650A1

  公开（公告）日：2014-01-09

  The invention relates generally to compounds and methods for imaging and/or selective ablation of nitroreductase-expressing cells and/or biological agents. More particularly, although not exclusively, the invention provides compounds that are selectively metabolised by bacterial nitroreductases and are substantially insensitive to metabolism under oxic or hypoxic conditions by human nitroreductase enzymes.

  本发明涉及一般化合物和方法，用于成像和/或选择性消融硝基还原酶表达细胞和/或生物制剂。更具体地，尽管不是唯一的，本发明提供了一些选择性被细菌硝基还原酶代谢并且在氧化或缺氧条件下对人体硝基还原酶酶不敏感的化合物。
• Compounds And Methods For Selective Imaging And/Or Ablation
  申请人：Auckland Uniservices Limited

  公开号：US20150010474A1

  公开（公告）日：2015-01-08

  The invention relates generally to compounds and methods for imaging and/or selective ablation of nitroreductase-expressing cells and/or biological agents. More particularly, although not exclusively, the invention provides compounds that are selectively metabolised by bacterial nitroreductases and are substantially insensitive to metabolism under oxic or hypoxic conditions by human nitroreductase enzymes.

  本发明涉及化合物和方法，用于成像和/或选择性消融硝基还原酶表达的细胞和/或生物制剂。更具体地说，虽然不仅限于此，本发明提供的化合物被细菌硝基还原酶选择性代谢，且在人类硝基还原酶酶下氧化或缺氧条件下代谢相对不敏感。
• ALKYNE-, AZIDE- AND TRIAZOLE-CONTAINING FLAVONOIDS AS MODULATORS FOR MULTIDRUG RESISTANCE IN CANCERS
  申请人：The Hong Kong Polytechnic University

  公开号：US20150011513A1

  公开（公告）日：2015-01-08

  A triazole bridged flavonoid dimer compound library was efficiently constructed via the cycloaddition reaction of a series of flavonoid-containing azides (Az 1-15) and alkynes (Ac 1-17). These triazole bridged flavonoid dimers and their precursor alkyne- and azide-containing flavonoids were screened for their ability to modulate multidrug resistance (MDR) in P-gp-overexpressed cell line (LCC6MDR), MRP1-overexpressed cell line (2008/MRP1) and BCRP-overexpressed cell line (HEK293/R2 and MCF7-MX100). Generally, they displayed very promising MDR reversal activity against P-gp-, MRP1- and BCRP-mediated drug resistance. Moreover, they showed different levels of selectivity for various transporters. Overall, they can be divided into mono-selective, dual-selective and multi-selective modulators for the P-gp, MRP1 and BCRP transporters. The EC50 values for reversing paclitaxel resistance (141-340 nM) of LCC6MDR cells, DOX (78-590 nM) and vincristine (82-550 nM) resistance of 2008/MRP1 cells and topotecan resistance (0.9-135 nM) of HEK293/R2 and MCF7-MX100 cells were at nanomolar range. Importantly, a number of compounds displayed EC50 at or below 10 nM in BCRP-overexpressed cell lines, indicating that these bivalent triazoles more selectively inhibit BCRP transporter than the P-gp and MRP1 transporters. Most of the dimers are notably safe MDR chemosensitizers as indicated by their high therapeutic index values.

  通过一系列含有三唑桥联类黄酮二聚物的合成，使用环加成反应，利用一系列含有黄酮基团的叠氮化物（Az1-15）和炔烃（Ac1-17）构建了一个高效的化合物库。这些三唑桥联的类黄酮二聚体及其前体炔基和叠氮基类黄酮被筛选，以评估它们对过表达P-gp的细胞系（LCC6MDR）、MRP1过表达的细胞系（2008/MRP1）和BCRP过表达的细胞系（HEK293/R2和MCF7-MX100）调节多药耐药性（MDR）的能力。总体而言，它们展现了极具前景的P-gp、MRP1和BCRP介导的药物耐药性的MDR逆转活性。此外，它们显示出对各种转运体的不同程度的选择性。总体而言，它们可以分为单选择性、双选择性和多选择性的P-gp、MRP1和BCRP转运体调节剂。对于LCC6MDR细胞的紫杉醇耐药性（141-340 nM）、2008/MRP1细胞的DOX（78-590 nM）和长春新碱（82-550 nM）耐药性以及HEK293/R2和MCF7-MX100细胞的拓扑替康耐药性（0.9-135 nM），它们的EC50值处于纳摩尔范围。重要的是，许多化合物在BCRP过表达的细胞系中显示出EC50值在或低于10 nM，表明这些双价三唑更有选择性地抑制BCRP转运体而不是P-gp和MRP1转运体。大多数二聚体的治疗指数值非常高，表明它们是非常安全的MDR化疗敏感剂。
• Alkyne-, azide- and triazole-containing flavonoids as modulators for multidrug resistance in cancers
  申请人：The Hong Kong Polytechnic University

  公开号：US10208025B2

  公开（公告）日：2019-02-19

  A triazole bridged flavonoid dimer compound library was efficiently constructed via the cycloaddition reaction of a series of flavonoid-containing azides (Az 1-15) and alkynes (Ac 1-17). These triazole bridged flavonoid dimers and their precursor alkyne- and azide-containing flavonoids were screened for their ability to modulate multidrug resistance (MDR) in P-gp-overexpressed cell line (LCC6MDR), MRP1-overexpressed cell line (2008/MRP1) and BCRP-overexpressed cell line (HEK293/R2 and MCF7-MX100). Generally, they displayed very promising MDR reversal activity against P-gp-, MRP1- and BCRP-mediated drug resistance. Moreover, they showed different levels of selectivity for various transporters. Overall, they can be divided into mono-selective, dual-selective and multi-selective modulators for the P-gp, MRP1 and BCRP transporters. The EC50 values for reversing paclitaxel resistance (141-340 nM) of LCC6MDR cells, DOX (78-590 nM) and vincristine (82-550 nM) resistance of 2008/MRP1 cells and topotecan resistance (0.9-135 nM) of HEK293/R2 and MCF7-MX100 cells were at nanomolar range. Importantly, a number of compounds displayed EC50 at or below 10 nM in BCRP-overexpressed cell lines, indicating that these bivalent triazoles more selectively inhibit BCRP transporter than the P-gp and MRP1 transporters. Most of the dimers are notably safe MDR chemosensitizers as indicated by their high therapeutic index values.

  通过一系列含类黄酮的叠氮化物（Az 1-15）和炔烃（Ac 1-17）的环加成反应，有效地构建了三唑桥接类黄酮二聚体化合物库。研究人员筛选了这些三唑桥接类黄酮二聚体及其前体炔烃和叠氮化物类黄酮在P-gp过表达细胞系（LCC6MDR）、MRP1过表达细胞系（2008/MRP1）和BCRP过表达细胞系（HEK293/R2和MCF7-MX100）中调节多药耐药性（MDR）的能力。总体而言，它们对 P-gp、MRP1 和 BCRP 介导的耐药性表现出非常好的 MDR 逆转活性。此外，它们对各种转运体表现出不同程度的选择性。总的来说，它们可分为针对 P-gp、MRP1 和 BCRP 转运体的单选择性、双选择性和多选择性调节剂。这些化合物逆转 LCC6MDR 细胞紫杉醇耐药性（141-340 nM）、2008/MRP1 细胞 DOX 耐药性（78-590 nM）和长春新碱耐药性（82-550 nM）以及 HEK293/R2 和 MCF7-MX100 细胞拓扑替康耐药性（0.9-135 nM）的 EC50 值均在纳摩尔范围内。重要的是，一些化合物在BCRP过表达细胞系中的EC50达到或低于10 nM，表明这些二价三唑类化合物对BCRP转运体的抑制作用比对P-gp和MRP1转运体的抑制作用更具选择性。大多数二聚物的治疗指数值都很高，表明它们是安全的 MDR 化疗增敏剂。
• US9611256B2
  申请人：——

  公开号：US9611256B2

  公开（公告）日：2017-04-04