2-(4-(pent-4-yn-1-yloxy)phenyl)-4H-chromen-4-one | 1451739-67-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2-(4-(pent-4-yn-1-yloxy)phenyl)-4H-chromen-4-one
• 英文别名: 2-(4-(Pent-4-yn-1-yloxy)phenyl)-4H-chromen-4-one；2-(4-pent-4-ynoxyphenyl)chromen-4-one
• CAS: 1451739-67-5
• 化学式: C₂₀H₁₆O₃
• 分子量: 304.345
• InChiKey: ZISHFWZBVQMZHG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(4-(pent-4-yn-1-yloxy)phenyl)-4H-chromen-4-one 、 2-(4'-(4-chlorobutoxy)phenyl)-4H-chromen-4-one 在 sodium azide 、 铜 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 叔丁醇 为溶剂， 反应 0.25h， 以75.2%的产率得到2-(4'-(3-(1-(4-(4-(4-oxo-4H-chromen-2-yl)phenoxy)butyl)-1H-1,2,3-triazol-4-yl)propoxy)phenyl)-4H-chromen-4-one
  参考文献：
  名称：

  Microwave-Assisted Synthesis of Novel Bis-Flavone Dimers as New Anticancer Agents

  摘要：

  在这项研究中，我们描述了一种基于微波的点击化学方法，用于制备一系列新型的双黄酮二聚体。取代的7-羟基和4'-羟基黄酮通过三唑环连接在一起。这些化合物易于合成，并且收率高。双黄酮在包括HCT116、HepG2、MCF7和MOLT-4在内的不同细胞系上进行了测试。几种类似物显示出抗癌活性，IC50值在20-60μM范围内。黄酮以其抗癌特性而闻名，这种方法为新的药用结构奠定了基础。

  DOI：

  10.2174/1570178615666180621094529
• 作为产物：
  描述：

  对羟基苯乙酮 在 potassium tert-butylate 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 24.77h， 生成 2-(4-(pent-4-yn-1-yloxy)phenyl)-4H-chromen-4-one
  参考文献：
  名称：

  Microwave-Assisted Synthesis of Novel Bis-Flavone Dimers as New Anticancer Agents

  摘要：

  在这项研究中，我们描述了一种基于微波的点击化学方法，用于制备一系列新型的双黄酮二聚体。取代的7-羟基和4'-羟基黄酮通过三唑环连接在一起。这些化合物易于合成，并且收率高。双黄酮在包括HCT116、HepG2、MCF7和MOLT-4在内的不同细胞系上进行了测试。几种类似物显示出抗癌活性，IC50值在20-60μM范围内。黄酮以其抗癌特性而闻名，这种方法为新的药用结构奠定了基础。

  DOI：

  10.2174/1570178615666180621094529

文献信息

• [EN] ALKYNE-, AZIDE- AND TRIAZOLE-CONTAINING FLAVONOIDS AS MODULATORS FOR MULTIDRUG RESISTANCE IN CANCERS<br/>[FR] FLAVONOÏDES CONTENANT DE L'ALCYNE, DE L'AZIDE ET DU TRIAZOLE UTILISÉS COMME MODULATEURS DE RÉSISTANCE MULTIPLE AUX MÉDICAMENTS DANS LES CANCERS
  申请人：UNIV HONG KONG POLYTECHNIC

  公开号：WO2013127361A1

  公开（公告）日：2013-09-06

  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-continaing flavonoids were screened for their ability to modulate multidrug resistance (MDR) in P-gp-overexpressed cell line (LCC6MDR), MRPl-overexpressed cell line (2008/MRPl) and BCRP-overexpressed cell line (HEK293/R2 and MCF7-MX100). Generally, they displayed very promising MDR reversal activity against P-gp-, MRPl- 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, MRPl 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/MRPl 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 MRPl transporters. Most of the dimers are notably safe MDR chemosensitizers as indicated by their high therapeutic index values.

  通过对一系列含有三唑基的黄酮类化合物（Az 1-15）和炔烃（Ac 1-17）进行环加成反应，高效构建了一个三唑桥联的黄酮二聚体化合物库。对这些三唑桥联的黄酮二聚体及其前体炔烃和三唑基的黄酮类化合物进行了筛选，以评估它们对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）调节多药耐药性（MDR）的能力。总体而言，它们显示出对P-gp、MRP1和BCRP介导的药物耐药性具有非常有前景的MDR逆转活性。此外，它们对各种转运蛋白显示出不同程度的选择性。总体而言，它们可以分为对P-gp、MRP1和BCRP转运蛋白具有单选择性、双选择性和多选择性调节剂。逆转LCC6MDR细胞对紫杉醇耐药性（141-340 nM）、2008/MRP1细胞对阿霉素（78-590 nM）和长春碱（82-550 nM）耐药性以及HEK293/R2和MCF7-MX100细胞对托泊替康耐药性（0.9-135 nM）的EC50值在纳摩尔范围内。重要的是，许多化合物在BCRP过表达的细胞系中显示出EC50在或低于10 nM，表明这些双价三唑更具选择性地抑制BCRP转运蛋白而不是P-gp和MRP1转运蛋白。大多数二聚体根据其高治疗指数值显示出明显安全的MDR化疗敏感化剂特性。
• Discovery of Novel Flavonoid Dimers To Reverse Multidrug Resistance Protein 1 (MRP1, ABCC1) Mediated Drug Resistance in Cancers Using a High Throughput Platform with “Click Chemistry”
  作者：Iris L. K. Wong、Xuezhen Zhu、Kin-Fai Chan、Man Chun Law、Aya M. Y. Lo、Xuesen Hu、Larry M. C. Chow、Tak Hang Chan

  DOI：10.1021/acs.jmedchem.8b00834

  日期：2018.11.21

  A 300-member flavonoid dimer library of multidrug resistance-associated protein 1 (MRP1, ABCC1) modulators was rapidly assembled using “click chemistry”. Subsequent high-throughput screening has led to the discovery of highly potent (EC50 ranging from 53 to 298 nM) and safe (selective indexes ranging from >190 to >1887) MRP1 modulators. Some dimers have potency about 6.5- to 36-fold and 64- to 358-fold

  使用“点击化学”快速组装了具有300种成员的抗药性相关蛋白1（MRP1，ABCC1）调节剂的类黄酮二聚体文库。随后的高通量筛选导致发现了高效MRP1调节剂（EC 50为53至298 nM）和安全的（选择性指数为> 190至> 1887）。一些二聚体的效力分别比众所周知的MRP1抑制剂维拉帕米和MK571高约6.5至36倍和64至358倍。他们抑制DOX流出并恢复细胞内DOX浓度。预测最有效的调节剂Ac3Az11将以竞争方式与MRP1的两部分底物结合位点结合。此外，它提供了足够的浓度以使其血浆水平保持在体外EC以上50（对于DOX为53 nM）持续约90分钟。总体而言，我们证明，“点击化学”与高通量筛选相结合是发现具有强效MRP1修饰功能的化合物的一种快速，可靠和有效的工具。
• 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