2',4'-dihydroxy-3,4-dimethoxychalcone | 104236-80-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: 2',4'-dihydroxy-3,4-dimethoxychalcone
• 英文别名: (E)-1-(2,4-dihydroxyphenyl)-3-(3,4-dimethoxyphenyl)prop-2-en-1-one；2',4'-dihydroxy-3,4-dimethoxy-trans-chalcone；2',4'-Dihydroxy-3,4-dimethoxy-trans-chalkon
• CAS: 104236-80-8
• 化学式: C₁₇H₁₆O₅
• 分子量: 300.311
• InChiKey: ZMMIEHPFMMRMMN-XVNBXDOJSA-N

物化性质

• 沸点：
  517.6±50.0 °C(Predicted)
• 密度：
  1.279±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2',4'-dihydroxy-3,4-dimethoxychalcone 在 palladium on activated charcoal 吡啶 、 氢气 作用下， 生成 3-(3,4-dimethoxyphenyl)-1-(5-hydroxy-2,2-dimethyl-2H-chromen-6-yl)-propanone
  参考文献：
  名称：

  A convenient and biogenetic type synthesis of few naturally occurring chromeno dihydrochalcones and their in vitro antileishmanial activity

  摘要：

  2',2'-Dimethyl chromeno dihydrochalcones are very rare in nature as plant secondary metabolites. Recently we have reported three such compounds from the plant Crotalaria ramosissima. Chromeno dihydrochalcones contain a 2',2'-dimethyl benzopyran system, which are frequently encountered in many natural products and exhibit a variety of biological activities. We here report the strategy to conveniently synthesize naturally occurring chromeno dihydrochalcones by biogenetic type pyridine or Amberlyst-15 catalyzed chromenylation of dihydrochalcones and in vitro antileishmanial activity of chromeno dihydrochalcones and their intermediates. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.05.071
• 作为产物：
  描述：

  2,4-二羟基苯乙酮 在 盐酸 、 potassium carbonate 、 potassium hydroxide 作用下， 以 乙醇 、 丙酮 为溶剂， 生成 2',4'-dihydroxy-3,4-dimethoxychalcone
  参考文献：
  名称：

  Potentiation of ΔF508- and G551D-CFTR-Mediated Cl- Current by Novel Hydroxypyrazolines

  摘要：

  CFTR 最常见的突变是 508 位苯丙氨酸缺失（F508del、ΔF508），约影响 90% 的 CF 患者。 ΔF508-CFTR 的错误折叠会损害其向质膜的运输及其氯通道活性。为了鉴定可以恢复 ΔF508-CFTR 通道活性的小分子，我们合成并评估了 18 种新型羟基吡唑啉类似物作为 CFTR 增强剂。为了阐明羟基吡唑啉对 ΔF508-CFTR 的增强活性，使用卤化物敏感的 YFP 测定、尤斯室测定和膜片钳技术测量 CFTR 活性。化合物 7p、7q 和 7r 表现出优异的增强作用，EC50 值 <10 μM。在这些化合物中，7q（一种新型 CFTR 增强剂，CP7q）显示出最高的增强活性，野生型和 ΔF508-CFTR 的 EC50 值分别为 0.88 ± 0.11 和 4.45 ± 0.31 μM。此外，CP7q 显着增强了 G551D-CFTR（一种 CFTR 门控突变体）的氯电导；其最大增强活性比著名的CFTR增强剂金雀异黄素高1.9倍。与单独使用 VX-809 相比，CP7q 和 VX-809（ΔF508-CFTR 的校正剂）的联合治疗显着增强了 ΔF508-CFTR 的功能挽救。 CP7q 不会改变胞质 cAMP 水平，并且在显示最大功效的浓度下没有表现出细胞毒性。羟基吡唑啉类药物可能是囊性纤维化药物治疗的潜在开发候选者。

  DOI：

  10.1371/journal.pone.0149131

文献信息

• Diarylalkanes as potent inhibitors of binuclear enzymes
  申请人：Jia Qi

  公开号：US20050267047A1

  公开（公告）日：2005-12-01

  The present invention implements a strategy that combines an enzyme inhibition assay with a chemical dereplication process to identify active plant extracts and the particular compounds—diarylalkanes and/or diarylalkanols within those extracts that specifically inhibit binuclear enzyme function. Included in the present invention are compositions of matter comprised of one or more of diarylalkanes and/or diarylalkanols, which inhibit the activity of binuclear enzymes, particularly tyrosinase and which prevent melanin overproduction. The present invention also provides a method for inhibiting the activity of a binuclear enzyme, particularly tyrosinase and a method for preventing and treating diseases and conditions related to binuclear enzyme function. The present invention further includes a method for preventing and treating melanin overproduction and diseases and conditions of the skin related thereto. The method for preventing and treating diseases and conditions related to binuclear enzyme function and melanin overproduction is comprised of administering to a host in need thereof an effective amount of a composition comprising one or more diarylalkanes and/or diarylalkanols synthesized and/or isolated from one or more plants together with a pharmaceutically acceptable carrier.

  本发明实施了一种策略，将酶抑制测定与化学去重复过程相结合，以识别活性植物提取物和特定化合物——二芳基烷烃和/或二芳基醇，这些化合物特异性地抑制双核酶功能。本发明包括由一种或多种二芳基烷烃和/或二芳基醇组成的物质组合物，其抑制双核酶的活性，特别是酪氨酸酶，并防止黑色素过度产生。本发明还提供了一种抑制双核酶活性的方法，特别是酪氨酸酶，以及一种预防和治疗与双核酶功能相关的疾病和病况的方法。本发明还包括一种预防和治疗黑色素过度产生以及与之相关的皮肤疾病和病况的方法。预防和治疗与双核酶功能和黑色素过度产生相关的疾病和病况的方法包括向需要的宿主施用由一种或多种植物合成和/或分离的一种或多种二芳基烷烃和/或二芳基醇组成的组合物的有效量，以及药用载体。
• Synthesis of flavonoids and their effects on aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues
  作者：Soon Sung Lim、Sang Hoon Jung、Jun Ji、Kuk Hyun Shin、Sam Rok Keum

  DOI：10.1211/0022357011775983

  日期：2010.2.18

  chalcone derivatives and by examining the structure-activity relationships on the inhibition of rat lens aldose reductase as well as on antioxidant effects. A series of 35 flavonoid derivatives were synthesized by Winget's condensation, oxidation, and reduction of appropriate acetophenones with appropriate benzaldehydes. The inhibitory activity of these derivatives on rat lens aldose reductase and their

  已知醛糖还原酶，多元醇途径的关键酶和氧化应激在糖尿病并发症中起重要作用。因此，具有有效抑制醛糖还原酶和氧化应激作用的药物将是预防糖尿病并发症的最有前途的药物。这项研究的目的是通过合成查尔酮衍生物，并通过研究抑制大鼠晶状体醛糖还原酶以及抗氧化作用的构效关系，开发出具有上述双重作用的新化合物。通过Winget的缩合，氧化和适当的苯乙酮与适当的苯甲醛的还原反应，合成了35种黄酮类衍生物。这些衍生物对大鼠晶状体醛糖还原酶的抑制活性及其抗氧化作用，评估了使用Cu2 +螯合剂测得的化合物在体外的自由基清除活性。还评估了它们对链脲佐菌素诱发的糖尿病大鼠红细胞，晶状体和坐骨神经中山梨醇积累的影响。在合成的新类黄酮衍生物中，具有A环2'，4'-二羟基基团的衍生物，例如2,4,2'，4'-四羟基查耳酮（22），2,2'，4'-三羟基查耳酮（11 ），发现2'，4'-二羟基-2,4-二甲基查耳酮（21）和3,4
• Potentiation of ΔF508- and G551D-CFTR-Mediated Cl- Current by Novel Hydroxypyrazolines
  作者：Jinhong Park、Poonam Khloya、Yohan Seo、Satish Kumar、Ho K. Lee、Dong-Kyu Jeon、Sungwoo Jo、Pawan K. Sharma、Wan Namkung

  DOI：10.1371/journal.pone.0149131

  日期：——

  The most common mutation of CFTR, affecting approximately 90% of CF patients, is a deletion of phenylalanine at position 508 (F508del, ΔF508). Misfolding of ΔF508-CFTR impairs both its trafficking to the plasma membrane and its chloride channel activity. To identify small molecules that can restore channel activity of ΔF508-CFTR, we synthesized and evaluated eighteen novel hydroxypyrazoline analogues as CFTR potentiators. To elucidate potentiation activities of hydroxypyrazolines for ΔF508-CFTR, CFTR activity was measured using a halide-sensitive YFP assay, Ussing chamber assay and patch-clamp technique. Compounds 7p, 7q and 7r exhibited excellent potentiation with EC50 value <10 μM. Among the compounds, 7q (a novel CFTR potentiator, CP7q) showed the highest potentiation activity with EC50 values of 0.88 ± 0.11 and 4.45 ± 0.31 μM for wild-type and ΔF508-CFTR, respectively. In addition, CP7q significantly potentiated chloride conductance of G551D-CFTR, a CFTR gating mutant; its maximal potentiation activity was 1.9 fold higher than the well-known CFTR potentiator genistein. Combination treatment with CP7q and VX-809, a corrector of ΔF508-CFTR, significantly enhanced functional rescue of ΔF508-CFTR compared with VX-809 alone. CP7q did not alter the cytosolic cAMP level and showed no cytotoxicity at the concentration showing maximum efficacy. The hydroxypyrazolines may be potential development candidates for drug therapy of cystic fibrosis.

  CFTR 最常见的突变是 508 位苯丙氨酸缺失（F508del、ΔF508），约影响 90% 的 CF 患者。 ΔF508-CFTR 的错误折叠会损害其向质膜的运输及其氯通道活性。为了鉴定可以恢复 ΔF508-CFTR 通道活性的小分子，我们合成并评估了 18 种新型羟基吡唑啉类似物作为 CFTR 增强剂。为了阐明羟基吡唑啉对 ΔF508-CFTR 的增强活性，使用卤化物敏感的 YFP 测定、尤斯室测定和膜片钳技术测量 CFTR 活性。化合物 7p、7q 和 7r 表现出优异的增强作用，EC50 值 <10 μM。在这些化合物中，7q（一种新型 CFTR 增强剂，CP7q）显示出最高的增强活性，野生型和 ΔF508-CFTR 的 EC50 值分别为 0.88 ± 0.11 和 4.45 ± 0.31 μM。此外，CP7q 显着增强了 G551D-CFTR（一种 CFTR 门控突变体）的氯电导；其最大增强活性比著名的CFTR增强剂金雀异黄素高1.9倍。与单独使用 VX-809 相比，CP7q 和 VX-809（ΔF508-CFTR 的校正剂）的联合治疗显着增强了 ΔF508-CFTR 的功能挽救。 CP7q 不会改变胞质 cAMP 水平，并且在显示最大功效的浓度下没有表现出细胞毒性。羟基吡唑啉类药物可能是囊性纤维化药物治疗的潜在开发候选者。
• Breast cancer-resistant protein inhibitor
  申请人：Yamazaki Ryuta

  公开号：US20060135445A1

  公开（公告）日：2006-06-22

  The invention provides a cancer cell useful in screening BCRP-inhibitors, and a BCRP-inhibitor. The BCRP-inhibitor contains, as the active ingredient, a flavonoid represented by any of the following formulae (1), (2), (3), (4), and (5): and glycosides, esters, or salts thereof; and an anticancer agent containing the BCRP-inhibitor together with an anticancer agent available as the substrate of BCRP.

  本发明提供了一种用于筛选BCRP抑制剂的癌细胞，以及一种含有BCRP抑制剂的药物。所述BCRP抑制剂包含以下式(1)、(2)、(3)、(4)和(5)中的任何一种黄酮类化合物，以及它们的糖苷、酯或盐；以及含有BCRP抑制剂和可作为BCRP底物的抗癌药物。
• BREAST CANCER-RESISTANT PROTEIN INHIBITOR
  申请人：YAMAZAKI Ryuta

  公开号：US20080287374A1

  公开（公告）日：2008-11-20

  The invention provides a cancer cell useful in screening BCRP-inhibitors, and a BCRP-inhibitor. The BCRP-inhibitor contains, as the active ingredient, a flavonoid represented by any of the following formulae (1), (2), (3), (4), and (5): and glycosides, esters, or salts thereof; and an anticancer agent containing the BCRP-inhibitor together with an anticancer agent available as the substrate of BCRP.

  本发明提供了一种用于筛选BCRP抑制剂的癌细胞，以及一种BCRP抑制剂。BCRP抑制剂包含以下任一式（1）、（2）、（3）、（4）和（5）所表示的黄酮类化合物及其糖苷、酯或盐作为活性成分；以及含有BCRP抑制剂和可作为BCRP底物的抗癌剂的抗癌剂。