2-乙基-1,3-二(4-甲氧基苯基)-1,3-丙烷二酮 | 71526-44-8

• 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
• 中文名称: 2-乙基-1,3-二(4-甲氧基苯基)-1,3-丙烷二酮
• 英文名称: 1,3-bis(4-methoxyphenyl)-2-ethyl-propane-1,3-dione
• 英文别名: 2-ethyl-1,3-bis(4-methoxyphenyl)propane-1,3-dione；1,3-bis(4-methoxyphenyl)-2-ethylpropane-1,3-dione
• CAS: 71526-44-8
• 化学式: C₁₉H₂₀O₄
• mdl: MFCD05667195
• 分子量: 312.365
• InChiKey: ADOUYSBKSXTAMH-UHFFFAOYSA-N

物化性质

• 熔点：
  65 °C
• 沸点：
  478.1±30.0 °C(Predicted)
• 密度：
  1.122±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  52.6
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2914509090

反应信息

• 作为反应物：
  描述：

  2-乙基-1,3-二(4-甲氧基苯基)-1,3-丙烷二酮 在 copper(l) iodide 、 溶剂黄146 、 L-脯氨酸 、 potassium hydroxide 作用下， 以 乙二醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.0h， 生成 3-ethyl-1,2,4-tris(4-methoxyphenyl)-1H-pyrrole
  参考文献：
  名称：

  C3 / C5-烷基1,2,4-三芳基吡咯作为雌激素受体配体的合成及氧化降解研究

  摘要：

  在这项研究中，我们合成了1,2,4-三芳基吡咯作为雌激素受体（ER）的配体。制备了两个带有C3-烷基或C3 / C5-二烷基残基的吡咯系列。这两个系列的化合物都易于氧化降解，二烷基化化合物（t 1/2 = 33–66 h）的程度高于其单烷基化同类物（t 1/2 = 140–211 h）。然而，稳定性足以确定体外ER结合亲和力。在激素依赖性，ERα阳性的MCF-7 / 2a和U2-OS /α细胞中最活跃的激动剂是1,2,4-三（4-羟苯基）-3-丙基-1 H-吡咯（6 d） （MCF-7 / 2a：EC 50 = 70 n M ; U2-OS /α：EC 50 = 1.6 nM）。在U2-OS /β细胞中相应的无活性表现出较高的ERα选择性。在使用雌二醇（E2）以及纯化的hERα和hERβ蛋白的竞争实验中证实了这种趋势（计算6 d的相对结合亲和力（RBA）：RBA（ERα）= 1.85％； RBA（ERβ）<0

  DOI：

  10.1002/cmdc.201000537
• 作为产物：
  描述：

  4'-甲氧基苯丁酮 以 [(CH3)2Si]2NLi 为溶剂， 生成 2-乙基-1,3-二(4-甲氧基苯基)-1,3-丙烷二酮
  参考文献：
  名称：

  Estrogen receptor modulators

  摘要：

  除了描述了调节雌激素受体的吡唑化合物外，还提供了用于治疗或预防雌激素受体介导疾病的方法和组合物。已发现所描述的化合物在调节雌激素受体活性方面具有意想不到和令人惊讶的活性。因此，本发明的化合物在预防或治疗雌激素受体介导的疾病，如骨质疏松症、乳腺和子宫内膜癌、动脉粥样硬化和阿尔茨海默病方面具有实用价值。

  公开号：

  US06291505B1

文献信息

• Base-free two-step synthesis of 1,3-diketones and β-ketoesters from α-diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes
  作者：Miguel A. Sanchez-Carmona、David A. Contreras-Cruz、Luis D. Miranda

  DOI：10.1039/c1ob05150d

  日期：——

  We describe a convergent, base-free two-step synthesis of 1,3-diketones and β-ketoesters from α-diazocarbonyl compounds, trialkylboranes, and aromatic aldehydes in a three-component process. The synthetic potential of this protocol was underscored by the synthesis of several symmetrical 1,3,5-triaryl-4-alkyl and 1,3,4,5-tetraryl substituted pyrazoles in a three-step sequence.

  我们描述了一种收敛的无基团两步合成方法，通过三组分反应从α-二氮碳酰化合物、三烷基硼烷和芳香醛合成1,3-二酮和β-酮酯。这一合成方法的潜力在于能够在三步反应中合成多种对称的1,3,5-三芳基-4-烷基和1,3,4,5-四芳基取代的吡唑。
• ESTROGEN RECEPTOR MODULATORS
  申请人：Chiron Corporation

  公开号：US20040034081A9

  公开（公告）日：2004-02-19

  Estrogen receptor-modulating pyrazole compounds are described in addition to methods and compositions for treating or preventing estrogen receptor-mediated disorders. The compounds described have been found to have unexpected and surprising activity in modulating estrogen receptor activity. Thus, the compounds of the present invention have utility in preventing or treating estrogen receptor-mediated disorders such as osteoporosis, breast and endometrial cancers, atherosclerosis, and Alzheimer's disease.

  本文描述了调节雌激素受体的吡唑类化合物，以及用于治疗或预防雌激素受体介导的疾病的方法和组合物。所述化合物已被发现具有意外和惊人的调节雌激素受体活性的活性。因此，本发明的化合物在预防或治疗雌激素受体介导的疾病，如骨质疏松症、乳腺和子宫内膜癌、动脉粥样硬化和阿尔茨海默病中具有实用价值。
• Triarylpyrazoles with basic side chains
  作者：Shaun R Stauffer、Ying R Huang、Zachary D Aron、Christopher J Coletta、Jun Sun、Benita S Katzenellenbogen、John A Katzenellenbogen

  DOI：10.1016/s0968-0896(00)00226-1

  日期：2001.1

  Recently, we developed a novel triaryl-substituted pyrazole ligand system that has high affinity for the estrogen receptor (ER) (Fink, B. E.; Mortenson, D. S.; Stauffer, S. R.; Aron, Z. D.; Katzenellenbogen, J. A. Chem. Biol. 1999, 6, 205). Subsequent work has shown that some analogues in this series are very selective for the ERT alpha. subtype in terms of binding affinity and agonist potency (Stauffer, S. R.; Coletta, C. J.; Tedesco, R.; Sun, J.; Katzenellenbogen, J. A. J. Med. Chem. 2000, submitted). We now investigate how this pyrazole ER agonist system might be converted into an antagonist or a selective estrogen receptor modifier (SERM) by incorporating a basic or polar side chain like those typically found in antiestrogens and known to be essential determinants of their mixed agonist/antagonist character. We selected an N-piperidinyl-ethyl chain as a first attempt, and introduced it at the four possible sites of substitution on the pyrazole core structure to determine the orientation that the pyrazole might adopt in the ER ligand binding pocket. Of these four, the C(5) piperidinyl-ethoxy-substituted pyrazole 5 had by far the highest affinity. Also, it bound to the ER subtype alpha (ER alpha) with 20-fold higher affinity than to ERP. In cell-based transcription assays, pyrazole 5 was an antagonist on both ER alpha and ER beta, and it was also more potent on ER alpha. Based on structure-binding affinity relationships and on molecular modeling studies of these pyrazoles in a crystal structure of the ER alpha -raloxifene complex, we propose that pyrazoles having a basic substituent on the C(5) phenyl group adopt a binding mode that is different from that of the pyrazole agonists that lack this group. The most favorable orientation appears to be one which places the N(1) phenol in the A-ring binding pocket so that the basic side chain can adopt an orientation similar to that of the basic side chain of raloxifene. (CV) 2000 Elsevier Science Ltd. All rights reserved.
• Pyrazole Ligands:  Structure−Affinity/Activity Relationships and Estrogen Receptor-α-Selective Agonists
  作者：Shaun R. Stauffer、Christopher J. Coletta、Rosanna Tedesco、Gisele Nishiguchi、Kathryn Carlson、Jun Sun、Benita S. Katzenellenbogen、John A. Katzenellenbogen

  DOI：10.1021/jm000170m

  日期：2000.12.1

  We have found that certain tetrasubstituted pyrazoles are high-affinity ligands for the estrogen receptor (ER) (Fink et al. Chem. Biol. 1999, 6, 205-219) and that one pyrazole is considerably more potent as an agonist on the ER alpha than on the ER beta subtype (Sun et al. Endocrinology 1999, 140, 800-804). To investigate what substituent pattern provides optimal ER binding affinity and the greatest enhancement of potency as an ER alpha -selective agonist, we prepared a number of tetrasubstituted pyrazole analogues with defined variations at certain substituent positions. Analysis of their binding affinity pattern shows that a C(4)-propyl substituent is optimal and that a p-hydroxyl group on the N(1)-phenyl group also enhances affinity and selectivity for ER alpha. The best compound in this series, a propylpyrazole triol (PPT, compound 4g), binds to ER alpha with high affinity (ca. 50% that of estradiol), and it has a 410-fold binding affinity preference for ER alpha. It also activates gene transcription only through ER alpha. Thus, this compound represents the first ER alpha -specific agonist. We investigated the molecular basis for the exceptional ER alpha binding affinity and potency selectivity of pyrazole 4g by a further study of structure-affinity relationships in this series and by molecular modeling. These investigations suggest that the pyrazole triols prefer to bind to ER alpha with their C(3)-phenol in the estradiol A-ring binding pocket and that binding selectivity results from differences in the interaction of the pyrazole core and C(4)-propyl group with portions of the receptor where ER alpha has a smaller residue than ER beta. These ER subtype-specific interactions and the ER subtype-selective ligands that can be derived from them should prove useful in defining those biological activities in estrogen target cells that can be selectively activated through ER alpha.
• Antiproliferative novel isoxazoles: Modeling, virtual screening, synthesis, and bioactivity evaluation
  作者：Evangelia Tzanetou、Sandra Liekens、Konstantinos M. Kasiotis、Georgia Melagraki、Antreas Afantitis、Nikolas Fokialakis、Serkos A. Haroutounian

  DOI：10.1016/j.ejmech.2014.05.011

  日期：2014.6

  A series of novel isoxazole derivatives were efficiently synthesized through the adaptation/modification of an in situ synthetic procedure for pyrazoles. All novel compounds were tested against four different cell lines to evaluate their antiproliferative activity. Based on the Hela cells results of this study and previous work, a classification model to predict the anti-proliferative activity of isoxazole and pyrazole derivatives was developed. Random Forest modeling was used in view of the development of an accurate and reliable model that was subsequently validated. A virtual screening study was then proposed for the design of novel active derivatives. Compounds 9 and 11 demonstrated significant cytostatic activity; the fused isoxazole derivative 18 and the virtually proposed compound 2v, were proved at least 10 times more potent as compared to compound 9, with IC50 values near and below 1 mu M. In conclusion, a new series of isoxazoles was exploited with some of them exhibiting promising cytostatic activities. Further studies on the substitution pattern of the isoxazole core can potentially provide compounds with cytostatic action at the nM scale. In this direction the in silica approach described herein can also be used to screen existing databases to identify derivatives with anticipated activity. (C) 2014 Elsevier Masson SAS. All rights reserved.