5-(2-hydroxyphenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole | 58721-63-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 5-(2-hydroxyphenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole
• 英文别名: 2-[5-(4-methoxy-phenyl)-3,4-dihydro-2H-pyrazol-3-yl]-phenol；2-[3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-5-yl]phenol
• CAS: 58721-63-4
• 化学式: C₁₆H₁₆N₂O₂
• 分子量: 268.315
• InChiKey: BSDMXYPLVTZYAU-UHFFFAOYSA-N

物化性质

• 熔点：
  159-160 °C(Solv: methanol (67-56-1))
• 沸点：
  396.4±52.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  53.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(2-hydroxyphenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole 在 对甲苯磺酸 、 三乙胺 作用下， 以 二氯甲烷 、 氯仿 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成
  参考文献：
  名称：

  新型异烟肼-螺环吲哚衍生物：设计、合成、生物学评价、计算机 ADMET 预测和计算研究

  摘要：

  摘要 在目前的情况下，合成新的和理想的抗分枝杆菌药物对抵抗结核分枝杆菌 (MTB) 有着永恒的需求。设计和鉴定用于治疗结核病的新分子是有机和药物化学研究中的一项重要任务。在本研究中，我们报告了使用两种通用且重要的部分、异烟肼和螺吲哚衍生物组合所需化合物。一系列新型异烟肼-螺环吲哚杂化分子 (6a-6ao) 被设计、合成并通过各种光谱方法充分表征。我们已经评估了它们对结核分枝杆菌 H37Rv (MTB) 菌株和耐多药结核病的体外抗分枝杆菌活性。其中，与其他化合物相比，化合物 6ab 被发现是最有效的。将计算所有化合物的 ADMET 相关描述符，以预测用于选择有效和生物可利用化合物的药代动力学特性。此外，分子对接和分子动力学研究表明，所有化合物在耐异烟肼烯酰-ACP(COA)还原酶活性位点的结合模式，有助于建立抑制结核分枝杆菌的结构基础。

  DOI：

  10.1016/j.molstruc.2020.128881
• 作为产物：
  描述：

  1-(2-hydroxyphenyl)-3-(4-methoxyphenyl)-2-propen-1-one 在 盐酸肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以64%的产率得到5-(2-hydroxyphenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole
  参考文献：
  名称：

  Thakare, V. G.; Wadodkar, K. N., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1986, vol. 25, p. 610 - 612

  摘要：

  DOI：

文献信息

• Novel tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one: Design, synthesis, model and use as hMAO-B inhibitors
  作者：Rui Chen、Jie Xiao、Yong Ni、Han-Fei Xu、Min Zheng、Xu Tong、Tong-Tian Zhang、Chenzhong Liao、Wen-Jian Tang

  DOI：10.1016/j.bmc.2016.02.045

  日期：2016.4

  hMAO-A inhibitors, on which, the intramolecular cyclization led to a very interesting change of isoform selectivity. A series of selective hMAO-B inhibitors (3a–3u) with novel scaffold of tricyclic pyrazolo[1,5-d][1,4]benzoxazepin-5(6H)-one were designed and synthesized. Compound 3u (IC50 = 221 nM) exhibited the best inhibitory activity and isoform selectivity against hMAO-B, superior to selegiline (IC50 = 321 nM)

  基于我们最近报道的选择性hMAO-A抑制剂，分子内环化作用导致异构体选择性发生了非常有趣的变化。设计并合成了一系列具有新型三环吡唑并[1,5- d ] [1,4]苯并恶嗪-5（6 H）-支架的选择性hMAO-B抑制剂（3a - 3u）。化合物3u（IC 50  = 221 nM）表现出最佳的抑制活性和对hMAO-B的同工型选择性，优于司来吉兰（IC 50 ＝ 321nM），其是用于帕金森氏病的商业选择性hMAO-B抑制剂。模型研究表明，我们的化合物对hMAO-B的选择性取决于至少两个残基，即Ile 199和Cys 172（或对应于hMAO-A的Phe 208和Asn 181）。这些数据支持进一步的研究，以评估更有效的选择性hMAO-B抑制剂的合理设计。
• Spiro Derivatives of 1,10b-dihydro-5H-pyrazolo[1,5-c][1,3]-benzoxazines and their Antimicrobial, Anti-Inflammatory, and Antioxidant Activity
  作者：Lidiya Z. Mandzyuk、Vasyl S. Matiychuk、Taras I. Chaban、Olesya V. Bodnarchuk、Julia E. Matiychuk、Mykola D. Obushak

  DOI：10.1007/s10593-020-02842-x

  日期：2020.11

  The reaction of 2-(3-aryl-4,5-dihydro-1H-pyrazol-5-yl)phenols with cyclopentanone, cyclohexanone, or 4-methylcyclohexanone gave spiro derivatives of 1,10b-dihydropyrazolo[1,5-c][1,3]benzoxazines. The antimicrobial, anti-inflammatory, and antioxidant activities of these compounds were studied. A compound with a high antimicrobial activity against S. aureus ATCC 43300, together with compounds possessing an anti-inflammatory effect superior to the reference drug diclofenac, as well as high antioxidant activity, were identified.

  2-(3-芳基-4,5-二氢-1H-吡唑-5-基)酚与环戊酮、环己酮或4-甲基环己酮的反应生成了1,10b-二氢吡唑[1,5-c][1,3]苯并噁嗪的螺旋衍生物。研究了这些化合物的抗菌、抗炎和抗氧化活性。鉴定出一种对金黄色葡萄球菌 ATCC 43300 具有高抗菌活性的化合物，以及一些抗炎效果优于参考药物双氟氯噻吨和具有高抗氧化活性的化合物。
• Anthocyanidins and related compounds—XVII
  作者：L. Jurd

  DOI：10.1016/0040-4020(75)80304-8

  日期：1975.1

  Flavylium salts and 2-hydroxychalcones (1-phenyl-3-(2-hydroxyphenyl)-2-propen-1-ones) react with hydroxylamine in pyridine to form 2,5-dihydroisoxazoles. These undergo thermal and acid-catalyzed rearrangements to isomeric 4,5-dihydroisoxazoles and chalcone oximes, respectively. With hydrazine, flavylium salts yield phenolic 4,5-dihydro-3,5-diphenyl-1H-pyrazoles. Since these readily condense with acetone

  黄酮盐和2-羟基查耳酮（1-苯基-3-（2-羟基苯基）-2-丙烯-1-酮）与吡啶中的羟胺反应形成2,5-二氢异恶唑。它们分别进行热和酸催化重排，分别形成异构体4,5-二氢异恶唑和查尔酮肟。黄酮盐与肼一起产生酚类4,5-二氢-3,5-二苯基-1H-吡唑。由于这些很容易与丙酮缩合形成环丙酮化物，因此酰化反应涉及在黄酮核的2位发生最初的亲核攻击。
• Multi-Targeting Anticancer Activity of a New 4-Thiazolidinone Derivative with Anti-HER2 Antibodies in Human AGS Gastric Cancer Cells
  作者：Agnieszka Gornowicz、Roman Lesyk、Robert Czarnomysy、Serhii Holota、Yulia Shepeta、Bożena Popławska、Magdalena Podolak、Wojciech Szymanowski、Krzysztof Bielawski、Anna Bielawska

  DOI：10.3390/ijms24076791

  日期：——

  Combining chemotherapy with immunotherapy still remains a regimen in anticancer therapy. Novel 4-thiazolidinone-bearing hybrid molecules possess well-documented anticancer activity, and together with anti-HER2 antibodies, may represent a promising strategy in treating patients with gastric cancer with confirmed human epidermal growth factor receptor 2 (HER2) expression. The aim of the study was to synthesize a new 4-thiazolidinone derivative (Les-4367) and investigate its molecular mechanism of action in combination with trastuzumab or pertuzumab in human AGS gastric cancer cells. AGS cell viability and antiproliferative potential were examined. The effect of the tested combinations as well as monotherapy on apoptosis and autophagy was also determined. Metalloproteinase-2 (MMP-2), intercellular adhesion molecule 1 (ICAM-1), pro-inflammatory and anti-inflammatory cytokine concentrations were also demonstrated by the ELISA technique. We proved that pertuzumab and trastuzumab were very effective in increasing the sensitivity of AGS gastric cancer cells to novel Les-4367. The molecular mechanism of action of the tested combination is connected with the induction of apoptosis. Additionally, the anticancer activity is not associated with the autophagy process. Decreased concentrations of pro-inflammatory cytokines, MMP-2 and ICAM-1—were observed. The novel combination of drugs based on anti-HER2 antibodies with Les-4367 is a promising strategy against AGS gastric cancer cells.

  化疗与免疫疗法相结合仍然是抗癌治疗的一种方案。新型 4-噻唑烷酮杂交分子具有公认的抗癌活性，与抗 HER2 抗体一起可能是治疗已证实有人类表皮生长因子受体 2（HER2）表达的胃癌患者的一种有前途的策略。本研究的目的是合成一种新的 4-噻唑烷酮衍生物（Les-4367），并研究其与曲妥珠单抗或百妥珠单抗联用在人 AGS 胃癌细胞中的分子作用机制。研究考察了 AGS 细胞的活力和抗增殖潜力。此外，还测定了所测试的组合疗法和单一疗法对细胞凋亡和自噬的影响。此外，还通过 ELISA 技术检测了金属蛋白酶-2（MMP-2）、细胞间粘附分子 1（ICAM-1）、促炎和抗炎细胞因子的浓度。我们证明，百妥珠单抗和曲妥珠单抗能有效提高 AGS 胃癌细胞对新型 Les-4367 的敏感性。测试组合的分子作用机制与诱导细胞凋亡有关。此外，抗癌活性与自噬过程无关。此外，还观察到促炎细胞因子、MMP-2 和 ICAM-1 的浓度有所降低。基于抗HER2抗体的药物与Les-4367的新型组合是一种治疗AGS胃癌细胞的有效策略。
• Design and synthesis of novel 2-pyrazoline-1-ethanone derivatives as selective MAO inhibitors
  作者：Xu Tong、Rui Chen、Tong-Tian Zhang、Yan Han、Wen-Jian Tang、Xin-Hua Liu

  DOI：10.1016/j.bmc.2014.12.010

  日期：2015.2

  Thirty seven novel 2-pyrazoline-1-ethanone derivatives were designed, synthesized and evaluated as selective hMAO inhibitors. Among them, compounds 7h (IC50 = 2.40 mu M) and 12c (IC50 = 2.00 mu M) exhibited best inhibitory activity and selectivity against hMAO-A, surpassing that of the positive control Clorgyline (IC50 = 2.76 mu M). Based on selective activity of hMAO-A, SAR analysis showed that the order of N1 substituent contribution was bromo (3) > piperidinyl (4) > morpholinyl (5) > imidazolyl (6), and compounds with electron-withdrawing substituents (-F, -Cl) at C3 or C5 phenyl ring of 2-pyrazoline nucleus dedicated stronger MAO-A inhibitory activity. Molecular docking showed that compounds 7h and 12c were nicely bound to hMAO-A via two hydrogen bonds (SER209, GLU216), one Pi-Pi interaction and three hydrogen bonds (SER209, GLU216, TYR69), one Sigma-Pi interaction, respectively. In addition, the substituent at C3 position of 2-pyrazoline with the N1 acetyl has little effect on MAO-A inhibitory activity. These data support further studies to assess rational design of more efficiently selective hMAO inhibitors in the future. (C) 2014 Elsevier Ltd. All rights reserved.