4-[(2,4-difluorobenzyl)oxy]-3-methoxybenzaldehyde | 883975-24-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[(2,4-difluorobenzyl)oxy]-3-methoxybenzaldehyde
• 英文别名: 4-[(2,4-Difluorophenyl)methoxy]-3-methoxybenzaldehyde
• CAS: 883975-24-4
• 化学式: C₁₅H₁₂F₂O₃
• 分子量: 278.255
• InChiKey: YHWOKYUMCYFSSO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[(2,4-difluorobenzyl)oxy]-3-methoxybenzaldehyde 在 吡啶 、 氧气 、 铜 、 氯化铵 作用下， 反应 24.0h， 生成 4-[(2,4-Difluorophenyl)methoxy]-3-methoxybenzonitrile
  参考文献：
  名称：

  2-芳基-1，2，2，4-三唑并[1，5-a]吡啶衍生物的合成及抗肿瘤活性。

  摘要：

  合成了一系列新颖的2-芳基-1,2,4-三唑并[1,5-a]吡啶衍生物，并评估了它们在体外对人卵巢癌细胞系（HO-8910）和人肝癌的细胞毒活性。细胞系（贝尔7402）。与顺铂相比，大多数化合物对癌细胞系表现出高或中等活性。测试了其中两个在Bel 7402上的凋亡。

  DOI：

  10.2174/157340610791321505
• 作为产物：
  描述：

  2,4-二氟氯苄 、 香草醛 在 potassium carbonate 、 potassium iodide 作用下， 以 丙酮 为溶剂， 生成 4-[(2,4-difluorobenzyl)oxy]-3-methoxybenzaldehyde
  参考文献：
  名称：

  喹唑啉衍生物作为选择性CYP1B1抑制剂。

  摘要：

  CYP1B1与乳腺癌，卵巢癌，肾癌，皮肤癌和肺癌的发生有关。有人提出，确定有效的和特定的CYP1B1抑制剂可以导致癌症的新治疗。类黄酮具有紧密的刚性骨架，可以精确地装配在CYP1B1的结合腔内。用“ N”原子对类黄酮“ O”原子进行系统等位取代，导致预测“喹唑啉”骨架可能是设计潜在CYP1B1抑制剂的基础。合成了总共20种喹唑啉类似物，并在Sacchrosomes™中筛选了CYP1B1和CYP1A1抑制作用。六种具有抑制CYP1B1能力的化合物的IC50测定结果表明，喹唑啉5c和5h是CYP1B1抑制作用的最佳候选者，IC50值在nM范围内。属于CYP1，CYP2和CYP3酶家族的同源CYP的进一步选择性研究表明，这些化合物可能没有关键的药物相互作用。进行分子建模研究以合理化所观察到的酶促抑制作用。对具有CYP1A1和CYP1B1酶的活酵母和人细胞的进一步生物学研究表明，最有效的化合物具有

  DOI：

  10.1016/j.ejmech.2017.02.032

文献信息

• Substituted Benzyloxy-Phenylmethylamide Derivatives
  申请人：Lampe Thomas

  公开号：US20080214654A1

  公开（公告）日：2008-09-04

  The present invention relates to novel substituted benzyloxy-phenylmethylamide derivatives, processes for their preparation, and their use in medicaments, especially for the prophylaxis and treatment of diseases associated with Cold Menthol Receptor 1 (CMR-1) activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor oeractivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD).

  本发明涉及新型取代苯氧基苯甲酰胺衍生物、其制备方法以及它们在药物中的应用，特别是用于预防和治疗与冷薄荷受体1（CMR-1）活性相关的疾病，特别是用于治疗泌尿系统疾病或障碍，如膀胱过度活动（过度活动的膀胱）、尿失禁、神经原性膀胱过度活动（膀胱过度活动）、特发性膀胱过度活动（膀胱不稳定）、良性前列腺增生和下尿路症状；慢性疼痛、神经病性疼痛、术后疼痛、类风湿性关节炎疼痛、神经痛、神经病、疼痛、神经损伤、缺血、神经退行性疾病、中风和哮喘以及慢性阻塞性肺（或气道）疾病（COPD）等炎症性疾病。
• Cink4T, a quinazolinone-based dual inhibitor of Cdk4 and tubulin polymerization, identified via ligand-based virtual screening, for efficient anticancer therapy
  作者：Vinay Sonawane、Mohd Usman Mohd Siddique、Surender Singh Jadav、Barij Nayan Sinha、Venkatesan Jayaprakash、Bhabatosh Chaudhuri

  DOI：10.1016/j.ejmech.2019.01.011

  日期：2019.3

  Inhibition of cyclin dependent kinase 4 (Cdk4) prevents cancer cells from entering the early G(0)/G(1) phase of the cell division cycle whereas inhibiting tubulin polymerization blocks cancer cells' ability to undergo mitosis (M) late in the cell cycle. We had reported earlier that two non-planar and relatively non-toxic fascaplysin derivatives, an indole and a tryptoline, inhibit Cdk4 with IC50 values of 6.2 and 10 mu M, respectively. Serendipitously, we had also found that they inhibited tubulin polymerization. The molecules were efficacious in mouse tumor models. We have now identified Cink4T in a 59-compound quinazolinone library, designed on the basis of ligand-based virtual screening, as a compound that inhibits Cdk4 and tubulin. Its IC50 value for Cdk4 inhibition is 0.47 mu M and >50 mu M for inhibition of Cdk1, Cdk2, Cdk6, Cdk9. Cink4T inhibits tubulin polymerization with an IC50 of 0.6 mu M. Molecular modelling studies on Cink4T with Cdk4 and tubulin crystal structures lend support to these observations. Cancer cell cycle analyses confirm that Cink4T blocks cells at both G(0)/G(1) and M phases as it should if it were to inhibit both Cdk4 and tubulin polymerization. Our results show, for the very first time, that virtual screening can be used to design novel inhibitors that can potently block two crucial phases of the cell division cycle. (C) 2019 Elsevier Masson SAS. All rights reserved.
• [EN] SUBSTITUDED BENZYLOXY-PHENYLMETHYLUREA DERIVATIVES<br/>[FR] DÉRIVÉS DE BENZYLOXYPHÉNYLMÉTHYLURÉE SUBSTITUÉS
  申请人：BAYER HEALTHCARE AG

  公开号：WO2007080109A1

  公开（公告）日：2007-07-19

  [EN] The present invention relates to novel substituted benzyloxy-phenylmethylurea derivatives, processes for their preparation, and their use in medicaments, especially for the prophylaxis and treatment of diseases associated with Cold Menthol Receptor 1 (CMR-1) activity, in particular for the treatment of urological diseases or disorders, such as detrusor overactivity (overactive bladder), urinary incontinence, neurogenic detrusor oeractivity (detrusor hyperflexia), idiopathic detrusor overactivity (detrusor instability), benign prostatic hyperplasia, and lower urinary tract symptoms; chronic pain, neuropathic pain, postoperative pain, rheumatoid arthritic pain, neuralgia, neuropathies, algesia, nerve injury, ischaemia, neurodegeneration, stroke, and inflammatory disorders such as asthma and chronic obstructive pulmonary (or airways) disease (COPD).
  [FR] La présente invention concerne de nouveaux dérivés de benzyloxyphénylméthylurée substitués, des procédés pour leur préparation et leur utilisation dans des médicaments, notamment pour la prévention et le traitement de maladies associées à l'activité du récepteur 1 du menthol froid (CMR-1), en particulier pour le traitement de maladies ou de troubles urologiques tels que l'hyperactivité du détrusor (vessie hyperactive), l'incontinence urinaire, l'hyperactivité neurogène du détrusor (hyperflexie du détrusor), l'hyperactivité idiopathique du détrusor (instabilité du détrusor), l'hyperplasie prostatique bénigne et les symptômes du système urinaire inférieur ; la douleur chronique, la douleur neuropathique, la douleur post-opératoire, la douleur liée à la polyarthrite rhumatoïde, la névralgie, les neuropathies, l'algésie, les lésions nerveuses, l'ischémie, la neurodégénérescence, l'accident vasculaire cérébral et des troubles inflammatoires tels que l'asthme et la broncho-pneumopathie chronique obstructive (BPCO).
• Quinazoline derivatives as selective CYP1B1 inhibitors
  作者：Mohd Usman Mohd Siddique、Glen J.P. McCann、Vinay R. Sonawane、Neill Horley、Linda Gatchie、Prashant Joshi、Sandip B. Bharate、Venkatesan Jayaprakash、Barij N. Sinha、Bhabatosh Chaudhuri

  DOI：10.1016/j.ejmech.2017.02.032

  日期：2017.4

  potent and specific CYP1B1 inhibitors can lead to a novel treatment of cancer. Flavonoids have a compact rigid skeleton which fit precisely within the binding cavity of CYP1B1. Systematic isosteric replacement of flavonoid 'O' atom with 'N' atom led to the prediction that a 'quinazoline' scaffold could be the basis for designing potential CYP1B1 inhibitors. A total of 20 quinazoline analogs were synthesized

  CYP1B1与乳腺癌，卵巢癌，肾癌，皮肤癌和肺癌的发生有关。有人提出，确定有效的和特定的CYP1B1抑制剂可以导致癌症的新治疗。类黄酮具有紧密的刚性骨架，可以精确地装配在CYP1B1的结合腔内。用“ N”原子对类黄酮“ O”原子进行系统等位取代，导致预测“喹唑啉”骨架可能是设计潜在CYP1B1抑制剂的基础。合成了总共20种喹唑啉类似物，并在Sacchrosomes™中筛选了CYP1B1和CYP1A1抑制作用。六种具有抑制CYP1B1能力的化合物的IC50测定结果表明，喹唑啉5c和5h是CYP1B1抑制作用的最佳候选者，IC50值在nM范围内。属于CYP1，CYP2和CYP3酶家族的同源CYP的进一步选择性研究表明，这些化合物可能没有关键的药物相互作用。进行分子建模研究以合理化所观察到的酶促抑制作用。对具有CYP1A1和CYP1B1酶的活酵母和人细胞的进一步生物学研究表明，最有效的化合物具有
• Synthesis and Antitumor Activity of 2-Aryl-1, 2, 4-Triazolo[1, 5-a] Pyridine Derivatives
  作者：Xuefen Tao、Yongzhou Hu

  DOI：10.2174/157340610791321505

  日期：2010.3.1

  A novel series of 2-aryl-1, 2, 4-triazolo [1, 5-a] pyridine derivatives have been synthesized and evaluated for their cytotoxic activities in vitro against Human ovarian cancer cell line (HO-8910) and Human liver cancer cell line (Bel 7402). Most compounds showed high or mediate activity against the cancer cell lines when compared with Cisplatin. Two of them were tested the apoptosis on Bel 7402.

  合成了一系列新颖的2-芳基-1,2,4-三唑并[1,5-a]吡啶衍生物，并评估了它们在体外对人卵巢癌细胞系（HO-8910）和人肝癌的细胞毒活性。细胞系（贝尔7402）。与顺铂相比，大多数化合物对癌细胞系表现出高或中等活性。测试了其中两个在Bel 7402上的凋亡。