1-(3-chloro-5-methoxyphenyl)-2-(pyridin-4-yl)ethanone | 950525-41-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(3-chloro-5-methoxyphenyl)-2-(pyridin-4-yl)ethanone
• 英文别名: 1-(3-Chloro-5-methoxyphenyl)-2-pyridin-4-ylethanone
• CAS: 950525-41-4
• 化学式: C₁₄H₁₂ClNO₂
• 分子量: 261.708
• InChiKey: LWZBQQIAIDQUMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  39.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(3-chloro-5-methoxyphenyl)-2-(pyridin-4-yl)ethanone 在 copper(l) iodide 、 palladium 10% on activated carbon 、 氢气 、 potassium carbonate 、 一水合肼 、 L-脯氨酸 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 40.0h， 生成 1-(3-(3-(3-chloro-5-methoxyphenyl)-4-(pyridin-4-yl)-1H-pyrazol-1-yl)phenyl)-3-(3-(trifluoromethyl)phenyl)urea
  参考文献：
  名称：

  含吡唑的二芳基脲和二芳基酰胺的合成，体外抗增殖活性和激酶抑制作用

  摘要：

  设计并合成了二十种含吡唑的二芳基脲和二芳基酰胺。在美国NCI的58癌细胞系中测试了它们的体外抗增殖活性。二芳基脲衍生物1b-e和1g发挥最强的抗增殖活性。其中，具有3，5-双（三氟甲基）苯基末端环和连接在中心吡唑环上的3′-甲氧基-5′-氯苯基环的化合物1e是最有效的。其IC 50相对于大多数测试细胞系，该值在亚微摩尔范围内。在所有测试的细胞系中，它显示出比参比二芳基脲参考药物索拉非尼优越的功效。与非癌细胞相比，它对癌细胞的选择性也极高（针对RAW 264.7巨噬细胞的IC 50高于100μM）。在分子水平上，化合物1e选择性抑制V600E突变的B-RAF激酶（IC 50  = 0.39μM）。它还刺激RPMI-8226白血病细胞中的半胱天冬酶3/7酶（浓度为10μM时增加2.79倍，EC 50  = 1.52μM）。因此，化合物1e可能通过诱导细胞凋亡来杀死癌细胞。可以考虑将该有前途的候选物用于开发新的有效抗癌剂。

  DOI：

  10.1016/j.ejmech.2018.07.008
• 作为产物：
  描述：

  3-氯-5-甲氧基苯甲酸 在 乙酰氯 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 15.0h， 生成 1-(3-chloro-5-methoxyphenyl)-2-(pyridin-4-yl)ethanone
  参考文献：
  名称：

  三芳基吡唑类化合物的合成及其对RAW 264.7巨噬细胞中LPS诱导的NO和PGE 2产生的抑制作用

  摘要：

  摘要一氧化氮和前列腺素E 2产生的抑制是抗炎药开发领域中非常有趣的研究课题。在当前的研究中，合成了一系列新的1,3,4-三芳基吡唑衍生物，并评估了它们在脂多糖诱导的RAW 264.7巨噬细胞中抑制一氧化氮和前列腺素E 2产生的能力。在所有目标类似物中，分别具有苯基和3-（三氟甲基）苯基末端部分的二芳基脲羟基化合物1f和1h对前列腺素E 2的产生具有最高的抑制作用。。两种化合物在3 µM的浓度下均具有与参考化合物NS-398相同的活性。该作用是由于抑制环氧合酶2的酶活性而不是抑制环氧合酶2的蛋白表达。化合物1f对巨噬细胞中脂多糖诱导的前列腺素E 2产生的IC 50值为1.12μM。另外，具有脲连接基，羟基和3，5-双（三氟甲基）苯基末端环的化合物1j是最强的一氧化氮抑制剂。Western blot研究表明，它通过抑制诱导型一氧化氮合酶蛋白的表达发挥了这种作用。 图形概要

  DOI：

  10.1007/s00044-017-1923-9

文献信息

• Synthesis of 1H-Pyrazole-1-carboxamide Derivatives and Their Antiproliferative Activity against Melanoma Cell Line
  作者：Mohammed I. El-Gamal、Tae Bo Sim、Jun Hee Hong、Jung-Hyuck Cho、Kyung Ho Yoo、Chang-Hyun Oh

  DOI：10.1002/ardp.201000057

  日期：2011.3

  Synthesis of a new series of 1H‐pyrazole‐1‐carboxamide derivatives is described. Their antiproliferative activity against A375 human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The pharmacological results indicated that most of the newly synthesized compounds showed moderate activity against A375, compared with sorafenib. Among all of

  描述了一系列新的 1H - 吡唑 - 1 - 甲酰胺衍生物的合成。测试了它们对 A375 人黑色素瘤细胞系的抗增殖活性，并研究了替代物对二芳基吡唑支架的影响。药理结果表明，与索拉非尼相比，大多数新合成的化合物对 A375 表现出中等活性。在所有这些衍生物中，具有 N-甲基哌嗪基和酚基部分的化合物 IIe 对 A375 人黑色素瘤细胞系显示出最有效的抗增殖活性。
• Antiproliferative Diarylpyrazole Derivatives as Dual Inhibitors of the ERK Pathway and COX-2
  作者：Mohammed I. El-Gamal、Hong Seok Choi、Kyung Ho Yoo、Daejin Baek、Chang-Hyun Oh

  DOI：10.1111/cbdd.12186

  日期：2013.9

  A series of 3,4‐diarylpyrazole‐1‐carboxamide derivatives was designed and synthesized. A selected group of the target compounds was tested for in vitro antiproliferative activities over a panel of 60 cancer cell lines at the National Cancer Institute (NCI, Bethesda, MD, USA) at a single‐dose concentration of 10 μm, and the four most active compounds 9a, 9l, 9n, and 10o were further tested in a five‐dose testing mode to determine their IC50 values over the 60 cell lines. In addition, a selected group of target compounds were tested for inhibitory effect over cyclooxygenase isozymes. Compounds 9a, 9l, 9n, and 10o were also tested for MEK and ERK kinase inhibitory activity using Western blot assay. Compound 10o was selective toward melanoma cell line subpanel, and its antiproliferative activity may be attributed to selective cyclooxygenase‐2 inhibition and ERK pathway inhibition.
• [EN] PYRAZOLE COMPOUNDS<br/>[FR] PYRAZOLES
  申请人：PFIZER PROD INC

  公开号：WO2007105058A3

  公开（公告）日：2007-12-21
• Discovery of highly potent V600E-B-RAF kinase inhibitors: Molecular modeling study
  作者：Hamadeh Tarazi、Mohammed I. El-Gamal、Chang-Hyun Oh

  DOI：10.1016/j.bmc.2019.01.004

  日期：2019.2

  A series of 20 triarylpyrazole derivatives containing amide or urea linker have been synthesized. Their in vitro antiproliferative activity against NCI-60 cancer cell lines panel has been reported. Upon investigating the mechanism of action at molecular level, compound 1e showed selectivity and potency against V600E-B-RAF (IC50 = 390 nM). Herein, we decided to investigate the potency of the other nineteen target compounds against V600E-B-RAF. This led to discovery of several more potent compounds against that kinase. The IC50 values of compounds 1g-i and 2f-i were within the range of 7-47 nM. Among them, the diarylurea compound 1i was the most potent (IC50 = 7 nM). Results of docking and molecular dynamic analysis suggested the presence of consistent binding mode among our compound series with type-IIA class of inhibition pattern. Subsequently, the contribution of structural features to bioactivity were explored by means of QSAR analysis, where such effort led to the development of predictive QSAR model with significant statistical parameters (R-2 = 0.912, F = 38.64, Q(LOO)(2) = 0.834, Q(LMO)(2) = 0.816, s = 0.334). Furthermore, pharmacophoric features existed among our compound series were investigated employing molecular interaction field (MIF) analysis, which led to the development of partial least squares model consisted of four latent variables (4LV-PLS) with statistical parameters of (R(2)acc. = 0.98, Q(2)acc. = 0.81).
• PYRAZOLE COMPOUNDS
  申请人：Pfizer Products Inc.

  公开号：EP2024353A2

  公开（公告）日：2009-02-18