1-(4-chloro-3-methoxyphenyl)-2-(pyridin-4-yl)ethanone | 342435-01-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-chloro-3-methoxyphenyl)-2-(pyridin-4-yl)ethanone
• 英文别名: 1-(4-Chloro-3-methoxy-phenyl)-2-pyridin-4-yl-ethanone；1-(4-chloro-3-methoxyphenyl)-2-pyridin-4-ylethanone
• CAS: 342435-01-2
• 化学式: C₁₄H₁₂ClNO₂
• 分子量: 261.708
• InChiKey: BAZVCUKGXCALRS-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-(4-chloro-3-methoxyphenyl)-2-(pyridin-4-yl)ethanone 在 copper(l) iodide 、 potassium carbonate 、 L-脯氨酸 作用下， 以 二甲基亚砜 为溶剂， 反应 26.0h， 生成 4-[3-(4-chloro-3-methoxyphenyl)-1-(4-nitrophenyl)-1H-pyrazol-4-yl]pyridine
  参考文献：
  名称：

  New diarylureas and diarylamides containing 1,3,4-triarylpyrazole scaffold: Synthesis, antiproliferative evaluation against melanoma cell lines, ERK kinase inhibition, and molecular docking studies

  摘要：

  Synthesis of a new series of diarylureas and diarylamides possessing 1,3,4-triarylpyrazole scaffold is described. Their in vitro antiproliferative activities against 9 human melanoma cell lines were tested. Compounds 12, 13, 15, and 21-23 showed the highest potency against A375P melanoma cell line. In addition, compounds 10-15 and 19-24 showed high potency over the NCl 8 tested melanoma cell-lines panel. The IC50 values for compound 23 were 0.36 mu M and 0.84 mu M over LOX IMVI and M14 cell lines, respectively. Compounds 21 and 23 showed high, dose-dependent inhibition of ERK kinase. Virtual screening was carried out through docking of compound 21 into the domain of V600E-B-RAF and the binding mode was studied. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.08.013
• 作为产物：
  描述：

  2-氯-5-甲酚 在 吡啶 、 potassium permanganate 、 potassium carbonate 、 乙酰氯 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 水 、 丙酮 为溶剂， 反应 40.0h， 生成 1-(4-chloro-3-methoxyphenyl)-2-(pyridin-4-yl)ethanone
  参考文献：
  名称：

  Evaluation of the Inhibitory Effects of Pyridylpyrazole Derivatives on LPS-Induced PGE2 Productions and Nitric Oxide in Murine RAW 264.7 Macrophages

  摘要：

  一系列十三个三芳基吡唑类似物被研究作为抑制RAW 264.7巨噬细胞中脂多糖（LPS）诱导的前列腺素E2（PGE2）和一氧化氮（NO）产生的抑制剂。首先评估了目标化合物1a-m对RAW 264.7巨噬细胞的细胞毒性，以确定它们的非细胞毒浓度，用于抗炎测试，以确保PGE2和NO产生的抑制不是由细胞毒性引起的。发现化合物1f和1m是最有效的PGE2抑制剂，IC50值分别为7.1和1.1μM。此外，这些化合物还分别显示对LPS诱导的NO产生的抑制效果为11.6%和37.19%。COX-2和iNOS的免疫印迹分析显示，化合物1m的PGE2和NO抑制效应归因于通过抑制p38使COX-2和iNOS蛋白表达失活。

  DOI：

  10.3390/molecules26216489

文献信息

• Design, Synthesis, and Antiproliferative Activity of 3,4-Diarylpyrazole-1-carboxamide Derivatives Against Melanoma Cell Line
  作者：Mohammed I. El-Gamal、Hong Seok Choi、Hae-Guk Cho、Jun Hee Hong、Kyung Ho Yoo、Chang-Hyun Oh

  DOI：10.1002/ardp.201000375

  日期：2011.11

  Synthesis of a new series of 3,4‐diarylpyrazole‐1‐carboxamide derivatives is described. Their antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The biological results indicated that five synthesized compounds (Ig, Ii, IIc, IIg, and IIh) exhibited similar activity to Sorafenib. In addition, three

  描述了一系列新的 3,4-二芳基吡唑-1-甲酰胺衍生物的合成。测试了它们对 A375P 人黑色素瘤细胞系的抗增殖活性，并研究了取代基对二芳基吡唑支架的影响。生物学结果表明，五种合成化合物（Ig、Ii、IIc、IIg 和 IIh）表现出与索拉非尼相似的活性。此外，三种化合物（IIa、IIb 和 IIi）比索拉非尼更有效。在所有这些衍生物中，具有二甲氨基和酚部分的化合物 IIa 对 A375P 人黑色素瘤细胞系显示出最有效的抗增殖活性。通过将最有效的化合物 IIa 对接到 V600E-b-Raf 域中进行虚拟筛选，并研究了结合模式。
• Design, synthesis, <i>in vitro</i> potent antiproliferative activity, and kinase inhibitory effects of new triarylpyrazole derivatives possessing different heterocycle terminal moieties
  作者：Mahmoud M. Gamal El-Din、Mohammed I. El-Gamal、Mohammed S. Abdel-Maksoud、Kyung Ho Yoo、Chang-Hyun Oh

  DOI：10.1080/14756366.2019.1653292

  日期：2019.1.1

  triarylpyrazole derivatives having different heterocycle terminal groups have been designed and synthesised. Compounds 1h-j and 1l exhibited the highest mean percentage inhibition against the 58 cancer cell lines at a concentration of 10 μM, and thus were next examined in 5-dose testing mode to detect their IC50 value. The four compounds showed stronger antiproliferative activities upon comparing their

  已经设计并合成了具有不同杂环末端基团的一系列新的三芳基吡唑衍生物。化合物1h-j和1l在10μM的浓度下对58种癌细胞系表现出最高的平均抑制百分比，因此接下来在5剂量测试模式下进行检测以检测其IC50值。与索拉非尼作为参考化合物进行比较后，这四种化合物显示出更强的抗增殖活性。其中，在10μM浓度下，具有58个细胞系的化合物通过乙烯连接基具有N-乙基哌嗪基和N-苄基哌嗪基末端部分的化合物1j和1l显示出最大的平均抑制百分比值（分别为97.72和107.18％）。化合物1j在几种癌细胞系中的IC50值处于亚微摩尔级（0.26〜0.38μM）。而且，
• Imidazol-2-carboxamide derivatives as raf kinase inhibitors
  申请人：——

  公开号：US20030134837A1

  公开（公告）日：2003-07-17

  Compounds of the formula (I) wherein X is O, CH 2 , S or NH, or the moiety X—R 1 is hydrogen; V is CH or N; R 1 is hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, aryl, arylC 1-6 alkyl, heterocyclyl, hererocyclylC 1-6 alkyl, heteroaryl, or heteroarylC 1-6 alkyl any of which except hydrogen may be optionally substituted; R 2 and R 3 independently represent hydrogen, C 1-6 alkyl, C 3-7 cycloalkyl, aryl, arylC 1-6 alkyl, heteroaryl, heteroarylC 1-6 alkyl, heterocyclyl, or heterocyclylC 1-6 alkyl any one of which except hydrogen may be optionally substituted, or R 2 and R 3 together with the nitrogen atom to which they are attached form a 4- to 10-membered optionally substituted monocyclic or bicyclic ring; Ar is an aryl or heteroaryl ring either of which may be optionally substituted; one of X 1 and X 2 is N and the other is NR 4 , wherein R 4 is hydrogen, C 1-6 alkyl, or arylC 1-6 alkyl; or pharmaceutically acceptable salts thereof; their use as inhibitors of Raf kinases and pharmaceutical compositions containing them.

  化合物的公式（I），其中X为O，CH2，S或NH，或者X-R1基团为氢；V为CH或N；R1为氢，C1-6烷基，C3-7环烷基，芳基，芳基C1-6烷基，杂环基，杂环基C1-6烷基，杂芳基或杂芳基C1-6烷基，其中除氢外任何一种均可选择性地被取代；R2和R3独立地表示氢，C1-6烷基，C3-7环烷基，芳基，芳基C1-6烷基，杂芳基，杂芳基C1-6烷基，杂环基或杂环基C1-6烷基，其中除氢外任何一种均可选择性地被取代，或者R2和R3与它们所附着的氮原子一起形成一个4-至10-成员的可选择性取代的单环或双环环；Ar为芳基或杂芳基环，其中任何一个都可以选择性地被取代；X1和X2中的一个为N，另一个为NR4，其中R4为氢，C1-6烷基或芳基C1-6烷基；或其药学上可接受的盐；它们作为Raf激酶抑制剂的用途和含有它们的制药组合物。
• Imidazol derivatives as Raf kinase inhibitors
  申请人：SmithKline Beecham p.l.c.

  公开号：US07235658B2

  公开（公告）日：2007-06-26

  Compounds of formula (I): wherein X is O, CH2, S or NH, or the moiety X—R1 is hydrogen; V is CH or N; R1 is hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl, arylC1-6alkyl, heterocyclyl, heterocyclylC1-6alkyl, heteroaryl, or heteroarylC1-6alkyl any of which except for hydrogen may be optionally substituted; R2 and R3 independently represent optionally substituted C1-6alkyl, or R2 and R3 together with the carbon atom to which they are attached form an optionally substituted C3-7cycloalkyl or C3-7cycloalkenyl ring; or R2 and R3 together with the carbon atom to which they are attached form an optionally substituted 5 to 7-membered heterocyclyl ring containing up to 3 heteroatoms selected from N, O, S.R4 and R5 independently represent hydrogen, C1-6alkyl, C3-7cycloalkyl, aryl, arylC1-6alkyl, heteroaryl, heteroarylC1-6alkyl, heterocyclyl, or heterocyclylC1-6alkyl, any of which except for hydrogen may be optionally substituted or R4 and R5 together with the nitrogen atom to which they are attached form 4- to 8-membered ring; Ar is an aryl or heteroaryl ring either of which may be optionally substituted; one of X1 and X2 is N and the other is NR6, wherein R6 is hydrogen, C1-6alkyl, or arylC1-6alkyl or pharmaceutically acceptable salts thereof, their use as inhibitors of Raf kinases, and pharmaceutical compositions containing them.

  化合物的式子（I）： 其中， X为O，CH2，S或NH，或者X-R1是氢； V为CH或N； R1为氢，C1-6烷基，C3-7环烷基，芳基，芳基C1-6烷基，杂环基，杂环基C1-6烷基，杂芳基或杂芳基C1-6烷基，除氢外任何一种都可以选择性地被取代； R2和R3独立地表示选择性取代的C1-6烷基，或者R2和R3与它们所附着的碳原子一起形成一个选择性取代的C3-7环烷基或C3-7环烯基环；或者R2和R3与它们所附着的碳原子一起形成一个选择性取代的5到7成员的杂环烷基环，其中含有最多3个从N，O，S中选择的杂原子。 R4和R5独立地表示氢，C1-6烷基，C3-7环烷基，芳基，芳基C1-6烷基，杂芳基，杂芳基C1-6烷基，杂环基或杂环基C1-6烷基，除氢外任何一种都可以选择性地被取代，或者R4和R5与它们所附着的氮原子一起形成4到8成员的环； Ar是芳基或杂芳基环，任意一种都可以选择性地被取代； X1和X2中的一个是N，另一个是NR6，其中R6是氢，C1-6烷基或芳基C1-6烷基； 或其药学上可接受的盐，它们用作Raf激酶的抑制剂，以及含有它们的制药组合物。
• Compounds
  申请人：SmithKline Beecham p.l.c.

  公开号：US07026336B1

  公开（公告）日：2006-04-11

  Compounds of formula (I) wherein X is O, CH2, S or NH, or the moiety X—R1 is hydrogen; V is CH or N; Y is NR10R11, NR10C(Z)NR10R11, NR10COOR11 or NR10SO2R11; Ar is phenyl or a 5- or 6-membered heteroaryl ring either of which may be optionally substituted; n is 0, 1, 2, 3 or 4; and R1, R2, R3, R4, R10 and R11 have the meanings given in the description; and pharmaceutically acceptable salt thereof.

  化合物的公式（I），其中X为O，CH2，S或NH，或者X-R1基团为氢；V为CH或N；Y为NR10R11，NR10C（Z）NR10R11，NR10COOR11或NR10SO2R11；Ar为苯基或5或6成员的杂环，其中任何一个都可以选择性地被取代；n为0，1，2，3或4；R1，R2，R3，R4，R10和R11具有描述中给出的含义；以及其药学上可接受的盐。