3-chloro-4-(p-tolyloxy)aniline | 56966-55-3

• 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: 3-chloro-4-(p-tolyloxy)aniline
• 英文别名: 3-Chloro-4-(4-methylphenoxy)aniline
• CAS: 56966-55-3
• 化学式: C₁₃H₁₂ClNO
• mdl: MFCD00459648
• 分子量: 233.697
• InChiKey: DDTQHROTTBWWTI-UHFFFAOYSA-N

物化性质

• 沸点：
  348.9±37.0 °C(Predicted)
• 密度：
  1.226±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  35.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chloro-4-(p-tolyloxy)aniline 、 3,5-二氯-2-羟基苯甲酰氯 在 苯酐 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 3,5-dichloro-N-(3-chloro-4-(p-tolyloxy)phenyl)-2-hydroxybenzamide
  参考文献：
  名称：

  Discovery and Structure–Activity Relationships of Modified Salicylanilides as Cell Permeable Inhibitors of Poly(ADP-ribose) Glycohydrolase (PARG)

  摘要：

  The metabolism of poly(ADP-ribose) (PAR) in response to DNA strand breaks, which involves the concerted activities of poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolase (PARG), modulates cell recovery or cell death depending upon the level of DNA damage. While PARP inhibitors show high promise in clinical trials because of their low toxicity and selectivity for BRCA related cancers, evaluation of the therapeutic potential of PARG is limited by the lack of well-validated cell permeable inhibitors. In this study, target-related affinity profiling (TRAP), an alternative to high-throughput screening, was used to identify a number of druglike compounds from several chemical classes that demonstrated PARG inhibition in the low-micromolar range. A number of analogues of one of the most active chemotypes were synthesized to explore the structure activity relationship (SAR) for that series. This led to the discovery of a putative pharmacophore for PARG inhibition that contains a modified salicylanilide structure. Interestingly, these compounds also inhibit PARP-1, indicating strong homology in the active sites of PARG and PARP-1 and raising a new challenge for development of PARG specific inhibitors. The cellular activity of a lead inhibitor was demonstrated by the inhibition of both PARP and PARG activity in squamous cell carcinoma cells, although preferential inhibition of PARG relative to PARP was observed. The ability of inhibitors to modulate PAR metabolism via simultaneous effects on PARPs and PARG may represent a new approach for therapeutic development.

  DOI：

  10.1021/jm200325s
• 作为产物：
  描述：

  1-溴-2-氯-4-硝基苯 在 caesium carbonate 、 tin(ll) chloride 作用下， 以 乙醇 、 甲苯 为溶剂， 生成 3-chloro-4-(p-tolyloxy)aniline
  参考文献：
  名称：

  Discovery and Structure–Activity Relationships of Modified Salicylanilides as Cell Permeable Inhibitors of Poly(ADP-ribose) Glycohydrolase (PARG)

  摘要：

  The metabolism of poly(ADP-ribose) (PAR) in response to DNA strand breaks, which involves the concerted activities of poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolase (PARG), modulates cell recovery or cell death depending upon the level of DNA damage. While PARP inhibitors show high promise in clinical trials because of their low toxicity and selectivity for BRCA related cancers, evaluation of the therapeutic potential of PARG is limited by the lack of well-validated cell permeable inhibitors. In this study, target-related affinity profiling (TRAP), an alternative to high-throughput screening, was used to identify a number of druglike compounds from several chemical classes that demonstrated PARG inhibition in the low-micromolar range. A number of analogues of one of the most active chemotypes were synthesized to explore the structure activity relationship (SAR) for that series. This led to the discovery of a putative pharmacophore for PARG inhibition that contains a modified salicylanilide structure. Interestingly, these compounds also inhibit PARP-1, indicating strong homology in the active sites of PARG and PARP-1 and raising a new challenge for development of PARG specific inhibitors. The cellular activity of a lead inhibitor was demonstrated by the inhibition of both PARP and PARG activity in squamous cell carcinoma cells, although preferential inhibition of PARG relative to PARP was observed. The ability of inhibitors to modulate PAR metabolism via simultaneous effects on PARPs and PARG may represent a new approach for therapeutic development.

  DOI：

  10.1021/jm200325s

文献信息

• New thieno[2,3‐<scp><i>d</i></scp>]pyrimidine derivatives as <scp>EGFR^WT</scp> and <scp>EGFR^T790M</scp> inhibitors: Design, synthesis, antiproliferative activities, docking studies, <scp>ADMET</scp>, toxicity, <scp>MD</scp> simulation studies
  作者：Eman A. Sobh、Mohammed A. Dahab、Eslam B. Elkaeed、Bshra A. Alsfouk、Ibrahim M. Ibrahim、Ahmed M. Metwaly、Ibrahim H. Eissa

  DOI：10.1002/jhet.4757

  日期：2024.2

  A series of thieno[2,3‐d]pyrimidines were designed and synthesized as epidermal growth factor receptor (EGFR) inhibitors. These compounds were tested for their ability to inhibit MCF‐7 and A549 cancer cells. The most active compound, 12c, inhibited the growth of both cell lines, with IC₅₀ values of 15.67 and 12.16 μM, respectively. It was found that 12c had inhibitory effects on both EGFR^WT and EGFR^T790M isoforms, with inhibitory partialities of 37.50 and 148.90 nM, respectively. Additionally, 12c was found to be safer than erlotinib against normal cell lines (IC₅₀ = 38.61 μM). Compound 12c induced early and late apoptosis in A549 cells and arrested cell growth at G1 and G2/M phases. 12c was also found to increase caspases 3 and 8 ratios. Molecular docking indicated the correct binding modes of the synthesized compounds. MD simulations, MM‐GBSA, and PLIP studies confirmed the precise binding of 12c to the EGFR protein over 100 ns.

  摘要 设计并合成了一系列噻吩并[2,3-d]嘧啶类表皮生长因子受体（EGFR）抑制剂。对这些化合物抑制 MCF-7 和 A549 癌细胞的能力进行了测试。活性最强的化合物 12c 可抑制这两种细胞株的生长，其 IC50 值分别为 15.67 和 12.16 μM。研究发现，12c对表皮生长因子受体WT和表皮生长因子受体T790M两种异构体都有抑制作用，抑制偏度分别为37.50和148.90 nM。此外，研究发现 12c 对正常细胞株的抑制作用（IC50 = 38.61 μM）比厄洛替尼更安全。化合物 12c 可诱导 A549 细胞早期和晚期凋亡，并阻止细胞在 G1 和 G2/M 期生长。研究还发现 12c 能提高 caspases 3 和 8 的比例。分子对接表明合成的化合物具有正确的结合模式。MD 模拟、MM-GBSA 和 PLIP 研究证实 12c 与表皮生长因子受体蛋白的结合时间超过 100 ns。
• PICOLINAMIDE DERIVATIVES AND PEST CONTROLLERS CONTAINING THE SAME AS THE ACTIVE INGREDIENT
  申请人：Meiji Seika Kaisha, Ltd.

  公开号：EP1134214A1

  公开（公告）日：2001-09-19

  Disclosed are novel compounds useful for the control of harmful organisms, harmful organism control agents using the same, and processes for producing the novel compounds. The useful novel compounds according to the present invention include compounds represented by formula (1). The compounds represented by formula (1) have potent activity against harmful organisms, and do not have phytotoxicity against agricultural and gardening plants, as objects to which the compounds of the present invention are applied for preventive and exterminating purposes, and human beings and beasts. wherein A represents a bond or an optionally substituted alkylene chain; R1 represents one or more groups, which may be the same or different, selected from the group consisting of a hydrogen atom, alkoxy, and haloalkoxy; R2 represents a hydrogen atom, benzyl, alkyl or alkanoyl, in which the groups other than the hydrogen atom may be substituted; and R3 represents a hydrogen atom, cycloalkyl, cycloalkenyl, aryl or a heterocyclic group, in which the groups other than the hydrogen atom may be substituted, excluding the case where R1 represents a hydrogen atom, A represents a bond or a methylene chain, and R3 represent phenyl or cyclohexyl, and the case where A represents an alkylene chain and R3 represents a hydrogen atom.

  本发明公开了用于控制有害生物的新型化合物、使用这些化合物的有害生物控制剂以及生产这些新型化合物的工艺。根据本发明，有用的新型化合物包括由式（1）代表的化合物。式（1）代表的化合物对有害生物具有强效活性，并且对农业和园艺植物没有植物毒性，而农业和园艺植物是本发明化合物用于预防和消灭的对象，人类和野兽也是本发明化合物的对象。 其中 A 代表键或任选取代的亚烷基链；R1 代表一个或多个基团，它们可以相同或不同，选自由氢原子、烷氧基和卤代烷氧基组成的组；R2 代表氢原子、苄基、烷基或烷酰基，其中氢原子以外的基团可以被取代；以及 R3 代表氢原子、环烷基、环烯基、芳基或杂环基，其中氢原子以外的基团可被取代，但不包括 R1 代表氢原子、A 代表键或亚甲基链、R3 代表苯基或环己基的情况，以及 A 代表亚烷基链、R3 代表氢原子的情况。
• ——
  作者：BOZGA E. -R.、 CILIANU B. S.、 CUNESCU F. I.、 TAMAS V.、 JEGU C.

  DOI：——

  日期：——
• US7183278B1
  申请人：——

  公开号：US7183278B1

  公开（公告）日：2007-02-27