4-chloro-3-(pyridin-4-yl)aniline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-chloro-3-(pyridin-4-yl)aniline
• 英文别名: 4-Chloro-3-pyridin-4-ylaniline；4-chloro-3-pyridin-4-ylaniline
• 化学式: C₁₁H₉ClN₂
• 分子量: 204.659
• InChiKey: PEDMJOMZZABNGJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  38.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-chloro-3-(pyridin-4-yl)aniline 、 2-(4-(乙基磺酰基)苯基)乙酸 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以48 mg的产率得到N-(4-chloro-3-pyridin-4-ylphenyl)-2-(4-ethylsulfonylphenyl)acetamide
  参考文献：
  名称：

  [EN] NOVEL COMPOUNDS
  [FR] NOUVEAUX COMPOSÉS

  摘要：

  揭示了一种新型的视黄醇相关孤儿受体γ（RORγ）调节剂，以及它们在治疗由RORγ介导的疾病中的用途。

  公开号：

  WO2013029338A1
• 作为产物：
  描述：

  1-氯-2-碘-4-硝基苯 在 四(三苯基膦)钯 、 铁粉 、 氯化铵 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 27.0h， 生成 4-chloro-3-(pyridin-4-yl)aniline
  参考文献：
  名称：

  Discovery of 1-(3-aryl-4-chlorophenyl)-3-( p -aryl)urea derivatives against breast cancer by inhibiting PI3K/Akt/mTOR and Hedgehog signalings

  摘要：

  PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/ mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of molecules simultaneously inhibiting these two pathways is urgent needed. Based on the structures of P13K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design. Several compounds displayed excellent antiproliferative activities against several breast cancer cell lines, including triple-negative breast cancer (TNBC) MDA-MB-231 cell. Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1. Compound 9i could also induce apoptosis remarkably in T47D and MDA-MB-231 cells. In the transwell assay, 9i showed significant inhibition on the migration of MDA-MB-231. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.09.002

文献信息

• Dialkylimidazole inhibitors of Trypanosoma cruzi sterol 14α-demethylase as anti-Chagas disease agents
  作者：Praveen Kumar Suryadevara、Kishore Kumar Racherla、Srinivas Olepu、Neil R. Norcross、Hari Babu Tatipaka、Jennifer A. Arif、Joseph D. Planer、Galina I. Lepesheva、Christophe L.M.J. Verlinde、Frederick S. Buckner、Michael H. Gelb

  DOI：10.1016/j.bmcl.2013.08.015

  日期：2013.12

  New dialkylimidazole based sterol 14 alpha-demethylase inhibitors were prepared and tested as potential anti-Trypanosoma cruzi agents. Previous studies had identified compound 2 as the most potent and selective inhibitor against parasite cultures. In addition, animal studies had demonstrated that compound 2 is highly efficacious in the acute model of the disease. However, compound 2 has a high molecular weight and high hydrophobicity, issues addressed here. Systematic modifications were carried out at four positions on the scaffold and several inhibitors were identified which are highly potent (EC50 <1 nM)against T. cruzi in culture. The halogenated derivatives 36j, 36k, and 36p, display excellent activity against T. cruzi amastigotes, with reduced molecular weight and lipophilicity, and exhibit suitable physicochemical properties for an oral drug candidate. (C) 2013 Elsevier Ltd. All rights reserved.
• GDC-0449—A potent inhibitor of the hedgehog pathway
  作者：Kirk D. Robarge、Shirley A. Brunton、Georgette M. Castanedo、Yong Cui、Michael S. Dina、Richard Goldsmith、Stephen E. Gould、Oivin Guichert、Janet L. Gunzner、Jason Halladay、Wei Jia、Cyrus Khojasteh、Michael F.T. Koehler、Karen Kotkow、Hank La、Rebecca L. LaLonde、Kevin Lau、Leslie Lee、Derek Marshall、James C. Marsters、Lesley J. Murray、Changgeng Qian、Lee L. Rubin、Laurent Salphati、Mark S. Stanley、John H.A. Stibbard、Daniel P. Sutherlin、Savita Ubhayaker、Shumei Wang、Susan Wong、Minli Xie

  DOI：10.1016/j.bmcl.2009.08.049

  日期：2009.10

  SAR for a wide variety of heterocyclic replacements for a benzimidazole led to the discovery of functionalized 2-pyridyl amides as novel inhibitors of the hedgehog pathway. The 2-pyridyl amides were optimized for potency, PK, and drug-like properties by modifications to the amide portion of the molecule resulting in 31 (GDC-0449). Amide 31 produced complete tumor regression at doses as low as 12.5 mg/kg BID in a medulloblastoma allograft mouse model that is wholly dependent on the Hh pathway for growth and is currently in human clinical trials, where it is initially being evaluated for the treatment of BCC. (C) 2009 Elsevier Ltd. All rights reserved.
• Discovery of 1-(3-aryl-4-chlorophenyl)-3-( p -aryl)urea derivatives against breast cancer by inhibiting PI3K/Akt/mTOR and Hedgehog signalings
  作者：Wenlu Li、Qinsheng Sun、Lu Song、Chunmei Gao、Feng Liu、Yuzong Chen、Yuyang Jiang

  DOI：10.1016/j.ejmech.2017.09.002

  日期：2017.12

  PI3K/Akt/mTOR and hedgehog (Hh) signalings are two important pathways in breast cancer, which are usually connected with the drug resistance and cancer migration. Many studies indicated that PI3K/Akt/ mTOR inhibitors and Hh inhibitors displayed synergistic effects, and the combination of the two signaling drugs could delay drug resistance and inhibit cancer migration in breast cancer. Therefore, the development of molecules simultaneously inhibiting these two pathways is urgent needed. Based on the structures of P13K inhibitor buparlisib and Hh inhibitor vismodegib, a series of hybrid structures were designed and synthesized utilizing rational drug design and computer-based drug design. Several compounds displayed excellent antiproliferative activities against several breast cancer cell lines, including triple-negative breast cancer (TNBC) MDA-MB-231 cell. Further mechanistic studies demonstrated that the representative compound 9i could inhibit both PI3K/Akt/mTOR and hedgehog (Hh) signalings by inhibiting the phosphorylation of S6K and Akt as well as decreasing the SAG elevated expression of Gli1. Compound 9i could also induce apoptosis remarkably in T47D and MDA-MB-231 cells. In the transwell assay, 9i showed significant inhibition on the migration of MDA-MB-231. (C) 2017 Elsevier Masson SAS. All rights reserved.
• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2013029338A1

  公开（公告）日：2013-03-07

  Disclosed are novel retinoid-related orphan receptor gamma (RORy) modulators and their use in the treatment of diseases mediated by RORy.

  揭示了一种新型的视黄醇相关孤儿受体γ（RORγ）调节剂，以及它们在治疗由RORγ介导的疾病中的用途。