N-(bis(4-methoxybenzyl)carbamothioyl)benzamide | 1361413-53-7

• 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: N-(bis(4-methoxybenzyl)carbamothioyl)benzamide
• 英文别名: N-[(bis{[4-(methyloxy)phenyl]methyl}amino)carbonothioyl]benzamide；N-[bis[(4-methoxyphenyl)methyl]carbamothioyl]benzamide
• CAS: 1361413-53-7
• 化学式: C₂₄H₂₄N₂O₃S
• 分子量: 420.532
• InChiKey: FXIXYKQPJNGBIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(bis(4-methoxybenzyl)carbamothioyl)benzamide 在 lithium hydroxide monohydrate 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 2-[4-(ethylsulfonyl)phenyl]-N-(5-{[4-(2-hydroxyethyl)phenyl]carbonyl}-4-phenyl-1,3-thiazol-2-yl)acetamide
  参考文献：
  名称：

  [EN] NOVEL COMPOUNDS
  [FR] NOUVEAUX COMPOSÉS

  摘要：

  揭示了与视黄醇相关孤儿受体γ（RORγ）调节剂及其在治疗由RORγ介导的疾病中的应用。

  公开号：

  WO2012027965A1
• 作为产物：
  描述：

  4-甲氧基苄胺 以 甲醇 、 丙酮 为溶剂， 反应 4.5h， 生成 N-(bis(4-methoxybenzyl)carbamothioyl)benzamide
  参考文献：
  名称：

  [EN] NOVEL COMPOUNDS
  [FR] NOUVEAUX COMPOSÉS

  摘要：

  揭示了与视黄醇相关孤儿受体γ（RORγ）调节剂及其在治疗由RORγ介导的疾病中的应用。

  公开号：

  WO2012027965A1

文献信息

• Discovery of novel VX-809 hybrid derivatives as F508del-CFTR correctors by molecular modeling, chemical synthesis and biological assays
  作者：Alice Parodi、Giada Righetti、Emanuela Pesce、Annalisa Salis、Bruno Tasso、Chiara Urbinati、Valeria Tomati、Gianluca Damonte、Marco Rusnati、Nicoletta Pedemonte、Elena Cichero、Enrico Millo

  DOI：10.1016/j.ejmech.2020.112833

  日期：2020.12

  Cystic fibrosis (CF) is the autosomal recessive disorder most recurrent in Caucasian populations. It is caused by different mutations in the cystic fibrosis transmembrane regulator protein (CFTR) gene, with F508del being the most common. During the last years, small-molecule therapy chosen to contrast CF relied on compounds that correct CFTR misfolding and ER retention (correctors such as VX-809), or defective channel gating (potentiators such as VX-770). Combination therapy with the two series of drugs has been applied, leading to the approval of several multi-drugs such as Orkambi. Despite this, this treatment proved to be only partially effective making the search for novel modulators an urgent need to contrast CF. Recently, we reported compound 2a as reference compound of a series of aminoarylthiazole-VX-809 hybrid derivatives exhibiting promising F508del-CFTR corrector ability. Herein, we report exploring the docking mode of the prototype VX-809 and of 2a in order to derive useful guidelines for the rational design of novel optimized analogues. To demonstrate experimentally their effective F508del-CFTR-binding and rescuing potential, the most promising derivatives had been synthesized and evaluated in biological assays including YFP functional assay on F508del-CFTR CFBE41o-cells, trans epithelial electrical resistance (TEER) and surface plasmon resonance (SPR). This multidisciplinary strategy led to the discovery of a second series of hybrids including 7j and 7m endowed with higher potency than the prototype.
• ROR GAMMA (RORY) MODULATORS
  申请人：LEAD PHARMA HOLDING B.V.

  公开号：US20180170863A1

  公开（公告）日：2018-06-21

  Compounds according to Formula I: or a pharmaceutically acceptable salt thereof wherein: A 1 is NR 1 or CR 1 , with R 1 being H or methyl, with methyl, if present, optionally being substituted with one or more F; the cyclopropyl moiety can be optionally substituted with one or more methyl and one or more F; A 2 -A 5 are N or CR 2 -CR 5 , respectively, with the proviso that no more than two of the four positions A in A 2 -A 5 can be simultaneously N; R 2 -R 5 are independently H, halogen, amino, C(1-3)alkoxy, (di)C(1-3)alkylamino or C(1-6)alkyl; R 6 and R 7 are independently H, F, methyl, ethyl, hydroxyl or methoxy or R 2 and R 3 together is carbonyl, all alkyl groups, if present, optionally being substituted with one or more F; R 8 is H or C(1-6)alkyl; R 9 is selected from the group consisting of Formula II, III, IV and V The compounds can be used as inhibitors of RORγ and are useful for the treatment of RORγ mediated diseases.
• [EN] NOVEL COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS
  申请人：GLAXO GROUP LTD

  公开号：WO2012027965A1

  公开（公告）日：2012-03-08

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

  揭示了与视黄醇相关孤儿受体γ（RORγ）调节剂及其在治疗由RORγ介导的疾病中的应用。