4-(4-aminosulfonylphenoxy)benzaldehyde | 1243604-82-1

• 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: 4-(4-aminosulfonylphenoxy)benzaldehyde
• CAS: 1243604-82-1
• 化学式: C₁₃H₁₁NO₄S
• 分子量: 277.301
• InChiKey: KNZQSBHNSJWXOZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.94
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  86.46
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (3S)-1-butyl-2,5-dioxo-3-cyclohexylmethyl-1,4,9-triazaspiro[5.5]undecane · hydrochloride 、 4-(4-aminosulfonylphenoxy)benzaldehyde 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-(4-{[(3S)-1-butyl-3-(cyclohexylmethyl)-2,5-dioxo-1,4,9-triazaspiro[5.5]undec-9-yl]methyl}phenoxy)benzenesulfonamide
  参考文献：
  名称：

  Discovery of orally available spirodiketopiperazine-based CCR5 antagonists

  摘要：

  Using the previously reported novel spirodiketopiperazine scaffold, the design and synthesis of orally available CCR5 antagonists was undertaken. Compounds possessing a carboxylic acid function in the appropriate position showed improved oral exposure (AUC) relative to the initial chemical leads without reduction in the antagonist activity. The optimized compound 40 was found to show potent anti-HIV activity. Full details of structure-activity relationship (SAR) study are presented. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.057
• 作为产物：
  描述：

  4-羟基苯磺酰胺 、 对氟苯甲醛 在 potassium carbonate 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 2.0h， 以18%的产率得到4-(4-aminosulfonylphenoxy)benzaldehyde
  参考文献：
  名称：

  Discovery of orally available spirodiketopiperazine-based CCR5 antagonists

  摘要：

  Using the previously reported novel spirodiketopiperazine scaffold, the design and synthesis of orally available CCR5 antagonists was undertaken. Compounds possessing a carboxylic acid function in the appropriate position showed improved oral exposure (AUC) relative to the initial chemical leads without reduction in the antagonist activity. The optimized compound 40 was found to show potent anti-HIV activity. Full details of structure-activity relationship (SAR) study are presented. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.05.057

文献信息

• Identification and characterization of potent, selective and metabolically stable IKKβ inhibitor
  作者：Doyeon Kim、Yun Gyeong Kim、Jae Hong Seo、Kye Jung Shin

  DOI：10.1016/j.bmcl.2016.01.065

  日期：2016.2

  We have previously reported the identification of a rhodanine compound (1) with well-balanced inhibitory activity against IKKβ and collagen-induced TNFα activated cells. However, we need more optimized compounds because of its instability over plasma and microsome. As part of a program directed toward the optimization of IKKβ inhibitor, we modified a substituent of parent compound to a series of functional

  我们以前曾报道过鉴定出具有对IKKβ和胶原蛋白诱导的TNFα活化细胞具有良好平衡的抑制活性的若丹宁化合物（1）。但是，由于其相对于血浆和微粒体的不稳定性，我们需要更多优化的化合物。作为针对IKKβ抑制剂优化的程序的一部分，我们将母体化合物的取代基修饰为一系列官能团。在取代的化合物中，苯环对位的氟取代基（12）恢复了对血浆和微粒体的稳定性，同时保持了对IKKβ的抑制力和对其他激酶的选择性。此外，我们已经证明化合物12 是一种非竞争性ATP抑制剂，安全性足以从急性毒性试验应用于动物实验。
• Discovery of 4-[4-({(3R)-1-butyl-3-[(R)-cyclohexyl(hydroxy)methyl]-2,5-dioxo-1,4,9-triazaspiro[5.5]undec-9-yl}methyl)phenoxy]benzoic acid hydrochloride: A highly potent orally available CCR5 selective antagonist
  作者：Rena Nishizawa、Toshihiko Nishiyama、Katsuya Hisaichi、Chiaki Minamoto、Masayuki Murota、Yoshikazu Takaoka、Hisao Nakai、Hideaki Tada、Kenji Sagawa、Shiro Shibayama、Daikichi Fukushima、Kenji Maeda、Hiroaki Mitsuya

  DOI：10.1016/j.bmc.2011.05.022

  日期：2011.7

  Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure-activity relationship (SAR) study and ADME properties are presented. (C) 2011 Elsevier Ltd. All rights reserved.