(2-(2-((3-p-toluyl-4-oxo-3,4-dihydroquinazolin-2-yl)sulfanyl)-acetyl hydrazinylidene)methylphenoxy)acetic acid | 380473-08-5

• 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: (2-(2-((3-p-toluyl-4-oxo-3,4-dihydroquinazolin-2-yl)sulfanyl)-acetyl hydrazinylidene)methylphenoxy)acetic acid
• 英文别名: 2-[2-[[[2-[3-(4-Methylphenyl)-4-oxoquinazolin-2-yl]sulfanylacetyl]hydrazinylidene]methyl]phenoxy]acetic acid
• CAS: 380473-08-5
• 化学式: C₂₆H₂₂N₄O₅S
• 分子量: 502.55
• InChiKey: WGIFMLLAMXWOEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  36
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  146
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  (4-oxo-3-p-tolyl-3,4-dihydro-quinazolin-2-ylsulfanyl)acetic acid ethyl ester 在 硫酸 、 lithium hydroxide 、 肼 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 22.0h， 生成 (2-(2-((3-p-toluyl-4-oxo-3,4-dihydroquinazolin-2-yl)sulfanyl)-acetyl hydrazinylidene)methylphenoxy)acetic acid
  参考文献：
  名称：

  Small molecule mimetics of an interferon-α receptor interacting domain

  摘要：

  Small molecules that mimic IFN-alpha epitopes that interact with the cell surface receptor, IFNAR, would be useful therapeutics. One such 8-amino acid region in IFN-alpha 2, designated IRRP-1, was used to derive 11 chemical compounds that belong to 5 distinct chemotypes, containing the molecular features represented by the key residues Leu30, Arg33, and Asp35 in IRRP-1. Three of these compounds exhibited potential mimicry to IRRP-1 and, in cell based assays, as predicted, effectively inhibited IFNAR activation by IFN-alpha. Of these, compound 3 did not display cell toxicity and reduced IFN-alpha-inducible STAT1 phosphorylation and STAT-DNA binding. Based on physicochemical properties' analyses, our data suggest that moieties with acidic pKa on the small molecule may be a necessary element for mimicking the carboxyl group of Asp35 in IRRP-1. Our data confirm the relevance of this strategy of molecular mimicry of ligand-receptor interaction domains of protein partners for small molecule drug discovery. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.049

文献信息

• Small molecule mimetics of an interferon-α receptor interacting domain
  作者：Angelica M. Bello、Lianhu Wei、Beata Majchrzak-Kita、Noruê Salum、Meena K. Purohit、Eleanor N. Fish、Lakshmi P. Kotra

  DOI：10.1016/j.bmc.2013.12.049

  日期：2014.2

  Small molecules that mimic IFN-alpha epitopes that interact with the cell surface receptor, IFNAR, would be useful therapeutics. One such 8-amino acid region in IFN-alpha 2, designated IRRP-1, was used to derive 11 chemical compounds that belong to 5 distinct chemotypes, containing the molecular features represented by the key residues Leu30, Arg33, and Asp35 in IRRP-1. Three of these compounds exhibited potential mimicry to IRRP-1 and, in cell based assays, as predicted, effectively inhibited IFNAR activation by IFN-alpha. Of these, compound 3 did not display cell toxicity and reduced IFN-alpha-inducible STAT1 phosphorylation and STAT-DNA binding. Based on physicochemical properties' analyses, our data suggest that moieties with acidic pKa on the small molecule may be a necessary element for mimicking the carboxyl group of Asp35 in IRRP-1. Our data confirm the relevance of this strategy of molecular mimicry of ligand-receptor interaction domains of protein partners for small molecule drug discovery. (C) 2014 Elsevier Ltd. All rights reserved.