1-[2-(4-甲基苯胺基)-5-硝基苯基]磺酰基-3-戊基脲 | 284465-11-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 1-[2-(4-甲基苯胺基)-5-硝基苯基]磺酰基-3-戊基脲
• 英文名称: Benzenesulfonamide, 2-((4-methylphenyl)amino)-5-nitro-N-((pentylamino)carbonyl)-
• 英文别名: 1-[2-(4-methylanilino)-5-nitrophenyl]sulfonyl-3-pentylurea
• CAS: 284465-11-8
• 化学式: C₁₉H₂₄N₄O₅S
• 分子量: 420.489
• InChiKey: ZXEYXJKZEQUHBP-UHFFFAOYSA-N

物化性质

• 熔点：
  145-147 °C(Solvent: Methanol)
• 密度：
  1.303±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-氯-5-硝基苯胺 在 盐酸 、 ammonium hydroxide 、 sodium hydroxide 、 sodium nitrite 作用下， 以 丙酮 为溶剂， 反应 0.17h， 生成 1-[2-(4-甲基苯胺基)-5-硝基苯基]磺酰基-3-戊基脲
  参考文献：
  名称：

  Synthesis and Pharmacological Evaluation of Novel Nitrobenzenic Thromboxane Modulators as Antiplatelet Agents Acting on Both the Alpha and Beta Isoforms of the Human Thromboxane Receptor

  摘要：

  Thromboxane A(2) ( TXA(2)) is an arachidonic acid metabolite involved in pathologies such as stroke, myocardial infarction, and atherosclerosis. Consequently, the design of TXA2 receptor ( TP) antagonists remains of great interest in cardiovascular medicine. The actions of TXA2 are mediated by its specific G-protein coupled receptor of which two alternative spliced isoforms, TP alpha and TP beta, have been described in humans. In this study, we report the synthesis of a series of original N-alkyl-N'-[2-( cycloalkyl, alkylaryl)-5-nitrobenzenesulfonyl] urea and N-alkyl-N'-[ 2-( alkylaryl)-5-nitrobenzenesulfonyl]-N"-cyanoguanidines and outline their pharmacological evaluation using the individual TP alpha and TP beta isoforms. Among compounds analyzed, several of them exhibited greater affinity and/or functional activity for either TP alpha or TP beta. The most promising molecules were also found to be antiplatelet agents. From the present results, structural features involved in isoform selectivity can be proposed, and thereby several lead compounds have been identified for the further development of selective TP isoform antagonists.

  DOI：

  10.1021/jm060108a

文献信息

• Development of Prodrugs Possessing a Nitric Oxide Donor Diazen-1-Ium-1,2-Diolate Noiety Using in Vitro/in Silico Predictions
  申请人：Tam Yun Kau

  公开号：US20080288176A1

  公开（公告）日：2008-11-20

  The present invention provides a method of using a physiologically-based pharmacokinetic model to select a prodrug molecule (NO—X) comprising a therapeutic agent X (e.g. nonsteroidal anti-inflammatory drug, (NSAID)) and an appropriate nitric oxide donor NO. The NSAID can be a non-selective or selective cyclooxygenase inhibitor or other biocompatible compound comprising a carboxyl group. The pharmacokinetic model uses in vitro and/or in silico data to estimate an optimal set of parameters that can predict whether a particular NO—X candidate is capable of producing desirable therapeutic effects, e.g. enhanced anti-inflammatory activity, reduced intestinal, cardiac and renal toxicity. Accordingly, the present invention can greatly enhance proper selection of an appropriate candidate for drug development, thereby minimizing development time and conserving costs.

  本发明提供了一种使用基于生理学的药代动力学模型选择一种前药分子(NO—X)的方法，该前药分子包括一种治疗剂X（例如非甾体抗炎药(NSAID)）和一个适当的一氧化氮供体NO。NSAID可以是非选择性或选择性环氧化酶抑制剂或其他生物相容性化合物，包括羧基。药代动力学模型使用体外和/或体内计算数据来估计一组最佳参数，可以预测特定的NO—X候选者是否能够产生理想的治疗效果，例如增强抗炎活性，减少肠道，心脏和肾脏毒性。因此，本发明可以极大地增强适当选择药物开发的合适候选者，从而最小化开发时间并节约成本。