4-[3-(5-chlorofuran-2-yl)-5-methylisoxazol-4-yl]benzenamine | 1579976-84-3

• 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-[3-(5-chlorofuran-2-yl)-5-methylisoxazol-4-yl]benzenamine
• 英文别名: 4-(3-(5-chlorofuran-2-yI)-5-methylisoxazol-4-yl)benzenamine；MPA35；4-[3-(5-Chlorofuran-2-yl)-5-methyl-1,2-oxazol-4-yl]aniline；4-[3-(5-chlorofuran-2-yl)-5-methyl-1,2-oxazol-4-yl]aniline
• CAS: 1579976-84-3
• 化学式: C₁₄H₁₁ClN₂O₂
• 分子量: 274.707
• InChiKey: MEEQMSFMUXWSIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  65.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-硝基苯丙酮 在 盐酸 、 sodium hydride 、 氯化铵 、 tin(ll) chloride 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 17.0h， 生成 4-[3-(5-chlorofuran-2-yl)-5-methylisoxazol-4-yl]benzenamine
  参考文献：
  名称：

  Selective COX-1 inhibition as a target of theranostic novel diarylisoxazoles

  摘要：

  Cyclooxygenase(COX)-1 role in some diseases is increasingly studied. 3-(5-Chlorofuran-2-yl)-5-methy14-phenylisoxazole (P6), a highly selective cyclooxygenase-1 inhibitor, was used as a "lead" to design new isoxazoles (2a-m), differently selective towards COX-1. Those isoxazoles might be useful as novel theranostic agents and also to better clarify COX-1 role in the human physiology and diseases. 2a-m were prepared in fair to good yields developing suitable synthetic strategies. They were evaluated in vitro for their COX-inhibitory activity and selectivity. Structure activity relationship studies of the novel set of diarylisoxazoles allowed to identify new key determinants for COX-1 selectivity, and to uncover compounds appropriate for a deep pharmacokinetic and pharmacodynamic investigation. 3-(5-Chlorofuran2yl)-4-phenylisoxazol-5-amine (2f) was the most active compound of the series, its inhibitory activity was assessed in purified enzyme (COX-1 IC50 = 1.1 mu M; COX-2 IC50 > 50 mu M) and in the ovarian cancer cell line (OVCAR-3) expressing only COX-1 (IC50 = 0.58 mu M). Furthermore, the high inhibitory potency of 2f was rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-1 binding site. We found critical interactions between the inhibitor and constriction residues R120 and Y355 at the base of the active site, as well as with S530 at the top of the side pocket. (C) 2014 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2013.12.023

文献信息

• [EN] HETEROCYCLES AND THEIR RADIOLABELED ANALOGS USEFUL AS COX-1 SELECTIVE INHIBITORS<br/>[FR] HÉTÉROCYCLES ET LEURS ANALOGUES RADIOMARQUÉS UTILES EN TANT QU'INHIBITEURS SÉLECTIFS DE COX-1
  申请人：UNIV BARI

  公开号：WO2014115020A1

  公开（公告）日：2014-07-31

  The present invention relates to novel heterocycles which are potent and selective inhibitors of cyclooxygenase-1 (COX-1) and to their radiolabeled derivatives thereof which are both useful as theranostics of a number of pathologies.

  本发明涉及一种新型杂环化合物，这些化合物是环氧合酶-1（COX-1）的有效和选择性抑制剂，以及它们的放射标记衍生物，这些衍生物既可用作多种病理病变的诊疗药物。
• HETEROCYCLES AND THEIR RADIOLABELED ANALOGS USEFUL AS COX-1 SELECTIVE INHIBITORS
  申请人：Universita' Degli Studi di Bari

  公开号：EP2948187B1

  公开（公告）日：2019-10-16
• Selective COX-1 inhibition as a target of theranostic novel diarylisoxazoles
  作者：Paola Vitale、Maria Grazia Perrone、Paola Malerba、Antonio Lavecchia、Antonio Scilimati

  DOI：10.1016/j.ejmech.2013.12.023

  日期：2014.3

  Cyclooxygenase(COX)-1 role in some diseases is increasingly studied. 3-(5-Chlorofuran-2-yl)-5-methy14-phenylisoxazole (P6), a highly selective cyclooxygenase-1 inhibitor, was used as a "lead" to design new isoxazoles (2a-m), differently selective towards COX-1. Those isoxazoles might be useful as novel theranostic agents and also to better clarify COX-1 role in the human physiology and diseases. 2a-m were prepared in fair to good yields developing suitable synthetic strategies. They were evaluated in vitro for their COX-inhibitory activity and selectivity. Structure activity relationship studies of the novel set of diarylisoxazoles allowed to identify new key determinants for COX-1 selectivity, and to uncover compounds appropriate for a deep pharmacokinetic and pharmacodynamic investigation. 3-(5-Chlorofuran2yl)-4-phenylisoxazol-5-amine (2f) was the most active compound of the series, its inhibitory activity was assessed in purified enzyme (COX-1 IC50 = 1.1 mu M; COX-2 IC50 > 50 mu M) and in the ovarian cancer cell line (OVCAR-3) expressing only COX-1 (IC50 = 0.58 mu M). Furthermore, the high inhibitory potency of 2f was rationalized through docking simulations in terms of interactions with a crystallographic model of the COX-1 binding site. We found critical interactions between the inhibitor and constriction residues R120 and Y355 at the base of the active site, as well as with S530 at the top of the side pocket. (C) 2014 Published by Elsevier Masson SAS.