1-[5-chloro-2-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenyl]-3-(3-bromophenyl)urea

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-[5-chloro-2-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenyl]-3-(3-bromophenyl)urea
• 英文别名: 1-[5-Chloro-2-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)-phenyl]-3-(3-bromophenyl)urea；1-(3-bromophenyl)-3-[5-chloro-2-(5-oxo-4H-1,2,4-oxadiazol-3-yl)phenyl]urea
• 化学式: C₁₅H₁₀BrClN₄O₃
• 分子量: 409.626
• InChiKey: BIAYVBTUMYRJBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  91.8
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-氨基-4-氯苯腈 在 盐酸羟胺 、 sodium ethanolate 、 碳酸氢钠 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 26.0h， 生成 1-[5-chloro-2-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-3-yl)phenyl]-3-(3-bromophenyl)urea
  参考文献：
  名称：

  Bioisosteric Modifications of 2-Arylureidobenzoic Acids:  Selective Noncompetitive Antagonists for the Homomeric Kainate Receptor Subtype GluR5

  摘要：

  2-Arylureidobenzoic acids (AUBAs) have recently been presented as the first series of selective noncompetitive GluR5 antagonists. In this paper we have modified the acidic moiety of the AUBAs by introducing different acidic and neutral groups, and similarly, we have replaced the urea linker of the AUBAs with other structurally related linkers. Replacing the acid with neutral substituents led to inactive compounds in all instances, showing that an acidic moiety is necessary for activity. Replacing the carboxylic moiety in 2a with a sulfonic acid (5c) or a tetrazole ring (5d) improved the potency at GluR5 receptors (compounds 5c and 5d showed IC50 values of 1.5 and 2.0 muM, respectively, compared to compound 2a with IC50 = 4.8 muM). Compound 5c did not show improved in vivo activity in the ATPA rigidity test compared to 2a, whereas compound 5d was 4 times more potent than 2a. All compounds wherein the urea linker had been replaced showed lower or no activity. The results described extend the knowledge of structure-activity relationships for the AUBAs, and compound 5d may prove to be a good candidate for studying GluR5 receptors in vitro and in vivo.

  DOI：

  10.1021/jm030638w

文献信息

• Novel aryl ureido benzoic acid derivatives and their use
  申请人：Valgeirsson Jon

  公开号：US20060069255A1

  公开（公告）日：2006-03-30

  This invention relates to novel aryl ureido benzoic acid derivatives useful as selective and non-competitive antagonists of the ionotropic GluR5 receptor. Due to their biological activity, the aryl ureido derivatives of the invention are considered useful for treating diseases that are responsive to modulation of an aspartate or a glutamate receptor. Moreover the invention provides chemical compounds for use according to the invention, as well as pharmaceutical compositions comprising the chemical compounds, and methods of treating diseases or disorders or conditions responsive to modulation of an aspartate or a glutamate receptor.

  本发明涉及新型芳基脲基苯甲酸衍生物，可用作离子型GluR5受体的选择性和非竞争性拮抗剂。由于它们的生物活性，本发明的芳基脲基衍生物被认为对于治疗对天冬氨酸或谷氨酸受体调节敏感的疾病有用。此外，本发明提供了用于本发明的化学化合物，以及包含该化学化合物的药物组合物和治疗对天冬氨酸或谷氨酸受体调节敏感的疾病、障碍或状况的方法。
• ARYL UREIDO DERIVATIVES AND THEIR MEDICAL USE
  申请人：NEUROSEARCH A/S

  公开号：EP1565429A2

  公开（公告）日：2005-08-24
• DIARYL UREIDO DERIVATIVES AND THEIR MEDICAL USE
  申请人：NeuroSearch A/S

  公开号：EP1565429B1

  公开（公告）日：2009-05-13
• US7521480B2
  申请人：——

  公开号：US7521480B2

  公开（公告）日：2009-04-21
• [EN] NOVEL ARYL UREIDO BENZOIC ACID DERIVATIVES AND THEIR USE<br/>[FR] NOUVEAUX DERIVES D'ACIDE ARYL UREIDO BENZOIQUE ET LEUR UTILISATION
  申请人：NEUROSEARCH AS

  公开号：WO2004046090A2

  公开（公告）日：2004-06-03

  This invention relates to novel aryl ureido benzoic acid derivatives useful as selective and non-competitive antagonists of the ionotropic GluR5 receptor. Due to their biological activity, the aryl ureido derivatives of the invention are considered useful for treating diseases that are responsive to modulation of an aspartate or a glutamate receptor. Moreover the invention provides chemical compounds for use according to the invention, as well as pharmaceutical compositions comprising the chemical compounds, and methods of treating diseases or disorders or conditions responsive to modulation of an aspartate or a glutamate receptor.