4-chloro-2-(3-naphtalen-2-yl-ureido)-benzoic acid | 639010-14-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-chloro-2-(3-naphtalen-2-yl-ureido)-benzoic acid
• 英文别名: 4-chloro-2-(naphthalen-2-ylcarbamoylamino)benzoic Acid
• CAS: 639010-14-3
• 化学式: C₁₈H₁₃ClN₂O₃
• 分子量: 340.766
• InChiKey: ODWUYZAAMNLBKT-UHFFFAOYSA-N

物化性质

• 熔点：
  176-179 °C (decomp)(Solv: ethyl acetate (141-78-6); heptane (142-82-5))
• 沸点：
  464.6±35.0 °C(Predicted)
• 密度：
  1.491±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 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：
  78.4
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  2-萘甲酸 、 alkaline earth salt of/the/ methylsulfuric acid 在 二苯基膦叠氮化物 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 2.0h， 生成 4-chloro-2-(3-naphtalen-2-yl-ureido)-benzoic acid
  参考文献：
  名称：

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

  摘要：

  A series of 2-arylureidobenzoic acids (AUBAs) was prepared by a short and effective synthesis, and the pharmacological activity at glutamate receptors was evaluated in vitro and in vivo. The compounds showed noncompetitive antagonistic activity at the kainate receptor subtype GluR5. The most potent compounds showed more than 50-fold selectivity for GluR5 compared to GluR6 and the AMPA receptor subtypes GluR1-4. The structure-activity relationships for the AUBAs showed distinct structural requirements for the substituents on the two aromatic ring systems. Only para-substituents were tolerated on the benzoic acid moiety (ring A), whereas ring B tolerated a variety of substituents, but with a preference for lipophilic substituents. The most potent compounds had a 4-chloro substituent on ring A and 3-chlorobenzene (6b), 2-naphthalene (8h), or 2-indole (8k) as ring B and had IC50 values of 1.3, 1.2, and 1.2,muM, respectively, in a functional GluR5 assay. Compound 6c (IC50 = 4.8 muM at GluR5) showed activity in the in vivo ATPA rigidity test, indicating that 6c has better pharmacokinetic properties than 8h, which was inactive in this test. The AUBAs are the first example of a series of noncompetitive GluR5-selective antagonists and may prove to be important pharmacological tools and leads in the search for therapeutic glutamatergic agents.

  DOI：

  10.1021/jm030428j

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
• 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.
• 2-Arylureidobenzoic Acids:  Selective Noncompetitive Antagonists for the Homomeric Kainate Receptor Subtype GluR5
  作者：Jon Valgeirsson、Elsebet Ø. Nielsen、Dan Peters、Thomas Varming、Claus Mathiesen、Anders S. Kristensen、Ulf Madsen

  DOI：10.1021/jm030428j

  日期：2003.12.1

  A series of 2-arylureidobenzoic acids (AUBAs) was prepared by a short and effective synthesis, and the pharmacological activity at glutamate receptors was evaluated in vitro and in vivo. The compounds showed noncompetitive antagonistic activity at the kainate receptor subtype GluR5. The most potent compounds showed more than 50-fold selectivity for GluR5 compared to GluR6 and the AMPA receptor subtypes GluR1-4. The structure-activity relationships for the AUBAs showed distinct structural requirements for the substituents on the two aromatic ring systems. Only para-substituents were tolerated on the benzoic acid moiety (ring A), whereas ring B tolerated a variety of substituents, but with a preference for lipophilic substituents. The most potent compounds had a 4-chloro substituent on ring A and 3-chlorobenzene (6b), 2-naphthalene (8h), or 2-indole (8k) as ring B and had IC50 values of 1.3, 1.2, and 1.2,muM, respectively, in a functional GluR5 assay. Compound 6c (IC50 = 4.8 muM at GluR5) showed activity in the in vivo ATPA rigidity test, indicating that 6c has better pharmacokinetic properties than 8h, which was inactive in this test. The AUBAs are the first example of a series of noncompetitive GluR5-selective antagonists and may prove to be important pharmacological tools and leads in the search for therapeutic glutamatergic agents.