4-氰基-2-[[2-(4-氟-1-萘基)-1-氧代丙基]氨基]苯基丁酸 | 402473-54-5

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 中文名称: 4-氰基-2-[[2-(4-氟-1-萘基)-1-氧代丙基]氨基]苯基丁酸
• 英文名称: ONO-AE3-208
• 英文别名: 4-cyano-2-[[2-(4-fluoro-1-naphthalenyl)-1-oxopropyl]amino]-benzenebutanoic acid；4-[4-cyano-2-[2-(4-fluoronaphthalen-1-yl)propanoylamino]phenyl]butanoic acid
• CAS: 402473-54-5
• 化学式: C₂₄H₂₁FN₂O₃
• 分子量: 404.441
• InChiKey: MTDIMKNAJUQTIO-UHFFFAOYSA-N

物化性质

• 沸点：
  662.4±55.0 °C(Predicted)
• 密度：
  1.30
• 溶解度：
  DMSO 中≥40.4 mg/mL，温和加热；不溶于水； ≥8.1 mg/mL，乙醇溶液，温和加热和超声波

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  90.2
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P280
• 危险性描述：
  H302,H312,H332

制备方法与用途

生物活性

ONO-AE3-208 是一种 EP4 拮抗剂，能够抑制前列腺癌细胞的侵袭、迁移与代谢。

靶点

| EP4 |

体外研究

ONO-AE3-208 在剂量依赖性方式下抑制细胞侵袭和迁移，而不影响细胞增殖。ONO-AE3-208 可以在 EET 合成抑制剂 MS-PPOH 的存在下阻断 CTGF。花生四烯酸 (AA) 会导致附着的 Af-Art 剂量依赖性扩张，并且此效应被 ONO-AE3-208 阻断。

体内研究

ONO-AE3-208 在小鼠中显著抑制 PC3 细胞的骨转移。与治疗组相比，对照组的肿瘤负荷在时间上呈显著增加趋势。前者形成转移的比率高于后者。接受 ONO-AE3-208 治疗的动物出现转移的中位时间为 29 天，而对照组为 21 天。

文献信息

• COMBINATIONS OF MEDICAMENTS, CONTAINING PDE4-INHIBITORS AND EP4-RECEPTOR-ANTAGONISTS
  申请人：Nickolaus Peter

  公开号：US20130225609A1

  公开（公告）日：2013-08-29

  The present invention relates to new medicament combinations which contain in addition to one or more PDE4-inhibitors (1) at least one EP4 receptor antagonist (2), as well as the use thereof for the treatment of preferably respiratory complaints such as particularly COPD, chronic sinusitis and asthma. The invention relates in particular to those medicament combinations which contain, in addition to one or more, preferably one, PDE4 inhibitor of general formula 1 wherein X is SO or SO 2 , but preferably SO, and wherein R 1 , R 2 , R 3 and R 4 have the meanings given in claim 1, at least one EP4 receptor antagonist (2), the preparation thereof and the use thereof for the treatment of respiratory complaints.

  本发明涉及新的药物组合物，其包含除了一个或多个PDE4抑制剂（1）之外，至少一个EP4受体拮抗剂（2），以及其用于治疗特别是呼吸系统疾病，如慢性阻塞性肺病（COPD）、慢性鼻窦炎和哮喘的用途。本发明特别涉及那些药物组合物，其除了一个或多个，优选一个，PDE4抑制剂的一般通式1之外，还包含至少一个EP4受体拮抗剂（2），其中X是SO或SO2，但优选SO，并且其中R1、R2、R3和R4具有权利要求1中给出的含义，所述组合物的制备及其用于治疗呼吸系统疾病的用途。
• Carboxylic acid derivatives, process for producing the same and drugs containing the same as the active ingredient
  申请人：——

  公开号：US20030216381A1

  公开（公告）日：2003-11-20

  A carboxylic acid derivative of formula (1) 1 wherein R 1 is COOH, COOR 6 etc.; A is alkylene etc.; R 2 is alkyl, alkenyl, alkynyl etc.; B is carbocyclic ring or heterocyclic ring; R 4 is alkyl, cycloalkyl etc.; R 6 is carbocyclic ring or heterocyclic ring; or non-toxic salts thereof, a process for the preparation thereof and a pharmaceutical agent comprising the same as active ingredient. The compound of the formula (I) can bind to Prostaglandin E 2 receptors, especially, EP 3 receptor and/or EP 4 receptor and show the antagonizing activity, and useful for the prevention and/or treatment of disease, for example, pain, allergy, Alzheimer's disease, cancer.

  化学式（1）1的羧酸衍生物，其中R1是COOH，COOR6等；A是烷基等；R2是烷基，烯基，炔基等；B是碳环或杂环；R4是烷基，环烷基等；R6是碳环或杂环；或其无毒盐，以其为活性成分的制备方法和含有其的药物制剂。化合物的化学式（I）可以结合到前列腺素E2受体，特别是EP3受体和/或EP4受体，并显示拮抗活性，对于预防和/或治疗疾病，例如疼痛，过敏，阿尔茨海默病，癌症等非常有用。
• Carboxylic acid derivatives, processes for the preparation thereof and pharmaceutical agents comprising the same as active ingredient
  申请人：ONO PHARMACEUTICAL CO., LTD.

  公开号：US20040235825A1

  公开（公告）日：2004-11-25

  A carboxylic acid derivative of formula (I) 1 wherein R 1 , COOH, COOR 6 etc.; A is alkylene etc.; R 2 is alkyl, alkenyl, alkynyl etc.; B is carbocyclic ring or heterocyclic ring; R 4 is alkyl, cycloalkyl etc.; R 5 is carbocyclic ring or heterocyclic ring; or non-toxic salts thereof, a process for the preparation thereof and a pharmaceutical agent comprising the same as active ingredient. The compound of the formula (I) can bind to Prostaglandin E 2 receptors, especially, EP 3 receptor and/or EP 4 receptor and show the antagonizing activity, and useful for the prevention and/or treatment of disease, for example, pain, allergy, Alzheimer's disease, cancer.

  化合物的式(I)1为羧酸衍生物，其中R1，COOH，COOR6等; A为亚烷基等; R2为烷基，烯基，炔基等; B为碳环或杂环; R4为烷基，环烷基等; R5为碳环或杂环;或其无毒盐，其制备方法以及包含其作为活性成分的药物制剂。公式(I)的化合物可以结合到前列腺素E2受体，特别是EP3受体和/或EP4受体，并表现出拮抗活性，可用于预防和/或治疗疾病，例如疼痛，过敏，阿尔茨海默病，癌症。
• Carboxylic acid derivatives, processes for the preparation thereof and pharmaceutical aggents comprising the same as active ingredient
  申请人：Tani Kousuke

  公开号：US20050026908A1

  公开（公告）日：2005-02-03

  A carboxylic acid derivative of formula (I) wherein R 1 is COOH, COOR 6 etc.; A is alkylene etc.; R 2 is alkyl, alkenyl, alkynyl etc.; B is carbocyclic ring or heterocyclic ring; R 4 is alkyl, cycloalkyl etc.; R 6 is carbocyclic ring or heterocyclic ring; or non-toxic salts thereof, a process for the preparation thereof and a pharmaceutical agent comprising the same as active ingredient. The compound of the formula (I) can bind to Prostaglandin E 2 receptors, especially, EP 3 receptor and/or EP 4 receptor and show the antagonizing activity, and useful for the prevention and/or treatment of disease, for example, pain, allergy, Alzheimer's disease, cancer.

  化合物公式（I）的羧酸衍生物，其中R1为COOH，COOR6等; A为烷基等; R2为烷基，烯基，炔基等; B为碳环或杂环; R4为烷基，环烷基等; R6为碳环或杂环; 或其非毒性盐，其制备方法以及包含其作为活性成分的制药剂。公式（I）的化合物可以结合到前列腺素E2受体，特别是EP3受体和/或EP4受体，并显示拮抗活性，有助于预防和/或治疗疾病，例如疼痛，过敏，阿尔茨海默病，癌症。
• COMBINATIONS OF MEDICAMENTS, CONTAINING PDE4-INHIBITORS AND EP4-RECEPTOR- ANTAGONISTS
  申请人：NICKOLAUS Peter

  公开号：US20140350035A1

  公开（公告）日：2014-11-27

  The present invention relates to new medicament combinations which contain in addition to one or more PDE4-inhibitors ( 1 ) at least one EP4 receptor antagonist ( 2 ), as well as the use thereof for the treatment of preferably respiratory complaints such as particularly COPD, chronic sinusitis and asthma. The invention relates in particular to those medicament combinations which contain, in addition to one or more, preferably one, PDE4 inhibitor of general formula 1 wherein X is SO or SO 2 , but preferably SO, and wherein R 1 , R 2 , R 3 and R 4 have the meanings given in claim 1, at least one EP4 receptor antagonist ( 2 ), the preparation thereof and the use thereof for the treatment of respiratory complaints.

  本发明涉及一种新的药物组合，除了一种或多种PDE4抑制剂（1）外，还包含至少一种EP4受体拮抗剂（2），以及其在治疗呼吸道疾病，如慢性阻塞性肺疾病、慢性鼻窦炎和哮喘等方面的应用。本发明特别涉及那些药物组合，除了一种或多种，首选一种通式1的PDE4抑制剂，其中X为SO或SO2，但优选为SO，R1、R2、R3和R4具有权利要求1中所给出的含义，还包含至少一种EP4受体拮抗剂（2），其制备和在治疗呼吸道疾病方面的应用。