2-methoxy-4-[(1E)-3-methoxy-3-oxo-1-propenyl]benzoic acid | 177478-58-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 2-methoxy-4-[(1E)-3-methoxy-3-oxo-1-propenyl]benzoic acid
• 英文别名: methyl 4-carboxy-3-methoxycinnamate；2-methoxy-4-[(E)-3-methoxy-3-oxoprop-1-enyl]benzoic acid
• CAS: 177478-58-9
• 化学式: C₁₂H₁₂O₅
• 分子量: 236.224
• InChiKey: CHAOWOJRRUBXPU-GQCTYLIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-methoxy-4-[(1E)-3-methoxy-3-oxo-1-propenyl]benzoic acid 在 sodium hydroxide 、 1-(3-dimethylaminopropyl)-3-ethoxycarbodiimide hydrochloride 、 1-羟基苯并三唑 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 13.0h， 生成 4-[(1E)-3-({2-[2,4-dichloro-3-({[4-(dimethylamino)-2-methyl-8-quinolinyl]oxy}methyl)methylanilino]-2-oxoethyl}amino)-3-oxo-1-propenyl]-2-methoxy-N-methylbenzamide
  参考文献：
  名称：

  A New Class of Nonpeptide Bradykinin B₂ Receptor Ligand, Incorporating a 4-Aminoquinoline Framework. Identification of a Key Pharmacophore To Determine Species Difference and Agonist/Antagonist Profile

  摘要：

  Introduction of various aliphatic amino groups at the 4-position of the quinoline moiety of our nonpeptide bradykinin (BK) B-2 receptor antagonists afforded highly potent ligands for human B-2 receptor with various affinities for guinea pig B-2 receptor, indicating remarkable species difference. A representative 4-dimethyamino derivative 40a exhibited subnanomolar and nanomolar binding affinities for human and guinea pig B-2 receptors, respectively, and significantly inhibited BK-induced bronchoconstriction in guinea pigs at 10 mug/kg by intravenous administration. Further chemical modification led us to discover unique partial agonists for the human B-2 receptor that increase inositol phosphates (IPs) production by themselves in Chinese hamster ovary (CHO) cells expressing the cloned human B-2 receptor. Although their potency and efficacy were much lower than those of BK, we identified them as screening leads for nonpeptide B-2 agonists. In these studies it was revealed the 4-substituent of the quinoline moiety is the key pharmacophore to determine species difference and agonist/antagonist profiles.

  DOI：

  10.1021/jm030326t
• 作为产物：
  描述：

  4-(羟甲基)-2-甲氧基苯甲酸 在 pyridine-SO3 complex 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 3.0h， 生成 2-methoxy-4-[(1E)-3-methoxy-3-oxo-1-propenyl]benzoic acid
  参考文献：
  名称：

  A New Class of Nonpeptide Bradykinin B₂ Receptor Ligand, Incorporating a 4-Aminoquinoline Framework. Identification of a Key Pharmacophore To Determine Species Difference and Agonist/Antagonist Profile

  摘要：

  Introduction of various aliphatic amino groups at the 4-position of the quinoline moiety of our nonpeptide bradykinin (BK) B-2 receptor antagonists afforded highly potent ligands for human B-2 receptor with various affinities for guinea pig B-2 receptor, indicating remarkable species difference. A representative 4-dimethyamino derivative 40a exhibited subnanomolar and nanomolar binding affinities for human and guinea pig B-2 receptors, respectively, and significantly inhibited BK-induced bronchoconstriction in guinea pigs at 10 mug/kg by intravenous administration. Further chemical modification led us to discover unique partial agonists for the human B-2 receptor that increase inositol phosphates (IPs) production by themselves in Chinese hamster ovary (CHO) cells expressing the cloned human B-2 receptor. Although their potency and efficacy were much lower than those of BK, we identified them as screening leads for nonpeptide B-2 agonists. In these studies it was revealed the 4-substituent of the quinoline moiety is the key pharmacophore to determine species difference and agonist/antagonist profiles.

  DOI：

  10.1021/jm030326t

文献信息

• Benzimidazole compounds as bradykinin antagonists
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06083961A1

  公开（公告）日：2000-07-04

  This invention relates to a heterocyclic compound of the formula: ##STR1## wherein a group of the formula: ##STR2## is a group of the formula: ##STR3## etc., X is O, S or N--R.sup.5, R.sup.1 is lower alkyl, etc., R.sup.5 is hydrogen, lower alkyl, etc., R.sup.2 is hydrogen, halogen, lower alkyl, etc., R.sup.3 is halogen, lower alkyl, etc., R.sup.4 is amino optionally having suitable substituent(s), and A is lower alkylene, and a salt thereof, to processes for preparation thereof, and to a pharmaceutical composition comprising the same for the prevention and/or the treatment of bradykinin or its analogues mediated diseases in human being or animals.

  这项发明涉及一种杂环化合物，其化学式为：##STR1## 其中，##STR2## 是一个化学式为：##STR3## 的基团，X为O、S或N--R.sup.5，R.sup.1为较低烷基等，R.sup.5为氢、较低烷基等，R.sup.2为氢、卤素、较低烷基等，R.sup.3为卤素、较低烷基等，R.sup.4为氨基，可选地具有适当的取代基，A为较低烷基，以及其盐，制备方法和包含该化合物的药物组合物，用于预防和/或治疗人类或动物体内由激肽酶或其类似物介导的疾病。
• HETEROCYCLIC COMPOUND
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0774462A1

  公开（公告）日：1997-05-21

  This invention relates to a heterocyclic compound of the formula :    wherein    a group of the formula : is a group of the formula : etc., X is O, S or N-R5, R1 is lower alkyl, etc., R5 is hydrogen, lower alkyl, etc., R2 is hydrogen, halogen, lower alkyl, etc., R3 is halogen, lower alkyl, etc., R4 is amino optionally having suitable substituent(s), and A is lower alkylene, and a salt thereof, to processes for preparation thereof, and to a pharmaceutical composition comprising the same for the prevention and/or the treatment of bradykinin or its analogues mediated diseases in human being or animals.

  本发明涉及一种式......的杂环化合物： 其中 式中的一个基团是式中的一个基团： 等等、 X是O、S或N-R5、 R1 是低级烷基等、 R5 是氢、低级烷基等、 R2 是氢、卤素、低级烷基等、 R3 是卤素、低级烷基等、 R4 是氨基，可选择具有合适的取代基、 和 A 是低级亚烷基、 及其盐、制备工艺，以及包含上述物质的药物组合物，用于预防和/或治疗缓激肽或其类似物介导的人类或动物疾病。
• CHINOLINE AND BENZIMIDAZOLE DERIVATIVES AS BRADYKININ AGONISTS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0879233B1

  公开（公告）日：2003-08-13
• US6015818A
  申请人：——

  公开号：US6015818A

  公开（公告）日：2000-01-18
• US6127389A
  申请人：——

  公开号：US6127389A

  公开（公告）日：2000-10-03