5-<<2-nitro-5-(1-piperidinyl)phenyl>methylene>-2,4-imidazolidinedione | 113259-86-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 5-<<2-nitro-5-(1-piperidinyl)phenyl>methylene>-2,4-imidazolidinedione
• 英文别名: 5-[[2-Nitro-5-(1-piperidinyl)phenyl]methylene]-2,4-imidazolidinedione；5-[(2-nitro-5-piperidin-1-ylphenyl)methylidene]imidazolidine-2,4-dione
• CAS: 113259-86-2
• 化学式: C₁₅H₁₆N₄O₄
• 分子量: 316.316
• InChiKey: VNYRBVBFWGPQIC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  107
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-<<2-nitro-5-(1-piperidinyl)phenyl>methylene>-2,4-imidazolidinedione 在 palladium on activated charcoal 盐酸 、 氢气 、 碘 作用下， 生成 1,3-dihydro-7-(1-piperidinyl)-2H-imidazo<4,5-b>quinolin-2-one dihydrochloride
  参考文献：
  名称：

  Inhibitors of blood platelet cAMP phosphodiesterase. 3. 1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives with enhanced aqueous solubility

  摘要：

  Two series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives incorporating an additional site for acid salt formation were synthesized and evaluated as inhibitors of human blood platelet cAMP phosphodiesterase (PDE) and ADP-induced platelet aggregation. The objective of this study was to identify compounds that blended potent biological activity with a satisfactory level of aqueous solubility. From a series of 7-aminoimidazo[4,5-b]quinolin-2-ones, biological and physical properties were optimally combined in the 1-piperidinyl derivative 11c. However, this compound offered no significant advantage over earlier studied compounds as an antithrombotic agent in an animal model of small vessel thrombosis. A series of 7-alkoxy alkanoic piperazinamide derivatives, in which the additional basic nitrogen atom was remote from the heterocyclic nucleus and accommodated in a secondary binding region of the cAMP PDE enzyme, demonstrated greater intrinsic cAMP PDE inhibitory activity. Structural modifications of this series focused on variation of the piperazine substituent and side-chain length. The lipophilicity of the N-substituent influenced biological potency and aqueous solubility, with substituents of seven carbon atoms or less generally providing acceptable solubility properties. The N-(cyclohexylmethyl)piperazinamide 21h was identified from this series of compounds as a potent inhibitor of platelet cAMP PDE, IC50 = 0.4 nM, and ADP-induced platelet aggregation, IC50 = 0.51-mu-M after a 3-min exposure and 0.1-mu-M after a 15-min exposure of platelet-rich plasma to the drug. Evaluation of 21h and representative analogues in vivo using a rabbit model of small vessel thrombosis revealed significantly greater antithrombotic efficacy compared to that of previously studied compounds with similar intrinsic biological activity measured in vitro but inferior aqueous solubility.

  DOI：

  10.1021/jm00092a020
• 作为产物：
  描述：

  5-氯-2-硝基苯甲醛 在 盐酸 、 sodium ethanolate 、 对甲苯磺酸 作用下， 以 苯 为溶剂， 反应 32.92h， 生成 5-<<2-nitro-5-(1-piperidinyl)phenyl>methylene>-2,4-imidazolidinedione
  参考文献：
  名称：

  Inhibitors of blood platelet cAMP phosphodiesterase. 3. 1,3-Dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives with enhanced aqueous solubility

  摘要：

  Two series of 1,3-dihydro-2H-imidazo[4,5-b]quinolin-2-one derivatives incorporating an additional site for acid salt formation were synthesized and evaluated as inhibitors of human blood platelet cAMP phosphodiesterase (PDE) and ADP-induced platelet aggregation. The objective of this study was to identify compounds that blended potent biological activity with a satisfactory level of aqueous solubility. From a series of 7-aminoimidazo[4,5-b]quinolin-2-ones, biological and physical properties were optimally combined in the 1-piperidinyl derivative 11c. However, this compound offered no significant advantage over earlier studied compounds as an antithrombotic agent in an animal model of small vessel thrombosis. A series of 7-alkoxy alkanoic piperazinamide derivatives, in which the additional basic nitrogen atom was remote from the heterocyclic nucleus and accommodated in a secondary binding region of the cAMP PDE enzyme, demonstrated greater intrinsic cAMP PDE inhibitory activity. Structural modifications of this series focused on variation of the piperazine substituent and side-chain length. The lipophilicity of the N-substituent influenced biological potency and aqueous solubility, with substituents of seven carbon atoms or less generally providing acceptable solubility properties. The N-(cyclohexylmethyl)piperazinamide 21h was identified from this series of compounds as a potent inhibitor of platelet cAMP PDE, IC50 = 0.4 nM, and ADP-induced platelet aggregation, IC50 = 0.51-mu-M after a 3-min exposure and 0.1-mu-M after a 15-min exposure of platelet-rich plasma to the drug. Evaluation of 21h and representative analogues in vivo using a rabbit model of small vessel thrombosis revealed significantly greater antithrombotic efficacy compared to that of previously studied compounds with similar intrinsic biological activity measured in vitro but inferior aqueous solubility.

  DOI：

  10.1021/jm00092a020

文献信息

• 7-amino-1,3-dihydro-2H-imidazo[4,5-b]quinolin 2-ones and method for
  申请人：Bristol-Myers Company

  公开号：US04701459A1

  公开（公告）日：1987-10-20

  Novel series of 2,3-dihydro-2-oxo-1H-imidazo[4,5-b]quinolinyl amine derivatives of Formula ##STR1## wherein R.sub.1 is hydrogen, lower alkyl; R.sub.2 is hydrogen, lower alkyl, lower alkoxy, halogen; R.sub.3 is hydrogen, lower alkyl; R.sub.4 is hydrogen, lower alkyl, alkanoyl, phenylalkanoyl wherein phenyl is optionally substituted with halogen, lower alkyl, lower alkoxy; R.sub.3 and R.sub.4 are joined together to form morpholinyl, piperidinyl or pyrrolidinyl optionally substituted with --CO.sub.2 R.sub.5 or ##STR2## wherein R.sub.5 is hydrogen or lower alkyl, and R.sub.6 is hydrogen, lower alkyl, cycloalkyl; 4-R.sub.7 -piperazinyl wherein R.sub.7 is --CO.sub.2 R.sub.8 wherein R.sub.8 is lower alkyl, phenyl optionally substituted with up to 2 halogen, lower alkyl or lower alkoxy; phenylalkanoyl of 7 to 10 carbon wherein phenyl is unsubstituted or independently substituted with up to 2 halogen, lower alkyl, lower alkoxy. The compounds are cyclic AMP phosphodiesterase inhibitors and are particularly useful as inhibitors of blood platelet aggregation and/or as cardiotonic agents.

  化合物系列是2,3-二氢-2-氧代-1H-咪唑[4,5-b]喹啉基氨基衍生物，其化学式为##STR1##其中R.sub.1为氢，低碳基；R.sub.2为氢，低碳基，低氧代基，卤素；R.sub.3为氢，低碳基；R.sub.4为氢，低碳基，脂肪酰基，苯基脂肪酰基，其中苯基可选择性地用卤素，低碳基，低氧代基取代；R.sub.3和R.sub.4连接在一起形成吗啉基，哌啶基或吡咯烷基，可选择性地用--CO.sub.2 R.sub.5或##STR2##取代，其中R.sub.5为氢或低碳基，R.sub.6为氢，低碳基，环烷基；4-R.sub.7-哌嗪基，其中R.sub.7为--CO.sub.2 R.sub.8，其中R.sub.8为低碳基，苯基，可选择性地用最多2个卤素，低碳基或低氧代基取代；含有7到10个碳的苯基脂肪酰基，其中苯基未取代或独立取代最多2个卤素，低碳基，低氧代基。这些化合物是环磷酸腺苷磷酸二酯酶抑制剂，特别适用于抑制血小板聚集和/或作为心力衰竭药物。