1,3-dihydro-7-(1-piperidinyl)-2H-imidazo<4,5-b>quinolin-2-one dihydrochloride | 113259-75-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1,3-dihydro-7-(1-piperidinyl)-2H-imidazo<4,5-b>quinolin-2-one dihydrochloride
• 英文别名: dihydrochloride salt of 1,3-dihydro-7-(1-piperidinyl)-2H-imidazo[4,5-b]quinolin-2-one
• CAS: 113259-75-9
• 化学式: C₁₅H₁₆N₄O*2ClH
• 分子量: 341.24
• InChiKey: RHAAUGLZOFXPIM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.82
• 重原子数：
  21.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  64.78
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  5-氯-2-硝基苯甲醛 在 palladium on activated charcoal 盐酸 、 氢气 、 碘 、 sodium ethanolate 、 对甲苯磺酸 作用下， 以 苯 为溶剂， 反应 57.42h， 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

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.

  2,3-二氢-2-氧基-1H-咪唑并[4,5-b]喹啉基胺衍生物的小说系列，化学式如下：其中R.sub.1是氢，较低的烷基；R.sub.2是氢，较低的烷基，较低的烷氧基，卤素；R.sub.3是氢，较低的烷基；R.sub.4是氢，较低的烷基，烷酰基，苯基烷酰基，其中苯基可以选择性地用卤素，较低的烷基，较低的烷氧基取代；R.sub.3和R.sub.4结合在一起形成吗啡啉基，哌啶基或吡咯啉基，可以选择性地用--CO.sub.2 R.sub.5或##STR2##取代，其中R.sub.5是氢或较低的烷基，R.sub.6是氢，较低的烷基，环烷基；4-R.sub.7-哌嗪基，其中R.sub.7是--CO.sub.2 R.sub.8，其中R.sub.8是较低的烷基，苯基，可以选择性地用最多2个卤素，较低的烷基或较低的烷氧基取代；含有7至10碳的苯基烷酰基，其中苯基未取代或独立地取代最多2个卤素，较低的烷基，较低的烷氧基。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/或作为心力补充剂。