4-<(1,2,3,5-tetrahydro-2-oxoimidazo<2,1-b>quinazolin-7-yl)oxy>butyric acid | 94193-55-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-<(1,2,3,5-tetrahydro-2-oxoimidazo<2,1-b>quinazolin-7-yl)oxy>butyric acid
• 英文别名: 4-(2-oxo-1,2,3,5-tetrahydroimadazo[2,1-b]quinazolin-7-yl)oxybutyric acid；4-(2-oxo-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-7-yl)oxybutyric acid；4-(2-Oxo-1,2,3,5-tetrahydro-imidazo[2,1-b]quinazolin-7-yloxy)-butyric acid；4-[(2-oxo-3,5-dihydro-1H-imidazo[2,1-b]quinazolin-7-yl)oxy]butanoic acid
• CAS: 94193-55-2
• 化学式: C₁₄H₁₅N₃O₄
• 分子量: 289.291
• InChiKey: OIZMRPRXMAYUAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  91.2
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-环己甲基哌嗪 、 4-<(1,2,3,5-tetrahydro-2-oxoimidazo<2,1-b>quinazolin-7-yl)oxy>butyric acid 在 4-二甲氨基吡啶 二苯基磷酸 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 7-[4-(4-Cyclohexylmethyl-piperazin-1-yl)-4-oxo-butoxy]-1,5-dihydro-imidazo[2,1-b]quinazolin-2-one
  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：

  Ethyl 4-(2-oxo-1,2,3,5-tetrahydroimadazo[2,1-b]quinazolin-7-yl)oxybutyrate 生成 4-<(1,2,3,5-tetrahydro-2-oxoimidazo<2,1-b>quinazolin-7-yl)oxy>butyric acid
  参考文献：
  名称：

  JONES, G. H.;VENUTI, M. C.;ALVAREZ, R.;BRUNO, J. J.

  摘要：

  DOI：

文献信息

• (2-Oxo-1,2,3,5-tetrahydroimidazo-(2,1-b)quinazolinyl)-oxyalkyl-amides
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0116948A2

  公开（公告）日：1984-08-29

  Compounds according to the formula and the pharmaceutically acceptable acid addition salts thereof wherein: n is an integer of 1 to 6; R, is hydrogen or alkyl of 1 to 4 carbon; R2 is hydrogen or R, and R2 are combined to form a carbonyl group; R3 is hydrogen, alkyl of 1 to 6 carbons, phenyl, benzyl, hydroxy lower alkyl and its acylates, carbamoyl alkyl, carboxyalkyl, alkoxycarbonylalkyl or amino acid side chains; R4 is hydrogen, alkyl of 1 to 6 carbons, benzyl, or hydroxy lower alkyl; Y is hydrogen, alkyl of 1 to 4 carbon atoms, halo or lower alkoxy; is an amide forming group wherein the nitrogen substituents are: hydrogen; alkyl of 1 to 6 carbon atoms; hydroxyalkyl of 1 to 6 carbon atoms and its aliphatic acylates of 1 to 6 carbon atoms or aryl acylates of 7 to 12 carbon atoms; cycloalkyl of 3 to 8 carbon atoms or cycloalkyl lower alkyl of 4 to 12 carbon atoms wherein the cycloalkyl ring is unsubstituted or substituted with a lower alkyl, lower alkoxy, -OH, -OCOR5, halo, -NH2, -N(R5)2, -NHCORs, -COOH, or -COO(R5) group wherein Rs is lower alkyl; phenyl or phenyl lower alkyl wherein phenyl is unsubstituted or substituted with 1 or more lower alkyl, halo or lower alkoxy groups or an -NH2, -N(R5)2, -NHCOR5, -COOH, or -COOR5 group wherein R5 is lower alkyl; morpholinyl; piperidinyl; perhexylenyl; N-loweralkylpiperazinyl; pyrrolidinyl; tetrahydroquinolinyl; tetrahydroisoquinolinyl; (±)-decahydroquinolinyl or indolinyl. These compounds are cyclic AMP phosphodiesterase inhibitors useful as antithrombotic agents and the like in mammals. The compounds also have inotropic and anti-metastatic activities.

  符合以下式子的化合物 及其药学上可接受的酸加成盐 其中 n 是 1 至 6 的整数； R，是氢或 1 至 4 个碳的烷基； R2 是氢或 R 和 R2 结合形成一个羰基； R3 是氢、1 至 6 碳的烷基、苯基、苄基、羟基低级烷基及其酰化物、氨基甲酰基烷基、羧基烷基、烷氧基羰基烷基或氨基酸侧链； R4 是氢、1 至 6 碳原子的烷基、苄基或羟基低级烷基； Y 是氢、1 至 4 个碳原子的烷基、卤代或低级烷氧基； 是酰胺形成基团，其中氮取代基是氢；1 至 6 个碳原子的烷基；1 至 6 个碳原子的羟基烷基及其 1 至 6 个碳原子的脂肪酰基或 7 至 12 个碳原子的芳基酰基；3 至 8 个碳原子的环烷基或 4 至 12 个碳原子的环烷基低级烷基，其中环烷基环未被取代或被低级烷基、低级烷氧基、-OH、-OCOR5、卤代、-NH2、-N(R5)2、-NHCORs、-COOH 或-COO(R5)基团取代，其中 Rs 为低级烷基；苯基或苯基低级烷基，其中苯基未被取代或被 1 个或多个低级烷基、卤代或低级烷氧基或 -NH2、-N(R5)2、-NHCOR5、-COOH 或 -COOR5 基团取代，其中 R5 为低级烷基；吗啉基；哌啶基；过己烯基；N-低烷基哌嗪基；吡咯烷基；四氢喹啉基；四氢异喹啉基；(±)-十氢喹啉基或吲哚啉基。这些化合物是环 AMP 磷酸二酯酶抑制剂，可用作哺乳动物体内的抗血栓等药物。这些化合物还具有促肌力和抗转移活性。
• (2-Oxo-1,2,3,5-tetrahydroimidazo-/2,1-b/quinnazolinyl)-oxyalkylamides, their preparation, compositions containing them and their use in making medicaments
  申请人：SYNTEX (U.S.A.) INC.

  公开号：EP0153152A2

  公开（公告）日：1985-08-28

  Compounds according to the formula and their pharmaceutically acceptable salts. These compounds are 3',5'-cyclic AMP phosphodiesterase inhibitors useful as antithrombotic agents and the like in mammals.

  根据式 及其药学上可接受的盐类。 这些化合物是 3',5'-环 AMP 磷酸二酯酶抑制剂，可用作哺乳动物体内的抗血栓药等。
• JONES, G. H.;VENUTI, M. C.;ALVAREZ, R.;BRUNO, J. J.
  作者：JONES, G. H.、VENUTI, M. C.、ALVAREZ, R.、BRUNO, J. J.

  DOI：——

  日期：——
• US4551459A
  申请人：——

  公开号：US4551459A

  公开（公告）日：1985-11-05
• US4490371A
  申请人：——

  公开号：US4490371A

  公开（公告）日：1984-12-25