2,3-dimethyl-11-oxo-N-<4-(5-pyrimidinyl)butyl>-11H-pyrido<2,1-b>quinazoline-8-carboxamide | 88940-17-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 2,3-dimethyl-11-oxo-N-<4-(5-pyrimidinyl)butyl>-11H-pyrido<2,1-b>quinazoline-8-carboxamide
• 英文别名: 2,3-Dimethyl-N-[4-(5-pyrimidinyl)butyl]-11-oxo-11H-pyrido[2,1-b]quinazoline-8-carboxamide；2,3-Dimethyl-11-oxo-11H-pyrido[2,1-b]quinazoline-8-carboxylic acid (4-pyrimidin-5-yl-butyl)-amide；2,3-dimethyl-11-oxo-N-(4-pyrimidin-5-ylbutyl)pyrido[2,1-b]quinazoline-8-carboxamide
• CAS: 88940-17-4
• 化学式: C₂₃H₂₃N₅O₂
• 分子量: 401.468
• InChiKey: GAXHRSHQGJGGRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  87.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,3-dimethyl-11-oxo-N-<4-(5-pyrimidinyl)butyl>-11H-pyrido<2,1-b>quinazoline-8-carboxamide 、 碘甲烷 以30%的产率得到
  参考文献：
  名称：

  TILLEY, JEFFERSON W.;BURGHARD, BARBARA;BURGHARDT, CHARLES;MOWLES, THOMAS +, J. MED. CHEM., 31,(1988) N 2, 466-472

  摘要：

  DOI：
• 作为产物：
  描述：

  2,3-dimethyl-11-oxo-11H-pyrido<2,1-b>quinazoline-8-carboxylic acid 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 27.0h， 生成 2,3-dimethyl-11-oxo-N-<4-(5-pyrimidinyl)butyl>-11H-pyrido<2,1-b>quinazoline-8-carboxamide
  参考文献：
  名称：

  Pyrido[2,1-b]quinazolinecarboxamide derivatives as platelet activating factor antagonists

  摘要：

  A series of N-[(heteroaryl)alkyl]pyrido[2,1-b]quinazolines were evaluated for their ability to inhibit the binding of radiolabeled platelet activating factor (PAF) to its receptor on dog platelets. The most potent compounds in this series were found to be pyrido[2,1-b]quinazoline-8-carboxamides possessing a four- or six-carbon chain between the carboxamide nitrogen atom and a 3-pyridinyl or 5-pyrimidinyl moiety. Since earlier metabolism studies with pyridoquinazolinecarboxamides suggest that the carboxamide moiety is labile to hydrolysis in vivo, attempts were made to find isosteric replacements for this group. The substitutions examined led to a loss of activity; however, insertion of a methyl group on the carbon atom alpha to the carboxamide nitrogen led to an enantioselective enhancement of potency. (R)-2-(1-Methylethyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-11-oxo-11H- pyrido[2,1-b]quinazoline-8-carboxamide (34) was more potent than the corresponding S enantiomer in the PAF binding assay and was also shown to be more resistant to degradation by amidases present in whole liver homogenates obtained from guinea pig, dog, and squirrel monkey. The corresponding rac-2-(1-methylethyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-11-oxo-11H- pyrido[2,1-b]quinazoline-8-carboxamide (33) was found to inhibit transient PAF-induced thrombocytopenia and decreases in blood pressure in guinea pigs after intravenous or oral administration and to have a duration of action of greater than 5 h after an oral dose of 200 mg/kg. Compound 33 thus represents the prototype of a new class of orally active PAF antagonists.

  DOI：

  10.1021/jm00397a034

文献信息

• Pyrido(2,1-b)chinazolinderivate
  申请人：F. HOFFMANN-LA ROCHE & CO. Aktiengesellschaft

  公开号：EP0094080A2

  公开（公告）日：1983-11-16

  Es werden Verbindungen der allgemeinen Formel worin eines von D und D' ein Stickstoffatom und das andere ein Kohlenstoffatom, die gestrichelte Linie zwei zusätzliche Bindungen, R1 und R2 unabhängig von einander Wasserstoff, niederes Alkyl, niederes Alkoxy, Hydroxy oder Halogen, X -0-oder -N(R5)-, R5 Wasserstoff oder niederes Alkyl, R3 (C2-7)-Alkylen, R4(C1-7)-Alkylen Y -0- oder -S-, m 0 oder 1, n 0 oder 1 und A eine unsubstituierte oder substituierte aromatische, 5-oder 6-gliedrige heterocyclische Gruppe bedeuten, mit der Massgabe, daß m und n beide 0 sind, wenn A über ein heterocyclisches Stickstoffatom gebunden ist, beschrieben. Diese Verbindungen und ihre pharmazeutisch annehmbaren Säureadditionssalze sind nützlich als Mittel für die Behandlung von Allergien und thrombotischen Gefässerkrankungen.

  通式如下的化合物 其中 D 和 D'之一为氮原子，另一个为碳原子，虚线为两个附加键，R1 和 R2 独立地为氢、低级烷基、低级烷氧基、羟基或卤素，X 为-0-或-N(R5)-，R5 为氢或低级烷基、R3为(C2-7)-烯烃，R4为(C1-7)-烯烃，Y为-0-或-S-，m为0或1，n为0或1，A为未取代或取代的芳香族、5或6元杂环基团，但当A通过杂环氮原子连接时，m和n均为0。这些化合物及其药学上可接受的酸加成盐可作为治疗过敏症和血栓性血管疾病的药物。
• TILLEY, JEFFERSON W.;BURGHARD, BARBARA;BURGHARDT, CHARLES;MOWLES, THOMAS +, J. MED. CHEM., 31,(1988) N 2, 466-472
  作者：TILLEY, JEFFERSON W.、BURGHARD, BARBARA、BURGHARDT, CHARLES、MOWLES, THOMAS +

  DOI：——

  日期：——
• US4551460A
  申请人：——

  公开号：US4551460A

  公开（公告）日：1985-11-05
• Pyrido[2,1-b]quinazolinecarboxamide derivatives as platelet activating factor antagonists
  作者：Jefferson W. Tilley、Barbara Burghardt、Charles Burghardt、Thomas F. Mowles、Franz Josef Leinweber、Larry Klevans、Richard Young、Gerry Hirkaler、Kenneth Fahrenholtz

  DOI：10.1021/jm00397a034

  日期：1988.2

  A series of N-[(heteroaryl)alkyl]pyrido[2,1-b]quinazolines were evaluated for their ability to inhibit the binding of radiolabeled platelet activating factor (PAF) to its receptor on dog platelets. The most potent compounds in this series were found to be pyrido[2,1-b]quinazoline-8-carboxamides possessing a four- or six-carbon chain between the carboxamide nitrogen atom and a 3-pyridinyl or 5-pyrimidinyl moiety. Since earlier metabolism studies with pyridoquinazolinecarboxamides suggest that the carboxamide moiety is labile to hydrolysis in vivo, attempts were made to find isosteric replacements for this group. The substitutions examined led to a loss of activity; however, insertion of a methyl group on the carbon atom alpha to the carboxamide nitrogen led to an enantioselective enhancement of potency. (R)-2-(1-Methylethyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-11-oxo-11H- pyrido[2,1-b]quinazoline-8-carboxamide (34) was more potent than the corresponding S enantiomer in the PAF binding assay and was also shown to be more resistant to degradation by amidases present in whole liver homogenates obtained from guinea pig, dog, and squirrel monkey. The corresponding rac-2-(1-methylethyl)-N-[1-methyl-4-(3-pyridinyl)butyl]-11-oxo-11H- pyrido[2,1-b]quinazoline-8-carboxamide (33) was found to inhibit transient PAF-induced thrombocytopenia and decreases in blood pressure in guinea pigs after intravenous or oral administration and to have a duration of action of greater than 5 h after an oral dose of 200 mg/kg. Compound 33 thus represents the prototype of a new class of orally active PAF antagonists.