(5-methoxy-6,7,8,9-tetrahydroimidazol[1,2-a]quinazolin-2-yl)-phenylmethanone | 90807-98-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (5-methoxy-6,7,8,9-tetrahydroimidazol[1,2-a]quinazolin-2-yl)-phenylmethanone
• 英文别名: (5-Methoxy-6,7,8,9-tetrahydroimidazo[1,2-a]quinazolin-2-yl)-phenylmethanone
• CAS: 90807-98-0
• 化学式: C₁₈H₁₇N₃O₂
• 分子量: 307.352
• InChiKey: AOPXWEKLKULIEW-UHFFFAOYSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  4

制备方法与用途

生物活性方面，Ru-32514 是一种苯二氮受体（benzodiazepine receptor）激动剂。

反应信息

• 作为反应物：
  描述：

  (5-methoxy-6,7,8,9-tetrahydroimidazol[1,2-a]quinazolin-2-yl)-phenylmethanone 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 氯仿 为溶剂， 反应 0.17h， 以80%的产率得到(1-bromo-5-methoxy-6,7,8,9-tetrahydroimidazo<1,2-a>quinazolin-2-yl)phenylmethanone
  参考文献：
  名称：

  (Imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones and related compounds as potential nonsedative anxiolytics

  摘要：

  Several series of heterocyclic carboxylic esters were found to be active in the benzodiazepine receptor binding assay, a typical example being ethyl 7-ethyl-5-methoxyimidazo[1,2-a]quinoline-2-carboxylate (4b) with an IC50 of 150 nM. The corresponding phenylmethanone 5d was more potent with an IC50 of 14 nM and was orally active in animal models thought to predict anxiolytic effects. The synthesis of a large number of compounds resulted in the optimization of this activity in a series of (imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones of which compounds 7e, 8b, 8h, 8j, and 8k were equipotent with chlordiazepoxide while exhibiting reduced anticonvulsant activity, little or no muscle relaxation, and negligible sedative effects.

  DOI：

  10.1021/jm00401a025
• 作为产物：
  描述：

  3-bromo-1-phenylpropane-1,2-dione 、 4-Methoxy-5,6,7,8-tetrahydro-quinazolin-2-ylamine 生成 (5-methoxy-6,7,8,9-tetrahydroimidazol[1,2-a]quinazolin-2-yl)-phenylmethanone
  参考文献：
  名称：

  (Imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones and related compounds as potential nonsedative anxiolytics

  摘要：

  Several series of heterocyclic carboxylic esters were found to be active in the benzodiazepine receptor binding assay, a typical example being ethyl 7-ethyl-5-methoxyimidazo[1,2-a]quinoline-2-carboxylate (4b) with an IC50 of 150 nM. The corresponding phenylmethanone 5d was more potent with an IC50 of 14 nM and was orally active in animal models thought to predict anxiolytic effects. The synthesis of a large number of compounds resulted in the optimization of this activity in a series of (imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones of which compounds 7e, 8b, 8h, 8j, and 8k were equipotent with chlordiazepoxide while exhibiting reduced anticonvulsant activity, little or no muscle relaxation, and negligible sedative effects.

  DOI：

  10.1021/jm00401a025

文献信息

• Imidazo(1,2-a)pyrimidines and their salts useful for treating anxiety
  申请人：Roussel Uclaf

  公开号：US04532243A1

  公开（公告）日：1985-07-30

  Novel imidazo[1,2-a]pyrimidines of the formula ##STR1## wherein R is selected from the group consisting of alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, cycloalkylalkyl of 4 to 12 carbon atoms, aryl of 6 to 12 carbon atoms, thienyl and pyridyl, each of said group being optionally substituted with at least one member of the group consisting of halogen, alkyl of 1 to 5 carbon atoms, alkoxy and alkylthio of 1 to 5 carbon atoms, trifluoromethyl, amino, alkylamino of 1 to 5 alkyl carbon atoms and dialkylamino with alkyl of 1 to 5 carbons atoms, R.sub.1 and R.sub.2 are individually selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 5 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, cycloalkylalkyl of 4 to 12 carbon atoms, benzyl and phenethyl, or taken together form alkylene of 3 to 5 carbon atoms, each of said groups being optionally substituted with at least one member of the group consisting of halogen, alkyl of 1 to 5 carbon atoms, alkoxy and alkylthio of 1 to 5 carbon atoms, trifluoromethyl, amino, alkylamino of 1 to 5 alkyl carbon atoms and dialkylamino with alkyls of 1 to 5 carbon atoms, X is selected from the group consisting of oxygen and sulfur and R.sub.3 is alkyl of 1 to 5 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts, having anxiolytic activity and novel intermediates.

  该专利涉及一种具有抗焦虑活性的新型中间体和公式为##STR1##的新型咪唑并[1,2-a]嘧啶化合物，其中R选自1至8碳原子的烷基，2至8碳原子的烯基，3至7碳原子的环烷基，4至12碳原子的环烷基烷基，6至12碳原子的芳基，噻吩基和吡啶基等组中的每个，其中每个组都可以选择性地用1至5碳原子的卤素，烷基，1至5碳原子的烷氧基和烷硫基，三氟甲基，氨基，1至5碳原子的烷基氨基和烷基二烷基氨基进行取代，R1和R2分别选自1至8碳原子的烷基，2至5碳原子的烯基，3至7碳原子的环烷基，4至12碳原子的环烷基烷基，苄基和苯乙基，或一起形成3至5碳原子的烷基，其中每个组都可以选择性地用1至5碳原子的卤素，烷基，1至5碳原子的烷氧基和烷硫基，三氟甲基，氨基，1至5碳原子的烷基氨基和烷基二烷基氨基进行取代，X选自氧和硫，R3为1至5碳原子的烷基，以及它们的非毒性、药学上可接受的酸盐。
• Imidazo[1,2-a]pyrimidines
  申请人：Roussel Uclaf

  公开号：US04588720A1

  公开（公告）日：1986-05-13

  Novel imidazo[1,2-a]pyrimidines of the formula ##STR1## wherein R is selected from the group consisting of alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 8 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, cycloalkylalkyl of 4 to 12 carbon atoms, aryl of 6 to 12 carbon atoms, thienyl and pyridyl, each of said group being optionally substituted with at least one member of the group consisting of halogen, alkyl of 1 to 5 carbon atoms, alkoxy and alkylthio of 1 to 5 carbon atoms, trifluoromethyl, amino, alkylamino of 1 to 5 alkyl carbon atoms and dialkylamino with alkyl of 1 to 5 carbon atoms, R.sub.1 and R.sub.2 are individually selected from the group consisting of hydrogen, alkyl of 1 to 8 carbon atoms, alkenyl of 2 to 5 carbon atoms, cycloalkyl of 3 to 7 carbon atoms, cycloalkylalkyl of 4 to 12 carbon atoms, benzyl and phenethyl, or taken together form alkylene of 3 to 5 carbon atoms, each of said groups being optionally substituted with at least one member of the group consisting of halogen, alkyl of 1 to 5 carbon atoms, alkoxy and alkylthio of 1 to 5 carbon atoms, trifluoromethyl, amino, alkylamino of 1 to 5 alkyl carbon atoms and dialkylamino with alkyls of 1 to 5 carbon atoms, X is selected from the group consisting of oxygen and sulfur and R.sub.3 is alkyl of 1 to 5 carbon atoms and their non-toxic, pharmaceutically acceptable acid addition salts, having anxiolytic activity and novel intermediates.

  该专利描述了一种新型的咪唑并[1,2-a]嘧啶类化合物，其化学式为##STR1##其中R选择自1到8个碳原子的烷基、2到8个碳原子的烯基、3到7个碳原子的环烷基、4到12个碳原子的环烷基烷基、6到12个碳原子的芳基、噻吩基和吡啶基，所述的每个基团都可以选择性地用卤素、1到5个碳原子的烷基、1到5个碳原子的烷氧基和烷硫基、三氟甲基、氨基、1到5个烷基碳原子的烷基氨基和带有1到5个碳原子烷基的二烷基氨基中的至少一种成员进行取代；R.sub.1和R.sub.2单独选择自1到8个碳原子的烷基、2到5个碳原子的烯基、3到7个碳原子的环烷基、4到12个碳原子的环烷基烷基、苄基和苯乙基，或者一起形成3到5个碳原子的烷基，所述的每个基团都可以选择性地用卤素、1到5个碳原子的烷基、1到5个碳原子的烷氧基和烷硫基、三氟甲基、氨基、1到5个烷基碳原子的烷基氨基和带有1到5个碳原子烷基的二烷基氨基中的至少一种成员进行取代；X选择自氧和硫，R.sub.3为1到5个碳原子的烷基，以及其无毒、药学上可接受的酸盐，具有抗焦虑活性和新型中间体。
• Nouvelles imidazo/1,2-a/pyrimidines et leurs sels, leur procédé et leurs intermédiaires de préparation, leur application à titre de médicaments et les compositions les renfermant
  申请人：ROUSSEL-UCLAF

  公开号：EP0104104A1

  公开（公告）日：1984-03-28

  L'invention a pour objet les nouvelles imidazo/1,2-a/ pyrimidines 1 : où R est un alcoyle (1-8C), un alcényle (2-8C), un cycloalcoyle (3-7C), un cycloalcoylalcoyle (4-12C), un aryle (6-12C), un thiényle ou pyridyle, éventuellement substitué R, et R2 représentent un hydrogène, un alcoyle (1-8C), un alcényle (2-5C), un cycloalcoyle (3-7C), un cycloalcoylalcoyle (4-12C), un benzyle ou un phénéthyle, ou R, et R2 forment un alcoylène (3-5C), R1 et R2 pouvant être substitués, X est un oxygène ou un soufre, R3 est un alcoyle (1-5C), ainsi que leurs sels d'acides, leur procédé et leurs intermédiaires de préparation, leur application comme médicaments, notamment anxiolytiques et les compositions les renfermant.

  本发明涉及新的咪唑/1,2-a/嘧啶 1： 其中R是烷基(1-8C)、烯基(2-8C)、环烷基(3-7C)、环烷烃基(4-12C)、芳基(6-12C)、噻吩基或吡啶基，任选取代的R和R2代表氢、烷基(1-8C)、烯基(2-5C)、环烷基(3-7C)、环烷烃基(4-12C)、苄基或苯乙基、或 R 和 R2 组成亚烷基（3-5C），R1 和 R2 有可能被取代，X 是氧或硫，R3 是烷基（1-5C），以及它们的酸盐、制备过程和中间体、作为药物（尤其是抗焦虑药）的用途和含有它们的组合物。
• CLEMENTS-JEWERY, STEPHEN;DANSWAN, GEOFFREY;GARDNER, COLIN R.;MATHARU, SAR+, J. MED. CHEM., 31,(1988) N 6, 1220-1226
  作者：CLEMENTS-JEWERY, STEPHEN、DANSWAN, GEOFFREY、GARDNER, COLIN R.、MATHARU, SAR+

  DOI：——

  日期：——
• US4532243A
  申请人：——

  公开号：US4532243A

  公开（公告）日：1985-07-30