[6-ethyl-5-methyl-7-(methylthio)imidazo[1,2-a]-pyrimidin-2-yl]phenylmethanone | 90808-45-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [6-ethyl-5-methyl-7-(methylthio)imidazo[1,2-a]-pyrimidin-2-yl]phenylmethanone
• 英文别名: [6-Ethyl-5-methyl-7-(methylthio)imidazo[1,2-a]pyrimidin-2-yl]phenylmethanone；(6-ethyl-5-methyl-7-methylsulfanylimidazo[1,2-a]pyrimidin-2-yl)-phenylmethanone
• CAS: 90808-45-0
• 化学式: C₁₇H₁₇N₃OS
• 分子量: 311.407
• InChiKey: BGKUHIDYYBXDRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  72.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [6-ethyl-5-methyl-7-(methylthio)imidazo[1,2-a]-pyrimidin-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， 生成 (3-bromo-6-ethyl-5-methyl-7-(methylthio)imidazo<1,2-a>pyrimidin-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：

  5-ethyl-4-methyl-6-methylthio-2-pyrimidinamine 、 3-bromo-1-phenylpropane-1,2-dione 在 pyrimidinium salt 、 乙醚 、 乙醇 、 氯仿 、 potassium carbonate 、 magnesium sulfate 作用下， 以 乙醚 为溶剂， 反应 49.0h， 以yielded 4.1 g (53% yield) of [6-ethyl-5-methyl-7-(methylthio)imidazo[1,2-a]pyrimidin-2-yl]phenylmethanone的产率得到[6-ethyl-5-methyl-7-(methylthio)imidazo[1,2-a]-pyrimidin-2-yl]phenylmethanone
  参考文献：
  名称：

  Imidazo(1,2-a)pyrimidines and their salts useful for treating anxiety

  摘要：

  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。

  公开号：

  US04532243A1

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。
• 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
• US4588720A
  申请人：——

  公开号：US4588720A

  公开（公告）日：1986-05-13
• (Imidazo[1,2-a]pyrimidin-2-yl)phenylmethanones and related compounds as potential nonsedative anxiolytics
  作者：Stephen Clements-Jewery、Geoffrey Danswan、Colin R. Gardner、Saroop S. Matharu、Robert Murdoch、W. Roger Tully、Robert Westwood

  DOI：10.1021/jm00401a025

  日期：1988.6

  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.