6-Chloro-N⁴-isobutyl-pyrimidine-4,5-diamine | 195252-59-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-Chloro-N⁴-isobutyl-pyrimidine-4,5-diamine
• 英文别名: 6-Chloro-N4-isobutylpyrimidine-4,5-diamine；6-chloro-4-N-(2-methylpropyl)pyrimidine-4,5-diamine
• CAS: 195252-59-6
• 化学式: C₈H₁₃ClN₄
• 分子量: 200.671
• InChiKey: HOFOWUSVCZKMGW-UHFFFAOYSA-N

物化性质

• 沸点：
  344.0±42.0 °C(Predicted)
• 密度：
  1.258±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-Chloro-N⁴-isobutyl-pyrimidine-4,5-diamine 在 乙基磺酸 作用下， 以 乙醇 为溶剂， 反应 86.0h， 生成 (9-Isobutyl-9H-purin-6-yl)-dimethyl-amine
  参考文献：
  名称：

  6-(Alkylamino)-9-alkylpurines. A New Class of Potential Antipsychotic Agents

  摘要：

  A series of 6-(alkylamino)-9-alkylpurines was synthesized and evaluated for the property of antagonizing the behavioral effects in animals of the dopamine agonist apomorphine. This model for identifying potential antipsychotic agents is based on the hypothesis that agents that antagonize apomorphine-induced aggressive behavior in rats and apomorphine-induced climbing in mice, but that do not block stereotyped behavior, could have an antipsychotic effect in humans without producing extrapyramidal side effects. The antiaggressive-behavior activity of lead compound 1 (6-(dimethylamino)-9-(3-phenylalaninamidobenzyl)-9H-purine) was improved 48-fold with 6-(cyclopropylamino)-9-(cyclopropylmethyl)-2-(trifluoromethyl)-9H-purine (80) (po ED50 of 2 mg/kg), which was obtained through an iterative sequence of structure-activity relationship studies that encompassed evaluation of the effects of structure variations at the purine 9-, 6-, and 2-positions. Potency was enhanced with a 9-cyclopropyl group, the duration of action was improved with the 6-(cyclopropylamino) substituent, potency was further enhanced with an N-formyl prodrug, and an agent with reduced cardiovascular effect emerged with the 2-trifluoromethyl purine 80. This potential antipsychotic agent was not developed further due to undesirable effects on the stomach.

  DOI：

  10.1021/jm960662s
• 作为产物：
  描述：

  4,6-二氯-5-氨基嘧啶 、 异丁胺 在 三乙胺 作用下， 以 正丁醇 为溶剂， 生成 6-Chloro-N⁴-isobutyl-pyrimidine-4,5-diamine
  参考文献：
  名称：

  嘌呤类似物的有效合成：FeCl 3 -SiO 2促进4,5-二氨基嘧啶与醛的环化反应，生成6,8,9-三取代嘌呤

  摘要：

  通过6-氯-4,5-二氨基嘧啶和FeCl 3 -SiO 2促进的各种醛的环化，可有效合成6,8,9-三取代嘌呤类似物。硅胶上的氯化亚铁（Fe（III））具有脱水剂和氧化剂的双重作用，并且在后处理过程中可以通过过滤方便地除去。

  DOI：

  10.1016/s0040-4039(00)01074-1

文献信息

• 6-(Alkylamino)-9-alkylpurines. A New Class of Potential Antipsychotic Agents
  作者：James L. Kelley、R. Morris Bullock、Mark P. Krochmal、Ed W. McLean、James A. Linn、Micheal J. Durcan、Barrett R. Cooper

  DOI：10.1021/jm960662s

  日期：1997.9.1

  A series of 6-(alkylamino)-9-alkylpurines was synthesized and evaluated for the property of antagonizing the behavioral effects in animals of the dopamine agonist apomorphine. This model for identifying potential antipsychotic agents is based on the hypothesis that agents that antagonize apomorphine-induced aggressive behavior in rats and apomorphine-induced climbing in mice, but that do not block stereotyped behavior, could have an antipsychotic effect in humans without producing extrapyramidal side effects. The antiaggressive-behavior activity of lead compound 1 (6-(dimethylamino)-9-(3-phenylalaninamidobenzyl)-9H-purine) was improved 48-fold with 6-(cyclopropylamino)-9-(cyclopropylmethyl)-2-(trifluoromethyl)-9H-purine (80) (po ED50 of 2 mg/kg), which was obtained through an iterative sequence of structure-activity relationship studies that encompassed evaluation of the effects of structure variations at the purine 9-, 6-, and 2-positions. Potency was enhanced with a 9-cyclopropyl group, the duration of action was improved with the 6-(cyclopropylamino) substituent, potency was further enhanced with an N-formyl prodrug, and an agent with reduced cardiovascular effect emerged with the 2-trifluoromethyl purine 80. This potential antipsychotic agent was not developed further due to undesirable effects on the stomach.
• Efficient synthesis of purine analogues: an FeCl3–SiO2-promoted cyclization reaction of 4,5-diaminopyrimidines with aldehydes leading to 6,8,9-trisubstituted purines
  作者：Qun Dang、Brian S Brown、Mark D Erion

  DOI：10.1016/s0040-4039(00)01074-1

  日期：2000.8

  6,8,9-Trisubstituted purine analogues were efficiently synthesized via cyclization of 6-chloro-4,5-diaminopyrimidines and various aldehydes promoted by FeCl3–SiO2. Fe(III) chloride on silica gel has a dual role of a dehydration agent and an oxidant, and was conveniently removed during work-up by filtration.

  通过6-氯-4,5-二氨基嘧啶和FeCl 3 -SiO 2促进的各种醛的环化，可有效合成6,8,9-三取代嘌呤类似物。硅胶上的氯化亚铁（Fe（III））具有脱水剂和氧化剂的双重作用，并且在后处理过程中可以通过过滤方便地除去。