6-Chloro-N⁴-cyclopropylmethyl-pyrimidine-4,5-diamine | 195252-60-9

• 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-cyclopropylmethyl-pyrimidine-4,5-diamine
• 英文别名: 6-Chloro-N4-(cyclopropylmethyl)pyrimidine-4,5-diamine；6-chloro-4-N-(cyclopropylmethyl)pyrimidine-4,5-diamine
• CAS: 195252-60-9
• 化学式: C₈H₁₁ClN₄
• 分子量: 198.655
• InChiKey: NSAKOTTZDXXUMX-UHFFFAOYSA-N

物化性质

• 沸点：
  376.6±42.0 °C(Predicted)
• 密度：
  1.430±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• 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-cyclopropylmethyl-pyrimidine-4,5-diamine 在 乙基磺酸 、 三乙胺 作用下， 以 乙醇 、 水 为溶剂， 反应 134.0h， 生成 N-cyclobutyl-9-(cyclopropylmethyl)purin-6-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-氯吡咯并嘧啶 、 环丙基甲胺 在 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 为溶剂， 反应 16.0h， 以53%的产率得到6-Chloro-N⁴-cyclopropylmethyl-pyrimidine-4,5-diamine
  参考文献：
  名称：

  Heterocyclic Compounds Useful as RAF Kinase Inhibitors

  摘要：

  本发明提供了作为Raf蛋白激酶抑制剂有用的化合物。本发明还提供了这些化合物的组合物，以及治疗Raf介导疾病的方法。

  公开号：

  US20090005359A1

文献信息

• Design, Synthesis, and Evaluation of Novel Isothiazole-Purines as a Pyruvate Kinase-Based Fungicidal Lead Compound
  作者：Weibo Wang、Zhixinyi Li、Wei Gao、Xiaoyu Liu、You Lv、Zesheng Hao、Liangfu Tang、Kun Li、Bin Zhao、Zhijin Fan

  DOI：10.1021/acs.jafc.1c01651

  日期：2021.8.18

  Target identification is one of the most important bases for novel pesticide development; pyruvate kinase (PK) was discovered as a potent fungicide target in our previous studies. To continue the PK-based fungicide development, novel isothiazole-purine derivatives were rationally designed and synthesized. Bioassay results showed that compound 5ai displayed excellent in vitro activity against Rhizoctonia

  目标鉴定是新型农药开发的最重要基础之一；在我们之前的研究中，丙酮酸激酶 (PK) 被发现是一种有效的杀菌剂靶标。为了继续开发基于 PK 的杀菌剂，我们合理设计和合成了新型异噻唑嘌呤衍生物。生物测定结果表明，化合物5ai对立枯丝核菌表现出优异的体外活性，EC 50为1.5 μg/mL，优于阳性对照diflumetorim的EC 50为19.8 μg/mL和基于PK的铅YZK - C22其 EC 50为 4.2 μg/mL。化合物3b(5.2 μg/mL) 和3c (4.5 μg/mL) 显示出更好的抗玉米赤霉活性，其 EC 50 s 介于 4.0 和 5.5 μg/mL 之间，而YZK-C22的 EC 50为 6.4 μg/mL。此外，5AH表现出有前途的体内活性对禾白粉菌和高粱柄锈菌SCHW。10 μg/mL 时具有 100% 的功效，2 μg/mL 时对P. sorghi Schw 的功效为
• US7968536B2
  申请人：——

  公开号：US7968536B2

  公开（公告）日：2011-06-28
• [EN] HETEROCYCLIC COMPOUNDS USEFUL AS RAF KINASE INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES UTILES EN TANT QU'INHIBITEURS DE LA KINASE RAF
  申请人：SUNESIS PHARMACEUTICALS INC

  公开号：WO2009006404A2

  公开（公告）日：2009-01-08

  The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases Formula (I) or a pharmaceutically acceptable salt thereof, wherein: Cy1 is an optionally substituted phenyl or an optionally substituted 5-6 membered saturated, partially unsaturated, or aromatic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur; Cy2 is an optionally substituted 5-10 membered saturated, partially unsaturated, or aromatic monocyclic or bicyclic ring having 0-4 heteroatoms, independently selected from nitrogen, oxygen, or sulfur; L1 is a direct bond of an optionally substituted, straight or branched C1-6 alkylene chain; L2 is a direct bond, or is an optionally substituted, straight or branched C1-6 alkylene chain wherein 1 or 2 methylene units of L2 are optionally and independently replaced by -O-, -S-, -N(R)-, -C(O)-, -C(O)N(R)-, -N(R)C(O)N(R)-, -N(R)C(O)-, -N(R)C(O)O-, -OC(O)N(R)-, -SO2-, -SO2N(R)-, -N(R)SO2-, -OC(O)-, -C(O)O-, or a 3-6 membered cycloalkylene; each R is independently hydrogen or an optionally substituted C1-6 aliphatic group;
• Heterocyclic Compounds Useful as RAF Kinase Inhibitors
  申请人：Cossrow Jennifer

  公开号：US20090005359A1

  公开（公告）日：2009-01-01

  The present invention provides compounds useful as inhibitors of Raf protein kinase. The present invention also provides compositions thereof, and methods of treating Raf-mediated diseases.

  本发明提供了作为Raf蛋白激酶抑制剂有用的化合物。本发明还提供了这些化合物的组合物，以及治疗Raf介导疾病的方法。
• 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.