5-amino-4-(tert-butylamino)-6-chloropyrimidine | 18202-61-4

• 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: 5-amino-4-(tert-butylamino)-6-chloropyrimidine
• 英文别名: 5-Amino-4-t-butylamino-6-chloropyrimidine；4-N-tert-butyl-6-chloropyrimidine-4,5-diamine
• CAS: 18202-61-4
• 化学式: C₈H₁₃ClN₄
• 分子量: 200.671
• InChiKey: QRGISIWSJMMCBF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  2
• 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：

  5-amino-4-(tert-butylamino)-6-chloropyrimidine 在 乙基磺酸 作用下， 以 乙醇 为溶剂， 反应 138.0h， 生成 (9-tert-Butyl-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：

  tert-butyl-(6-chloro-5-nitro-pyrimidin-4-yl)-amine 在 tin(II) chloride dihdyrate 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 5-amino-4-(tert-butylamino)-6-chloropyrimidine
  参考文献：
  名称：

  Synthesis of 6,8,9 poly-substituted purine analogue libraries as pro-apoptotic inducers of human leukemic lymphocytes and DAPK-1 inhibitors

  摘要：

  研究DAPK1在凋亡中的作用的嘌呤。

  DOI：

  10.1039/c5ob00230c

文献信息

• ¹ H and ¹³ C assignments of 6-, 8-, 9- substituted purines
  作者：Álvaro Lorente-Macías、Manuel Benítez-Quesada、Ignacio J. Molina、Asier Unciti-Broceta、Juan José Díaz-Mochón、María José Pineda de las Infantas Villatoro

  DOI：10.1002/mrc.4743

  日期：2018.9

  Purines are heterocyclic aromatic organic compounds consisting of two 5‐ and 6‐membered fused rings containing nitrogen. They are present in numerous compounds, including natural products, with potent biological activity. Purine analogs are used for the treatment of acute leukemias. Thiopurine derivatives are effective antiviral (acyclovir and ganciclovir) or antitumor agents such as vidarabine, among

  嘌呤是杂环芳香族有机化合物，由两个含氮的 5 元和 6 元稠环组成。它们存在于许多具有强大生物活性的化合物中，包括天然产物。嘌呤类似物用于治疗急性白血病。硫嘌呤衍生物是有效的抗病毒剂（阿昔洛韦和更昔洛韦）或抗肿瘤剂，例如阿糖腺苷，以及其他临床用途。多年来，嘌呤核已成为一个重要的药效团。它能够干扰酶和核酸的合成和功能。它也经常用于开发蛋白激酶抑制剂。我们的研究小组开发了生产嘌呤文库的新途径。其中一种途径是一锅法合成以获得 6-、8-、来自 4-烷基氨基-5-氨基-6-氯嘧啶、醇和 N,N-二甲基酰胺的 9-取代嘌呤。我们还提出了一种获得三取代嘌呤的新方法。我们能够制备多取代嘌呤库。发现该文库中的一些化合物是死亡相关蛋白激酶-1 的特异性抑制剂。该文库的主要化合物是肿瘤淋巴细胞凋亡的有效诱导剂，也降低锥虫的活力。我们在此报告了这些新嘌呤衍生物子集的 H 和 C 的明确分配。在化合物 3k 和 3n
• Synthesis and screening of 6‐alkoxy purine analogs as cell type‐selective apoptotic inducers in Jurkat cells
  作者：Álvaro Lorente‐Macías、Inmaculada Iañez、M. Carmen Jiménez‐López、Manuel Benítez‐Quesada、Sara Torres‐Rusillo、Juan J. Díaz‐Mochón、Ignacio J. Molina、María J. Pineda de las Infantas

  DOI：10.1002/ardp.202100095

  日期：2021.10

  scaffolds in drug design. In this study, we explored the key structural features of a purine-based proapoptotic hit, 8-tert-butyl-9-phenyl-6-benzyloxy-9H-purine (1), by setting up a library of 6-alkoxy purines with the aim of elucidating the structural requirements that govern its biological activity and to study the cell selectivity of this chemotype. This was done by a phenotypic screening approach based

  嘌呤是细胞生物学中普遍存在的结构，涉及多种细胞过程，因此取代的嘌呤和类似物被认为是药物设计中的优秀支架。在这项研究中，我们通过建立 6-烷氧基嘌呤文库，探索了基于嘌呤的促凋亡基因 8- tert -butyl-9-phenyl-6-benzyloxy-9 H -purine ( 1 ) 的关键结构特征目的是阐明控制其生物活性的结构要求并研究这种化学型的细胞选择性。这是通过基于六种人类癌细胞系（包括 T 细胞白血病 Jurkat 细胞）的细胞周期分析的表型筛选方法完成的。从这项研究中，两个衍生品（12和13) 被鉴定为 Jurkat 选择性促凋亡化合物，显示出比 hit 1更好的效力和细胞选择性。
• 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.
• Synthesis of 6,8,9 poly-substituted purine analogue libraries as pro-apoptotic inducers of human leukemic lymphocytes and DAPK-1 inhibitors
  作者：Maria J. Pineda de las Infantas、Sara Torres-Rusillo、Juan Diego Unciti-Broceta、Pablo Fernandez-Rubio、Maria Angelica Luque-Gonzalez、Miguel A. Gallo、Asier Unciti-Broceta、Ignacio J. Molina、Juan J. Diaz-Mochon

  DOI：10.1039/c5ob00230c

  日期：——

  Purines to study DAPK1 role in apoptosis.

  研究DAPK1在凋亡中的作用的嘌呤。