6-氯-N4-环戊基嘧啶-4,5-二胺 | 5452-43-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 6-氯-N4-环戊基嘧啶-4,5-二胺
• 英文名称: 5-amino-4-chloro-6-(N-cyclopentylamino)pyrimidine
• 英文别名: 6-chloro-N⁴-cyclopentyl-pyrimidine-4,5-diamine；6-chloro-N⁴-cyclopentyl-pyrimidine-4,5-diyldiamine；6-Chlor-N⁴-cyclopentyl-pyrimidin-4,5-diyldiamin；(+/-)-5-Amino-4-chloro-6[(2-cyclopent-1-yl)amino]pyrimidine；6-Chloro-n4-cyclopentylpyrimidine-4,5-diamine；6-chloro-4-N-cyclopentylpyrimidine-4,5-diamine
• CAS: 5452-43-7
• 化学式: C₉H₁₃ClN₄
• mdl: MFCD05819954
• 分子量: 212.682
• InChiKey: HPFRDZDLWJMHNH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.555
• 拓扑面积：
  63.8
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090

反应信息

• 作为反应物：
  描述：

  6-氯-N4-环戊基嘧啶-4,5-二胺 在 乙基磺酸 、 三乙胺 作用下， 以 乙醇 为溶剂， 反应 140.0h， 生成 9-cyclopentyl-N-cyclopropylpurin-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：

  4,6-二氯-5-氨基嘧啶 、 正丁醇 在 三乙胺 作用下， 以76%的产率得到6-氯-N4-环戊基嘧啶-4,5-二胺
  参考文献：
  名称：

  Antiparasitic 3(4-amino benzotriazo-1-yl-)1,2-cyclopentanediols

  摘要：

  本发明涉及使用式(I)的化合物，其中R代表氢原子；C.sub.1-4烷基；羟基COR^1，其中R^1代表氨基或C.sub.1-4烷氧基；或基团--CH_2R^2，其中R^2代表卤原子（例如氯或溴）、C.sub.1-4烷基硫醚，或叠氮基；X和Y分别独立地代表--CH--或--N；Z代表--CR^3，其中R^3是氢或C.sub.1-4烷基，或Z代表--N--；或其生理上可接受的盐、酯或其他生理功能衍生物，用于制备用于治疗和/或预防哺乳动物寄生虫感染的药物，以及式(I)的某些新化合物、含有它们的药物组合物和制备它们的方法。

  公开号：

  US05039689A1

文献信息

• Fructose-1,6-bisphosphatase Inhibitors. 1. Purine Phosphonic Acids as Novel AMP Mimics
  作者：Qun Dang、Brian S. Brown、Yan Liu、Robert M. Rydzewski、Edward D. Robinson、Paul D. van Poelje、M. Rami Reddy、Mark D. Erion

  DOI：10.1021/jm900078f

  日期：2009.5.14

  Inhibition of FBPase is considered a promising way to reduce hepatic gluconeogenesis and therefore could be a potential approach to treat type 2 diabetes. Herein we report the discovery of a series of purine phosphonic acids as AMP mimics targeting the AMP site of FBPase, which was achieved using a structure-guided drug design approach. These non-nucleotide purine analogues inhibit FBPase in a similar

  抑制FBPase被认为是减少肝脏糖异生的有前途的方法，因此可能是治疗2型糖尿病的潜在方法。本文中，我们报道了一系列嘌呤膦酸的发现，它们是针对FBPase AMP位点的AMP模拟物，这是使用结构指导药物设计方法实现的。这些非核苷酸嘌呤类似物以与AMP相似的方式和相似的效力抑制FBPase。更重要的是，几种嘌呤类似物表现出有效的细胞和体内降糖活性，从而获得了抑制FBPase作为药物发现靶标的概念证明。例如，就FBPase抑制而言，化合物4.11和4.13与AMP等价。此外，化合物4.11 抑制原代大鼠肝细胞中的葡萄糖生成，并显着降低禁食大鼠的血糖水平。
• 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
• Exploration of novel 6,8,9-trisubstituted purine analogues: synthesis, in vitro biological evaluation, and their effect on human cancer cells
  作者：Muhammed Fatih POLAT、İrem Durmaz ŞAHİN、Rengül ATALAY、Meral TUNÇBİLEK

  DOI：10.55730/1300-0527.3643

  日期：——

  This study focuses on the design and synthesis of a novel series of purine derivatives, specifically 6-(substituted phenyl piperazine)-8-(4-phenoxyphenyl)-9-cyclopentyl purine derivatives (5-11). The motivation behind this endeavor lies in addressing acquired resistance mechanisms in cancer cells, a significant hurdle in current treatment modalities. The synthesis, starting from 4,6-dichloro-5-nitropyrimidine

  癌症是全球主要的死亡原因，需要不断改进治疗策略。本研究重点是设计和合成一系列新型嘌呤衍生物，特别是 6-(取代苯基哌嗪)-8-(4-苯氧基苯基)-9-环戊基嘌呤衍生物 (5-11)。这项努力背后的动机在于解决癌细胞的获得性耐药机制，这是当前治疗方式的一个重大障碍。该合成从 4,6-二氯-5-硝基嘧啶开始，涉及多步过程，产生七种新的嘌呤衍生物。使用 SRB 测定对人肝癌细胞、结肠癌细胞和乳腺癌细胞（分别为 Huh7、HCT116 和 MCF7）进行生物学评估。合成的类似物中，化合物5和6表现出显着的细胞毒活性，其功效超过临床使用的阳性对照5-氟尿嘧啶和氟达拉滨。这项研究强调了 C-8 位带有苯基的嘌呤衍生物作为开发具有改善抗癌特性的化合物的支架的潜力。这些发现为癌症药物研究中新药的未来探索和开发提供了见解。
• Synthesis and cytotoxicity of novel 6,8,9-trisubstituted purine analogs against liver cancer cells
  作者：M. Fatih Polat、Irem Durmaz Şahin、Pınar Kul、Rengul Cetin Atalay、Meral Tuncbilek

  DOI：10.1016/j.bmcl.2024.129775

  日期：2024.7

  series of novel 6-(substituted phenyl piperazine)-8-(4-substituted phenyl)-9-cyclopentyl purines, 10–51, were synthesized by a four-step synthesis, achieving an overall yield of about 43 %. The reaction conditions were effectively optimized, and the final products were obtained with high purity and yield in all synthesis steps. The synthesized nucleobases were evaluated for their in vitro cytotoxic activities

  通过四步合成合成了一系列新型6-(取代苯基哌嗪)-8-(4-取代苯基)-9-环戊基嘌呤10-51，总收率约为43%。反应条件得到有效优化，各合成步骤均获得了高纯度和高收率的最终产物。使用磺胺罗丹明 B (SRB) 测定评估合成核碱基对选定人类癌细胞系（HUH7（肝脏）、HCT116（结肠）和 MCF7（乳腺癌））的体外细胞毒活性。在这些类似物中，嘌呤 C-8 处带有 4-三氟甲基苯基（19、20 和 21）、4-甲氧基苯基（27）和 4-氟苯基（34）取代的化合物是最有效的，并且还对它们进行了分析用于耐药性和药物敏感性肝细胞癌细胞 (HCC) 组。与阳性对照氟达拉滨相比，化合物 19 对 Huh7、FOCUS、SNU475、SNU182、HepG2 和 Hep3B 细胞表现出显着的抗癌活性 (IC50 = 2.9–9.3 μM)。此外，还分别通过 Swiss-ADME 和 Pro-Tox II
• 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.