2-chloro-N-cyclopropyl-9H-purin-6-amine | 195252-69-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 2-chloro-N-cyclopropyl-9H-purin-6-amine
• 英文别名: 6-Cyclopropylamino-2-chloropurine；2-chloro-N-cyclopropyl-7H-purin-6-amine
• CAS: 195252-69-8
• 化学式: C₈H₈ClN₅
• 分子量: 209.638
• InChiKey: VZFTVKCEUWKDPE-UHFFFAOYSA-N

物化性质

• 沸点：
  328.5±52.0 °C(Predicted)
• 密度：
  1.92±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  66.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-chloro-N-cyclopropyl-9H-purin-6-amine 在 sodium ethanolate 、 potassium carbonate 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 8.0h， 生成 N-cyclopropyl-9-(cyclopropylmethyl)-2-methylsulfanylpurin-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：

  2-chloro-N-(2,2,2-trifluoroethyl)-9H-purine-6-amine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 四氢呋喃 、 异丙醇 、 叔丁醇 为溶剂， 反应 20.0h， 生成 2-chloro-N-cyclopropyl-9H-purin-6-amine
  参考文献：
  名称：

  二氨基嘌呤化学型的药物化学优化：寻找布氏锥虫抑制剂的先导物。

  摘要：

  非洲人类锥虫病 (HAT) 或昏睡病是由原生动物寄生虫布氏锥虫引起的，并通过受感染的采采蝇叮咬传播。如果不治疗，这种疾病被认为是致命的。为了鉴定针对布氏锥虫的新化学型，之前我们鉴定了 797 种有效的激酶靶向抑制剂，这些抑制剂分为 59 个簇和 53 种单一化合物，其选择性至少是 HepG2 细胞的 100 倍。从这组命中中，鉴定了一组二氨基嘌呤衍生的化合物。在此，我们报告了我们的药物化学研究，涉及探索围绕高通量筛选 (HTS) 命中之一N 2 -(噻吩-3-基)-的结构-活性和结构-性质关系N 6 -(2,2,2-三氟乙基)-9 H-嘌呤-2,6-二胺( 1，NEU-1106)。这项工作导致鉴定出一种有效的先导化合物（4aa，NEU-4854），其具有改善的体外吸收、分布、代谢和排泄 (ADME) 特性，并已进展为体外抗寄生虫活性的概念验证翻译到体内功效。

  DOI：

  10.1021/acs.jmedchem.0c01017

文献信息

• Enantioselective and Regiodivergent Addition of Purines to Terminal Allenes: Synthesis of Abacavir
  作者：Niels Thieme、Bernhard Breit

  DOI：10.1002/anie.201610876

  日期：2017.2

  The rhodium‐catalyzed atom‐economic asymmetric N‐selective intermolecular addition of purine derivatives to terminal allenes is reported. Branched allylic purines were obtained in high yields, regioselectivity and outstanding enantioselectivity utilizing a Rh/Josiphos catalyst. Conversely, linear selective allylation of purines could be realized in good to excellent regio‐ and E/Z‐selectivity with

  据报道，铑催化的原子经济不对称的N选择性分子间嘌呤衍生物加成到末端亚丙基上。利用Rh / Josiphos催化剂以高收率，区域选择性和突出的对映选择性获得支链的烯丙基嘌呤。相反，使用Pd / dppf催化剂体系可以实现嘌呤的线性选择性烯丙基化，具有良好的区域选择性和E / Z选择性。此外，新方法被应用于碳环核苷阿巴卡韦的直接不对称合成。
• Purine derivatives inhibitors of tyrosine protein kinase SYK
  申请人：Novartis AG

  公开号：US06589950B1

  公开（公告）日：2003-07-08

  Disclosed are compounds of the formula in free or salt form, wherein X, R1, R2, R3, and R4 are as defined in the specification, their preparation and their use as pharmaceuticals, particularly for the treatment of inflammatory or obstructive airways disease.

  本文披露了以自由或盐形式呈现的公式化合物，其中X、R1、R2、R3和R4如规范中定义，它们的制备以及它们作为药物的用途，特别用于治疗炎症性或阻塞性呼吸道疾病。
• Regio- and Enantioselective [3+2] Cycloaddition of α-Purine Substituted Acrylates with Allenes: An Approach to Chiral Carbocyclic Nucleosides
  作者：Yao-Wei Gao、Hong-Ying Niu、Qi-Ying Zhang、Ming-Sheng Xie、Gui-Rong Qu、Hai-Ming Guo

  DOI：10.1002/adsc.201800523

  日期：2018.8.6

  employed in the phosphine‐catalyzed [3+2] annulation with allenes for the first time, affording regiospecific carbocyclic nucleoside analogues in an α‐addition manner. Various chiral carbocyclic nucleoside analogues containing a quaternary stereocenter and a C=C double bond are generated in good yields (up to 90% yield) and excellent enantioselectivities (up to 97% ee). α‐Purine‐containing disubstituted

  N-杂芳族取代的丙烯酸酯首次用于膦与丙二烯的[3 + 2]环合中，以α加成的方式提供了区域特异性的碳环核苷类似物。各种具有季立体中心和C = C双键的手性碳环核苷类似物的收率高（产率高达90％）和对映体选择性（ee高达97％）。含α-嘌呤的二取代丙烯酸酯和α-苯并咪唑取代的丙烯酸酯也是该反应的合适底物。
• N²-quinoline or isoquinoline substituted purine derivatives
  申请人：Wu Zhanggui

  公开号：US20060293274A1

  公开（公告）日：2006-12-28

  Novel compound having the following formula: wherein W represents a hydrogen, an optionally substituted C 1-6 alkyl, an optionally substituted C 3-6 cycloalkyl, or an optionally substituted C 1-6 haloalkyl, Y represents a hydrogen, or a saccharide, Q represents a quinoline or isoquinoline. Also disclosed are a pharmaceutical compositions comprising the same, methods for treating cancer using the same, and methods for the synthesis of the same.

  具有以下化学式的新化合物：其中W代表氢、可选择取代的C1-6烷基、可选择取代的C3-6环烷基或可选择取代的C1-6卤代烷基，Y代表氢或糖苷，Q代表喹啉或异喹啉。还披露了包含该化合物的药物组合物、使用该化合物治疗癌症的方法以及合成该化合物的方法。
• Importance of HMBC and NOE 2D NMR techniques for the confirmation of regioselectivity
  作者：Yashwantsinh Jadeja、Khushal Kapadiya、Anamik Shah、Ranjan Khunt

  DOI：10.1002/mrc.4315

  日期：2016.1

  activities. Moreover, natural purines are found to be the core skeleton of nucleic acid, which are directly correlated with enzymes and proteins. Recently, the synthesis of 6-amino-substituted purine analogs was carried out by the amination of halogenated purines using organic solvents, such as n-butanol, acetonitrile, dioxane, DMF, and DMSO in the presence of versatile bases such as Et3N, N,N-dimethylcyclohexylamine

  在现代化疗中，多功能嘌呤骨架发挥着核心作用。由于其显着的治疗潜力，嘌呤核在各种天然来源中的出现引起了极大的兴趣。其中，大量 6-氨基取代的嘌呤衍生物具有抗惊厥、抗病毒、抗炎、抗肿瘤、平喘和抗菌活性。此外，天然嘌呤被发现是核酸的核心骨架，与酶和蛋白质直接相关。最近，6-氨基取代的嘌呤类似物的合成是通过使用有机溶剂（如正丁醇​​、乙腈、二恶烷、DMF 和 DMSO）在通用碱（如 Et3N、N）存在下将卤化嘌呤胺化来进行的。 ,N-二甲基环己胺和二异丙基乙胺。嘌呤取代受其化学性质的影响，从而影响核磁共振 (NMR) 分析的结果，例如取决于电子环境的原子之间的化学位移和耦合常数。由于嘌呤碱支架中氯（C-2 和 C-6）的化学环境相同，因此有必要确定胺化的区域选择性。这将有助于正确的结构评估和确定原子核之间的相互作用。目前的工作包括使用各种技术，例如 H NMR、C NMR、核 Overhauser