ethyl 2-{2-[(tert-butoxycarbonyl)amino]-6-chloro-9H-purin-9-yl}acetate | 1236151-75-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 2-{2-[(tert-butoxycarbonyl)amino]-6-chloro-9H-purin-9-yl}acetate
• 英文别名: (N2-Boc-2-amino-6-chloro-purin-9-yl)-acetic acid ethyl ester；Ethyl 2-[2-(Boc-amino)-6-chloro-9H-purin-9-yl]acetate；ethyl 2-[6-chloro-2-[(2-methylpropan-2-yl)oxycarbonylamino]purin-9-yl]acetate
• CAS: 1236151-75-9
• 化学式: C₁₄H₁₈ClN₅O₄
• 分子量: 355.781
• InChiKey: SLCYGHNGEORWMQ-UHFFFAOYSA-N

物化性质

• 熔点：
  129-136 °C
• 密度：
  1.42±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 2-{2-[(tert-butoxycarbonyl)amino]-6-chloro-9H-purin-9-yl}acetate 在 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 ethyl 2-(2-amino-6-morpholino-9H-purin-9-yl)acetate
  参考文献：
  名称：

  通过 QSAR 研究鉴定 Stat3 激活的嘌呤支架小分子抑制剂

  摘要：

  为了促进临床上有用的 Stat3 抑制剂的发现，对现有 Stat3 二聚化干扰物与 Stat3 的结合和定量构效关系 (QSAR) 进行了计算分析，由此衍生了药效团模型来预测优化的 Stat3 二聚化抑制剂。对 2,6,9-三取代嘌呤支架进行功能化，以便进入 Stat3 SH2 结构域表面的三个亚袋并衍生出有效的 Stat3 结合抑制剂。选择的嘌呤支架对纯化的非磷酸化 Stat3 表现出良好的亲和力（KD ，0.8−12 μM） ，并在体外抑制 Stat3 DNA 结合活性，并在 20−60 μM 时抑制细胞内磷酸化。此外，药物选择性抑制人类前列腺癌细胞、乳腺癌细胞和胰腺癌细胞以及具有异常 Stat3 活性的 v-Src 转化小鼠成纤维细胞的活力。本文的研究确定了新型小分子三取代嘌呤作为持续活性 Stat3 和 Stat3 依赖性肿瘤细胞活力的有效抑制剂，并且首次验证了使用嘌呤碱基作为构建新型

  DOI：

  10.1021/ml100224d
• 作为产物：
  描述：

  2-amino-9-tert-butoxycarbonyl-6-chloropurine 在 偶氮二甲酸二异丙酯 、 sodium hydride 、 三苯基膦 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 2.26h， 生成 ethyl 2-{2-[(tert-butoxycarbonyl)amino]-6-chloro-9H-purin-9-yl}acetate
  参考文献：
  名称：

  [EN] SUBSTITUTED 2-(9H-PURIN-9-YL) ACETIC ACID ANALOGUES AS INHIBITORS OF STAT3
  [FR] ANALOGUES D'ACIDE 2-(9H-PURIN-9-YL)ACÉTIQUE SUBSTITUÉS EN TANT QU'INHIBITEURS DE STAT3

  摘要：

  公开号：

  WO2011163424A3

文献信息

• Development of a convenient route for the preparation of the N2-Cbz-protected guaninyl synthon required for Boc-mediated PNA synthesis
  作者：Amelie Heuer-Jungemann、Nicola M. Howarth、Saudatu C. Ja’Afaru、Georgina M. Rosair

  DOI：10.1016/j.tetlet.2013.09.034

  日期：2013.11

  An efficient, high yielding, chemo- and regioselective, five-step synthetic route to N2-Cbz-guanin-9-yl acetic acid has been developed, which avoids the use of triphosgene. After formation of the N2-Boc protected purine from 2-amino-6-chloropurine, two successive base-controlled alkylations allowed an N9-tert-butyl acetate function followed by an N2-Cbz moiety to be installed. The selectivities of

  已经开发了一种高效，高产，化学和区域选择性的五步合成N 2 -Cbz-鸟嘌呤-9-基乙酸的合成路线，该路线避免了使用三光气。在形成后Ñ 2 -Boc由2-氨基-6-氯嘌呤保护嘌呤，两个连续的基控制烷基化允许一个Ñ 9 -叔丁基乙酸酯功能后跟Ñ 2 -Cbz部分进行安装。通过对6-（2-硝基苯氧基）类似物的X射线晶体学研究证实了这些反应的选择性。最后水解脱氯并去除Boc和叔叔同时在酸性条件下完成叔丁酯保护基团，以总产率53％得到鸟嘌呤-9-基PNA单体合成子。
• Microwave-assisted solid-phase synthesis of antisense acpP peptide nucleic acid-peptide conjugates active against colistin- and tigecycline-resistant E. coli and K. pneumoniae
  作者：Anna Mette Hansen、Gitte Bonke、Wouter Frederik Johan Hogendorf、Fredrik Björkling、John Nielsen、Kenneth T. Kongstad、Dorota Zabicka、Magdalena Tomczak、Malgorzata Urbas、Peter E. Nielsen、Henrik Franzyk

  DOI：10.1016/j.ejmech.2019.02.024

  日期：2019.4

  antisense PNA-peptide conjugates encouraged development of a fast and efficient synthesis protocol that facilitates structure-activity studies. The use of an Fmoc/Boc protection scheme for both PNA monomers and amino acid building blocks in combination with microwave-assisted solid-phase synthesis proved to be a convenient procedure for continuous assembly of antisense PNA-peptide conjugates. A validated

  有效的抗菌反义PNA-肽缀合物的最新发现促进了快速，有效的合成方案的发展，该方案促进了结构活性研究。结合微波辅助固相合成，对PNA单体和氨基酸构件使用Fmoc / Boc保护方案已被证明是反义PNA-肽共轭物连续组装的便捷方法。 将经过验证的反义PNA低聚物（CTCATACTCT；靶向acpP基因的mRNA ）与N端修饰的drosocin（即RXR-PRPYSPRPTSHPRPIRV； X =氨基己酸）或截短的Pip1肽（即RXRRXR-IKILFQNRRMKWKK； X =氨基己酸），并确定所得缀合物的抗菌作用，从而可以评估不同接头的影响以及肽L型和D型之间的差异。 不含接头部分的德罗霉素衍生化合物对野生型大肠杆菌和肺炎克雷伯菌均表现出最高的抗菌活性（MIC在2-4μg/ mL〜0.3-0.7μM范围内），而类似物则显示乙二醇（例如1）部分或极性马来酰亚胺连接基也具有对野生型肺炎克雷伯菌的活性（MIC为4-8μg/
• SUBSTITUTED 2-(9H-PURIN-9-YL) ACETIC ACID ANALOGUES AS INHIBITORS OF STAT3
  申请人：Turkson James

  公开号：US20130172340A1

  公开（公告）日：2013-07-04

  In one aspect, the invention relates to substituted purine analogs, derivatives thereof, and related compounds, which are useful as inhibitors of STAT protein activity; synthetic methods for making the compounds; pharmaceutical compositions comprising the compounds; and methods of treating disorders of uncontrolled cellular proliferation associated with a STAT protein activity dysfunction using the compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在某个方面，本发明涉及取代嘌呤类似物、其衍生物和相关化合物，这些化合物可用作STAT蛋白活性的抑制剂；制备这些化合物的合成方法；包含这些化合物的药物组合物；以及使用这些化合物和组合物治疗与STAT蛋白活性功能障碍相关的细胞无控制增殖疾病的方法。本摘要旨在作为搜索特定技术领域的扫描工具，不旨在限制本发明。
• A 2,6,9-hetero-trisubstituted purine inhibitor exhibits potent biological effects against multiple myeloma cells
  作者：Vijay M. Shahani、Daniel P. Ball、Allan V. Ramos、Zhihua Li、Paul A. Spagnuolo、Sina Haftchenary、Aaron D. Schimmer、Suzanne Trudel、Patrick T. Gunning

  DOI：10.1016/j.bmc.2013.04.080

  日期：2013.9

  A focused library of hetero-trisubstituted purines was developed for improving the cell penetrating and biological efficacy of a series of anti-Stat3 protein inhibitors. From this SAR study, lead agent 22e was identified as being a promising inhibitor of MM tumour cells (IC50's <5 mu M). Surprisingly, biophysical and biochemical characterization proved that 22e was not a Stat3 inhibitor. Initial screening against the kinome, prompted by the purine scaffold's history for targeting ATP binding pockets, suggests possible targeting of the JAK family kinases, as well for ABL1 (nonphosphorylated F317L) and AAK1. (C) 2013 Elsevier Ltd. All rights reserved.
• Concise access to N9-mono-, N2-mono- and N2,N9-di-substituted guanines via efficient Mitsunobu reactions
  作者：Steven Fletcher、Vijay M. Shahani、Alan J. Lough、Patrick T. Gunning

  DOI：10.1016/j.tet.2010.03.118

  日期：2010.6

  Guanine poses several problems to the synthetic chemist owing to its polyfunctional nature and poor solubility. Over the past few decades, synthetic guanines have found applications as anti-cancer and anti-viral agents. Coupled with the ever-growing interest in designer PNAs and G-quartets, simple and efficient synthetic routes to novel guanines would be of significant benefit. We herein report that, upon simple protection and/or activation step(s), the guanine precursor 2-amino-6-chloropurine is rendered an excellent substrate for Mitsunobu chemistry, furnishing, after subsequent hydrolytic dechlorination and appropriate deprotection step(s), the desired N9-mono-, N2-mono- or N2,N9-di-substituted guanines in excellent yields (>= 80%). Importantly, we demonstrate that N9-functionalization proceeds with very good N9/N7 regioselectivity and with complete inversion of stereochemistry. (C) 2010 Elsevier Ltd. All rights reserved.