2-amino-6-(prop-2-ynyloxy)purine

• 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-amino-6-(prop-2-ynyloxy)purine
• 英文别名: NU2031；O6-propargylguanine；O6-Substituted Guanine Deriv. 12；6-prop-2-ynoxy-7H-purin-2-amine
• 化学式: C₈H₇N₅O
• 分子量: 189.176
• InChiKey: MVZMHAXNJPJZIS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  89.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-6-(prop-2-ynyloxy)purine 在 tetrafluoroboric acid 、 三氟乙酸 作用下， 以 2,2,2-三氟乙醇 、 水 为溶剂， 生成 2-sulfanilyl-6-(prop-2-ynyloxy)purine
  参考文献：
  名称：

  Cyclin-Dependent Kinase (CDK) Inhibitors: Structure–Activity Relationships and Insights into the CDK-2 Selectivity of 6-Substituted 2-Arylaminopurines

  摘要：

  Purines and related heterocycles substituted at C-2 with 4'-sulfamoylanilino and at C-6 with a variety of groups have been synthesized with the aim of achieving selectivity of binding to CDK2 over CDK1. 6-Substituents that favor competitive inhibition at the ATP binding site of CDK2 were identified and typically exhibited 10-80-fold greater inhibition of CDK2 compared to CDK1. Most impressive was 44(6-([1,1'-bipheny1]-3-y1)-9H-purin-2-yl)amino) benzenesulfonamide (73) that exhibited high potency toward CDK2 (IC50 0.044 mu M) but was similar to 2000-fold less active toward CDK1 (IC50 86 mu M). This compound is therefore a useful tool for studies of cell cycle regulation. Crystal structures of inhibitor kinase complexes showed that the inhibitor stabilizes a glycine-rich loop conformation that shapes the ATP ribose binding pocket and that is preferred in CDK2 but has not been observed in CDK1. This aspect of the active site may be exploited for the design of inhibitors that distinguish between CDK1 and CDK2.

  DOI：

  10.1021/acs.jmedchem.6b01254
• 作为产物：
  描述：

  鸟嘌呤 在 溶剂黄146 、 三氯氧磷 作用下， 以 二甲基亚砜 、 1,2-二氯乙烷 、 PEG-2000 为溶剂， 反应 23.83h， 生成 2-amino-6-(prop-2-ynyloxy)purine
  参考文献：
  名称：

  Hu, Yu Lin; Ge, Qiang; Lu, Ming, Bulletin of the Chemical Society of Ethiopia, 2010, vol. 24, # 3, p. 425 - 432

  摘要：

  DOI：

文献信息

• Facilitation of displacements at the 6-position of purines by the use of 1,4-diazabicyclo[2.2.2]octane as leaving group
  作者：Nicola K. Lembicz、Sharon Grant、William Clegg、Roger J. Griffin、Sarah L. Heath、Bernard T. Golding

  DOI：10.1039/a608207f

  日期：——

  Reactions of 6-chloropurines with 1,4-diazabicyclo[2.2.2]octane (DABCO) give the corresponding ‘DABCO-purines’ 1a–d, which undergo facile displacement reactions with alkoxides in dimethyl sulfoxide to afford 6-oxy-substituted purines.

  6-氯嘌呤与1,4-二氮杂双环[2.2.2]辛烷（DABCO）的反应生成相应的“DABCO-嘌呤”1a–d，这些化合物在二甲基亚砜中与醇盐发生容易的取代反应，生成6-氧取代的嘌呤。
• [EN] METHODS FOR IDENTIFYING INHIBITORS OF "STIMULATOR OF INTERFERON GENE"-DEPENDENT INTERFERON PRODUCTION<br/>[FR] PROCÉDÉS SERVANT À IDENTIFIER DES INHIBITEURS DE LA PRODUCTION D'INTERFÉRON DÉPENDANT DU STIMULATEUR DU GÈNE D'INTERFÉRON
  申请人：ADURO BIOTECH INC

  公开号：WO2017106740A1

  公开（公告）日：2017-06-22

  The present invention relates to the use cyclic-di-nucleotide and related scaffold molecules that measurably inhibit STING signaling, and methods for their use in identifying more potent inhibitors of STING signaling. In particular, the methods provided can be used to identify potent inhibitors of STING signaling, which are useful in the treatment of autoimmune and inflammatory diseases. Also provided are compounds having STING inhibitory activity useful in the treatment of autoimmune and inflammatory diseases.

  本发明涉及使用环二核苷酸和相关支架分子来可测地抑制STING信号传导的方法，以及利用这些方法来鉴定更强效的STING信号传导抑制剂的方法。具体而言，所提供的方法可用于鉴定强效的STING信号传导抑制剂，这些抑制剂在治疗自身免疫和炎症性疾病方面非常有用。同时还提供了具有STING抑制活性的化合物，可用于治疗自身免疫和炎症性疾病。
• Resistance-Modifying Agents. 8. Inhibition of <i>O</i>⁶-Alkylguanine-DNA Alkyltransferase by <i>O</i>⁶-Alkenyl-, <i>O</i>⁶-Cycloalkenyl-, and <i>O</i>⁶-(2-Oxoalkyl)guanines and Potentiation of Temozolomide Cytotoxicity in Vitro by <i>O</i>⁶-(1-Cyclopentenylmethyl)guanine
  作者：Roger J. Griffin、Christine E. Arris、Christine Bleasdale、F. Thomas Boyle、A. Hilary Calvert、Nicola J. Curtin、Christine Dalby、Sreenivas Kanugula、Nicola K. Lembicz、David R. Newell、Anthony E. Pegg、Bernard T. Golding

  DOI：10.1021/jm000961o

  日期：2000.11.1

  A series of O-6-allyl- and O-6-(2-oxoalkyl)guanines were synthesized and evaluated, in comp ari son with the corresponding O-6-alkylguanines, as potential inhibitors of the DNA-repair protein O-6-alkylguanine-DNA alkyltransferase (AGT). Simple O-6-alkyl- and O-6-cycloalkylguanines were weak AGT inactivators compared with O-6-allylguanine (IC50 = 8.5 +/- 0.6 muM) With IC50 values ranging from 100 to 1000 muM. The introduction of substituents at C-2 of the allyl group of O-6-allylguanine reduced activity compared with the parent compound, while analogous compounds in the O-6-(2-oxoalkyl)guanine series exhibited very poor activity (150-1000 muM) O-6-Cycloalkenylguanines proved to be excellent AGT inactivators, with 1-cyclobutenylmethylguanine (IC50 = 0.55 +/- 0.02 muM) and 1-cyclopentenylmethylguanine (IC50 = 0.39 +/- 0.04 muM) exhibiting potency approaching that of the benchmark AGT inhibitor O-6-benzylguanine (IC50 = 0.18 +/- 0.02 muM). 1-Cyclopentenylmethylguanine also inactivated AGT in intact HT29 human colorectal carcinoma cells (IC50 = 0.20 +/- 0.07 muM) and potentiated the cytotoxicity of the monomethylating antitumor agent Temozolomide by approximately 3- and 10-fold, respectively, in the HT29 and Colo205 tumor cell lines. The observation that four mutant AGT enzymes resistant to O-6-benzylguanine also proved strongly cross-resistant to 1-cyclopentenylmethylguanine indicates that the O-6-substituent of each compound makes similar binding interactions within the active site of AGT.
• METHODS FOR IDENTIFYING INHIBITORS OF "STIMULATOR OF INTERFERON GENE"- DEPENDENT INTERFERON PRODUCTION
  申请人：ADURO BIOTECH, INC.

  公开号：US20180369268A1

  公开（公告）日：2018-12-27

  The present invention relates to the use cyclic-di-nucleotide and related scaffold molecules that measurably inhibit STING signaling, and methods for their use in identifying more potent inhibitors of STING signaling. In particular, the methods provided can be used to identify potent inhibitors of STING signaling, which are useful in the treatment of autoimmune and inflammatory diseases. Also provided are compounds having STING inhibitory activity useful in the treatment of autoimmune and inflammatory diseases.
• US7799524B2
  申请人：——

  公开号：US7799524B2

  公开（公告）日：2010-09-21