3-(2'-deoxy-β-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: 3-(2'-deoxy-β-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one
• 英文别名: 1,N²-propano-2'-deoxyguanosine；1,N2-(prop-1,3-diyl)-2'-deoxyguanosine；3-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-4,6,7,8-tetrahydropyrimido[1,2-a]purin-10-one
• 化学式: C₁₃H₁₇N₅O₄
• 分子量: 307.309
• InChiKey: HGYWFMCWAWUWRE-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  112
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-(2'-deoxy-β-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one 、 4,4'-双甲氧基三苯甲基氯 生成 3-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-hydroxyoxolan-2-yl]-4,6,7,8-tetrahydropyrimido[1,2-a]purin-10-one
  参考文献：
  名称：

  MARINELLI, EDMUND R.;JOHNSON, FRANCIS;IDEN, CHARLES R.;YU, PEI-LIN, CHEM. RES. TOXICOL., 3,(1990) N, C. 49-58

  摘要：

  DOI：
• 作为产物：
  描述：

  2'-脱氧鸟苷 在 sodium hydroxide 、 sodium tetrahydroborate 、 sodium periodate 、 四氧化锇 、 N-甲基吗啉氧化物 作用下， 以 phosphate buffer 、 N,N-二甲基乙酰胺 、 水 、 丙酮 为溶剂， 反应 121.25h， 生成 3-(2'-deoxy-β-D-erythro-pentofuranosyl)-5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one
  参考文献：
  名称：

  丙烯醛的DNA加合物：含有6-羟基-5,6,7,8-四氢嘧啶[1,2-a]嘌呤-10（3H）-one（鸟嘌呤的丙烯醛加合物）的寡脱氧核苷酸的位点特异性合成。

  摘要：

  通过低产率形成3-（2-脱氧-β-D-赤型-呋喃呋喃糖基）-6-羟基-5,6,7,8-四氢嘧啶基[1,2-a]嘌呤-10（3H）-丙烯醛与2'-脱氧鸟苷的反应。已经合成了核苷和包含它的寡聚脱氧核苷酸。为了制备核苷，使用1-溴-3-丁烯在N1位置将2′-脱氧鸟苷烷基化，得到1-（3-丁烯基）-2′-脱氧鸟苷。用OsO（4）和N-甲基吗啉-N-氧化物氧化得到3,4-二羟基丁基加合物，然后用NaIO（4）氧化得到1-（3-氧代丙基）加合物，它自发环化，得到标题化合物，为两种非对映异构体的快速差向异构混合物。用NaBH（4）还原核苷，得到未官能化的化合物，加上1-（3-羟丙基）-2' -脱氧鸟苷显示差向异构化是通过亚胺和1-（3-氧代丙基）加合物发生的。用NaCNBH（3）还原仅得到未官能化的3-（2-脱氧-β-D-赤-五呋喃糖基）-5,6,7,8-四氢嘧啶基[1,2-a]嘌呤-10（3H）-。制

  DOI：

  10.1021/tx010181y

文献信息

• [EN] METHODS FOR TREATING CANCERS HAVING BRCA2 AND PALB2 MUTATIONS<br/>[FR] MÉTHODES DE TRAITEMENT DE CANCERS AYANT DES MUTATIONS DE BRCA2 ET DE PALB2
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2014078633A1

  公开（公告）日：2014-05-22

  The present invention provides a method for treating or preventing cancer in a subject wherein the subject is identified as having a BRCA2-/- and/or PALB2-/- mutation comprising: a) obtaining a sample from a subject; b) analyzing the sample for the presence of a BRCA2-/- and/or PALB2-/- mutation; c) administering to the subject a therapeutically effective amount of an C1-C6 aldehyde or prodrug or derivative thereof when the analysis of the sample of b) indicates the subject has a BRCA2-/- and/or PALB2-/- mutation. In addition, the use of a pharmaceutical composition comprising a therapeutically effective amount of an C1-C6 aldehyde or prodrug or derivative thereof, and/or an aldehyde dehydrogenase inhibitor is also provided for treating cancer in a subject wherein the subject is identified as having a BRCA2 -/- and/or PALB2 -/- mutation. Also provided herein is an isolated human adenocarcinoma cell line genetically modified to have a biallelic disruption of the PALB2 gene, and methods for identifying a compound or small molecule that modulates a function of a cancer cell or population of cells genetically modified to have a biallelic disruption of the PALB2 gene are also provided.

  本发明提供了一种用于治疗或预防患有BRCA2-/-和/或PALB2-/-突变的受试者的癌症的方法，包括：a）从受试者获取样品；b）分析样品以检测BRCA2-/-和/或PALB2-/-突变的存在；c）在b）的样品分析表明受试者具有BRCA2-/-和/或PALB2-/-突变时向受试者施用C1-C6醛或其前药或衍生物的治疗有效剂量。此外，还提供了一种制药组合物的用途，其包括治疗有效量的C1-C6醛或其前药或衍生物，和/或醛脱氢酶抑制剂，用于治疗患有BRCA2-/-和/或PALB2-/-突变的受试者的癌症。此外，还提供了一种经基因改造具有PALB2基因双等位基因破坏的孤立人类腺癌细胞系，以及用于识别调节经基因改造具有PALB2基因双等位基因破坏的癌细胞或细胞种群的功能的化合物或小分子的方法。
• Regioisomeric Synthesis and Characteristics of the α-Hydroxy-1,<i>N²</i>-propanodeoxyguanosine
  作者：Yanhe Huang、Francis Johnson

  DOI：10.1021/tx015568f

  日期：2002.2.1

  Acrolein, a known mutagen, undergoes reaction in vitro under physiological conditions with both 2'-deoxyguanosine and native DNA to give rise to exocyclic adducts of the 5,6,7,8-tetrahydropyrimido[1,2-a]purine-10(3H)-one class having a hydroxyl group at either the 6 or the 8 position (these positions are respectively designated alpha and gamma when referring to the 1,N(2)-(propano-bridge). Previously

  丙烯醛是一种已知的诱变剂，在生理条件下与2'-脱氧鸟苷和天然DNA进行体外反应，生成5,6,7,8-四氢嘧啶[1,2-a]嘌呤-10（ 3H）一类，在6或8位具有羟基（在提及1，N（2）-（丙烷桥）时，这些位置分别称为α和γ）。 8-羟基衍生物的诱变性很低，可能是因为在双链DNA中，该残基以开链醛形式[N（2）-（3-氧丙基）-2'-脱氧鸟苷]存在（5）。我们在这一领域的研究中，我们需要大量的6-羟基异构体。本论文描述了高产率的简单方法，用于批量合成6-羟基和6-甲氧基外环加合物1和3，以及一种新的有效合成1，N（2）（）-（prop-1,3 -diyl）-2'-deoxyguanosine（4），以前用作研究1，N（2）环外加成dG的物理生物学影响的化学稳定模型。
• INHIBITORS OF POLO-LIKE KINASE
  申请人：ELAN PHARMACEUTICALS, INC.

  公开号：US20130231335A1

  公开（公告）日：2013-09-05

  The present invention provides compounds having a structure according to Formula (I): or a salt or solvate thereof, wherein ring A, X, R 1 , R 2 , R 3 , R 4 , R 5 and R 6 , are defined herein. The invention further provides pharmaceutical compositions including the compounds of the invention and methods of making and using the compounds and compositions of the invention, e.g., in the treatment and prevention of various disorders, such as Parkinson's disease.

  本发明提供具有以下式子（I）的结构的化合物，或其盐或溶剂，其中，环A、X、R1、R2、R3、R4、R5和R6在此定义。本发明还提供包括本发明化合物的制药组合物以及本发明化合物和组合物的制备和使用方法，例如，在治疗和预防各种疾病，如帕金森病方面的应用。
• Method for providing current assessments of genetic risk
  申请人：——

  公开号：US20030040002A1

  公开（公告）日：2003-02-27

  This invention concerns an integrated method for providing individuals with current assessments of genetic risk based on genetic tests and genomic research. While existing genetic tests can provide an estimate of genetic risk for many common diseases, genomic research is expected to provide a large number of new genetic tests that will enable more definitive assessments of an individuals risk of disease. The invention provides an integrated method and systems for providing individuals with current assessments of their genetic risk based on such advances. This method has utility in enabling individuals and healthcare professions to use genetic tests in important healthcare and lifestyle decisions.

  本发明涉及一种综合方法，可根据基因测试和基因组研究为个人提供当前的遗传风险评估。虽然现有的基因测试可以提供许多常见疾病的遗传风险估计，但预计基因组研究将提供大量新的基因测试，从而能够对个人的疾病风险进行更明确的评估。本发明提供了一种综合方法和系统，可根据这些进展为个人提供最新的遗传风险评估。该方法可帮助个人和医疗保健专业人员在重要的医疗保健和生活方式决策中使用基因检测。
• Oxidoreductase inhibitors and methods of screening and using thereof
  申请人：Balendiran K. Ganesaratnam

  公开号：US20050004225A1

  公开（公告）日：2005-01-06

  The present invention relates to 1) the design and synthesis of analogs to glutathione conjugates which bind to or interact with aldose reductase (AR) through unique conformations that are distinctly different from the substrates and inhibitors of AR which are members of sugar metabolism; 2) the screening of the analogs to identify those that interact with or inhibit or enhance the activity of AR; and 3) the use of AR ligands, AR inhibitors (AR antagonsits) or AR enhancer (AR agonists) in the detection of AR activity, the modulation of AR activity, and the treatment of conditions in a subject in need of modulating AR activity. Such conditions include but not limited to cardiovascular disease, diabetes, artheriosclerosis, cancer, neoplasm, obesity, cataract, retinopathy, keratopathy, nephropathy, neurosis, thrombosis, faulty union of corneal injury and neuropathy. Examples of the treatment include the use of fibrates as AR inhibitors to treat these conditions.