3-[(2R,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10-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-[(2R,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5,6,7,8-tetrahydropyrimido[1,2-a]purin-10-one
• 化学式: C₁₃H₁₇N₅O₄
• 分子量: 307.31
• InChiKey: HGYWFMCWAWUWRE-CFCGPWAMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 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

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。
• 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。