2-Amino-9-[2-(2-hydroxy-1-hydroxymethyl-ethoxy)-ethyl]-1,9-dihydro-purin-6-one | 103025-19-0

• 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-9-[2-(2-hydroxy-1-hydroxymethyl-ethoxy)-ethyl]-1,9-dihydro-purin-6-one
• 英文别名: 2-amino-9-[2-[2-hydroxy-1-(hydroxymethyl)ethoxy]ethyl]-1H-purin-6-one；2-amino-9-[2-(1,3-dihydroxypropan-2-yloxy)ethyl]-1H-purin-6-one
• CAS: 103025-19-0
• 化学式: C₁₀H₁₅N₅O₄
• 分子量: 269.26
• InChiKey: WHKLVMBUWNFLSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.8
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  135
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  N-{9-[2-(2-Hydroxy-1-hydroxymethyl-ethoxy)-ethyl]-6-oxo-6,9-dihydro-1H-purin-2-yl}-acetamide 在 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 反应 18.0h， 生成 2-Amino-9-[2-(2-hydroxy-1-hydroxymethyl-ethoxy)-ethyl]-1,9-dihydro-purin-6-one
  参考文献：
  名称：

  与9-[（1,3-二羟基-2-丙氧基）甲基]鸟嘌呤有关的无环2'-脱氧鸟苷类似物的合成和抗疱疹病毒活性。

  摘要：

  合成了几种与9-[（1,3-二羟基-2-丙氧基）甲基]鸟嘌呤（DHPG，2）有关的“糖”修饰的无环核苷类似物，并评估了其抗病毒活性。制备通常涉及将醇6c-g和10-12a的乙酰氧基甲基醚与二乙酰鸟嘌呤缩合，得到加合物7c-g和14-16，然后将其脱保护得到类似物9c-g和17-19。或者，将醇12a和13a通过它们的甲苯磺酸酯12b和13b转化为碘化物，然后与鸟嘌呤的钠盐反应，得到脱保护后的类似物22和23。醛27上的醛醇-Cannizzaro交叉反应容易得到28，其脱保护得到类似物29。针对HSV-1的体外分析表明，所测试的所有化合物的活性均低于DHPG，尽管有几种是病毒胸苷激酶的良好底物。在小鼠脑炎模型中评估了更有前途的无环核苷9c，19和29，并证明在20 mg / kg的剂量下无法有效预防死亡。

  DOI：

  10.1021/jm00158a011

文献信息

• $i(IN VIVO) GENE TRANSFER USING IMPLANTED RETROVIRAL PRODUCER CELLS
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：EP0602118A1

  公开（公告）日：1994-06-22
• EP0602118A4
  申请人：——

  公开号：EP0602118A4

  公开（公告）日：1996-02-28
• READY-FOR-USE INJECTABLE SOLUTION OF 9-((1,3-DIHYDROXYPROPAN-2-ILOXY)METHYL)-2-AMINE-1H-PURIN-6(9H)-ONE, STERILE, STABLE; CLOSED SYSTEM FOR PACKING THE SOLUTION, PROCESS FOR ELIMINATING ALKALINE RESIDUALS OF 9-((1,3-DIHYDROXYPROPAN-2-ILOXY)METHYL)-2-AMINE-1H-PURIN-6(9H)-ONE CRYSTALS; PHARMACEUTICAL
  申请人：Halex Istar Industria Farmaceutica Ltda.

  公开号：EP1691813A2

  公开（公告）日：2006-08-23
• [EN] IN VIVO GENE TRANSFER USING IMPLANTED RETROVIRAL PRODUCER CELLS
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：WO1993004167A1

  公开（公告）日：1993-03-04

  (EN) The present invention is directed to methods of transferring therapeutic genes to brain tumor cells in order to kill the cells. In general, the method of the present invention comprises: (1) introducing a retrovirus containing a selectable marker and at least one gene required for its replication into producer cells such that integration of the proviral DNA corresponding to the retrovirus into the genome of the producer cell results in the generation of a modified retrovirus wherein at least one of the genes required for replication of the retrovirus is replaced by the therapeutic gene or genes; (2) selecting producer cells in which the modified retrovirus is incorporated as part of the genome of the producer cells; (3) grafting the producer cells in proximity to the dividing tumor cell in order to infect the tumor cell with the modified retrovirus, thereby transferring the therapeutic gene or genes to the tumor cell; and (4) killing the cells by administering a substance that is metabolized by the therapeutic gene transferred to the tumor cells into a metabolite that kills the cells. Suitable retroviral vectors and methods for generating them, producer cells, and grafting methods are described.(FR) Cette invention concerne des procédés permettant de transférer des gènes thérapeutiques dans des cellules tumorales du cerveau afin de tirer ces cellules. Dans ce procédé (1) on introduit un rétrovirus contenant un traceur sélectionnable et au moins un gène nécessaire pour sa réplication dans des cellules productrices de sorte que l'intégration de l'ADN proviral correspondant au rétrovirus dans le génome de la cellule productrice provoque la création d'un rétrovirus modifié dans lequel au moins un des gènes nécessaires pour la réplication du rétrovirus est remplacé par le ou les gènes thérapeutiques; (2) on sélectionne des cellules productrices dans lesquelles le rétrovirus modifié est incorporé comme faisant partie du génome des cellules productrices; (3) on greffe les cellules productrices à proximité de la cellule tumorale diviseuse afin d'infecter la cellule tumorale avec le retrovirus modifié, et on transfère ainsi le ou les gènes thérapeutiques dans la cellule tumorale; et (4) on tue les cellules en administrant une substance qui est métabolisée par le gène thérapeutique transféré dans les cellules tumorales, sous forme d'un métabolite qui tue les cellules. Cette invention concerne également des vecteurs de retrovirus appropriés et des procédés permettant de les produire, des cellules productrices et des procédés de greffe.
• [EN] READY-FOR-USE INJECTABLE SOLUTION OF 9-((1,3-DIHYDROXYPROPAN-2-ILOXY)METHYL)-2-AMINE-1H-PURIN-6(9H)-ONE, STERILE, STABLE; CLOSED SYSTEM FOR PACKING THE SOLUTION, PROCESS FOR ELIMINATING ALKALINE RESIDUALS OF 9-((1,3-DIHYDROXYPROPAN-2-ILOXY)METHYL)-2-AMINE-1H-PURIN-6(9H)-ONE CRYSTALS; PHARMACEUTICAL PRESENTATION AS A CLOSED<br/>[FR] SOLUTION INJECTABLE PRETE A L'EMPLOI, STERILE, STABLE, DE 9-((1,3-DIHYDROXYPROPAN-2-ILOXY)METHYL)-2-AMINE-1H-PURIN-6(9H)-ONE; SYSTEME FERME PERMETTANT DE CONDITIONNER LA SOLUTION, PROCEDE D'ELIMINATION DES RESIDUS ALCALINS DES CRISTAUX DE 9-((1,3-DIHYDROXYPROPAN-2-ILOXY)METHYL)-2-AMINE-1H-PURIN-6(9H)-ONE; PRESENTATION PHARM
  申请人：HALEX ISTAR IND FARMACEUTICA L

  公开号：WO2005051286A2

  公开（公告）日：2005-06-09

  The present invention describes a sterile, stable and ready-for-use injectable solution comprising 9-((1,3-dihydroxypropan-2-iloxy)methyl)-2-amino-1H-purin-6(9H)-one in glucose 5% aqueous solution or sodium chloride 0.9% aqueous solution. It also describes a closed system used for packing the solution, which consists of a flexible bag manufactured with a tri-laminated material. The present invention also describes a process for eliminating the residual alkalinity that is present in the 9-((1,3-dihydroxypropan-2-iloxy)methyl)-2-amino-1H-purin-6(9H)-one, so obtaining crystals that are free from alkaline residues and suitable for the direct preparation of the solution. The present invention relates to the medical and therapeutic areas, mainly for treating immunodepressed patients carrying viral infections.