[1R-(1α,2β,3α)]-2-amino-9-[2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one

• 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: [1R-(1α,2β,3α)]-2-amino-9-[2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one
• 英文别名: lobucavir；BMS 180194；2-amino-9-[(2R,3S)-2,3-bis(hydroxymethyl)cyclobutyl]-1H-purin-6-one
• 化学式: C₁₁H₁₅N₅O₃
• 分子量: 265.272
• InChiKey: GWFOVSGRNGAGDL-CQMSUOBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,2-环丁二甲醇,3-(2-氨基-6-碘-9H-嘌呤-9-基)-,二苯酸酯(ester),(1S,2R,3R)- 在 sodium methylate 、 盐酸 作用下， 以 水 为溶剂， 以93%的产率得到[1R-(1α,2β,3α)]-2-amino-9-[2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one
  参考文献：
  名称：

  A Practical Asymmetric Synthesis of the Antiviral Agent Lobucavir, BMS-180194

  摘要：

  A practical synthesis of the antiviral agent lobucavir, [1R(1 alpha,2 beta,3 alpha)] -2-amino-9-[2,3-bis(hydroxymethyl)cyclobutyl]-6H-purin-6-one (BMS-180194), is described. The key chiral intermediate, [1S-(1 alpha,2 beta,3 alpha)]-3-hydroxy-1,2-cyclobutanedimethanol, dihenzoate ester, was made by an asymmetric [2 + 2] cycloaddition of dimenthyl fumarate with ketene dimethyl acetal followed by sequential diester reduction, benzoylation, deketalization, and stereoselective ketone reduction. Regioselective N9-alkylation of the tetra-n-butylammonium salt of 2-amino-6-iodopurine with the derived cyclobutyltriflate furnished the purinecyclobutyl dibenzoate. Methanolysis followed by acid hydrolysis produced lobucavir in a 35% overall yield with an ee, 99%.

  DOI：

  10.1021/op970214+

文献信息

• Synthesis and antiviral activities of carbocyclic oxetanocin analogues.
  作者：Tokumi MARUYAMA、Yoshiko SATO、Takahiko HORII、Hiroshi SHIOTA、Keiko NITTA、Takuma SHIRASAKA、Hiroaki MITSUYA、Mikio HONJO

  DOI：10.1248/cpb.38.2719

  日期：——

  cyclobutyl]adenine(4d) were prepared from the corresponding cyclobutylamine derivatives (1a, 1b and 1d). Guanine congeners (9a, cis- and trans-9b and 9d) and carbocyclic oxetanocin G (1',2'-trans-9f) were also prepared. Carbocyclic oxetanocin A(1',2'-trans-4f), the preparation of which we have already published, and G were found to be active against herpes simplex virus (type 1 and 2) in vitro, while

  由相应的环丁胺制备9-环丁基腺嘌呤（4a），顺式和反式9- [3-（羟甲基）环丁基]腺嘌呤（4b）和9- [3,3-双（羟甲基）环丁基]腺嘌呤（4d）。导数（1a，1b和1d）。还制备了鸟嘌呤同源物（9a，顺式和反式9b和9d）和碳环氧杂环丁霉素G（1'，2'-trans-9f）。我们已经公开了碳氧杂环丁烷素A（1'，2'-trans-4f）和G在体外对单纯疱疹病毒（1型和2型）具有活性，而cis-4b和cis具有活性。 -9b显示了针对人类免疫缺陷病毒（1型）的体外抗逆转录病毒活性。
• CYCLOBUTYL PURINE DERIVATIVE, ANGIOGENESIS PROMOTING AGENT, LUMEN FORMATION PROMOTING AGENT, NEUROCYTE GROWTH PROMOTING AGENT, AND DRUG
  申请人：Tsukamoto Ikuko

  公开号：US20110230659A1

  公开（公告）日：2011-09-22

  Provided is a compound having at least one selected from the group consisting of cell growth promoting activity, angiogenesis promoting activity, lumen formation promoting activity, cell migration promoting activity, and neurocyte growth promoting activity, which is a chemically stable low-molecular-weight substance that has high absorbability and can be supplied stably at a low cost because of its low molecular weight. A cyclobutyl purine derivative, a tautomer or stereoisomer thereof, or a salt, solvate, or hydrate thereof according to the present invention is a cyclobutyl purine derivative represented by the following general formula (1), a tautomer or stereoisomer thereof, or a salt, solvate, or hydrate thereof.

  提供的化合物具有至少以下一种活性：细胞生长促进活性、血管生成促进活性、腔隙形成促进活性、细胞迁移促进活性和神经元生长促进活性。该化合物是一种化学稳定的低分子量物质，具有高吸收性，并且由于其低分子量，可以以低成本稳定供应。根据本发明，环丁基嘌呤衍生物、其互变异构体或对映异构体、或其盐、溶剂或水合物是由下式（1）表示的环丁基嘌呤衍生物、其互变异构体或对映异构体、或其盐、溶剂或水合物。
• CYCLOBUTYL PURINE DERIVATIVE, ANGIOGENESIS PROMOTING AGENT, LUMENIZATION PROMOTING AGENT, NEUROCYTE GROWTH PROMOTING AGENT, AND DRUG
  申请人：National University Corporation Kagawa University

  公开号：EP2377865A1

  公开（公告）日：2011-10-19

  Provided is a compound having at least one selected from the group consisting of cell growth promoting activity, angiogenesis promoting activity, lumen formation promoting activity, cell migration promoting activity, and neurocyte growth promoting activity, which is a chemically stable low-molecular-weight substance that has high absorbability and can be supplied stably at a low cost because of its low molecular weight. A cyclobutyl purine derivative, a tautomer or stereoisomer thereof, or a salt, solvate, or hydrate thereof according to the present invention is a cyclobutyl purine derivative represented by the following general formula (1), a tautomer or stereoisomer thereof, or a salt, solvate, or hydrate thereof.

  本发明提供了一种化合物，该化合物具有至少一种选自细胞生长促进活性、血管生成促进活性、管腔形成促进活性、细胞迁移促进活性和神经细胞生长促进活性组成的组的活性，它是一种化学性质稳定的低分子量物质，具有高吸收性，并且由于其分子量低，可以以较低的成本稳定供应。根据本发明的环丁基嘌呤衍生物、其同分异构体或立体异构体，或其盐、溶液或水合物是由以下通式（1）表示的环丁基嘌呤衍生物、其同分异构体或立体异构体，或其盐、溶液或水合物。
• BISACCHI, GREGORY S.;BRAITMAN, ABBE;CIANCI, CHRISTOPHER W.;CLARK, JUNIUS +, J. MED. CHEM., 34,(1991) N, C. 1415-1421
  作者：BISACCHI, GREGORY S.、BRAITMAN, ABBE、CIANCI, CHRISTOPHER W.、CLARK, JUNIUS +

  DOI：——

  日期：——
• PRODRUGS
  申请人：MEDIVIR AB

  公开号：EP1054891A1

  公开（公告）日：2000-11-29