(+/-)-dioxolane-T | 145414-65-9

• 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: (+/-)-dioxolane-T
• 英文别名: 1-[(2S,4S)-2-(hydroxymethyl)-1,3-dioxolan-4-yl]-5-methylpyrimidine-2,4-dione
• CAS: 145414-65-9
• 化学式: C₉H₁₂N₂O₅
• 分子量: 228.205
• InChiKey: BCAWWPAPHSAUQZ-BQBZGAKWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  cis-2-acetoxymethyl-4-(thymin-1'-yl)-1,3-dioxolane 生成 (+/-)-dioxolane-T
  参考文献：
  名称：

  2-Substituted-4-substituted-1,3-dioxolanes and use thereof

  摘要：

  含有1,3-二氧杂环戊烷结构的核苷类似物是适用的抗病毒药物，特别适用于治疗哺乳动物，尤其是人类的HIV感染。核苷类似物的例子包括：顺式-2-乙酰氧甲基-4-(胸腺嘧啶-1'-基)-1,3-二氧杂环戊烷，顺式-2-羟甲基-4-(胸腺嘧啶-1'-基)-1,3-二氧杂环戊烷，顺式-2-苯甲酰氧甲基-4-(胞嘧啶-1'-基)-1,3-二氧杂环戊烷，以及顺式-2-羟甲基-4-(胞嘧啶-1'-基)-1,3-二氧杂环戊烷。这些化合物可以是它们的外消旋体或它们的单独对映体形式。

  公开号：

  US06350753B1

文献信息

• L-.beta.-(2S,4S)- and L-.alpha.-(2S,4R)-dioxolanyl nucleosides as potential anti-HIV agents: asymmetric synthesis and structure-activity relationships
  作者：Hea O. Kim、Raymond F. Schinazi、Kirupathevy Shanmuganathan、Lak S. Jeong、J. Warren Beach、Satyanarayana Nampalli、Deborah L. Cannon、Chung K. Chu

  DOI：10.1021/jm00057a001

  日期：1993.3

  In order to study the structure-activity relationships of L-(2S,4S)- and L-(2S,4R)-dioxolanyl nucleoside as potential anti-HIV agents, various enantiomerically pure L-(2S,4S)- and (2S,4R)-dioxolanylpyrimidine and -purine nucleosides have been synthesized and evaluated against HIV-1 in human peripheral blood mononuclear (PBM) cells. The enantiomerically pure key intermediate 8 has been synthesized in

  为了研究L-（2S，4S）-和L-（2S，4R）-二氧戊环核苷作为潜在抗HIV药物的构效关系，各种对映体纯的L-（2S，4S）-和（2S合成了（4R）-二氧戊环基嘧啶和-嘌呤核苷，并对人外周血单核（PBM）细胞中的HIV-1进行了评估。对映体纯的关键中间体8是由1,6-脱水β-L-古洛糖（2）六步合成的，化合物8与5-取代的嘧啶，6-氯嘌呤和2,6-二取代的嘌呤缩合分别获得各种二氧戊环基嘧啶和-嘌呤核苷。在合成的化合物中，发现5-氟胞嘧啶衍生物29尽管具有毒性（IC50 = 10.0 microM），却显示出最有效的抗HIV活性（EC50 = 0.0012 microM）。嘧啶类似物的抗HIV效能的顺序如下：5-氟胞嘧啶（β-异构体）>胞嘧啶（β-异构体）> 5-氟胞嘧啶（α-异构体）> 5-碘胞嘧啶（β-异构体）>胞嘧啶（ （α-异构体）> 5-溴胞嘧啶（β-异构体）>胸腺嘧啶（β-异构体）>
• (±)-Dioxolane-T ((±)-1-[(2β,4β)-2-(hydroxymethyl)-4-dioxolanyl]thymine)
  作者：Daniel W. Norbeck、Stephen Spanton、Samuel Broder、Hiroaki Mitsuya

  DOI：10.1016/s0040-4039(01)93868-7

  日期：1989.1
• Choi, Woo-Baeg; Wilson, Lawrence J.; Yeola, Suresh, Journal of the American Chemical Society, 1991, vol. 113, # 24, p. 9377 - 9379
  作者：Choi, Woo-Baeg、Wilson, Lawrence J.、Yeola, Suresh、Liotta, Dennis C.、Schinazi, Raymond F.

  DOI：——

  日期：——
• Potent anti-HIV and anti-HBV activities of (−)-L-β-dioxolane-C and (+)-L-β-dioxolane-T and their asymmetric syntheses.
  作者：Hea O. Kim、Kirupathevy Shanmuganathan、Antonio J. Alves、Lak S. Jeong、J. Warren Beach、Raymond F. Schinazi、Chang Chien-Neng、Cheng Yung-Chi、Chung K. Chu

  DOI：10.1016/s0040-4039(00)60890-0

  日期：1992.11

  The asymmetric syntheses of (+)-L-beta-dioxolane-T and (-)-L-beta-dioxolane-C were accomplished starting from 1,6-anhydro-L-beta-gulopyranose, and their anti-HIV and anti-HBV activities were evaluated in human PBM cells, CEM cells and 2.2.15 cells, respectively.
• Phosphoramidate nucleoside prodrug for treating viral diseases and cancer, processes for their preparation and their use
  申请人：Ivachtchenko Alexandre Vasilievich

  公开号：US20180030080A1

  公开（公告）日：2018-02-01

  The present invention pertains to chemotherapeutic agents and their use for treating viral and cancerous diseases. These compounds are inhibitors of HCV NS5B polymerase, HBV DNA polymerase and, HIV-1 reverse transcriptase (RT) inhibitor, and for treatment of hepatitis B and C infection in mammals. These compounds are also of interest for the treatment of cancer. The phosphoramidate nucleoside prodrug of the general formula 1, a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof, wherein: Ar is aryl or hetaryl; R 1 is H or CH 3 ; R 2 is the substituent selected from OCH 2 CH═CH 2 , OCH 2 CH≡CH, OCH 2 CH 2 CH 2 OCH 3 , R 3 is H or CH 3 ; R 4 is OH, OR 5 , NR 6 R 7 ; R 5 is C 1 -C 4 -alkyl; R 6 and R 7 are not necessarily the same substituents selected from H or CH 3 ; Z═O, or NH; an arrow (→) indicates the place of substituent connection; Nuc is R 8 and R 9 are not necessarily the same substituents selected from H, F, Cl, CH 3 or OH provided when continuous line and its accompanying dotted line ( ) together are the single carbon-carbon (C—C) bond or R 8 and R 9 are hydrogen provided when continuous line and its accompanying dotted line ( ) together are the double carbon-carbon bond (C═C); R 10 is the substituent selected from R 10.1 -R 10.5 ; R 11 is the substituent selected from H, F, Cl, CH 3 , or CF 3 ; R 12 is hydrogen, C 1 -C 4 -alkyl or C 3 -C 6 -cycloalkyl; X is oxygen or ethanediyl-1,1 (C═CH 2 ); Y is O, S, CH 2 , or HO—CH group provided when continuous line and its accompanying dotted line ( ) together are the single carbon-carbon (C—C) bond or Y is CH group provided when continuous line and its accompanying dotted line ( ) together are the double carbon-carbon bond (C═C), and compound of the general formula 1, stereoisomers, isotope-enriched analogues, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, wherein: Ar is aryl or hetaryl; R 1 is H or CH 3 ; R is isopropyl; Nuc is