methyl 5-deoxy-5-chloro-2,3-O-sulfinyl-D-ribofuranoside | 151378-76-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 5-deoxy-5-chloro-2,3-O-sulfinyl-D-ribofuranoside
• 英文别名: (3aR,6S,6aR)-6-(chloromethyl)-4-methoxy-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3,2]dioxathiole 2-oxide
• CAS: 151378-76-6
• 化学式: C₆H₉ClO₅S
• 分子量: 228.653
• InChiKey: CFTBGBQASQGCLQ-HPSGJIPHSA-N

物化性质

• 沸点：
  346.3±42.0 °C(predicted)
• 密度：
  1.62±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  73.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 5-deoxy-5-chloro-2,3-O-sulfinyl-D-ribofuranoside 在 吡啶 、 ammonium hydroxide 、 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 5.0h， 生成 methyl 5-deoxy-2,3-di-O-benzoyl-D-ribofuranoside
  参考文献：
  名称：

  New adenosine kinase inhibitors with oral antiinflammatory activity: synthesis and biological evaluation

  摘要：

  Several 5-iodotubercidin analogues in the pyrazolo[3,4-d]pyrimidine ring system were synthesized as potential inhibitors of adenosine kinase by a direct Lewis acid-catalyzed glycosylation procedure using both the preformed carbohydrate and the heterocyclic base as starting materials. The 5'-hydroxyl, -chloro, -azido, -deoxy, -amino, and -fluoro derivatives were prepared and evaluated in three systems for biological activity relative to adenosine, the true substrate, and 5-iodotubercidin, a known inhibitor. First, each compound was studied kinetically for inhibition of purified human placental adenosine kinase activity. The order of potency was: iodotubercidin > hydroxyl > amino greater-than-or-equal-to deoxy > fluoro> chloro >> azido. The K(i) values for the 5'-hydroxyl and 5'-amino compounds, the two most potent inhibitors, were 80 and 150 nM, respectively. The inhibition appeared to be essentially competitive in nature, although a noncompetitive component of significance for the more potent inhibitors cannot be ruled out. Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds. The order of effectiveness of the compounds in this system, representing a functional inhibition of adenosine kinase in cultured cells, was about the same as that with the purified enzyme, except that the 5'-chloro and 5'-fluoro compounds were ineffective. Third, the 5'-hydroxyl derivative was evaluated in vivo in a rat pleurisy inflammation model and displayed biological activity at a dose of 30 mg/kg given orally. Finally, the in vitro toxicity of each compound was assessed in CEM lymphoblasts. Results indicated that the two most potent inhibitors in the pyrazolo[3,4-d]pyrimidine ring system, the 5'-hydroxyl (7) and the 5'-amino (20), were 15-fold and 75-fold, respectively, less growth inhibitory than 5-iodotubercidin.

  DOI：

  10.1021/jm00074a024
• 作为产物：
  描述：

  α,β-1-甲基-D-呋喃核糖苷 在 吡啶 、 氯化亚砜 作用下， 以 乙腈 为溶剂， 生成 methyl 5-deoxy-5-chloro-2,3-O-sulfinyl-D-ribofuranoside
  参考文献：
  名称：

  New adenosine kinase inhibitors with oral antiinflammatory activity: synthesis and biological evaluation

  摘要：

  Several 5-iodotubercidin analogues in the pyrazolo[3,4-d]pyrimidine ring system were synthesized as potential inhibitors of adenosine kinase by a direct Lewis acid-catalyzed glycosylation procedure using both the preformed carbohydrate and the heterocyclic base as starting materials. The 5'-hydroxyl, -chloro, -azido, -deoxy, -amino, and -fluoro derivatives were prepared and evaluated in three systems for biological activity relative to adenosine, the true substrate, and 5-iodotubercidin, a known inhibitor. First, each compound was studied kinetically for inhibition of purified human placental adenosine kinase activity. The order of potency was: iodotubercidin > hydroxyl > amino greater-than-or-equal-to deoxy > fluoro> chloro >> azido. The K(i) values for the 5'-hydroxyl and 5'-amino compounds, the two most potent inhibitors, were 80 and 150 nM, respectively. The inhibition appeared to be essentially competitive in nature, although a noncompetitive component of significance for the more potent inhibitors cannot be ruled out. Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds. The order of effectiveness of the compounds in this system, representing a functional inhibition of adenosine kinase in cultured cells, was about the same as that with the purified enzyme, except that the 5'-chloro and 5'-fluoro compounds were ineffective. Third, the 5'-hydroxyl derivative was evaluated in vivo in a rat pleurisy inflammation model and displayed biological activity at a dose of 30 mg/kg given orally. Finally, the in vitro toxicity of each compound was assessed in CEM lymphoblasts. Results indicated that the two most potent inhibitors in the pyrazolo[3,4-d]pyrimidine ring system, the 5'-hydroxyl (7) and the 5'-amino (20), were 15-fold and 75-fold, respectively, less growth inhibitory than 5-iodotubercidin.

  DOI：

  10.1021/jm00074a024

文献信息

• [EN] ADENOSINE ANALOGUES AND METHOD OF INCREASING ADENOSINE RELEASE<br/>[FR] ANALOGUES DE L'ADENOSINE ET PROCEDE D'INTENSIFICATION DE LA LIBERATION DE L'ADENOSINE
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：WO1994006438A1

  公开（公告）日：1994-03-31

  (EN) Nucleoside analogues such as ribofuranosyl-$g(b)-D-pyrrolopyrimidine compounds and ribofuranosyl pyrrolopyrimidine N-oxide compounds and pharmaceutically acceptable salts and mixtures thereof. Compositions comprising these compounds and pharmaceutically acceptable carriers have also been disclosed. The invention further includes ribofuranosyl compounds having the anomeric position substituted with substituents selected from the group consisting of: -O-(C1-C18)alkyl, -O-(C1-C18)acyl, halogen, O-tosyl, or -OSO2R11, wherein R11 is -(C1-C18)alkyl or -(C6-C24)aryl. Methods of preparing said compounds have also been disclosed. Methods of treating a disease or condition such as inflammation, certain heart conditions, gastric ulcers, osteoarthritis, neutrophil function, or promoting vasodilation, among others comprise administering to a subject in need of the treatment an adenosine kinase activity inhibitory effective amount of claimed compounds or compositions thereof.(FR) L'invention se rapporte à des analogues de nucléosides tels que des composés de ribofuranosyl-$g(b)-D-pyrrolopyrimidine et des composés de ribofuranosyl pyrrolopyrimidine N-oxyde et des sels pharmaceutiquement acceptables et des mélanges de ceux-ci. L'invention se rapporte également à des compositions comprenant ces composés et ces excipients pharmaceutiquement acceptables. L'invention comprend en outre des composés de ribofuranosyl ayant la position anomérique substituée par des substituants sélectionnés parmi le groupe constitué par -O-(C1-C18)alkyle, -O-(C1-C18)acyle, halogène, O-tosyle, ou -OSO2R11 dans lequel R11 représente -(C1-C18)alkyle ou -(C6-C24)aryle. Des procédé de préparation de ces composés sont également décrits. Des procédés pour traiter d'une maladie ou un état pathologique, tel qu'une inflammation, certaines maladies du coeur, des ulcères gastriques, l'arthrose, la fonction neutrophile ou pour faciliter la vasodilatation, notamment, consistent à administrer à un sujet nécessitant ce traitement une quantité efficace inhibitrice de l'activité de l'adénosine kinase des composés revendiqués ou des compositions de ceux-ci.
• New adenosine kinase inhibitors with oral antiinflammatory activity: synthesis and biological evaluation
  作者：Howard B. Cottam、D. Bruce Wasson、Hsien C. Shih、Anil Raychaudhuri、Gene Di Pasquale、Dennis A. Carson

  DOI：10.1021/jm00074a024

  日期：1993.10

  Several 5-iodotubercidin analogues in the pyrazolo[3,4-d]pyrimidine ring system were synthesized as potential inhibitors of adenosine kinase by a direct Lewis acid-catalyzed glycosylation procedure using both the preformed carbohydrate and the heterocyclic base as starting materials. The 5'-hydroxyl, -chloro, -azido, -deoxy, -amino, and -fluoro derivatives were prepared and evaluated in three systems for biological activity relative to adenosine, the true substrate, and 5-iodotubercidin, a known inhibitor. First, each compound was studied kinetically for inhibition of purified human placental adenosine kinase activity. The order of potency was: iodotubercidin > hydroxyl > amino greater-than-or-equal-to deoxy > fluoro> chloro >> azido. The K(i) values for the 5'-hydroxyl and 5'-amino compounds, the two most potent inhibitors, were 80 and 150 nM, respectively. The inhibition appeared to be essentially competitive in nature, although a noncompetitive component of significance for the more potent inhibitors cannot be ruled out. Second, a bioassay was conducted in which the toxicity of 6-methylmercaptopurine riboside toward human CEM lymphoblasts was reversed by varying concentrations of the compounds. The order of effectiveness of the compounds in this system, representing a functional inhibition of adenosine kinase in cultured cells, was about the same as that with the purified enzyme, except that the 5'-chloro and 5'-fluoro compounds were ineffective. Third, the 5'-hydroxyl derivative was evaluated in vivo in a rat pleurisy inflammation model and displayed biological activity at a dose of 30 mg/kg given orally. Finally, the in vitro toxicity of each compound was assessed in CEM lymphoblasts. Results indicated that the two most potent inhibitors in the pyrazolo[3,4-d]pyrimidine ring system, the 5'-hydroxyl (7) and the 5'-amino (20), were 15-fold and 75-fold, respectively, less growth inhibitory than 5-iodotubercidin.