[(3aR,4R,6R,6aS)-4-[2-chloro-6-(cyclopentylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrothieno[3,4-d][1,3]dioxol-6-yl]methyl benzoate | 871913-85-8

• 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: [(3aR,4R,6R,6aS)-4-[2-chloro-6-(cyclopentylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrothieno[3,4-d][1,3]dioxol-6-yl]methyl benzoate
• CAS: 871913-85-8
• 化学式: C₂₅H₂₈ClN₅O₄S
• 分子量: 530.047
• InChiKey: CRRANPKDCJIPOO-WGQQHEPDSA-N

物化性质

• 沸点：
  665.9±65.0 °C(Predicted)
• 密度：
  1.57±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  126
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  [(3aR,4R,6R,6aS)-4-[2-chloro-6-(cyclopentylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrothieno[3,4-d][1,3]dioxol-6-yl]methyl benzoate 在 吡啶 、 重铬酸吡啶 、 sodium methylate 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 41.0h， 生成 (2S,3S,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[2-chloro-6-(cyclopentylamino)purin-9-yl]thiolane-2-carboxylic acid
  参考文献：
  名称：

  Structure−Activity Relationships of 2-Chloro-N⁶-substituted-4‘-thioadenosine-5‘-uronamides as Highly Potent and Selective Agonists at the Human A₃ Adenosine Receptor

  摘要：

  We have established structure-activity relationships of novel 4'-thionucleoside analogues as the A(3) adenosine receptor (AR) agonists. Binding affinity, selectivity toward other AR subtypes.. and efficacy in inhibition of adenylate cyclase were studied. From this study, 2-chloro-N-6-methyl-4'-thioadenosine-5'-methyluronamide (36a) emerged as the most potent and selective agonist at the human A(3) AR. We have also revealed that. similar to 4'-oxoadenosine analogues, at least one hydrogen on the 5'-uronamide moiety was necessary for high-affinity binding at the human A(3) AR, presumably to allow this group to donate a H bond within the binding site. Furthermore, bulky substituents on the 5'-uronarnide reduced binding affinity, but in some cases large 5'-uronamide substituents, such as substituted benzyl and 2-phenylethyl groups. maintained moderate affinity with reduced efficacy, leading to A(3) AR partial agonists or antagonists. In several cases for which the corresponding 4'-oxonucleosides have been studied, the 4'-thionucleosides showed higher binding affinity to the A(3) AR.

  DOI：

  10.1021/jm050595e
• 作为产物：
  描述：

  2,3:5,6-di-O-isopropylidene-D-gulitol 在 吡啶 、 lead(IV) acetate 、 sodium sulfide 、 sodium tetrahydroborate 、 三氟甲磺酸三甲基硅酯 、 溶剂黄146 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 48.42h， 生成 [(3aR,4R,6R,6aS)-4-[2-chloro-6-(cyclopentylamino)purin-9-yl]-2,2-dimethyl-3a,4,6,6a-tetrahydrothieno[3,4-d][1,3]dioxol-6-yl]methyl benzoate
  参考文献：
  名称：

  Structure−Activity Relationships of 2-Chloro-N⁶-substituted-4‘-thioadenosine-5‘-uronamides as Highly Potent and Selective Agonists at the Human A₃ Adenosine Receptor

  摘要：

  We have established structure-activity relationships of novel 4'-thionucleoside analogues as the A(3) adenosine receptor (AR) agonists. Binding affinity, selectivity toward other AR subtypes.. and efficacy in inhibition of adenylate cyclase were studied. From this study, 2-chloro-N-6-methyl-4'-thioadenosine-5'-methyluronamide (36a) emerged as the most potent and selective agonist at the human A(3) AR. We have also revealed that. similar to 4'-oxoadenosine analogues, at least one hydrogen on the 5'-uronamide moiety was necessary for high-affinity binding at the human A(3) AR, presumably to allow this group to donate a H bond within the binding site. Furthermore, bulky substituents on the 5'-uronarnide reduced binding affinity, but in some cases large 5'-uronamide substituents, such as substituted benzyl and 2-phenylethyl groups. maintained moderate affinity with reduced efficacy, leading to A(3) AR partial agonists or antagonists. In several cases for which the corresponding 4'-oxonucleosides have been studied, the 4'-thionucleosides showed higher binding affinity to the A(3) AR.

  DOI：

  10.1021/jm050595e

文献信息

• Structure–activity relationships of 2-chloro-N6-substituted-4′-thioadenosine-5′-N,N-dialkyluronamides as human A3 adenosine receptor antagonists
  作者：Lak Shin Jeong、Hyuk Woo Lee、Hea Ok Kim、Dilip K. Tosh、Shantanu Pal、Won Jun Choi、Zhan-Guo Gao、Amit R. Patel、Wanda Williams、Kenneth A. Jacobson、Hee-Doo Kim

  DOI：10.1016/j.bmcl.2008.01.070

  日期：2008.3

  On the basis of potent and selective A(3) adenosine receptor (AR) antagonist, 2-chloro-N-6-(3-iodobenzyl)-4'-thioadenosine-5'-N,N-dimethyluronamide, structure-activity relationships were studied for a series of 5'-N,N-dialkyluronamide derivatives, synthesized from D-gulonic gamma-lactone. From this study, it was revealed that removal of the hydrogen bond-donating ability of the 5'-uronamide was essential for the pure A(3)AR antagonism. 5'-N,N-Dimethyluronamide derivatives exhibited higher binding affinity than larger 5'-N,N-dialkyl or 5'-N,N-cycloalkylamide derivatives, indicating that steric factors are crucial in binding to the human A(3)AR. A N-6-(3-bromobenzyl) derivative 6c (K-i = 9.32 nM) exhibited the highest binding affinity at the human A3AR with very low binding affinities to other AR subtypes. (c) 2008 Elsevier Ltd. All rights reserved.
• Structure−Activity Relationships of 2-Chloro-<i>N</i>⁶-substituted-4‘-thioadenosine-5‘-uronamides as Highly Potent and Selective Agonists at the Human A₃ Adenosine Receptor
  作者：Lak Shin Jeong、Hyuk Woo Lee、Kenneth A. Jacobson、Hea Ok Kim、Dae Hong Shin、Jeong A Lee、Zhan-Guo Gao、Changrui Lu、Heng T. Duong、Prashantha Gunaga、Sang Kook Lee、Dong Zhe Jin、Moon Woo Chun、Hyung Ryong Moon

  DOI：10.1021/jm050595e

  日期：2006.1.1

  We have established structure-activity relationships of novel 4'-thionucleoside analogues as the A(3) adenosine receptor (AR) agonists. Binding affinity, selectivity toward other AR subtypes.. and efficacy in inhibition of adenylate cyclase were studied. From this study, 2-chloro-N-6-methyl-4'-thioadenosine-5'-methyluronamide (36a) emerged as the most potent and selective agonist at the human A(3) AR. We have also revealed that. similar to 4'-oxoadenosine analogues, at least one hydrogen on the 5'-uronamide moiety was necessary for high-affinity binding at the human A(3) AR, presumably to allow this group to donate a H bond within the binding site. Furthermore, bulky substituents on the 5'-uronarnide reduced binding affinity, but in some cases large 5'-uronamide substituents, such as substituted benzyl and 2-phenylethyl groups. maintained moderate affinity with reduced efficacy, leading to A(3) AR partial agonists or antagonists. In several cases for which the corresponding 4'-oxonucleosides have been studied, the 4'-thionucleosides showed higher binding affinity to the A(3) AR.