MRS-3642 | 876314-89-5

• 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: MRS-3642
• 英文别名: 5-(2-chloro-6-(3-iodobenzylamino)purin-9-yl)-3,4-dihydroxytetrahydrothiophene-2-carboxylic acid dimethylamide；2-chloro-N⁶-(3-iodobenzyl)-4'-thioadenosine-5'-N,N-dimethyluronamide；(2S,3S,4R,5R)-5-(6-(3-iodobenzylamino)-2-chloro-9H-purin-9-yl)-3,4-dihydroxy-N,N-dimethyl-tetrahydrothiophene-2-carboxamide；(2S,3S,4R,5R)-5-[2-chloro-6-[(3-iodophenyl)methylamino]purin-9-yl]-3,4-dihydroxy-N,N-dimethylthiolane-2-carboxamide
• CAS: 876314-89-5
• 化学式: C₁₉H₂₀ClIN₆O₃S
• 分子量: 574.83
• InChiKey: JXJRUAGROQMNET-MOROJQBDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  MRS-3642 、 乙酸酐 在 吡啶 、 4-二甲氨基吡啶 作用下， 反应 16.0h， 以99%的产率得到(2R,3R,4S,5S)-2-{2-chloro-6-[(3-iodobenzyl)amino]-9H-purin-9-yl}-5-(dimethylcarbamoyl)tetrahydrothiophene-3,4-diyl diacetate
  参考文献：
  名称：

  Nucleoside Prodrugs of A3 Adenosine Receptor Agonists and Antagonists

  摘要：

  9-(β-D-Ribosfuranosyluronamide)腺嘌呤衍生物被改造成为A3腺苷受体（AR）的选择性激动剂和拮抗剂的前药，用于体内输送。激动剂2-氯-N6-(3-碘苯甲基)-9-(N-甲基-(β-D-核糖呋喃脲酰脲)腺嘌呤2b，对应的4'-硫代核苷2c，以及拮抗剂4a和4b（分别与2b和2c相关的5'-N,N-二甲酰胺）的2'和3'位的游离羟基通过简单的酰基化反应进行了改造。在AR的放射配体结合测定和A3AR腺苷酸环化酶功能测定中，发现这些前药衍生物比原药物活性明显降低。在人类血液中证明了核苷2',3'-二酯的水解可以再生原药物。2',3'-二丙酸丙酯化合物2b和4a可以在两步反应中迅速裂解，再生原药物，时间尺度为两小时。2',3'-二己酸酯的裂解速率较慢。这表明这些前药适合作为生物活性A3AR激动剂和拮抗剂的掩蔽形式，以供未来体内评估。

  DOI：

  10.1135/cccc20060912
• 作为产物：
  描述：

  (2S,3S,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[2-chloro-6-[(3-iodophenyl)methylamino]purin-9-yl]thiolane-2-carboxylic acid 在 盐酸二甲胺 N-(3-dimethylaminopropyl)-N'ethylcarbonyldiimidazole*HCl 、 四丁基氟化铵 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 13.0h， 生成 MRS-3642
  参考文献：
  名称：

  Conversion of A3 adenosine receptor agonists into selective antagonists by modification of the 5′-ribofuran-uronamide moiety

  摘要：

  The highly selective agonists of the A(3) adenosine receptor (AR), Cl-IB-MECA (2-chloro-N-6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine), and its 4'-thio analogue, were successfully converted into selective antagonists simply by appending a second N-methyl group on the 5'-uronamide position. The 2-chloro-5'-(N,N-dimethyl)uronamido analogues bound to, but did not activate, the human A(3)AR, with K-i values of 29 nM (4'-O) and 15 nM (4'-S), showing > 100-fold selectivity over A(1), A(2A), and A(2B)ARs. Competitive antagonism was demonstrated by Schild analysis. The 2-(dimethylamino)-5'-(N,N-dimethyl)uronamido substitution also retained A3AR selectivity but lowered affinity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.10.054

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.