benzoic acid (3aS,4R,6S,6aR)-6-(2,6-dichloro-purin-9-yl)-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-ylmethyl ester | 596103-19-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: benzoic acid (3aS,4R,6S,6aR)-6-(2,6-dichloro-purin-9-yl)-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-ylmethyl ester
• 英文别名: [(3aR,4S,6R,6aS)-4-(2,6-dichloropurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrothieno[3,4-d][1,3]dioxol-6-yl]methyl benzoate
• CAS: 596103-19-4
• 化学式: C₂₀H₁₈Cl₂N₄O₄S
• 分子量: 481.359
• InChiKey: KESYWIUKTYSEFH-GDLHICMESA-N

物化性质

• 沸点：
  590.6±60.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  3-碘苄胺盐酸盐 、 benzoic acid (3aS,4R,6S,6aR)-6-(2,6-dichloro-purin-9-yl)-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-ylmethyl ester 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 72.0h， 以90%的产率得到benzoic acid (3aS,4R,6S,6aR)-6-[2-chloro-6-(3-iodo-benzylamino)purin-9-yl]-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-yl-methyl ester
  参考文献：
  名称：

  Purine nucleosides

  摘要：

  揭示了对A3腺苷受体具有选择性的嘌呤核苷化合物，可用于治疗癌症和炎症性疾病。所述化合物由以下一般式（I）表示，包括其异构体：其中X为硫或氧；R1为氢、烷基、苄基、卤代苄基或苯基烷基；R2为氢、卤素、烷氧基、烯基、炔基、烷基硫基或硫基；R3和R3'为氢、羟基烷基、烷氧羰基或烷基氨羰基，其中R3和R3'不同时具有相同的取代基；R4为氢或烷基。还揭示了一种包含一种式（I）的化合物、其异构体或其药理学上可接受的盐作为活性成分的药物组合物，以及一种用于预防或治疗各种疾病、状态或症状的方法，包括哮喘、炎症、脑缺血、心脏疾病和癌症。

  公开号：

  US20050256143A1
• 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 、 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 42.42h， 生成 benzoic acid (3aS,4R,6S,6aR)-6-(2,6-dichloro-purin-9-yl)-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-ylmethyl ester
  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

• N⁶-Substituted D-4‘-Thioadenosine-5‘-methyluronamides:  Potent and Selective Agonists at the Human A₃ Adenosine Receptor
  作者：Lak Shin Jeong、Dong Zhe Jin、Hea Ok Kim、Dae Hong Shin、Hyung Ryong Moon、Prashantha Gunaga、Moon Woo Chun、Yong-Chul Kim、Neli Melman、Zhan-Guo Gao、Kenneth A. Jacobson

  DOI：10.1021/jm034098e

  日期：2003.8.1

  4'-Thio analogues 3-5 of Cl-IB-MECA (2) (K-i = 1.0 +/- 0.2 nM at the human A(3) adenosine receptor) were synthesized from D-gulono-gamma-lactone via 4-thioribosyl acetate 14 as the key intermediate. All synthesized 4-thionucleosides exhibited higher binding affinity to the human A(3) adenosine receptor than Cl-IB-MECA, among which 4 showed the most potent binding affinity (K-i = 0.28 +/- 0.09 nM). 4 was also selective for A(3) vs human A(1) and human A(2A) receptors by 4800- and 36000-fold, respectively.
• Design, synthesis, and biological activity of N6-substituted-4′-thioadenosines at the human A3 adenosine receptor
  作者：Lak Shin Jeong、Hyuk Woo Lee、Hea Ok Kim、Ji Young Jung、Zhan-Guo Gao、Heng T. Duong、Srikar Rao、Kenneth A. Jacobson、Dae Hong Shin、Jeong A Lee

  DOI：10.1016/j.bmc.2006.03.030

  日期：2006.7.15

  A large series of N-6-substituted-4'-thioadenosines were synthesized starting from D-gulonic-gamma-Iactone, and structure-activity relationships were studied at the human A(3) and other subtypes of adenosine receptors (ARs). 2-Chloro-substituted and 2-H analogues were compared. 2-Chloro-N-6-methyl-4'-thioadeno sine 19b was a highly potent and selective agonist (K-i = 0.8 +/- 0.1 nM in binding) at the A(3)AR, and displayed the same relative efficacy in receptor activation as a known full agonist, Cl-IB-MECA. Most of N6-substituted-4'-thioadenosines were less potent in binding than the corresponding N-6-substituted-adenosines or N-6-substituted-4'thioadenosine-5'-uronamides. N-6-(3-lodobenzyl) derivative 19g was demonstrated to be an A(3)AR-selective partial agonist displaying a Ki value of 3.2 nM. (c) 2006 Elsevier Ltd. All rights reserved.