benzoic acid (3aS,4R,6R,6aR)-6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-ylmethyl ester | 900810-19-7

• 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,6R,6aR)-6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-ylmethyl ester
• 英文别名: 6-chloro-9-(5-O-benzoyl-2,3-O-isopropylidene-4-thio-β-D-ribofuranos-1-yl)-9H-purine；6-chloro-9-[(5-O-benzoyl-2,3-O-isopropylidene)-4-thio-β-D-ribofuranosyl]purine
• CAS: 900810-19-7
• 化学式: C₂₀H₁₉ClN₄O₄S
• 分子量: 446.914
• InChiKey: YIWPFRLHCRAVNK-SCFUHWHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.47
• 重原子数：
  30.0
• 可旋转键数：
  4.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  88.36
• 氢给体数：
  0.0
• 氢受体数：
  9.0

反应信息

• 作为反应物：
  描述：

  benzoic acid (3aS,4R,6R,6aR)-6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-ylmethyl ester 在 甲基碘化镁 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 乙醚 、 乙醇 、 水 为溶剂， 反应 16.0h， 生成 6-morpholino-9-(4-thio-β-D-ribofuranosyl)purine
  参考文献：
  名称：

  Design, synthesis, and biological activity of N6-substituted-4′-thioadenosines at the human A3 adenosine receptor

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2006.03.030
• 作为产物：
  描述：

  苯甲酰氯 在 吡啶 、 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 sodiumsulfide nonahydrate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 127.0h， 生成 benzoic acid (3aS,4R,6R,6aR)-6-(6-chloro-purin-9-yl)-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-ylmethyl ester
  参考文献：
  名称：

  N6-(3-碘苄基)腺苷-5'-N-甲基脲酰胺 (IB-MECA) 和相关 A3 腺苷受体配体的多药理学：过氧化物酶体增殖物激活受体 (PPAR) γ 部分激动剂和 PPARδ 拮抗剂活性表明其具有抗糖尿病潜力。

  摘要：

  检查 A3 腺苷受体 (AR) 配体（包括 A3 AR 激动剂、N6-(3-碘苄基)腺苷-5'-N-甲基脲酰胺 (1a, IB-MECA)）在人骨髓间充质干细胞 (hBM-MSC) 中的脂联素生成情况）。在该模型中，1a 显着增加了脂联素的产生，这与胰岛素敏感性的改善有关。然而，A3 AR 拮抗剂也促进 hBM-MSC 中脂联素的产生，表明 A3 AR 途径可能不直接参与脂联素促进活性。在一项靶标解卷积研究中，它们的脂联素促进活性与其与过氧化物酶体增殖物激活受体 (PPAR) γ 和 PPARδ 的结合活性显着相关。它们既充当 PPARγ 部分激动剂又充当 PPARδ 拮抗剂。在糖尿病小鼠模型中，1a 及其结构类似物 A3 AR 拮抗剂显着降低血清葡萄糖和甘油三酯水平，支持其抗糖尿病潜力。这些发现表明，这些化合物的多药效团可以为它们针对各种人类疾病的多效功效提供治疗见解。

  DOI：

  10.1021/acs.jmedchem.7b00805

文献信息

• Design and synthesis of N6-substituted-4′-thioadenosine-5′-uronamides as potent and selective human A3 adenosine receptor agonists
  作者：Won Jun Choi、Hyuk Woo Lee、Hea Ok Kim、Moshe Chinn、Zhan-Guo Gao、Amit Patel、Kenneth A. Jacobson、Hyung Ryong Moon、Young Hoon Jung、Lak Shin Jeong

  DOI：10.1016/j.bmc.2009.10.011

  日期：2009.12

  On the basis of a bioisosteric rationale, 4'-thionucleoside analogues of IB-MECA (N-6-(3-Iodo-benzyl)-9-(5'-methylaminocarbonyl-beta-D-ribofuranosyl)adenine), which is a potent and selective A(3) adenosine receptor (AR) agonist, were synthesized from D-gulonic acid gamma-lactone. The 4'-thio analogue (5h) of IB-MECA showed extremely high binding affinity (K-i = 0.25 nM) at the human A(3)AR and was more potent than IB-MECA (K-i = 1.4 nM). Bulky substituents at the 5'-uronamide position, such as cyclohexyl and 2-methylbenzyl, in this series of 2-H nucleoside derivatives were tolerated in A3AR binding, although small alkyl analogues were more potent. (c) 2009 Elsevier Ltd. All rights reserved.
• Synthesis of 4’-Thiopurine Nucleosides Using Hypervalent Iodine Compounds
  作者：Naozumi Nishizono、Kayo Soma、Ryosuke Baba、Minoru Machida、Kazuaki Oda

  DOI：10.3987/com-07-11250

  日期：——

  The reaction of a silylated purine base with thiofuranoid using phenyl iodosyl bis(trifluoroacetate) gave 4'-thio purine nucleosides.