benzoic acid (3aS,4R,6aR)-2,2-dimethyl-5-oxotetrahydro-5λ4-thieno[3,4-d][1,3]dioxol-4-yl methyl ester | 683275-15-2

• 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,6aR)-2,2-dimethyl-5-oxotetrahydro-5λ4-thieno[3,4-d][1,3]dioxol-4-yl methyl ester
• 英文别名: benzoic acid (3aS,4R,5R,6aR)-(3aS,4R,5S,6aR)-2,2-dimethyl-5-oxotetrahydro-5λ4-thieno[3,4-d][1,3]dioxol-4-yl methyl ester；[(3aS,4R,6aR)-2,2-dimethyl-5-oxo-3a,4,6,6a-tetrahydrothieno[3,4-d][1,3]dioxol-4-yl]methyl benzoate
• CAS: 683275-15-2
• 化学式: C₁₅H₁₈O₅S
• 分子量: 310.371
• InChiKey: OYEPEJIJKBOVEQ-ZMIURYRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  81
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  benzoic acid (3aS,4R,6aR)-2,2-dimethyl-5-oxotetrahydro-5λ4-thieno[3,4-d][1,3]dioxol-4-yl methyl ester 在 acetate source 作用下， 反应 8.0h， 以54%的产率得到benzoic acid (3aS,4R,6aR)-6-acetoxy-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-ylmethyl ester
  参考文献：
  名称：

  [EN] 4-THIORIBOSE NAD ANALOGUES AND METHODS OF SYNTHESIZING AND USING THE SAME
  [FR] ANALOGUES DU 4-THIORIBOSE NAD ET PROCÉDÉS DE SYNTHÈSE ET D'UTILISATION DE CEUX-CI

  摘要：

  本公开提供了一种合成4'-硫核糖NAD+及其类似物的方法，使用高效的化学酶法途径。还提供了抑制CD38酶的方法和包括4'-硫核糖NAD+及相关化合物的化合物。

  公开号：

  WO2020073026A1
• 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 、 溶剂黄146 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.42h， 生成 benzoic acid (3aS,4R,6aR)-2,2-dimethyl-5-oxotetrahydro-5λ4-thieno[3,4-d][1,3]dioxol-4-yl methyl ester
  参考文献：
  名称：

  N⁶-Substituted D-4‘-Thioadenosine-5‘-methyluronamides:  Potent and Selective Agonists at the Human A₃ Adenosine Receptor

  摘要：

  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.

  DOI：

  10.1021/jm034098e

文献信息

• Purine nucleosides
  申请人：Jeong Shin Lak

  公开号：US20050256143A1

  公开（公告）日：2005-11-17

  Disclosed are purine nucleoside compounds that are selective to A 3 adenosine receptors and are useful for the treatment of cancer and inflammatory diseases. The compounds are shown by the following general formula (I), including isomers thereof: wherein X is sulfur or oxygen; R 1 is hydrogen, alkyl, benzyl, halobenzyl, or phenylalkyl; R 2 is hydrogen, halogen, alkoxy, alkenyl, alkynyl, alkylthio, or thio; R 3 and R 3′ are hydrogen, hydroxyalkyl, alkoxycarbonyl, or alkylaminocabonyl, whereas R 3 and R 3 ′ do not have identical substituents simultaneously; and R 4 is hydrogen or alkyl. Also disclosed are a pharmaceutical composition comprising a compound of formula (I), an isomer, or its pharmacologically acceptable salt as an active ingredient and a method for preventing or treating various diseases, state, or condition, including asthma, inflammation, cerebral ischemia, heart diseases, and cancer.

  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。
• Polypharmacology of <i>N</i>⁶-(3-Iodobenzyl)adenosine-5′-<i>N</i>-methyluronamide (IB-MECA) and Related A₃ Adenosine Receptor Ligands: Peroxisome Proliferator Activated Receptor (PPAR) γ Partial Agonist and PPARδ Antagonist Activity Suggests Their Antidiabetic Potential
  作者：Jinha Yu、Seyeon Ahn、Hee Jin Kim、Moonyoung Lee、Sungjin Ahn、Jungmin Kim、Sun Hee Jin、Eunyoung Lee、Gyudong Kim、Jae Hoon Cheong、Kenneth A. Jacobson、Lak Shin Jeong、Minsoo Noh

  DOI：10.1021/acs.jmedchem.7b00805

  日期：2017.9.14

  A3 adenosine receptor (AR) ligands including A3 AR agonist, N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (1a, IB-MECA) were examined for adiponectin production in human bone marrow mesenchymal stem cells (hBM-MSCs). In this model, 1a significantly increased adiponectin production, which is associated with improved insulin sensitivity. However, A3 AR antagonists also promoted adiponectin production

  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。
• 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.
• 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.
• 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.