benzoic acid (3aS,4R,6aR)-6-acetoxy-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-ylmethyl ester | 596103-09-2

• 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)-6-acetoxy-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-ylmethyl ester
• 英文别名: benzoic acid (3aS,4R,6RS,6aR)-6-acetoxy-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-ylmethyl ester；((3aS,4R,6aR)-6-acetoxy-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-yl)methyl benzoate；benzoic acid (3aS,4R,6R,6aR)-(3aS,4R,6S,6aR)-6-acetoxy-2,2-dimethyl-tetrahydro-thieno[3,4-d][1,3]dioxol-4-ylmethyl ester；[(3aR,6R,6aS)-4-acetyloxy-2,2-dimethyl-3a,4,6,6a-tetrahydrothieno[3,4-d][1,3]dioxol-6-yl]methyl benzoate
• CAS: 596103-09-2
• 化学式: C₁₇H₂₀O₆S
• 分子量: 352.408
• InChiKey: FEFUGUJYYQHMRM-QFBZGTDSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  96.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  benzoic acid (3aS,4R,6aR)-6-acetoxy-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxol-4-ylmethyl ester 在 三氟甲磺酸三甲基硅酯 、 三乙胺 作用下， 以 乙醇 、 1,2-二氯乙烷 、 乙腈 为溶剂， 反应 24.0h， 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
• 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 24.42h， 生成 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：

  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

• 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。
• [EN] 4-THIORIBOSE NAD ANALOGUES AND METHODS OF SYNTHESIZING AND USING THE SAME<br/>[FR] ANALOGUES DU 4-THIORIBOSE NAD ET PROCÉDÉS DE SYNTHÈSE ET D'UTILISATION DE CEUX-CI
  申请人：UNIV SOUTHERN CALIFORNIA

  公开号：WO2020073026A1

  公开（公告）日：2020-04-09

  This disclosure provides a method of synthesis of 4'-thioribose NAD+ and analogues thereof, using an efficient chemoenzymatic approach. Also provided are methods of inhibiting the CD38 enzyme and compounds including 4'-thioribose NAD+ and compounds related thereto.

  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。
• Facile chemoenzymatic synthesis of a novel stable mimic of NAD⁺
  作者：Zhefu Dai、Xiao-Nan Zhang、Fariborz Nasertorabi、Qinqin Cheng、Hua Pei、Stan G. Louie、Raymond C. Stevens、Yong Zhang

  DOI：10.1039/c8sc03899f

  日期：——

  variety of important enzyme-catalyzed physiological and pathophysiological processes. Analogues of NAD+ provide key and valuable agents for investigating NAD+-dependent enzymes. In this study, we report the preparation of a novel stable NAD+ mimic, 4′-thioribose NAD+ (S-NAD+), using a facile and efficient chemoenzymatic approach. Substrate activity assays indicated the resulting S-NAD+ is chemically inert

  烟酰胺腺嘌呤二核苷酸（NAD +）是参与多种重要的酶催化生理和病理生理过程的重要辅助因子。NAD +类似物为研究 NAD +依赖性酶提供了关键且有价值的试剂。在这项研究中，我们报道了一种新型稳定的 NAD +模拟物，4'-硫核糖 NAD + (S-NAD + )，使用一种简单有效的化学酶方法。底物活性测定表明，所得的 S-NAD +对人 CD38 和 Sirtuin 2 酶呈化学惰性，但能够以类似于 NAD +的方式参与氧化还原反应。X 射线晶体分析揭示了 S-NAD +与人 CD38 的活性位点以及参与离去基团激活和催化的关键残基的结合。通过在几何学和静电学上更接近地模仿 NAD +，生成的 S-NAD +提供了一种独特且重要的工具，可以扩展到利用 NAD +研究酶。
• 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.