(3aS,4S,6aR)-2,2-dimethyltetrahydrothieno[3,4- d][1,3]dioxole-4-carbaldehyde | 666750-24-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3aS,4S,6aR)-2,2-dimethyltetrahydrothieno[3,4- d][1,3]dioxole-4-carbaldehyde
• 英文别名: 1,4-anhydro-2,3-O-isopropylidene-4-thio-D-ribitol 5-aldehyde；(3aS,4S,6aR)-2,2-dimethyltetrahydrothieno[3,4-d][1,3]dioxole-4-carbaldehyde；(3aS,4S,6aR)-2,2-dimethyl-3a,4,6,6a-tetrahydrothieno[3,4-d][1,3]dioxole-4-carbaldehyde
• CAS: 666750-24-9
• 化学式: C₈H₁₂O₃S
• 分子量: 188.247
• InChiKey: PLJDPCKBUDCRQP-XVMARJQXSA-N

物化性质

• 熔点：
  79-80 °C
• 沸点：
  288.2±40.0 °C(Predicted)
• 密度：
  1.259±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  60.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3aS,4S,6aR)-2,2-dimethyltetrahydrothieno[3,4- d][1,3]dioxole-4-carbaldehyde 在 吡啶 、 sodium tetrahydroborate 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 13.25h， 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
• 作为产物：
  描述：

  2,3:5,6-di-O-isopropylidene-D-gulitol 在 吡啶 、 lead(IV) acetate 、 sodium sulfide 、 溶剂黄146 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 11.17h， 生成 (3aS,4S,6aR)-2,2-dimethyltetrahydrothieno[3,4- d][1,3]dioxole-4-carbaldehyde
  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] PRMT5 INHIBITORS<br/>[FR] INHIBITEURS DE PRMT5
  申请人：MERCK SHARP & DOHME

  公开号：WO2020033282A1

  公开（公告）日：2020-02-13

  The present invention provides a compound of Formula (I) Formula (I) or the pharmaceutically acceptable salts thereof, which are PRMT5 inhibitors.

  本发明提供了化合物式(I)的化合物，或其药用可接受的盐，这些化合物是PRMT5抑制剂。
• Synthesis and Properties of 4′-ThioLNA/BNA
  作者：Rion Maeda、Noriko Saito-Tarashima、Hideaki Wakamatsu、Yoshihiro Natori、Noriaki Minakawa、Yuichi Yoshimura

  DOI：10.1021/acs.orglett.1c01306

  日期：2021.5.21

  applicable to oligonucleotide therapeutics, we designed a 4′-thio analogue of an LNA/BNA monomer. Synthesis of 4′-hydroxymethyl-4′-thioribonucleoside was achieved by a tandem ring-contraction-aldol reaction of a 5-thiopyranose derivative and the subsequent Pummerer-type thioglycosylation reaction of the corresponding sulfoxide. Treatment of 4′-hydroxymethyl-4′-thiopyrimidine nucleosides with diphenyl

  为了开发适用于寡核苷酸治疗的新核苷类似物，我们设计了LNA / BNA单体的4'-硫代类似物。4'-羟甲基-4'-硫代核糖核苷的合成是通过5-硫代吡喃糖衍生物的串联环缩合-醛醇缩合反应和随后的相应亚砜的Pummerer型硫代糖基化反应实现的。在催化NaHCO 3存在下用碳酸二苯酯处理4'-羟甲基-4'-硫代嘧啶核苷，得到所需的4'-thioLNA / BNA单体，将其引入寡核苷酸中。
• 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.
• Stereoselective Functionalization of the 1‘-Position of 4‘-Thionucleosides
  作者：Prashantha Gunaga、Hea Ok Kim、Hyuk Woo Lee、Dilip K. Tosh、Jae-Sang Ryu、Sun Choi、Lak Shin Jeong

  DOI：10.1021/ol061548z

  日期：2006.9

  Stereoselective synthesis of novel 1'-alpha-substituted-4'-thionucleosides was achieved starting from D-gulonic acid gamma-lactone via stereoselective nucleophilic substitution.