5'-S-methyl-5'-thioguanosine | 142646-57-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 5'-脱氧核糖核苷
• 英文名称: 5'-S-methyl-5'-thioguanosine
• 英文别名: 5′-deoxy-5′-(methylthio)guanosine；hamiguanosinol；5'-deoxy-5'-methylthioguanosine；2-amino-9-[(2R,3R,4S,5S)-3,4-dihydroxy-5-(methylsulfanylmethyl)oxolan-2-yl]-1H-purin-6-one
• CAS: 142646-57-9
• 化学式: C₁₁H₁₅N₅O₄S
• 分子量: 313.337
• InChiKey: XZBAOIZOOACFSY-KQYNXXCUSA-N

物化性质

• 密度：
  1.98±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  ——	5'-chloro-5'-deoxyguanosine	21017-09-4	C10H12ClN5O4	301.689
  鸟苷	GUANOSINE	118-00-3	C10H13N5O5	283.244

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	2-hydrazino-5'-S-methyl-5'-thioadenosine	398139-12-3	C11H17N7O3S	327.367
  ——	2-iodo-5'-S-methyl-5'-thio-Adenosine	398139-03-2	C11H14IN5O3S	423.234
  ——	2-(1-hexynyl)-5'-S-methyl-5'-thioadenosine	——	C17H23N5O3S	377.467

反应信息

• 作为反应物：
  描述：

  5'-S-methyl-5'-thioguanosine 在 copper(l) iodide 4-二甲氨基吡啶 、 二碘甲烷 、 四乙基氯化铵 、 氨 、 碘 、 一水合肼 、 N,N-二甲基苯胺 、 三乙胺 、 三氯氧磷 、 亚硝酸异戊酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 异丙醇 、 乙腈 为溶剂， 反应 83.25h， 生成 2-(N'-3-methyl-1-butylidenehydrazino)-5'-S-methyl-5'-thioadenosine
  参考文献：
  名称：

  2,5‘-Disubstituted Adenosine Derivatives:  Evaluation of Selectivity and Efficacy for the Adenosine A₁, A_2A, and A₃ Receptor

  摘要：

  Novel 2,5'-disubstituted adenosine derivatives were synthesized in good overall yields starting from commercially available guanosine. Binding affinities were determined for rat adenosine A(1) and A(2A) receptors and human A(3) receptors. E-max values were determined for the stimulation or inhibition of cAMP production in CHO cells expressing human adenosine A(2A) (EC50 values as well) or A(3) receptors, respectively. The compounds displayed affinities in the nanomolar range for both the adenosine A(2A) and A(3) receptor, without substantial preference for either receptor. The derivatives with a 2-(1-hexynyl) group had the highest affinities for both receptors; compound 4 (2-(1-hexynyl)adenosine) had the highest affinity for the adenosine A(2A) receptor with a K-i value of 6 nM (A(3)/A(2A) selectivity ratio of approximately 3), whereas compound 37 (2-(1-hexynyl)-5'-S-methyl-5'-thioadenosine) had the highest affinity for the adenosine A(3) receptor with a K-i value of 15 nM (A(2A)/A(3) selectivity ratio of 4). In general, compounds with a relatively small 5'-S-alkyl-5'-thio substituent (methyl-5'-thio) displayed the highest affinities for both the adenosine A(2A) and A(3) receptor; the larger ones (n- or i-propyl-5'-thio) increased the selectivity for the adenosine A(3) receptor. The novel compounds were also evaluated in cAMP assays for their (partial) agonistic behavior. Overall, the disubstituted derivatives behaved as partial agonists for both the adenosine A(2A) and A(3) receptor. The compounds showed somewhat higher intrinsic activities on the adenosine A(2A) receptor than on the A(3) receptor. Compounds 37, 40 and 45, 48, with either a 5'-S-methyl-5'-thio or a 5'-S-i-propyl-5'-thio substituent had the lowest intrinsic activities on the adenosine A(2A) receptor. For the A(3) receptor, compounds 34, 35, 38, 39, and 46, 47, with a 5'-S-ethyl-5'-thio or a 5'-S-n-propyl-5'-thio substituent had the lowest intrinsic activities.

  DOI：

  10.1021/jm010952v
• 作为产物：
  描述：

  鸟苷 在 氯化亚砜 、 sodium methylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 5'-S-methyl-5'-thioguanosine
  参考文献：
  名称：

  Salvadenosine，一种来自 Bahamian Tunicate Didemnum sp. 的 5'-Deoxy-5'-（甲硫基）核苷。

  摘要：

  Salvadenosine ( 1 ) 是一种罕见的 5'-deoxy-5'-(methylthio) 核苷，是从深水巴哈曼被囊类动物Didemnum sp. 中分离出来的。通过对 MS 和 1D 和 2D NMR 数据的综合分析来解析结构。我们修改已知的天然产物，hamiguanosinol，这是的构成异构体的结构1，以5由分光数据的解释，并与合成核苷比较。

  DOI：

  10.1021/jo501486p

文献信息

• Compounds, compositions, and methods for stimulating neuronal growth and elongation
  申请人：——

  公开号：US20020061881A1

  公开（公告）日：2002-05-23

  The present invention concerns methods, pharmaceutical compounds, and compositions for stimulating neuroite outgrowth in nerve cells leading to nerve regeneration. These methods, compounds and compositions inhibit rotamase enzyme activity associated with binding proteins.

  本发明涉及用于刺激神经元细胞中神经元生长的方法、药物化合物和组合物，从而导致神经再生。这些方法、化合物和组合物抑制了与结合蛋白相关的旋转酶酶活性。
• [EN] COMPOUNDS, COMPOSITIONS, AND METHODS FOR STIMULATING NEURONAL GROWTH AND ELONGATION<br/>[FR] COMPOSES, COMPOSITIONS ET PROCEDES DE STIMULATION DE LA CROISSANCE ET DE L'ALLONGEMENT NEURONAUX
  申请人：AGOURON PHARMA

  公开号：WO2000004020A1

  公开（公告）日：2000-01-27

  Compounds that inhibit the peptidyl-prolyl isomerase (rotamase) enzyme activity of the FK-506 binding protein (FKBP) and compositions comprising these compounds are described. The FKBP-inhibiting compounds have a bicyclic [3.3.1], [4.3.1] or polycyclic azaamide nucleus. Pharmaceutical compositions containing such compounds help stimulate the outgrowth of neurites in nerve cells and augmenting nerve regeneration. Methods of treating nerve cells with such compositions are useful to promote repair of neuronal damage caused by disease and physical trauma.

  本文描述了能抑制FK-506结合蛋白(FKBP)的肽酰脯氨酸异构酶(rotamase)酶活性的化合物，以及包含这些化合物的组合物。这些FKBP抑制化合物具有双环[3.3.1]、[4.3.1]或多环氮杂甲酰胺核。含有这些化合物的制药组合物有助于刺激神经细胞的突起生长和增强神经再生。使用这些组合物治疗神经细胞的方法有助于促进由疾病和物理创伤引起的神经损伤的修复。
• Pharmaceutical compositions having anti-inflammatory activity
  申请人：Fishman Pnina

  公开号：US20050277615A1

  公开（公告）日：2005-12-15

  An anti-inflammatory pharmaceutical composition comprising as active ingredient a compound of general formula (I): wherein W represents oxygen or sulfur atoms; R 1 represents lower alkyl or lower cycloalkyl; R 2 represents halogen, alkenyl, alkynyl or alkylidenhydrazino; R 3 represents a lower alkyl, lower cycloalkyl, aryl, (ar)alkyl or anilide, said cycloalkyl, aryl and (ar)alkyl may be substituted with one or more of the groups selected from halogen, hydroxyl, hydroxyalkyl; and a pharmaceutically acceptable additive. The composition may be used to threat diseases such as multiple sclerosis, rheumatoid arthritis and Crohn's disease.

  一种抗炎药物组合物，其有效成分为一般式（I）的化合物：其中W代表氧或硫原子；R1代表低碳基或低环烷基；R2代表卤素，烯基，炔基或烷基亚肼基；R3代表低碳基，低环烷基，芳基，（芳）烷基或苯酰基，所述的环烷基，芳基和（芳）烷基可以用从卤素，羟基，羟基烷基中选择的一个或多个基团替代；以及一种药学上可接受的添加剂。该组合物可用于治疗多发性硬化症，类风湿性关节炎和克罗恩病等疾病。
• C2,5'-disubstituted and N6,C2,5'-trisubstituted adenosine derivatives and pharmaceutical compositions containing them
  申请人：UNIVERSITEIT LEIDEN

  公开号：US20040127452A1

  公开（公告）日：2004-07-01

  The present invention concerns novel C2,5′-disubstituted and N6,C2,5′-trisubstituted adenosine derivatives and their different uses. These adenosine derivatives were found to be potent adenosine receptor agonists and thus are of a therapeutic value in the treatment and prophylaxis of diseases and disorders affected by adenosine receptor agonists.

  本发明涉及新型C2,5'-二取代和N6,C2,5'-三取代腺苷衍生物及其不同用途。这些腺苷衍生物被发现是有效的腺苷受体激动剂，因此在治疗和预防受腺苷受体激动剂影响的疾病和障碍方面具有治疗价值。
• C2,5'- disubstituted and N6, c2,5'- trisubstituted adenosine derivatives and their different uses
  申请人：——

  公开号：US20040132686A1

  公开（公告）日：2004-07-08

  The present invention concerns novel C2,5′-disubstituted and N 6 ′,C2,5′-trisubstituted adenosine derivatives and their different uses. These adenosine derivatives were found to be potent adenosine receptor agonists and thus are of a therapeutic value in the treatment and prophylaxis of diseases and disorders affected by adenosine receptor agonists.

  本发明涉及新型的C2,5'-二取代和N6',C2,5'-三取代腺苷衍生物及其不同的用途。发现这些腺苷衍生物是有效的腺苷受体激动剂，因此在治疗和预防受腺苷受体激动剂影响的疾病和障碍方面具有治疗价值。