5'-chloro-5'-deoxyguanosine | 21017-09-4

• 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'-chloro-5'-deoxyguanosine
• 英文别名: 5'-Chloro-5'-deoxyguanosine；2-amino-9-[(2R,3R,4S,5S)-5-(chloromethyl)-3,4-dihydroxyoxolan-2-yl]-1H-purin-6-one
• CAS: 21017-09-4
• 化学式: C₁₀H₁₂ClN₅O₄
• 分子量: 301.689
• InChiKey: YBIZLKQGKRXLAZ-UUOKFMHZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  135
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5'-chloro-5'-deoxyguanosine 在 copper(l) iodide 4-二甲氨基吡啶 、 sodium hydroxide 、 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-propyl-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 作用下， 反应 2.0h， 以75%的产率得到5'-chloro-5'-deoxyguanosine
  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

• Probing the molecular determinants of fluorinase specificity
  作者：W. L. Yeo、X. Chew、D. J. Smith、K. P. Chan、H. Sun、H. Zhao、Y. H. Lim、E. L. Ang

  DOI：10.1039/c6cc09213f

  日期：——

  Probing the structural determinants of fluorinase enzyme specificity with 5′-chloro-5′-deoxyadenosine (5′-ClDA) analog substrates generated fluorinases with improved and novel activity.

  用5'-氯-5'-脱氧腺苷（5'-ClDA）类似底物探究氟化酶酶特异性的结构决定因素，产生了具有改进和新活性的氟化酶。
• 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。
• Polymorphism, Crystal Packing, Twinning, and Molecular Conformations in 5′-Halo-5′-deoxyguanosines and a Hydrate of the Pseudohalide Analogue, 5′-Azido-5′-deoxyguanosine
  作者：Sean R. Parkin、William H. Coldren、Joseph P. Fernandez、Christopher M. Hadad、Edward J. Behrman

  DOI：10.1021/acs.cgd.8b01162

  日期：2018.11.7

  hybrid crystals that by visual inspection appear to be single crystals (Parkin et al. Cryst. Growth Des. 2016, 16, 6343–6352; hereafter PTGB). To investigate the generality and origin of the unusual polymorphism of the solvent-free forms, we have prepared and characterized the 5′-bromo- and 5′-chloro-5′-deoxyguanosine analogues (II and III, respectively), as well as the pseudohalide derivative 5′-az

  晶体5'-碘-5'-脱氧鸟苷（I）以一对无溶剂的多晶型物（Ia，Ib）和水/甲醇溶剂化物（Ic）的混合形式存在。无溶剂的多晶型物能够外延共生，得到混合晶体，通过目视检查看来是单晶（Parkin等人，CRYST生长辅。。2016，16，6343-6352;以下PTGB）。为了研究无溶剂形式异常多态性的普遍性和起源，我们制备并表征了5'-溴-和5'-氯-5'-脱氧鸟苷类似物（II和III），以及假卤化物衍生物5'-叠氮基5'-脱氧鸟苷（IV）。II的单斜晶型和正交晶型（分别为IIa和IIb）和III的正交晶型都从水中生长，形成小的非溶剂化，紧密堆积的针状或板条状。尽管IIa是同构的，具有I的主要多晶型（即PTGB中的Ia），但是所有这些晶体（IIa，IIb，III）都具有与Ia相似的分子构象和堆积特征，其中卤素采用薄纱相对于脱氧核糖环氧的构象。尽管具有不同空间群对称性的（P 2 1为IA和IIA