32865-86-4Relevant academic research and scientific papers
Search for New Purine- and Ribose-Modified Adenosine Analogues as Selective Agonists and Antagonists at Adenosine Receptors
Siddiqi, Suhaib M.,Jacobson, Kenneth A.,Esker, John L.,Olah, Mark E.,Ji, Xiao-duo,et al.
, p. 1174 - 1188 (1995)
The binding affinities at rat A1, A2a, and A3 adenosine receptors of a wide range of derivatives of adenosine have been determined.Sites of modification include the purine moiety (1-, 3-, and 7-deaza; halo, alkyne, and ami
Design and synthesis of novel threosyl-5′-deoxyphosphonic acid purine analogues as potent anti-HIV agents
Liu, Lian Jin,Kim, Eunae,Hong, Joon Hee
, p. 411 - 422 (2012)
The discovery of threosyl phosphonate nucleoside (PMDTA, EC50 = 2.53 μM) as a potent anti-HIV agent has led to the synthesis and biological evaluation of 5′-deoxyversions of threosyl phosphonate nucleosides from 1,4-dihydroxy-2-butene. The synthesized nucleoside phosphonic acid analogues 14 and 19 were tested for anti-HIV activity as well as cytotoxicity. The adenine analogue 14 exhibits moderate in vitro anti-HIV-1 activity (EC50 = 12.6 μM). Copyright Taylor and Francis Group, LLC.
Synthesis and Antiviral Activity Evaluation of 2′,5′,5′-Trifluoro-Apiosyl Nucleoside Phosphonic Acid Analogs
Kim, Eunae,Hong, Joon Hee
, p. 130 - 146 (2016)
Racemic synthesis of novel 2′,5′,5′-trifluoro-apiose nucleoside phosphonic acid analogs were performed as potent antiviral agents. Phosphonation was performed by direct displacement of triflate intermediate with diethyl (lithiodifluoromethyl) phosphonate
5'-O-alkyl ethers of N,2-substituted adenosine derivatives: partial agonists for the adenosine A1 and A3 receptors.
van Tilburg,van der Klein,von Frijtag Drabbe Kuenzel,de Groote,Stannek,Lorenzen,IJzerman
, p. 2966 - 2975 (2001)
New N,5'-di- and N,2,5'-trisubstituted adenosine derivatives were synthesized in good overall yields. Appropriate 5-O-alkyl-substituted ribose moieties were coupled to 6-chloropurine or 2,6-dichloropurine via Vorbrueggen's glycosylation method. Subsequent amination and deprotection of the intermediates yielded compounds 18-35. Binding affinities were determined for rat adenosine A1 and A2A receptors and the human A3 receptor. The ability of compounds 18-35 to inhibit forskolin-induced (10 microM) cyclic AMP (cAMP) production and their ability to stimulate guanosine 5'-O-(3-[35S]thio)triphosphate ([35S]GTPgammaS) binding, via either the adenosine A1 receptor or the adenosine A3 receptor, were assessed. N-Cyclopentyl-substituted adenosine derivatives displayed affinities in the low nanomolar range for the adenosine A1 receptor, whereas N-(3-iodobenzyl)-substituted derivatives had high affinity for the adenosine A3 receptor. Compound 22 had the highest affinity for the adenosine A1 receptor (K(i) value of 16 nM), and compounds 20 and 26 had the highest affinities for the adenosine A3 receptor (K(i) values of 4 and 3 nM, respectively). A chlorine substituent at the 2-position either did not affect or slightly increased the adenosine A1 receptor affinity, whereas the A3 receptor affinity was affected differently, depending on the N-substituent. Furthermore, the introduction of chlorine slightly increased the A3/A1 selectivity ratio. At the 5'-position, an O-methyl substituent induced the highest adenosine A1 receptor affinity, whereas an O-ethyl substituent did so for the A3 receptor. All compounds showed partial agonistic effects in both the cAMP and [35S]GTPgammaS assays, although more marked in the latter assay. In general, the 2-chloro derivatives seemed to have lower intrinsic activities compared to the 2-H-substituted compounds on both the adenosine A1 and the adenosine A3 receptors. The compounds with an N-(3-iodobenzyl) substituent displayed the lowest intrinsic activities. Finally, all compounds also showed partially antagonistic behavior in the [35S]GTPgammaS assay.
Efficient electrophilic fluorination for the synthesis of novel 2'-fluoro-3'-methyl-5'-deoxyphosphonic acid apiosyl nucleoside analogues
Kim, Kyung Mi,Hong, Joon Hee
, p. 555 - 570 (2013)
Novel 5'-deoxyapiosyl purine phosphonic acid analogues with a 2'-electropositive moiety, such as, a fluorine atom were designed and synthesized from commercially available hydroxylacetone. Condensation of a glycosyl donor 10 with purines under Vorbruggen conditions and cross-metathesis give the desired nucleoside phosphonic acid analogues 14, 17, 21, and 24. The synthesized nucleoside analogues were subjected to antiviral screening against HIV-1, and the adenine analogue 17 exhibited weak in vitro anti-HIV-1 activity (EC50 = 26.6 μM)
Regio- And Stereoselective Synthesis of C-4′ Spirocyclobutyl Ribofuranose Scaffolds and Their Use as Biologically Active Nucleoside Analogues
Jouffroy, Lucile,Verhoeven, Jonas,Brambilla, Marta,Verniest, Guido,Kong, Hanchu,Zhao, Yongbin,Wang, Wenbin,Meerpoel, Lieven,Thuring, Jan Willem,Winne, Johan M.
supporting information, p. 8828 - 8833 (2021/11/20)
Novel C-4′,C-5′ cyclobutane-fused spirocyclic ribonucleoside analogues were prepared. Thermal [2 + 2] cycloaddition between dichloroketene and readily derived 4′-exo-methylene furanoses afforded a first entry to the required constrained ribofuranoses, relying on a carbonyl transposition sequence. Alternatively, an unusual stereoselective ionic [2 + 2] cycloaddition using methyl propiolate promoted by methylaluminoxane gave a complementary, more direct approach to such ribofuranoses. Further conversion to the constrained adenosine analogues revealed promising structure-dependent inhibition of the protein methyltransferase PRMT5:MEP50 complex in the (sub)micromolar range.
Chitosan–silica sulfate nanohybrid: a highly efficient and green heterogeneous nanocatalyst for the regioselective synthesis of N-alkyl purine, pyrimidine and related N-heterocycles via presilylated method
Behrouz, Somayeh,Soltani Rad, Mohammad Navid,Piltan, Mohammad Amin
, p. 113 - 124 (2019/07/30)
Abstract: The presilylation of purine and pyrimidine nucleobases as well as other related N-heterocycles with HMDS utilizing chitosan–silica sulfate nanohybrid (CSSNH) is described. CSSNH is proved to be a useful, highly efficient and eco-friendly heterogeneous nanohybrid catalyst for silylation of nucleobases. The presilylated nucleobases then underwent the reaction with different sources of carbon electrophiles to afford the desired N-alkyl-substituted derivatives in good-to-excellent yields. CSSNH exhibits several advantageous involving ease of handling and preparation, low cost, reusability and environmental benignity. These unique properties render the CSSNH to be an ideal candidate for use in green industrial processes. Graphic abstract: [Figure not available: see fulltext.].
Asymmetric Synthesis of 2′- C-Methyl-4′-selenonucleosides as Anti-Hepatitis C Virus Agents
Lee, Hyejin,Jarhad, Dnyandev B.,Yu, Jinha,Lee, Choongho,Jeong, Lak Shin
, p. 14414 - 14426 (2019/11/11)
In search of a new template for anti-hepatitis C virus (HCV) agents, we designed and synthesized the 2′-C-methyl-4′-selenopyrimidine and -purine nucleosides and their phosphoramidate prodrugs to replace a furanose oxygen of anti-HCV nucleos(t)ides with a selenium atom on the basis that selenium is a chemical isostere of oxygen. These nucleosides are expected to show different physicochemical properties such as better lipophilicity which might enhance the penetration across cell membranes and the conformational constraint induced by a bulky selenium atom in the sugar ring. The 2′-C-methyl-4′-selenopyrimidine and -purine nucleosides 8 and 9 were synthesized from 2-C-methyl-d-ribono-γ-lactone (14) via construction of 2-C-methyl-d-selenosugar 18 through C-4 epimerization and SN2 cyclization with Se2- as key steps. The key 4′-selenosugar was converted to the 2′-C-methyl-4′-selenopyrimidine and -purine nucleosides using Pummerer-type rearrangement and Vorbrüggen glycosylation, respectively. In addition, the ProTide strategy has been applied to synthesize the adenine and uracil phosphoramidate derivatives 10a and 10b to overcome the limitations associated with parent nucleosides such as inefficient conversion to their corresponding 5′-monophosphate form and poor cellular uptake. The regio- and stereochemistry of 4′-selenonucleosides were confirmed by 2D NOESY NMR spectroscopy and X-ray crystallography. None of the final pyrimidine and purine nucleosides and their prodrugs exhibited significant anti-HCV activity up to 100 μM.
Synthesis and Evaluation of 2′-Deoxy-2′-Spirodiflurocyclopropyl Nucleoside Analogs
Liu, Xiao,Xia, Xueliang,Sun, Chenghai,Lin, Cai,Zhou, Yiqian,Hussain, Muzammal,Tang, Fei,Liu, Lu,Li, Xue,Zhang, Jiancun
, p. 479 - 494 (2016/09/04)
The preparation of 2′-deoxy-2′-siprodifluorocyclopropany-lnucleoside analogs has been achieved from α-d-glucose in several steps. The key step in the synthesis was the introduction of the difluorocyclopropane through a difluorocarbene type reaction at the 2′-position. Then, a series of novel 2′-deoxy-2′-spirodifluorocyclopropanyl nucleoside analogs were synthesized using the Vorbrüggen method. All the synthesized nucleosides were characterized and subsequently evaluated against hepatitis C and influenza A virus strains in vitro.
Structure-activity relationships of truncated C2- or C8-substituted adenosine derivatives as dual acting A2A and A3 adenosine receptor ligands
Hou, Xiyan,Majik, Mahesh S.,Kim, Kyunglim,Pyee, Yuna,Lee, Yoonji,Alexander, Varughese,Chung, Hwa-Jin,Lee, Hyuk Woo,Chandra, Girish,Lee, Jin Hee,Park, Seul-Gi,Choi, Won Jun,Kim, Hea Ok,Phan, Khai,Gao, Zhan-Guo,Jacobson, Kenneth A.,Choi, Sun,Lee, Sang Kook,Jeong, Lak Shin
experimental part, p. 342 - 356 (2012/03/10)
Truncated N6-substituted-4′-oxo- and 4′- thioadenosine derivatives with C2 or C8 substitution were studied as dual acting A2A and A3 adenosine receptor (AR) ligands. The lithiation-mediated stannyl transfer and palladium-c
