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1.
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) 相似文献
2.
Novel 4′-cyclopropyl-5′-norcarbocyclic adenosine phosphonic acid analogues were designed and racemically synthesized from propionaldehyde 5 through a de novo acyclic stereoselective route using triple Grignard addition and ring-closing metathesis (RCM) as key reactions. To improve cellular permeability and enhance the anti-HIV activity of this phosphonic acid, SATE phosphonodiester nucleoside prodrug 23 was prepared. The synthesized adenosine phosphonic acids analogues 17, 18, 19, 21, and 23 were subjected to antiviral screening against HIV-1. Compound 23 exhibits enhanced anti-HIV activity than its parent nucleoside phosphonic acid 18. 相似文献
3.
C. Pannecouque K. Van Poppel J. Balzarini P. Claes E. De Clercq P. Herdewijn 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):541-544
Abstract To assess the structure-activity relationship for antiviral activity, a series of 3′-deoxy-3′-N-functionalized thymidine analogues were synthesized. Several of these thymidine analogues show moderate in vitro activity against HIV-1 and HIV-2. 相似文献
4.
Lian Jin Liu Jin Cheol Yoo Joon Hee Hong 《Nucleosides, nucleotides & nucleic acids》2013,32(2):150-164
An efficient route for synthesizing novel allylic and cyclopropanoid phosphonic acid nucleoside analogues is described. The condensation of the bromine derivatives 6 and 18 with nucleoside bases (A, U, T, C, G) under standard nucleophilic substitution and deprotection conditions, afforded the target phosphonic acid nucleoside analogues. These compounds were evaluated for their antiviral properties against various viruses. Cyclopropanoid phosphonic adenine nucleoside analogue 23 showed significant anti-HIV activity. 相似文献
5.
Eunae Kim Lian Jin Liu Wonjae Lee Joon Hee Hong 《Nucleosides, nucleotides & nucleic acids》2013,32(2):85-96
Electronic parameters of 1′,3 ′-oxygen play significant roles in steering the conformation of nucleoside phosphonic acid analogues. To investigate the relationship of two oxygen atoms with antiviral enhancement, novel 1′,3 ′-dioxolane 5 ′-deoxyphosphonic acid purine analogues were synthesized via de novo acyclic stereoselective route from acrolein and glycolic acid. The synthesized nucleoside phosphonic acid analogues 14 and 19 were subjected to antiviral screening against several viruses, such as HIV-1, HSV-1, HSV-2, and HCMV. The guanine analogue 19 exhibits in vitro anti-HIV-1 activity similar to that of 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) in MT-4 cells. 相似文献
6.
Seyeon Kim 《Nucleosides, nucleotides & nucleic acids》2015,34(12):815-833
Novel 2′-deoxy-2′-β-fluoro-threose purine phosphonic acid analogues were designed and racemically synthesized from 2-propanone-1,3-diacetate. Condensation successfully proceeded from a glycosyl donor 9 under Vorbrüggen conditions. Cross-metathesis of vinyl analogues 13 and 23 with diethyl vinylphosphonate yielded the desired nucleoside phosphonate analogues 14 and 24, respectively. Ammonolysis and hydrolysis of phosphonates yielded the nucleoside phosphonic acid analogues 16, 19, 26, and 29. The synthesized nucleoside analogues were subjected to antiviral screening against human immunodeficiency virus (HIV)-1. Adenine analogue 18 exhibited weak in vitro activities against human immunodeficiency virus (HIV)-1. 相似文献
7.
Hirofumi Furusho Takahiro Ogata Akihisa Kato Yoshie Sato Tohru Endo Akira Kaji 《Nucleosides, nucleotides & nucleic acids》2013,32(4):739-753
Abstract Several acyclic analogues of guanosine, 2′-deoxy-2′, 3′-secoguanosine(3), 3′-deoxy-2′, 3′-secoguanosine (4), and 2′-, 3′-dideoxy-2′-, 3′-secoguanosine were synthesized from guanosine. In addition, the 3′-, 5′-cyclic phosphate (21) and 3′-, 5′-cyclic methylphosphonates (22a, b) of 3 were also prepared. At concentrations up to 300 μM none of these compounds had significant antiherpetic activity in antiviral assays in vitro. 相似文献
8.
Joon Hee Hong So-Young Kim Chang-Hyun Oh Kyung Ho Yoo Jung-Hyuck Cho Prof. Dr. 《Nucleosides, nucleotides & nucleic acids》2013,32(3):341-350
Novel acyclic nucleoside analogues were designed and synthesized as open-chain analogues of neplanocin A. The coupling of the allylic bromide with purine bases using cesium carbonate afforded a series of novel acyclic nucleosides. The synthesized compounds Ia – II were evaluated for their antiviral activity against various viruses such as HIV, HSV-1, HSV-2, and ECMV. 相似文献
9.
《Nucleosides, nucleotides & nucleic acids》2013,32(4-7):329-332
Synthesis and antiviral activity of methylenedifluorocyclopropane analogues 8a, 8b and 9a, 9b are described. 相似文献
10.
Krishna Upadhya Jay Dare Ernst M. Schubert Gwendolyn N. Chmurny Bjarne Gabrielsen 《Nucleosides, nucleotides & nucleic acids》2013,32(5):649-662
Abstract Ribavirin and tiazofurin, two nucleosides of known antiviral activity, have been transformed by previously reported methods to yield several deoxy,epoxy, or dideoxy analogues. The deoxygenated derivatives were evaluated for antiviral activity against a host of DNA and RNA viruses; however, no significant in vitro activity was detected. 相似文献
11.
Michel Legraverend Anne-Marie Aubertin Georges Obert Christiane Huel Emile Bisagni 《Nucleosides, nucleotides & nucleic acids》2013,32(4):915-923
Abstract Three analogues of Carbovir 1 have been synthesized and evaluated for antiviral activity in vitro. Anti-HIV-1 and anti-HIV-2 activities have been observed with 7-deaza analogues 3 and 5 of 1. Compound 5 was about ten times more potent than 3 against HIV-1 and HIV-2 on different cell lines. 相似文献
12.
J. A. Secrist R. M. Brash R. J. Gray R. N. Comber J. A. Montgomery 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):1153-1154
Abstract Various 5′-substituted analogues of carbocyclic 3-deazaadenosine (la), a potent antiviral agent, have been prepared and tested against nine viruses. 相似文献
13.
Novel 5′-deoxyfuranosyl purine phosphonic acid analogues with 2 ′-electropositive moiety, such as spirocyclopropanoid, were designed and synthesized from commercially available diethyl malonate. Condensation reaction successfully proceeded from a glycosyl donor 15 at low reaction temperature in Vorbruggen conditions to give desired phosphonate analogues 16b and 23b. The synthesized nucleotide analogues 19, 22, 26, and 29 were subjected to antiviral screening against HIV-1. Adenine phosphonic acid analogue 22 shows significant anti-HIV activity (EC50 = 7.9 μM). 相似文献
14.
Novel 4′(α)-ethyl-2′(β)-methyl carbocyclic nucleoside analogues have been prepared and evaluated for inhibition of hepatitis C virus (HCV) RNA replication in cell culture. The construction of cyclopentene intermediate 12β was successfully made via sequential Johnson-Claisen orthoester rearrangement and ring-closing metathesis (RCM) starting from Weinreb amide 5. Selective dihydroxylation and desilylation gave the target carbodine analogues. The synthesized nucleoside analogues mentioned above 18 and 19 were assayed for their ability to inhibit HCV RNA replication in a subgenomic replicon Huh7 cell line (LucNeo#2). However, the synthesized nucleosides neither showed any significant antiviral activity nor toxicity up to 50 μM. 相似文献
15.
A. Van Aerschot Z. Ni J. Rozenski P. Claes E. De Clercq P. Herdewijn 《Nucleosides, nucleotides & nucleic acids》2013,32(8):1791-1800
Abstract The synthesis and antiviral activity of a new series of acyclic nucleoside analogues containing a (2-hydroxyethoxy)ethyl moiety is discussed. 相似文献
16.
Stuart Bailey Colin T. Shanks Michael R. Harnden 《Nucleosides, nucleotides & nucleic acids》2013,32(5):565-585
Abstract Novel pyrimidine nucleoside analogues in which the N-1 ribosyl moiety is replaced by a 2,3-dihydroxy-1-methoxypropyl or 3-hydroxy-1-methoxypropyl substituent have been synthesized and tested for antiviral activity. 相似文献
17.
Joseph H. Chan Stanley D. Chamberlain Karen K. Biron Michelle G. Davis Robert J. Harvey Dean W. Selleseth 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):101-123
Abstract A series of 2′-deoxy analogues of the antiviral agent 5,6-dichloro-2-isopropylamino-1-(β-L-ribofuranosyl)-1H-benzimidazole (1263W94) were synthesized and evaluated for activity against human cytomegalovirus (HCMV) and for cytotoxicity. The 2-substituents in the benzimidazole moiety correspond to those that were used in the 1263W94 series. In general, as was found in the 1263W94 series, cyclic and branched alkylamino groups were needed for potent activity against HCMV. Three analogues 3a, 3b and 3d were as potent as 1263W94. Further evaluation of two analogues, 3a and 3b, suggested that these 2′-deoxy analogues may act via a novel mechanism of action similar to that of 1263W94. These 2′-deoxy analogues generally lacked cytotoxicity in vitro. Pharmacokinetic parameters in mice and protein binding properties of 3a were quite similar to 1263W94. However, the oral bioavailability of 3a was only half of that observed for 1263W94. 相似文献
18.
Staffan Eriksson Jianghai Wang Salo Gronowitz Nils Gunnar Johansson 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):507-510
Abstract Some 5-aryl-2′-deoxyuridine and -deoxycytidine analogues, many with known antiviral activity, were evaluated as substrates for pure deoxycytidine kinase (dCK) and pure mitochondrial thymidine kinase (TK2). Some of the deoxyuridine compounds were also tested with pure cytosolic thymidine kinase (TK1). TK2 showed the highest activity with this type of analogues. 相似文献
19.
Socrates C. H. Cavalcanti Yuejun Xiang M. Gary Newton Raymond F. Schinazi Yung-Chi Cheng Chung K. Chu 《Nucleosides, nucleotides & nucleic acids》2013,32(10):2233-2252
Abstract A series of 2′,3′-dideoxy-2′-fluoro-L-threo-pentofuranosyl nucleosides has been synthesized as potential antiviral agents. The synthesized compounds were evaluated against HIV-1, HBV, HSV-1, and HSV-2. Among the synthesized analogues, only the cytosine derivative showed moderate antiviral activity against HIV and HBV. 相似文献
20.
《Nucleosides, nucleotides & nucleic acids》2013,32(12):1975-2000
Various 2-halogen-substituted analogues (38, 39, 43 and 44), 3-halogen- substituted analogues (51 and 52), and 2′, 3′-dihalogen-substituted analogues (57–60) of 3-deazaadenosine and 3-halogen-substituted analogues (61 and 62) of 3-deazaguanosine have been synthesized as potential anticancer and/or antiviral agents. Among these compounds, 3-deaza-3-bromoguanosine (62) showed significant cytotoxicity against L1210, P388, CCRF-CEM and B16F10 cell lines in vitro, producing IC50 values of 3, 7, 9 and 7,μM, respectively. Several 3-deazaadenosine analogues (38, 51, 57 and 59) showed moderate to weak activity against hepatitis B virus. 相似文献