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1.
A new class of acyclic nucleoside phosphonates PMAMG, PMAMA, PMAMC, and PMAMT (compounds 1, 2, 3 and 4) have been synthesized and tested in vitro against a wide variety of viruses, fungi and bacteria. PMAMG (1) was synthesized by the alkylation reaction of acetylguanine with the phosphonate side-chain, diisopropyl [[2-(bromomethyl)aziridin-1-yl]]methylphosphonate (9), followed by deesterification reaction in the presence of TMSBr. In similar way, PMAMA, PMAMC, and PMAMT were prepared. 相似文献
2.
Robert W. Sidwell John H. Huffman Dale L. Barnard Elmer J. Reist 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):833-836
Abstract Eight phosphonic acid analogs of acyclovir (ACV) or ganciclovir (DHPG) inhibited human cytomegalovirus in vitro. Therapeutic indices were: phosphonate diacid of DHPG: 500; DHPG: 500; phosphonate monoethylester of DHPG: 258; phosphonate monoethylester of ACV: 94; cyclic phosphonate of DHPG: 64; ACV: 60; phosphonate monobutylester of ACV: 1.5; phosphonate monoethylester of deoxy DHPG: 4.6; 8-bromo ACV phosphonate monoethylester: >2; phosphonate monoethylester heptyl of ACV: 1. Types 1 and 2 herpesvirus (HSV-1, HSV-2) and varicella zoster virus (VZV) were poorly inhibited by these new compounds, suggesting highly specific anti-HCMV activity. None exhibited significant cytotoxic effects as measured by uptake of [3H]thymidine, [3H]uridine and [3H]leucine. 相似文献
3.
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
4.
Krystyna Lesiak Kyoichi A. Watanabe Krzysztof W. Pankiewicz 《Nucleosides, nucleotides & nucleic acids》2013,32(9-11):1857-1860
Abstract 2-(4-Nitrophenylethyl) methylenebis(phosphonate) (1) has been prepared by reaction of 2-(4-nitrophenyl)ethyl alcohol with methylenebis(phosphonyl) tetrachloride. Compound 1 was treated with diisopropylcarbodiimide (DIC) to give bicyclic intermediate 2, which in reaction with suitably protected 2′-deoxynucleosides 3 gave P1,P2-disubstituted methylenebis(phosphonate)s 4. Removal of the nitrophenylethyl group by β-elimination with DBU afforded the corresponding 2′-deoxynucleoside 5′-methylenebis(phosphonate) analogues 5. 相似文献
5.
《Nucleosides, nucleotides & nucleic acids》2013,32(9):1735-1750
A series of 3-alkyl-5-((Z))-arylidene-2-thiohydantoins 4a-l were synthesized from the direct condensation of the aromatic aldehydes with 3-alkyl-2-thiohydantoins 3a-c, which in turn were prepared from the reaction of glycine (1) and alkyl isothiocyanates 2a-c. The alkylation of 4a-l with methylthioethyl chloride gave 5-((Z))-arylidene-3-alkyl-S-(2-methylthioethyl)-2-thiohydantoins 5a-e. S-Glucosylation took place on the reaction of 4a-l with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide under anhydrous alkaline conditions. These structures have been confirmed from a model study of the coupling of 4a with methylthioethyl chloride and α-D-glucose pentaacetate, respectively under Lewis acid conditions. 相似文献
6.
《Nucleosides, nucleotides & nucleic acids》2013,32(4-7):1059-1062
Novel cyclopropyl nucleosides were synthesized as potential antiviral agents. The key intermediate 5, prepared from Feist's acid 1 was condensed with purine derivatives by the SN2 type reaction. All the synthesized compounds were evaluated for antiviral activity. 相似文献
7.
Novel 5′-deoxycarbocyclic purine phosphonic acid analogs with the 4′-electropositive moiety, fluorine were designed, and synthesized from glyceraldehyde. The cyclopentenol intermediate, 9, was successfully synthesized by the ring-closing metathesis of divinyl 8. The condensation reaction of cyclopentanol 15 with purine bases under Mitsunobu conditions successfully afforded the desired phosphonate analogs. The synthesized nucleoside phosphonic acid analogs, 19, 22, 26, and 29, were subjected to antiviral screening against human immunodeficiency virus (HIV)-1. Guanine phosphonic acid analog 29 showed significant anti-HIV activity (EC50 = 10.3 μM). 相似文献
8.
9.
Koray Oktay Leyla Polat Köse Kıvılcım Şendil Claudiu T. Supuran 《Journal of enzyme inhibition and medicinal chemistry》2016,31(6):939-945
The synthesis of (Z)-4-oxo-4-(arylamino)but-2-enoic acid (4) derivatives containing structural characteristics that can be used for the synthesis of several active molecules, is presented. Some of the butenoic acid derivatives (4a, 4c, 4e, 4i, 4j, 4k) are synthesized following literature procedures and at the end of the reaction. In addition, structures of all synthesized derivatives (4a–4m) were determined by 1H-NMR, 13C-NMR and IR spectroscopy. Carbonic anhydrase is a metalloenzyme involved in many crucial physiologic processes as it catalyzes a simple but fundamental reaction, the reversible hydration of carbon dioxide to bicarbonate and protons. Significant results were obtained by evaluating the enzyme inhibitory activities of these derivatives against human carbonic anhydrase hCA I and II isoenzymes (hCA I and II). Butenoic acid derivatives (4a–4m) strongly inhibited hCA I and II with Kis in the low nanomolar range of 1.85?±?0.58 to 5.04?±?1.46?nM against hCA I and in the range of 2.01?±?0.52 to 2.94?±?1.31?nM against hCA II. 相似文献
10.
Kyung Mi Kim 《Nucleosides, nucleotides & nucleic acids》2013,32(2):92-109
A series of purine 5′-deoxyphosphonate analogues were designed and synthesized to mimic naturally occurring purine monophosphate from 1,3-dihydroxyacetone as starting material. 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 2′,3′-modified 5′-deoxyversions of the threosyl phosphonate nucleosides. The synthesized 2′-fluoro-3′-hydroxymethyl 5′-deoxythreosyl phosphonic acid nucleoside analogues 14, 18, 23, and 27 were tested for anti-HIV activity as well as cytotoxicity. The adenine analogue 18 exhibits weak in vitro anti-HIV-1 activity (EC50 = 19.2 μM). 相似文献
11.
Wei Chen Michael T. Flavin Robert Filler Ze-Qi Xu 《Nucleosides, nucleotides & nucleic acids》2013,32(11-12):1771-1778
Abstract Unprotected adenine, 6-chloropurine, 2.6-diaminopurine. and 2-amino-6-chluropurine have been directly coupled with 2-(diethoxyphosphonomethoxy)ethanol under Mitsunobu reaction conditions to provide acyclic phosphonate nucleotide analogues which are intermediates for antiviral agents such as PMEA. 相似文献
12.
Shuhei Imoto Satoru Kohgo Ryoh Tokuda Hiroki Kumamoto Manabu Aoki Masayuki Amano 《Nucleosides, nucleotides & nucleic acids》2015,34(8):590-602
Exomethylene acycloguanine nucleosides 4, 6 and its monophosphate derivatives 5, 7, and 8 have been synthesized. Mitsunobu-type coupling of 2-N-acetyl-6-O-diphenylcarbamoylguanine (11) with primary alcohols proceeded regioselectively to furnish the desired N9-substituted products in moderate yield. Evaluation of 4-8 for anti-HBV activity in HepG2 cells revealed that the phosphonate derivative 8 was found to exhibit moderated activity (EC50 value of 0.29 μM), but cytotoxicity (CC50 value of 39 μM) against the host cells was also observed. 相似文献
13.
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
14.
《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
15.
New aziridine 2‐phosphonic acids were prepared by monohydrolysis of the aziridine 2‐phosphonates that were obtained by the modified Gabriel?Cromwell reaction of vinyl phosphonate or α‐tosylvinyl phosphonate with a primary amine or a chiral amine. The cellular cytotoxicity of these compounds was tested against the HCT‐116 colorectal cancer cell lines and the CCD‐18Co normal colon fibroblast lines using the MTT assay. Three of the synthesized phosphonic acid derivatives 2e (ethyl hydrogen {(2S)‐1‐[(1S)‐1‐(naphthalen‐2‐yl)ethyl]aziridin‐2‐yl}phosphonate), 2h (ethyl hydrogen (1‐benzylaziridin‐2‐yl)phosphonate), and 2i (ethyl hydrogen (1‐cyclohexylaziridin‐2‐yl)phosphonate) showed higher cytotoxicity than the reference cancer treatment agent etoposide. Cell death was through a robust induction of apoptosis even more effectively than etoposide, a well‐known apoptosis inducing agent. 相似文献
16.
Hinako Shirakata Hisashi Nishiwaki 《Bioscience, biotechnology, and biochemistry》2020,84(10):1986-1996
ABSTRACT All eight stereoisomers of conidendrin were synthesized from (1 R,2 S,3 S)-1-(4-benzyloxy-3-methoxyphenyl)-3-(4-benzyloxy-3-methoxybenzyl)-2- hydroxymethyl-1,4-butanediol ((+)-4) and its enantiomer with high optical purity. The configurations at 4-positions of the conidendrin stereoisomers were constructed by intramolecular Friedel-Crafts reaction of protected 4. After conversion to tetrahydronaphthalene intermediate 7a, the 2- and 3-position of tetrahydronaphthalene structure 7a were converted to 3a- and 9a-position of (+)-α-conidendrin (3a), respectively. By the epimerization process of 2- or 3-position of 7a, the other diastereomers were obtained. All enantiomers were also synthesized from (?)-4. 相似文献
17.
Palmarisa Franchetti Ghassan Abu Sheikha Loredana Cappellacci Mario Grifantini Emanuela Balestra Carlo-Federico Perno 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):989-990
Abstract A new antiviral drug with both anti-HSV and anti-HIV activity was synthesized by coupling Acyclovir and the acyclic nucleoside phosphonate (R)PMPA. The heterodinucleotide ACVpPMPA encapsulated into autologous erythrocytes was added to human macrophages providing an effective in vitro protection from HSV-1 and HIV-1 replication. 相似文献
18.
Eunae Kim Guang Huan Shen Lien Kang Joon Hee Hong 《Nucleosides, nucleotides & nucleic acids》2013,32(7):396-410
The authors describe highly efficient synthetic routes for the preparation of novel 6′,6′-difluoro 5′-deoxycarbocyclic phosphonic acid nucleosides from 1,4-dihydroxy-2-butene. The discovery that the 6′-fluorinated carbocyclic nucleoside (2, EC50 = 0.16 μM) is a potent anti-HSV-1 agent led to the syntheses and biological evaluations of 6′-modified 5′-deoxyversions of carbocyclic phosphonate nucleosides. The synthesized nucleoside analogues 15, 18, 22, and 25 were tested for anti-HIV activity and for cytotoxicity. However, none of them showed significant anti-HIV-1 activity or cytotoxicity at concentrations up to 100 μM. 相似文献
19.
Ahmed H. Moustafa Hassan A. El-Sayed Abd El-Fattah Z. Haikal El Sayed H. El Ashry 《Nucleosides, nucleotides & nucleic acids》2013,32(5):340-352
Reaction of pyridin-2(1H)-one 1 with 4-bromobutylacetate (2), (2-acetoxyethoxy)methyl bromide (3) gave the corresponding nicotinonitrile O-acyclonucleosides, 4 and 5, respectively. Deacetylation of 4 and 5 gave the corresponding deprotected acyclonucleosides 6 and 7, respectively. Treatment of pyridin-2(1H)-one 1 with 1,3-dichloropropan-2-ol (8), epichlorohydrin (10) and allyl bromide (12) gave the corresponding nicotinonitrile O-acyclonucleosides 9, 11, and 13, respectively. Furthermore, reaction of pyridin-2(1H)-one 1 with the propargyl bromide (14) gave the corresponding 2-O-propargyl derivative 15, which was reacted via [3+2] cycloaddition with 4-azidobutyl acetate (16) and [(2-acetoxyethoxy)methyl]azide (17) to give the corresponding 1,2,3-triazole derivatives 18 and 19, respectively. The structures of the new synthesized compounds were characterized by using IR, 1H, 13C NMR spectra, and microanalysis. Selected members of these compounds were screened for antibacterial activity. 相似文献
20.
Dagmara Baraniak Daniel Baranowski Piotr Ruszkowski Jerzy Boryski 《Nucleosides, nucleotides & nucleic acids》2016,35(4):178-194
A series of new 3′-O- and 5′-O-propargyl derivatives of 5-fluoro-2′-deoxyuridine (1–4) was synthesized by means of propargyl reaction of properly blocked nucleosides (2,4), followed by the deprotection reaction with ammonium fluoride. The synthesized propargylated 5-fluoro-2′-deoxyuridine analogues (1–4) were evaluated for their cytotoxic activity in three human cancer cell lines: cervical (HeLa), oral (KB) and breast (MCF-7), using the sulforhodamine B (SRB) assay. The highest activity and the best SI coefficient in all of the investigated cancer cells were displayed by 3′-O-propargyl-5-fluoro-2′-deoxyuridine (1), and its activity was higher than that of the parent nucleoside. The other new compounds exhibited moderate activity in all of the used cell lines. 相似文献