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1.
Abstract

Coupling of 1-O-acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-d-ribofuranose with 6-chloropurine and 2,6-dichloropurine gave a mixture of 9α and 9β anomers as major products. These anomers were separated and converted to 2′-deoxy-4′-thio analogues of adenosine, inosine, guanosine, 2-amino-adenosine, and 2-chloro adenosine as well as their α-anomers.  相似文献   

2.
Abstract

1-O-Acetyl-2-deoxy-3,5-di-O-toluoyl-4-thio-D-erythro-pentofuranose and 2-deoxy-1,3,5-tri-O-acetyl-4-thio-L-threo-pentofuranose were coupled with 5-azacytosine to obtain α and β anomers of nucleosides. All four nucleosides were reduced to the corresponding dihydro derivatives and deblocked to give target compounds. All eight target compounds were evaluated in a series of human cancer cell lines in culture. Only 2′-deoxy-4′-thio-5-azacytidine () was found to be cytotoxic in all the cell lines and was further evaluated in vivo. Details of the synthesis and biological activity are reported.  相似文献   

3.
Abstract

Two pathways are described for the synthesis of the 2′-deoxynucleosides of 2-thiocytosine and 5-fluoro-2-thiocytosine: (a) by nucleoside condensation, (b) by amination of the corresponding nucleosides of 2,4-dithiouracil. Biological activities vs two cell systems are described. The nucleosides are moderate to weak substrates of deoxycytidine kinase and, partly as a result of this, reasonable good inhibitors of the enzyme  相似文献   

4.
A number of new 5"-phosphonate derivatives of 4"-thio-5-ethyl-2"-deoxyuridine (TEDU) were synthesized. These compounds displayed a low cytotoxicity and, except for TEDU 5"-fluorophosphate, antiherpes activity similar to that of 9-[(2-hydroxyethoxy)methyl]guanine (acyclovir) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (pencyclovir). 5"-Ethoxycarbonylphosphonate and 5"-aminocarbonylphosphonate of TEDU were also found to suppress the reproduction of herpes simplex type 1 virus, which is resistant to acyclovir.  相似文献   

5.
Abstract

Synthesis and biological activity of 7- and 9-isomers (Z+E) of methylenecyclopropane analogues of 2-aminopurine nucleosides is described. The (S,Z)-9-isomer is a substrate for xanthine oxidase.  相似文献   

6.
Abstract

N3 -β-D-glucopyranosyl, galactopyranosyl and xylopyranosyl 6-methyl-2-methylthiouracil and their 5-bromo derivatives have been synthesized by coupling an a-acetobromosugar with the corresponding thiouracil. The new modified thiouridine analogues were evaluated for their inhibitory activity against Human Immunodeficiency Virus (HIV) replication in MT-4 cells as well as for their cytotoxicity.  相似文献   

7.
The synthesis and biological activity of chloroethyl pyrimidine nucleosides is presented. One of these new nucleosides analogues significantly inhibited cell proliferation, migration and invasion as tested in vitro on the A431 vulvar epidermal carcinoma cell line.  相似文献   

8.
Abstract

The procedure of Huang and Hui (Nucleosides & Nucleotide 1993, 12, 139-147) was found to give benzyl 3,5-di-O-benzyl-2-deoxy-1,4-dithio-α-L-threo-pentofuranoside (6) rather than the claimed D-erythro isomer. This sugar was converted to an anomeric mixture of the thymine nucleosides. The mixture was separated and the α-anomer (α-10) was found to be cytotoxic, whereas theβ-anomer (β-10) was inactive.  相似文献   

9.
Abstract

Various new haloindazole-1-β-D-ribofuranosides (10-17,20,21) and a 2-β-D-ribofuranoside (18) have been synthesized by the fusion method and by direct halogenations, respectively. The new nucleosides have been characterized by UV and 1H NMR spectra as well as pKa determinations. Indazole ribofuranosides behave in aqueous acid like purine and benzimidazole nucleosides showing the same mechanism of cleavage of the glycosidic bonds. Toxicity studies against various cell populations indicate only little biological activities.  相似文献   

10.
Abstract

Four methods are described for the synthesis of 2-thio-5-chlorouracil (1). β- and α-5-Chloro-2-thio-2′-deoxyuridines (12 and 13) were obtained by Lewis acid catalysed condensation of TMS derivative of 1 with 2-deoxy-3,5-di-O-p-toluyl-α-D-ribosyl chloride and deblocking of toluylated derivatives with methanolic ammonia. Selective enzymatic phosphorylation of 12 led to its 5′-monophosphate, the latter being a moderate inhibitor of thymidylate synthase, while 12 showed moderate cytotoxicity in vitro against mouse leukemic cells L15178Y.  相似文献   

11.
Abstract

The quantitative conversion of dihydro-5-azacytosine (5-DHAC) to 5-azacytosine (5-AC) has been accomplished in a dihydro-5-azacyti-dine/thymidine dimer (5-DHACpT). This newly developed procedure allows simi1ar possibilities with longer, 5-DHAC-modified oligodeoxynucleo-tides.  相似文献   

12.
Abstract

The use of D-(+)-ribonic γ-lactone 1a,b as a chiral synthon leads to an efficient synthesis of the ketose 1-deoxy-D-psicofuranose 2a,b. Condensation of the corresponding acetyl derivative 3a,b with silylated thymine, followed by deprotection of 4a,b affords an anomeric mixture of ketosyl nucleoside 6 (predominately the β-anomer) in an improved overall yield of 49%.  相似文献   

13.
Abstract

A series of 2′-deoxy, 2′,3′-unsaturdted and 2′,3′-dideoxynucleoside analogues, which have an additional methyl group at the 4′-position, have been synthesized. When evaluated for their inhibitory activity against HIV in MT-4 cell, 2′-deoxy-4′-C-methyl nucleosides exhibited potent activity.

  相似文献   

14.
Abstract

Purine analogues and derivatives exhibit a broad range of pharmacological activities and are used in the chemotherapy of cancer, parasitic and viral infections, and for the suppression of immune responses. Undoubtedly, this wide range of biological activities reflect an equally wide number of biochemical sites of action, one of which is the purine de novo pathway. New agents which can either serve as inhibitors of enzymes involved in this pathway or as substrates are continually sought. The unique series of nucleosides described herein should meet these desired needs.

The synthesis of 1involved glycosylation of a suitably 4,5-disubstituted imidazole and subsequent cyclization of the imidazole nucleoside so formed to the imidazo[4,5-d]pyridazine nucleoside. Such methodology was successfully employed1,2 in the preparation of certain 4,7-disubstituted imidazo[4,5-d]pyridazine nucleosides. Chlorination of 1furnished 4-chloro-1-(2,3,5-tri-O-acetyl-β-D-ribo-furanosyl)imidazo[4,5-dlpyridazine (2) in 80% yield. This versatile intermediate can now serve as a precursor to a variety of 4-substituted imidazo[4,5-d]pyridazine nucleosides.  相似文献   

15.
Abstract

The synthesis of new enantiomers of 5-o-carboranyl pyrimidine nucleosides is described. Some of these agents should be considered for boron neutron capture therapy.  相似文献   

16.
17.
Abstract

Treating carbocyclic N1-methoxymethyl-inosine and -2′-deoxyinosine with 1N-NaOH/aq.EtOH gave carbocyclic 5-amino-4-imidazolecarboxamide riboside and 2′-deoxyriboside, respectively. Reactions of both the useful key intermediates with benzoylisothiocyanate afforded the corresponding 5-(N-benzoylisothiocarbamoyl) derivatives. Methylation of the sulfhydryl groups, followed by treatment with NaOH, led to the purine ring-closure (guanine, isoguanine, and 3-methylxanthine) reaction. The conformational difference between 2′-deoxyguanosine and carbocyclic 2′-deoxyguanosine is also discussed.  相似文献   

18.
Abstract

1,2,3,5-Tetra-O-acetyl-4-thio-D-riboruranose, prepared from 2,3,5-tri-O-benzyl-D-ribofuranose in four steps, was converted to the corresponding 2-chloroadenine nucleoside (8), which was deoxygenated to obtain 2-chloro-2′-deoxy-4′-thioadenosine (12). This is the first report of a 2′-deoxy-4′-thioribonucleoside of a purine rather than a pyrimidine. These novel nucleosides (8 and 12) were cytotoric to several human tumor cell lines in culture.  相似文献   

19.
Abstract

The synthesis of a series of new nucleosides and nucleotides, including ribo-, 2-deoxyribo- and arabinofuranosides of 5-sulfur-substituted cytosines, is described. The synthetic methods employed involve 5-thiolation of the appropriate cytosine or 5-bromocytosine nucleosides and nucleotides, or alternatively, 4-thiation followed by amination of the corresponding protected 5-(S-benzyl)mercaptouracil nucleosides and subsequent deblocking with sodium and liquid ammonia.  相似文献   

20.
Abstract

C-acyclic nucleoside analogues of inosine and guanosine 8-[(RS)-2,3-dihydroxypropyl] imidazo [1,5-a]-1,3,5-triazin-4 (3H)-ones 6a, c, d were synthesized. The route involved the cyclization-rearrangement of 5-acylamino-5-allyl-6-amino-4,5-dihydropyrimidin-4-ones 4a-c to 8-allylimidazo [1,5-a]-1,3,5-triazin-4 (3H) ones 5a-c. 5a was transformed selectively into 5d by reductive desulfurization with highly deactivated Raney nickel. The poorly soluble compounds 5b and 5c were converted to N-2-acetylated 5f and 5g. Osmium tetroxide hydroxylation of 5d, f, g gave 6a, c, d. None of the newly synthesized C-acyclic nucleoside derivatives showed an appreciable antiviral or antitumor cell activity.  相似文献   

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