Assuntos
Erupções Acneiformes/induzido quimicamente , Vitamina B 12/efeitos adversos , Erupções Acneiformes/tratamento farmacológico , Adapaleno , Adulto , Peróxido de Benzoíla/administração & dosagem , Peróxido de Benzoíla/uso terapêutico , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/prevenção & controle , Lesões Encefálicas/complicações , Lesões Encefálicas/tratamento farmacológico , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Quimioterapia Combinada , Dermatoses Faciais/induzido quimicamente , Dermatoses Faciais/tratamento farmacológico , Feminino , Humanos , Limeciclina/administração & dosagem , Limeciclina/uso terapêutico , Masculino , Naftalenos/administração & dosagem , Naftalenos/uso terapêutico , Vitamina B 12/administração & dosagem , Vitamina B 12/uso terapêuticoRESUMO
Various cinnammoyl-based structures were synthesized and tested in enzyme assays as inhibitors of the HIV-1 integrase (IN). The majority of compounds were designed as geometrically or conformationally constrained analogues of caffeic acid phenethyl ester (CAPE) and were characterized by a syn disposition of the carbonyl group with respect to the vinylic double bond. Since the cinnamoyl moiety present in flavones such as quercetin (inactive on HIV-1-infected cells) is frozen in an anti arrangement, it was hoped that fixing our compounds in a syn disposition could favor anti-HIV-1 activity in cell-based assays. Geometrical and conformational properties of the designed compounds were taken into account through analysis of X-ray structures available from the Cambridge Structural Database. The polyhydroxylated analogues were prepared by reacting 3,4-bis(tetrahydropyran-2-yloxy)benzaldehyde with various compounds having active methylene groups such as 2-propanone, cyclopentanone, cyclohexanone, 1,3-diacetylbenzene, 2, 4-dihydroxyacetophenone, 2,3-dihydro-1-indanone, 2,3-dihydro-1, 3-indandione, and others. While active against both 3'-processing and strand-transfer reactions, the new compounds, curcumin included, failed to inhibit the HIV-1 multiplication in acutely infected MT-4 cells. Nevertheless, they specifically inhibited the enzymatic reactions associated with IN, being totally inactive against other viral (HIV-1 reverse transcriptase) and cellular (RNA polymerase II) nucleic acid-processing enzymes. On the other hand, title compounds were endowed with remarkable antiproliferative activity, whose potency correlated neither with the presence of catechols (possible source of reactive quinones) nor with inhibition of topoisomerases. The SARs developed for our compounds led to novel findings concerning the molecular determinants of IN inhibitory activity within the class of cinnamoyl-based structures. We hypothesize that these compounds bind to IN featuring the cinnamoyl residue C=C-C=O in a syn disposition, differently from flavone derivatives characterized by an anti arrangement about the same fragment. Certain inhibitors, lacking one of the two pharmacophoric catechol hydroxyls, retain moderate potency thanks to nonpharmacophoric fragments (i.e., a m-methoxy group in curcumin) which favorably interact with an "accessory" region of IN. This region is supposed to be located adjacent to the binding site accommodating the pharmacophoric dihydroxycinnamoyl moiety. Disruption of coplanarity in the inhibitor structure abolishes activity owing to poor shape complementarity with the target or an exceedingly high strain energy of the coplanar conformation.
Assuntos
Fármacos Anti-HIV , Cinamatos , Inibidores de Integrase de HIV , HIV-1/enzimologia , Modelos Moleculares , Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Cinamatos/síntese química , Cinamatos/química , Cinamatos/farmacologia , Cristalografia por Raios X , Inibidores de Integrase de HIV/síntese química , Inibidores de Integrase de HIV/química , Inibidores de Integrase de HIV/farmacologia , HIV-1/efeitos dos fármacos , HIV-1/crescimento & desenvolvimento , Humanos , Relação Estrutura-Atividade , Células Tumorais Cultivadas , Replicação Viral/efeitos dos fármacosRESUMO
IPCAR is a pyrazole nucleoside analog which belongs to a class of compounds structurally related to the inosine monophosphate (IMP) dehydrogenase (IMPDH) inhibitors ribavirin, selenazofurin and tiazofurin. Unlike other anticancer drugs, IPCAR showed a potent and broad-spectrum antiproliferative activity in vitro coupled with low cytotoxicity for resting PBL and CFU-GM. IPCAR proved fully inhibitory against human nasopharyngeal carcinoma KB cells expressing the MDR phenotype, whereas IPCAR-resistant renal adenocarcinoma ACHN/R1 cells were fully susceptible to inhibition by a number of anticancer drugs, with the exception of 6TG, 6MP and 5FU towards which they showed a partial cross-resistance. In combinations studies, IPCAR proved synergistic with 6MP, 6TG, 5FU and ribavirin, and additive with ara-A, MTX, doxorubicin, taxol and tiazofurin. Antagonistic effects were never observed. Although the precise molecular target of IPCAR remains to be identified, the data presented herein suggest that, unlike ribavirin and tiazofurin, this drug inhibits a step of the de novo purine biosynthesis different from the conversion of IMP into GMP. In vivo, IPCAR showed low acute toxicity (DL10 > 1000 mg/kg) and was active against the L1210 murine lymphocytic leukemia model. Drug doses of 125 and 250 mg/kg on a day-1, -3 and -5 dosing schedule increased the life span (ILS) relative to untreated control mice of 36.4 and 68.2%, respectively, whereas administration of 500 mg/kg on days 1 and 3 resulted in a ILS of 86.4% and also increased the 30-day survival rate (25% of the mice).
Assuntos
Antimetabólitos Antineoplásicos/toxicidade , Sobrevivência Celular/efeitos dos fármacos , Leucemia L1210/tratamento farmacológico , Nucleosídeos/toxicidade , Pirazóis/toxicidade , Animais , Antimetabólitos Antineoplásicos/uso terapêutico , Células CHO , Células Cultivadas , Cricetinae , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Células HeLa , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , IMP Desidrogenase/antagonistas & inibidores , Células KB , Linfócitos/citologia , Linfócitos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos DBA , Estrutura Molecular , Nucleosídeos/síntese química , Nucleosídeos/uso terapêutico , Purinas/farmacologia , Pirazóis/síntese química , Pirazóis/uso terapêutico , Pirimidinas/farmacologia , Ribavirina/análogos & derivados , Ribavirina/toxicidade , Ribonucleosídeos/farmacologia , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
We synthesized and tested as novel inhibitors of human immunodeficiency virus type 1 (HIV-1) bi- and tricyclic thiadiazine ring homologues of 7-chloro-2-ethyl-2H-1,2,4-benzothiadiazin-3-(4H)-one 1,1-dioxide, which is a compound endowed with anti-HIV-1 activity at low micromolar concentrations. Benzothiadiazepine derivatives were obtained by alkylation of 8-chloro-2,3-dihydro-3-methyl-1,2,5-benzothiadiazepin-4(5H)-one 1,1-dioxide, which was obtained by intramolecular cyclization of 2-(2-amino-5-chloro-benzenesulphonamido) propanoic acid. Pyrrolobenzothiadiazepines were synthesized from N-substituted 5-chloro-2-(1H-pyrrol-1-yl)benzene-sulphonamides by treating with triphosgene. N6-substituted pyrrolo[2,1-d][1,2,5]benzothiazepin-7(6H)-one 5,5-dioxides were active, though not very potent. Both a chlorine atom and an unsaturated alkyl chain were found to be determinants of anti-HIV-1 activity. The highest potency was shown by a derivative with a TIBO-related 3,3-dimethylallyl chain. 2,3-Dihydro-1,2,5-benzothiadiazepin-4(5H)-one 1,1-dioxides were scarcely active in HIV-1-infected MT-4 cell assays; however, the introduction of the dimethylallyl chain into 7-chloro-1,2,5-benzothiadiazepine moiety led to a bicyclic derivative which was more potent and less cytotoxic than the tricyclic pyrrole-containing counterpart.
Assuntos
Fármacos Anti-HIV/farmacologia , Azepinas/farmacologia , Benzotiadiazinas/farmacologia , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Fármacos Anti-HIV/química , Azepinas/química , Benzotiadiazinas/química , Linhagem Celular , Efeito Citopatogênico Viral/efeitos dos fármacos , HIV-1/patogenicidade , HIV-1/fisiologia , HIV-2/patogenicidade , HIV-2/fisiologia , Humanos , Relação Estrutura-Atividade , Replicação Viral/efeitos dos fármacosRESUMO
In the presence of sodium hydride, reaction of aryl-disulphides with ethyl esters of indole-2-carboxylic acids furnished ethyl 3-arylthioindole-2-carboxylates, which were cyclized intramolecularly to afford 5H-indolo[3,2-b][1,5]benzothiazepin-6(7H)-ones or hydrolysed in alkaline medium to give 3-arylthioindole-2-carboxylic acids. These acids, also obtained by the action of aryldisulphides on indole-2-carboxylic acids, afforded tetracyclic 5H-indolo [3,2-b][1,5]benzothiazepin-6(7H)-ones upon treatment with EDCI-DMAP. Transformation of cyclic sulphides into the required sulphones was achieved by treatment with hydrogen peroxide or with m-chloroperbenzoic acid. The title derivatives are conformationally constrained analogues of the potent human immunodeficiency virus type 1 (HIV-1) reverse transcriptase inhibitor 3-benzene-sulphonyl-5-chloroindole-2-carboxamide (L-737, 126). Although the indolobenzothiazepine derivatives, as well as the indolyl aryl sulphones used for their synthesis, were endowed with anti-HIV-1 activities in the submicromolar and micromolar range, none of them proved more potent than L-737,126.
Assuntos
Fármacos Anti-HIV/síntese química , Fármacos Anti-HIV/farmacologia , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Indóis/síntese química , Indóis/farmacologia , Inibidores da Transcriptase Reversa/síntese química , Inibidores da Transcriptase Reversa/farmacologia , Sulfonas/síntese química , Sulfonas/farmacologia , Fármacos Anti-HIV/química , Linhagem Celular , Transcriptase Reversa do HIV/efeitos dos fármacos , Humanos , Indóis/química , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Inibidores da Transcriptase Reversa/química , Relação Estrutura-Atividade , Sulfonas/químicaRESUMO
A series of human immunodeficiency virus (HIV) protease inhibitors, which are analogues of N-[2(R)-hydroxy-1(S)- indanyl]-5(S)-[(tert-butyloxycarbonyl)amino]-4(S)-hydroxy-6-phenyl-2-(R) - [[4-(carboxymethoxy)phenyl]methyl]hexanamide (L-694,746), a metabolite of the anti-HIV agent L-689,502, were synthesized. In these compounds, the acetic group linked to the para position of the P1' phenyl in the reference inhibitor was replaced either by the bioisosteric phosphonomethoxy group and its diisopropyl/dibenzyl derivatives, or the 1H-tetrazol-5-yl-methoxy group and its 1-benzyl derivative. In enzyme assays, phosphonomethoxy and tetrazolmethoxy analogues proved to be potent inhibitors of the HIV-1 protease, with IC50 values as low as 0.04 nM. When tested for anti-HIV-1 activity in cell-based assays, most of the new derivatives proved active, with benzyl derivatives being more active than their highly polar, unsubstituted counterparts. The dibenzylphosphonomethoxy analogue was the most active compound, with an EC50 value of 10 nM and a selectivity index of 20,000. When compounds were examined for their capability to reduce p24 levels in both acutely and chronically infected MT-4 and H9/IIIB cells, all of them were found to be active at concentrations close to those capable of preventing HIV-1-induced cytopathic effect.
Assuntos
Fármacos Anti-HIV/síntese química , Inibidores da Protease de HIV/síntese química , Peptídeos/farmacologia , Amidas/síntese química , Fármacos Anti-HIV/farmacologia , Antivirais/síntese química , Antivirais/farmacologia , Linhagem Celular , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Humanos , Estrutura Molecular , Morfolinas/farmacologiaRESUMO
The synthesis and biological activity of selenophenfurin (5-beta-D-ribofuranosylselenophene-3-carboxamide, 1), the selenophene analogue of selenazofurin, are described. Glycosylation of ethyl selenophene-3-carboxylate (6) under stannic chloride-catalyzed conditions gave 2- and 5-glycosylated regioisomers, as a mixture of alpha- and beta-anomers, and the beta-2,5-diglycosylated derivative. Deprotected ethyl 5-beta-D-ribofuranosylselenophene-3-carboxylate (12 beta) was converted into selenophenfurin by ammonolysis. The structure of 12 beta was determined by 1H- and 13C-NMR, crystallographic, and computational studies. Selenophenfurin proved to be antiproliferative against a number of leukemia, lymphoma, and solid tumor cell lines at concentrations similar to those of selenazofurin but was more potent than the thiophene and thiazole analogues thiophenfurin and tiazofurin. Incubation of K562 cells with selenophenfurin resulted in inhibition of IMP dehydrogenase (IMPDH) (76%) and an increase in IMP pools (14.5-fold) with a concurrent decrease in GTP levels (58%). The results obtained confirm the hypothesis that the presence of heteroatoms such as S or Se in the heterocycle in position 2 with respect to the glycosidic bond is essential for both cytotoxicity and IMP dehydrogenase inhibitory activity in this type of C-nucleosides.
Assuntos
Antineoplásicos , Inibidores Enzimáticos/síntese química , IMP Desidrogenase/antagonistas & inibidores , Compostos Organosselênicos/química , Compostos Organosselênicos/síntese química , Compostos Organosselênicos/farmacologia , Ribonucleosídeos/química , Ribonucleosídeos/síntese química , Ribonucleosídeos/farmacologia , Animais , Antineoplásicos/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Simulação por Computador , Cristalografia por Raios X , Guanosina Trifosfato/metabolismo , Humanos , Inosina Monofosfato/metabolismo , Leucemia/patologia , Linfoma/patologia , Espectroscopia de Ressonância Magnética , Camundongos , Modelos Moleculares , Estrutura Molecular , Neoplasias/patologia , Ribavirina/análogos & derivados , Células Tumorais CultivadasRESUMO
Novel compounds related to 2-(cyclohexylthio)-3,4-dihydro-5-methyl-6-(3-methylbenzyl)-4-ox opyrimidine (3c, MC 639) have been synthesized and tested as inhibitors of human immunodeficiency virus type-1 (HIV-1). Reaction of thiourea with ethyl arylmethylacetoacetates furnished 5-alkyl-6-(arylmethyl)-3,4-dihydro-2-mercapto-4-oxopyrimidines which were then alkylated at the sulfur atom to afford the required 2-alkylthio or 2-cycloalkylthio derivatives (S-DABOs). Chemical modifications at N-3, C-4, and C-6 of the pyrimidine ring were attempted with the aim of improving antiretroviral activity. In particular, replacement of the benzyl group with the 1-naphthylmethyl moiety enhanced the activity of S-DABOs, whereas N-3 alkylation and C=O transformation into C=S at position 4 of the pyrimidine ring led to compounds devoid of anti-HIV-1 activity. Lower activity was generally observed when 1-naphthylmethyl was replaced by the isomeric 2-naphthylmethyl moiety. The most active compounds showed activity in the low micromolar range with EC50 values comparable to that of nevirapine.
Assuntos
Transcriptase Reversa do HIV/antagonistas & inibidores , Pirimidinas/farmacologia , Inibidores da Transcriptase Reversa/farmacologia , Linhagem Celular , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Pirimidinas/química , Inibidores da Transcriptase Reversa/química , Relação Estrutura-AtividadeRESUMO
Previous studies showed that some 2'-alkyloxyisoxazoles 2b-d obtained from 3-(diethylamino)-5-(2'hydroxy-4'-methoxyphenyl)isoxazole 2a were endowed with an interesting anti-group B rhinovirus activity (action on HRV-2 serotype). Other isoxazoles (WIN compounds) are well known to have anti-group A rhinovirus activity (action on HRV-14 serotype). To obtain an action similar to that of WIN compounds, starting from 2a, the 2'-acyl (3,4,5) and 2'alkyl (6,8) derivatives were synthesized. Also some Mannich bases (9,10) and bisisoxazoles (7,11,13,14) were studied. Though some of the tested compounds mainly exhibited anti-group B rhinovirus activity, their potency was less intense with respect to the above mentioned compounds 2b-d. The only N-methylpiperazinomethyl derivative 10 was slightly active against both tested serotypes.
Assuntos
Antivirais/síntese química , Isoxazóis/síntese química , Rhinovirus/efeitos dos fármacos , Antivirais/farmacologia , Efeito Citopatogênico Viral/efeitos dos fármacos , HIV-1/efeitos dos fármacos , Células HeLa , Humanos , Isoxazóis/farmacologia , Replicação Viral/efeitos dos fármacosRESUMO
(R)- And (S)-8-aza-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-and (S)-8-aza-PMPG] were synthesized and tested in vitro for anti-human immunodeficiency virus (HIV) activity. The synthesis of the above compounds and of (R)-9(-)[2-(phosphonomethoxy)propyl]guanine [(R)-PMPG] was carried out through the alkylation of 8-azaguanine or guanine with (R)- and (S)-2-O(-)[(diisopropylphosphono)methyl]-1-O-(tolylsulfonyl) -1,2-propanediol followed by deprotection of the phosphonic moiety. A different, even more convenient synthesis of (R)-8-aza-PMPG starting from 2-amino-6-chloro-5-nitro-4(3H)-pyrimidinone and (R)(-)[2(-)[(diisopropylphosphono)-methoxy]propyl]amine is also reported. Both (R)-8-aza-PMPG and (R)-PMPG demonstrated anti-HIV activity in the MTT assay with EC50 values of 12 and 4.5 microM, respectively. The corresponding S enantiomers were found to be less potent. When evaluated in combination with AZT, ddI, or DABO 603, (R)-8-aza-PMPG gave additive, additive, and synergistic anti-HIV-1 effects, respectively.
Assuntos
Antivirais/síntese química , Compostos Aza/síntese química , Guanina/síntese química , HIV/efeitos dos fármacos , Antivirais/farmacologia , Compostos Aza/farmacologia , Linhagem Celular , Guanina/farmacologia , Humanos , EstereoisomerismoRESUMO
As an approach to more extensive structural modifications of [(oxazolylphenoxy)alkyl]isoxazoles, we synthesized new compounds characterized by the replacement of the isoxazole nucleus with furan, pyrrole, and thiophene rings and by the presence of a ketocarbonyl group in the aliphatic chain connecting these pentatomic heterocycles to the 4-(4,5-dihydro-2-oxazolyl)phenoxy, 4-(ethoxycarbonyl)phenoxy, and 4-carboxyphenoxy moieties. Some pentamethylene derivatives were also prepared, and their antirhinovirus activity was compared to that of the corresponding ketomethylene derivatives. Syntheses were carried out by Friedel-Crafts acylation of the above pentatomic heterocycles and subsequent reaction of chloroalkyl ketones with the proper 4-substituted phenol. Reduction of the ketone function afforded the related polymethylene derivatives. The new compounds were tested for antirhinovirus activity and cytotoxicity in comparison with WIN 51711, used as reference drug. Inspection of the structure-activity relationships revealed that the thiophene ring and the carbonyl group are the structural components which to a large extent contribute to the positive biological profile in terms of both wideness of spectrum and low cytotoxicity. Among the various derivatives, compounds 8e,d showed in vitro the same potency of WIN 51711 but a cytotoxicity at least 10 times lower.
Assuntos
Antivirais/síntese química , Antivirais/farmacologia , Oxazóis/síntese química , Oxazóis/farmacologia , Rhinovirus/efeitos dos fármacos , Efeito Citopatogênico Viral/efeitos dos fármacos , Células HeLa , Humanos , Relação Estrutura-Atividade , Sais de Tetrazólio , TiazóisRESUMO
Novel 3,4-dihydro-6-benzyl-4-oxopyrimidines (DABOs), variously substituted at both the C-2 and C-5 positions of the pyrimidine ring, proved to be specific inhibitors of the human immunodeficiency virus type 1 (HIV-1) in vitro. Some compounds showed potency at micromolar doses, no cytotoxicity at the maximum testable doses and selectivity indexes comparable to that of 2'-3'-dideoxyinosine (ddI). Mode of action studies suggested that DABOs interfered with a step of the virus multiplication cycle following adsorption and preceding integration. Enzyme assays indicated that DABOs targeted HIV-1 reverse transcriptase: they inhibited the RNA-dependent DNA polymerase activity in a template-dependent manner and, to a lesser extent, the DNA-dependent DNA polymerase activity. No inhibition of the RNase-H associated activity was observed. When DABOs were assayed in combination with 3'-azido-3'-dideoxythymidine (AZT) or ddI against HIV-1 in cell cultures, a slightly synergistic inhibitory effect was observed. The combination of DABO 546 and AZTTP in enzyme assays showed that the two compounds were kinetically mutually exclusive.
Assuntos
Antivirais/farmacologia , HIV-1/efeitos dos fármacos , Pirimidinas/farmacologia , Inibidores da Transcriptase Reversa , Antivirais/química , Antivirais/toxicidade , Células Cultivadas , Didesoxinucleotídeos , Interações Medicamentosas , Transcriptase Reversa do HIV , HIV-1/enzimologia , HIV-1/crescimento & desenvolvimento , Pirimidinas/toxicidade , Pirimidinonas/farmacologia , Nucleotídeos de Timina/farmacologia , Replicação Viral/efeitos dos fármacos , Zidovudina/análogos & derivados , Zidovudina/farmacologiaRESUMO
Some aza and deaza analogues of the anti-HIV agent 2',3'-dideoxy-3'-oxoadenosine (isoddA) (8-aza-, 8-aza-1-deaza, 8-aza-3-deaza-, 1-deaza-, and 3-deaza-isoddA) were synthesized and found inactive against HIV in vitro. The hypothesis that the inactivity of these isonucleosides might be due to their poor affinity for cellular nucleoside kinases was checked by the synthesis of a series of 5'-[bis(2,2,2-trichloroethyl) phosphate] triesters and 5'-phenyl phosphoramidate derivatives which, acting as membrane soluble prodrugs, could release the free phosphate form inside the cell. The 5'-(phenylmethoxy)alaninyl phosphate derived from 8-aza-isoddA was found active against HIV-1 and HIV-2 with a potency similar to that of isoddA, while the anti-HIV potency of 5'-(phenylmethoxy)alaninyl phosphate of isoddA proved remarkably higher than that of isoddA, in particular against HIV-2, being similar to that of AZT. Further evidence that 8-aza-isoddA could behave as anti-HIV agent, provided that it is activated as phosphate, was obtained by the synthesis of its 5'-triphosphate derivative, which proved to be an active inhibitor of HIV-1 recombinant reverse transcriptase.
Assuntos
Trifosfato de Adenosina/análogos & derivados , Antivirais/síntese química , Compostos Aza/síntese química , Didesoxiadenosina/análogos & derivados , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Trifosfato de Adenosina/síntese química , Trifosfato de Adenosina/farmacologia , Antivirais/farmacologia , Compostos Aza/farmacologia , Didesoxiadenosina/química , Didesoxinucleotídeos , Transcriptase Reversa do HIV , HIV-1/enzimologia , Estrutura Molecular , Fosfatos/síntese química , Fosfatos/farmacologia , Proteínas Recombinantes/antagonistas & inibidores , Inibidores da Transcriptase ReversaRESUMO
-2',3'-Seco nucleosides 5 carrying fluorine and sulfur substituents at C-3' and C-5', respectively, of acyclic sugar moiety were synthesized in enantiomerically and diastereoisomerically pure form. These products and some structurally similar 1',2'-seco-2'-nor-and 1',2'-seco-nucleosides 3 and 4 were tested in vitro for cytotoxicity and antiviral activity. At non-cytotoxic concentrations the compounds were inactive against human immunodeficiency virus and herpes simplex virus type-1.