RESUMO
Several keto phosphonates, phosphonoacetates , and dialkyl phosphonates containing (aryloxy)aryl groups were synthesized and evaluated for antiherpteic activity. Two of the most active compounds, 12 and 16, were evaluated topically in the mouse vaginal model against herpes simplex virus (HSV) type 2. Compound 16 exhibited an increased survival rate, as well as increased survival time. Evaluation of 16 in the guinea pig skin test against HSV-2 produced a reduction in virus titer, as well as in mean vesicle score.
Assuntos
Antivirais/síntese química , Herpes Simples/tratamento farmacológico , Compostos Organofosforados/síntese química , Simplexvirus/efeitos dos fármacos , Animais , Avaliação Pré-Clínica de Medicamentos , Feminino , Cobaias , Indicadores e Reagentes , Camundongos , Compostos Organofosforados/toxicidade , Simplexvirus/crescimento & desenvolvimento , Dermatopatias/tratamento farmacológico , Relação Estrutura-AtividadeRESUMO
The synthesis and evaluation of a series of 3,5-disubstituted isoxazoles as antipicornavirus agents have led to the discovery of several compounds effective in vitro against rhinovirus type 2 and poliovirus type 2. Compound 32 was found more effective than 4',6-dichloroflavan against both viruses and was evaluated orally in mice infected intracerebrally with polio-2. At 31 mg/kg bid, compound 32 showed a 53% survival rate as compared to 22% for the nonmedicated animals.
Assuntos
Antivirais/farmacologia , Isoxazóis/farmacologia , Oxazóis/farmacologia , Picornaviridae/efeitos dos fármacos , Animais , Antivirais/síntese química , Isoxazóis/síntese química , Camundongos , Camundongos Endogâmicos ICR , Infecções por Picornaviridae/tratamento farmacológico , Relação Estrutura-AtividadeRESUMO
Several methylated derivatives of trilostane were prepared. Methylation of C-4 or C-4 and C-17 changes this relatively selective adrenal inhibitor to compounds with increased ovarian/placental inhibitory activity with decreased adrenal inhibitory activity.
Assuntos
3-Hidroxiesteroide Desidrogenases/antagonistas & inibidores , Abortivos Esteroides/farmacologia , Abortivos/farmacologia , Glândulas Suprarrenais/efeitos dos fármacos , Di-Hidrotestosterona/análogos & derivados , Hormônio Adrenocorticotrópico/farmacologia , Animais , Corticosterona/sangue , Di-Hidrotestosterona/farmacologia , Feminino , Macaca mulatta , Espectroscopia de Ressonância Magnética , Gravidez , Progesterona/sangue , Pseudogravidez/sangue , Ratos , Espectrofotometria InfravermelhoRESUMO
A series of aryloxy alkyl diketones II was synthesized and screened in vitro for antiviral activity. The effect of various substituents on the phenyl ring, as well as the length of the alkyl bridge, was examined to establish the requirements for optimum activity. One of the most active members of the series, 4-[6-(2-chloro-4-methoxy)phenoxy]hexyl-3,5-heptanedione (56), exhibited a high level of activity against both DNA and RNA viruses in both the tissue culture and organ culture screens and was particularly effective against herpesvirus type 1 and 2.
Assuntos
Antivirais/síntese química , Vírus de DNA/efeitos dos fármacos , Cetonas/farmacologia , Vírus de RNA/efeitos dos fármacos , Técnicas de Cultura , Cetonas/síntese química , Técnicas de Cultura de Órgãos , Picornaviridae/efeitos dos fármacos , Simplexvirus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
A series of bis(beta-diketones) was synthesized and tested in vitro for antiviral actitity against herpes simplex type 2. Two parameters which were studied in an effort to optimize activity were the nature of the aryl group and the length of the alkyl bridge. One of the more active compounds, 4,4'-[(1,4-phenylenedioxy)bis(6,1-hexanediyl)]-bis[3,5-heptanedione] (6), was evaluated more extensively and found to inhibit the cytopathic effect in tissue culture of herpes simplex virus type 1 as well as type 2. Compound 6 was evaluated in vivo topically against herpes simplex type 1 in experimentally induced skin infections in guinea pigs. A topical treatment with 2% of 6 in a vanishing cream base, administered 24 h postinfection applied five times daily for 4 days, significantly reduced the number and size of herpetic vesicles.
Assuntos
Antivirais/síntese química , Cetonas/síntese química , Simplexvirus/efeitos dos fármacos , Administração Tópica , Animais , Antivirais/uso terapêutico , Cobaias , Herpes Simples/tratamento farmacológico , Cetonas/farmacologia , Cetonas/uso terapêutico , Ensaio de Placa ViralRESUMO
The discovery that 4-[3-ethyl-6-[(3,4-methylenedioxy)phenyl]-3-hexenyl]-3,5-heptanedione (40) exhibited an in vitro inhibitory effect against equine rhinovirus led to a structure--activity study to establish the criteria for optimum activity. Modification of the bridge included removal of the ethyl group and reduction of the double bond. The heptanedione was replaced with hexanedione and pentanedione with a minimal effect. The effect of replacing the heptanedione with beta-keto esters and monoketones was also investigated. Maintaining the hexamethylene bridge and heptanedione, the methylenedioxy group was replaced with various substitutents. In general, most substituents did not adversely affect activity particularly against equine rhinovirus although there was some variation in activity against herpesvirus. Strongly hydrophilic groups significantly reduced activity. Finally, the effect of varying the length of the alkyl bridge was examined in the 4-hydroxyphenyl series, where peak activity was attained with n = 8.