RESUMO
The knowledge of SAR in a series of biphenyl anionic RSV inhibitors has been broadened by synthesis and testing of analogs with pyrimidine linkers. Generally, pyrimidine compounds were much harder to synthesize, and their anti-RSV activity was lower in comparison with triazine analogs.
Assuntos
Antivirais/farmacologia , Pirimidinas/farmacologia , Vírus Sinciciais Respiratórios/efeitos dos fármacos , Animais , Antivirais/síntese química , Pirimidinas/química , Vírus Sinciciais Respiratórios/metabolismo , Relação Estrutura-Atividade , Triazinas/química , Triazinas/farmacologiaRESUMO
We disclose here a new class of kinase inhibitors, obtained by replacing the phenyl ring of a 3-quinolinecarbonitrile system with a thiophene ring. When suitably substituted, the resultant 7-phenylaminothieno[3,2-b]pyridine-6-carbonitrile analogues show potent inhibition of Src kinase activity.
Assuntos
Inibidores Enzimáticos/síntese química , Piridinas/síntese química , Tiofenos/síntese química , Quinases da Família src/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Piridinas/farmacologia , Relação Estrutura-Atividade , Tiofenos/farmacologiaRESUMO
A series of substituted 4-anilino-7-phenyl-3-quinolinecarbonitriles has been prepared as Src kinase inhibitors. Optimal activity is observed with compounds that have basic amines attached via the para position of the 7-phenyl ring, and a hydrogen atom at the C-6 position. The best compounds are low nanomolar inhibitors of Src kinase, and have potent activity against Src-transformed fibroblast cells.
Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Nitrilas/síntese química , Nitrilas/farmacologia , Quinolinas/síntese química , Quinolinas/farmacologia , Quinases da Família src/antagonistas & inibidores , Indicadores e Reagentes , Relação Estrutura-AtividadeRESUMO
Human respiratory syncytial virus (RSV), a paramyxovirus, is a major cause of acute upper and lower respiratory tract infections in infants, young children, and adults. RFI-641 is a novel anti-RSV agent with potent in vitro and in vivo activity. RFI-641 is active against both RSV type A and B strains. The viral specificity and the large therapeutic window of RFI-641 (>100-fold) indicate that the antiviral activity of the compound is not due to adverse effects on normal cells. The potent in vitro activity of RFI-641 can be translated to efficacy in vivo: RFI-641 is efficacious when administered prophylactically by the intranasal route in mice, cotton rats, and African green monkeys. RFI-641 is also efficacious when administered therapeutically (24 h postinfection) in the monkey model. Mechanism of action studies indicate that RFI-641 blocks viral F protein-mediated fusion and cell syncytium formation.
