RESUMO
A novel series of potent blockers of the monocarboxylate transporter, MCT1, is disclosed. From very potent but lipophilic lead compounds, systematic changes to all parts of the molecule, targeting reduction in log D, afforded compounds with significantly improved overall properties. These compounds show potent immunomodulatory activity.
Assuntos
Hidrocarboneto de Aril Hidroxilases/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Herpesviridae/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Transportadores de Ácidos Monocarboxílicos/antagonistas & inibidores , Simportadores/antagonistas & inibidores , Linfócitos T/efeitos dos fármacos , Animais , Hidrocarboneto de Aril Hidroxilases/imunologia , Citocromo P-450 CYP2C9 , Citocromo P-450 CYP3A , Sistema Enzimático do Citocromo P-450/imunologia , Doença Enxerto-Hospedeiro/imunologia , Herpesviridae/imunologia , Herpesviridae/metabolismo , Humanos , Fatores Imunológicos/química , Transportadores de Ácidos Monocarboxílicos/imunologia , Transportadores de Ácidos Monocarboxílicos/metabolismo , Simportadores/imunologia , Simportadores/metabolismo , Linfócitos T/imunologia , Linfócitos T/metabolismoRESUMO
This article reviews the recent literature on selective inhibitors of nitric oxide synthase (NOS) between 1999 and the first quarter of 2001. The introduction highlights the major therapeutic objectives for NOS inhibitors, including rheumatoid arthritis (RA), osteoarthritis (OA) and pain. The review attempts to cover the structural diversity of small molecule NOS inhibitors currently being explored in the pharmaceutical and academic communities.
