RESUMO
The synthesis and in vivo pharmacokinetic profile of an analogue of cyclosporine is disclosed. An acyclic congener was also profiled in in vitro assays to compare cell permeability. The compounds possess similar calculated and measured molecular descriptors however have different behaviors in an RRCK assay to assess cell permeability.
Assuntos
Ciclosporina/farmacocinética , Oligopeptídeos/farmacocinética , Animais , Ciclosporina/administração & dosagem , Ciclosporina/química , Masculino , Conformação Molecular , Oligopeptídeos/administração & dosagem , Oligopeptídeos/química , Ratos , Ratos Wistar , EstereoisomerismoRESUMO
A concise and modular approach to synthesize a new type of cyclopentene-based diaminocyclitol library from D-serine and L-serine has been developed, and key steps in this synthesis are an aza-Claisen rearrangement, a ring-closing metathesis, and a Baylis-Hillman reaction. The developed chemistry may offer a unique way to investigate the neuraminidase (NA) mutation by systematically mapping the changes within its binding sites.
Assuntos
Ciclitóis/farmacologia , Vírus da Influenza A Subtipo H1N1/efeitos dos fármacos , Vírus da Influenza A Subtipo H1N1/enzimologia , Neuraminidase/antagonistas & inibidores , Orthomyxoviridae/genética , Catálise , Estrutura MolecularRESUMO
We reported herein a diversity-oriented synthesis of a range of fused pyran-gamma-lactones that was effected through a versatile Pd-thiourea complex-catalyzed intramolecular alkoxycarbonylative annulation.