RESUMEN
A series of novel steroidal pyrazoles was synthesized as substrates for bile acid transporters to explore their potential as drug carriers. The selected pyrazole fused bile acids were further conjugated with drugs and drug surrogates. Their in vitro transport activities were evaluated in human ileal bile acid transporter (hIBAT) and human liver bile acid transporter (hLBAT) expressing Chinese hamster ovary (CHO)-cells and Xenopus laevis oocytes. The results of synthetic efforts and transporter assays studies are described herein.
Asunto(s)
Proteínas Portadoras/efectos de los fármacos , Glicoproteínas de Membrana/efectos de los fármacos , Pirazoles/síntesis química , Pirazoles/farmacología , Animales , Células CHO , Proteínas Portadoras/metabolismo , Cricetinae , Evaluación Preclínica de Medicamentos , Humanos , Íleon/efectos de los fármacos , Íleon/metabolismo , Ligandos , Glicoproteínas de Membrana/metabolismo , Pirazoles/química , Pirazoles/metabolismo , Xenopus laevisRESUMEN
Solid-phase synthetic methods for biaryl-based compounds were developed resulting in the construction of two 1000-member libraries. Numerous compounds were identified by high-throughput screening using whole cell screens to exhibit anti-microbial activity against Gram-positive bacteria. A series of biaryl compounds containing natural and unnatural amino acids were made to explore the SAR of the amino acid functionality.