Synthesis and biological evaluation of novel steroidal pyrazoles as substrates for bile acid transporters

Bioorg Med Chem Lett. 2005 Jan 3;15(1):85-7. doi: 10.1016/j.bmcl.2004.10.027.

Abstract

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.

MeSH terms

  • Animals
  • CHO Cells
  • Carrier Proteins / drug effects*
  • Carrier Proteins / metabolism
  • Cricetinae
  • Drug Evaluation, Preclinical
  • Humans
  • Ileum / drug effects
  • Ileum / metabolism
  • Ligands
  • Membrane Glycoproteins / drug effects*
  • Membrane Glycoproteins / metabolism
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / chemistry
  • Pyrazoles / metabolism
  • Pyrazoles / pharmacology*
  • Xenopus laevis

Substances

  • Carrier Proteins
  • Ligands
  • Membrane Glycoproteins
  • Pyrazoles
  • bile acid binding proteins