title: Synthesis and biological evaluation of novel steroidal pyrazoles as substrates for bile acid transporters.
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.
authors.affiliation: XenoPort Inc., 3410 Central Expressway, Santa Clara, CA 95051, USA. lbhat@aryx.com
authors.forename: Laxminarayan
authors.initials: L
authors.lastname: Bhat
authors.forename: Bernd
authors.initials: B
authors.lastname: Jandeleit
authors.forename: Tracy M
authors.initials: TM
authors.lastname: Dias
authors.forename: Tristen L
authors.initials: TL
authors.lastname: Moors
authors.forename: Mark A
authors.initials: MA
authors.lastname: Gallop
mesh_terms: D000818:Animals; D016466:CHO Cells; D002352:Carrier Proteins / Q000187:drug effects* / Q000378:metabolism; D006224:Cricetinae; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D008024:Ligands; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000378:metabolism; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014982:Xenopus laevis
chemical_list: D002352:Carrier Proteins; D008024:Ligands; D008562:Membrane Glycoproteins; D011720:Pyrazoles; C037643:bile acid binding proteins