title: An evaluation of a C-glucuronide as a liver targeting group: conjugate of a glucocorticoid antagonist.
abstract: A beta-C-glucuronide conjugate of the glucocorticoid receptor antagonist, Mifepristone 1, was prepared which maintained binding affinity, had modest in vitro activity, and was metabolically more stable than the parent. Pharmacokinetic studies suggest that the conjugate is recognized by the liver like O-glucuronides and may undergo a portion of the enterohepatic recirculation loop.
authors.affiliation: Metabolic Disease Research, Abbott Laboratories, 100 Abbott Park Road, 60064, Abbott Park, IL, USA. bryan.k.sorensen@abbott.com
authors.forename: Bryan K
authors.initials: BK
authors.lastname: Sorensen
authors.forename: J T
authors.initials: JT
authors.lastname: Link
authors.forename: Thomas
authors.initials: T
authors.lastname: von Geldern
authors.forename: Maurice
authors.initials: M
authors.lastname: Emery
authors.forename: Jiahong
authors.initials: J
authors.lastname: Wang
authors.forename: Bach
authors.initials: B
authors.lastname: Hickman
authors.forename: Marlena
authors.initials: M
authors.lastname: Grynfarb
authors.forename: Annika
authors.initials: A
authors.lastname: Goos-Nilsson
authors.forename: Sherry
authors.initials: S
authors.lastname: Carroll
mesh_terms: D000284:Administration, Oral; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D003907:Dexamethasone / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D004764:Enterohepatic Circulation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D005938:Glucocorticoids / Q000493:pharmacokinetics; D020719:Glucuronides / Q000378:metabolism* / Q000493:pharmacokinetics; D006727:Hormone Antagonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008099:Liver / Q000187:drug effects*; D008862:Microsomes, Liver / Q000378:metabolism; D015735:Mifepristone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000644:Quaternary Ammonium Compounds; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*; D014444:Tyrosine Transaminase / Q000037:antagonists & inhibitors
chemical_list: D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D020719:Glucuronides; D006727:Hormone Antagonists; D007202:Indicators and Reagents; D000644:Quaternary Ammonium Compounds; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; C009405:tetrabutylammonium; D014444:Tyrosine Transaminase; D000469:Alkaline Phosphatase