title: Identification of nonabsorbable inhibitors of the scavenger receptor-BI (SR-BI) for tissue-specific administration.
abstract: The identification of a low-permeability scavenger receptor BI (SR-BI) inhibitor starting from the ITX-5061 template is described. Structure-activity and structure-permeability relationships were assessed for analogs leading to the identification of compound 8 as a potent and nonabsorbable SR-BI inhibitor.
authors.affiliation: GlaxoSmithKline, Enteroendocrine Discovery Performance Unit and Platform Technology and Science, 5 Moore Drive, Research Triangle Park, NC 27709, United States. Electronic address: ssparks@viamet.com.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Sparks
authors.affiliation: GlaxoSmithKline, Enteroendocrine Discovery Performance Unit and Platform Technology and Science, 5 Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Huiqiang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: GlaxoSmithKline, Enteroendocrine Discovery Performance Unit and Platform Technology and Science, 5 Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Claudia
authors.initials: C
authors.lastname: Generaux
authors.affiliation: GlaxoSmithKline, Enteroendocrine Discovery Performance Unit and Platform Technology and Science, 5 Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Lindsey
authors.initials: L
authors.lastname: Harston
authors.affiliation: GlaxoSmithKline, Enteroendocrine Discovery Performance Unit and Platform Technology and Science, 5 Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: David
authors.initials: D
authors.lastname: Moncol
authors.affiliation: GlaxoSmithKline, Enteroendocrine Discovery Performance Unit and Platform Technology and Science, 5 Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Channa
authors.initials: C
authors.lastname: Jayawickreme
authors.affiliation: GlaxoSmithKline, Enteroendocrine Discovery Performance Unit and Platform Technology and Science, 5 Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Janet
authors.initials: J
authors.lastname: Parham
authors.affiliation: GlaxoSmithKline, Enteroendocrine Discovery Performance Unit and Platform Technology and Science, 5 Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Condreay
authors.affiliation: GlaxoSmithKline, Enteroendocrine Discovery Performance Unit and Platform Technology and Science, 5 Moore Drive, Research Triangle Park, NC 27709, United States.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rimele
mesh_terms: D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D015394:Molecular Structure; D009928:Organ Specificity; D010655:Phenylenediamines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D051122:Scavenger Receptors, Class B / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C583499:ITX-5061; D010655:Phenylenediamines; C495124:SCARB1 protein, human; C495125:Scarb1 protein, rat; D051122:Scavenger Receptors, Class B; D013449:Sulfonamides
keywords: Intestinal SR-BI; Nonabsorbed SR-BI inhibitor; SR-BI inhibitor; Scavenger receptor class B type I