title: 1,2,3,4-Tetrahydroquinoline-containing alphaVbeta3 integrin antagonists with enhanced oral bioavailability.
abstract: Reduction of the quinoline ring in an alpha(v)beta(3) antagonist yielded a 1,2,3,4-tetrahydro derivative as two diastereomers, the four isomers of which were separated by sequential chiral HPLC. Two isomers had significant alpha(V)beta(3) antagonist activity with improved oral bioavailability, relative to the corresponding quinoline derivative.
authors.affiliation: Drug Discovery, Johnson & Johnson Pharmaceutical Research & Development, L.L.C., Welsh & McKean Roads, Spring House, PA 19477-0776, USA.
authors.forename: Shyamali
authors.initials: S
authors.lastname: Ghosh
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Santulli
authors.forename: William A
authors.initials: WA
authors.lastname: Kinney
authors.forename: Bart L
authors.initials: BL
authors.lastname: Decorte
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Joan M
authors.initials: JM
authors.lastname: Lewis
authors.forename: Jef C
authors.initials: JC
authors.lastname: Proost
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Leo
authors.forename: John
authors.initials: J
authors.lastname: Masucci
authors.forename: William E
authors.initials: WE
authors.lastname: Hageman
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Thompson
authors.forename: Ian
authors.initials: I
authors.lastname: Chen
authors.forename: Reiko
authors.initials: R
authors.lastname: Kawahama
authors.forename: Robert W
authors.initials: RW
authors.lastname: Tuman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Galemmo
authors.forename: Dana L
authors.initials: DL
authors.lastname: Johnson
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Damiano
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Maryanoff
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011804:Quinolines / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism*; D051381:Rats
chemical_list: D039302:Integrin alphaVbeta3; D011804:Quinolines