title: Piperidine-containing beta-arylpropionic acids as potent antagonists of alphavbeta3/alphavbeta5 integrins.
abstract: The synthesis and SAR of a new class of piperidine-based alphavbeta3/alphavbeta5 integrin antagonists is described. Replacement of an amide bond in a prototype isonipecotamide by a C-C isostere, and adjustment of the spacer length between the carboxylic acid and basic moieties, led to low nanomolar antagonists of alphavbeta3 and/or alphavbeta5 integrins with excellent selectivity versus alpha(IIb)beta3.
authors.affiliation: Drug Discovery, Johnson & Johnson Pharmaceutical Research and Development, Welsh & McKean Roads, Spring House, PA 19477-0776, USA. bdecorte@prdus.jnj.com
authors.forename: Bart L
authors.initials: BL
authors.lastname: De Corte
authors.forename: William A
authors.initials: WA
authors.lastname: Kinney
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Shyamali
authors.initials: S
authors.lastname: Ghosh
authors.forename: Livia
authors.initials: L
authors.lastname: Brunner
authors.forename: William J
authors.initials: WJ
authors.lastname: Hoekstra
authors.forename: Rosemary J
authors.initials: RJ
authors.lastname: Santulli
authors.forename: Robert W
authors.initials: RW
authors.lastname: Tuman
authors.forename: Judith
authors.initials: J
authors.lastname: Baker
authors.forename: Candace
authors.initials: C
authors.lastname: Burns
authors.forename: Jef C
authors.initials: JC
authors.lastname: Proost
authors.forename: Brett A
authors.initials: BA
authors.lastname: Tounge
authors.forename: Bruce P
authors.initials: BP
authors.lastname: Damiano
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Maryanoff
authors.forename: Dana L
authors.initials: DL
authors.lastname: Johnson
authors.forename: Robert A
authors.initials: RA
authors.lastname: Galemmo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D039302:Integrin alphaVbeta3; D016023:Integrins; D010880:Piperidines; D011422:Propionates; D019030:Receptors, Vitronectin; C064660:integrin alphaVbeta5