title: alpha(v)beta(3) Antagonists based on a central thiophene scaffold.
abstract: A series of novel, highly potent alpha(v)beta(3) antagonists based on a thiophene scaffold and containing an acylguanidine as an Arg-mimetic is described. A number of structural features, such as cyclic versus open guanidine and a variety of lipophilic side chains, carbamates, sulfonamides and beta-amino acids were explored with respect to inhibition of alpha(v)beta(3) mediated cell adhesion and selectivity versus alpha(IIb)beta(3) binding. In addition, compound 19 was found to be active in the TPTX model of osteoporosis.
authors.affiliation: Aventis Pharma Deutschland GmbH, D-65926, Frankfurt, Germany. anusch.peyman@aventis.com
authors.forename: A
authors.initials: A
authors.lastname: Peyman
authors.forename: K
authors.initials: K
authors.lastname: Scheunemann
authors.forename: D W
authors.initials: DW
authors.lastname: Will
authors.forename: J
authors.initials: J
authors.lastname: Knolle
authors.forename: V
authors.initials: V
authors.lastname: Wehner
authors.forename: G
authors.initials: G
authors.lastname: Breipohl
authors.forename: H U
authors.initials: HU
authors.lastname: Stilz
authors.forename: D
authors.initials: D
authors.lastname: Carniato
authors.forename: J
authors.initials: J
authors.lastname: Ruxer
authors.forename: J
authors.initials: J
authors.lastname: Gourvest
authors.forename: M
authors.initials: M
authors.lastname: Auberval
authors.forename: B
authors.initials: B
authors.lastname: Doucet
authors.forename: R
authors.initials: R
authors.lastname: Baron
authors.forename: M
authors.initials: M
authors.lastname: Gaillard
authors.forename: T R
authors.initials: TR
authors.lastname: Gadek
authors.forename: S
authors.initials: S
authors.lastname: Bodary
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002219:Carbamates / Q000737:chemistry; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D019791:Guanidine / Q000737:chemistry; D010024:Osteoporosis / Q000517:prevention & control*; D016105:Parathyroidectomy; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000737:chemistry; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology; D013965:Thyroidectomy
chemical_list: D002219:Carbamates; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; D013449:Sulfonamides; D013876:Thiophenes; D019791:Guanidine