title: Solid-phase synthesis of a small library of 3-phenylthio-3-nicotinyl propionic acid derivatives acting as antagonists of the integrin alphaVbeta3.
abstract: We describe the synthesis of a series of low molecular weight inhibitors of the alphavbeta3 integrin obtained by modifying a high-throughput screening hit with micromolar activity. A solid phase synthesis to prepare 3-phenylthio-3-nicotinyl propionic acid derivatives, exemplified by 13c, was set up. Compounds with nanomolar activity in the biochemical assay and able to efficiently inhibit cell adhesion mediated by vitronectin have been obtained.
authors.affiliation: Department of Chemistry, Pharmacia Italia SpA-Gruppo Pfizer, Discovery Research Oncology, Viale Pasteur 10, 20014 (MI), Nerviano, Italy. paola.vianello@pharmacia.com
authors.forename: Paola
authors.initials: P
authors.lastname: Vianello
authors.forename: Paolo
authors.initials: P
authors.lastname: Cozzi
authors.forename: Arturo
authors.initials: A
authors.lastname: Galvani
authors.forename: Maurizio
authors.initials: M
authors.lastname: Meroni
authors.forename: Mario
authors.initials: M
authors.lastname: Varasi
authors.forename: Daniele
authors.initials: D
authors.lastname: Volpi
authors.forename: Tiziano
authors.initials: T
authors.lastname: Bandiera
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D020650:Combinatorial Chemistry Techniques; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D009525:Niacin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D010636:Phenols / Q000737:chemistry* / Q000494:pharmacology; D011422:Propionates / Q000737:chemistry* / Q000494:pharmacology; D019030:Receptors, Vitronectin / Q000378:metabolism; D013329:Structure-Activity Relationship; D019096:Vitronectin / Q000494:pharmacology
chemical_list: D039302:Integrin alphaVbeta3; D010636:Phenols; D011422:Propionates; D019030:Receptors, Vitronectin; D019096:Vitronectin; D009525:Niacin; C029658:propionic acid