Solid-phase synthesis of a small library of 3-phenylthio-3-nicotinyl propionic acid derivatives acting as antagonists of the integrin alphaVbeta3.
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.
Vianello
Paola
P
Department of Chemistry, Pharmacia Italia SpA-Gruppo Pfizer, Discovery Research Oncology, Viale Pasteur 10, 20014 (MI), Nerviano, Italy. paola.vianello@pharmacia.com
Cozzi
Paolo
P
Galvani
Arturo
A
Meroni
Maurizio
M
Varasi
Mario
M
Volpi
Daniele
D
Bandiera
Tiziano
T
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
D039302:Integrin alphaVbeta3; D010636:Phenols; D011422:Propionates; D019030:Receptors, Vitronectin; D019096:Vitronectin; D009525:Niacin; C029658:propionic acid