Solid-phase synthesis of a small library of 3-phenylthio-3-nicotinyl propionic acid derivatives acting as antagonists of the integrin alphaVbeta3

Paola Vianello; Paolo Cozzi; Arturo Galvani; Maurizio Meroni; Mario Varasi; Daniele Volpi; Tiziano Bandiera

doi:10.1016/j.bmcl.2003.11.045

Solid-phase synthesis of a small library of 3-phenylthio-3-nicotinyl propionic acid derivatives acting as antagonists of the integrin alphaVbeta3

Bioorg Med Chem Lett. 2004 Feb 9;14(3):657-61. doi: 10.1016/j.bmcl.2003.11.045.

Authors

Paola Vianello¹, Paolo Cozzi, Arturo Galvani, Maurizio Meroni, Mario Varasi, Daniele Volpi, Tiziano Bandiera

Affiliation

¹ Department of Chemistry, Pharmacia Italia SpA-Gruppo Pfizer, Discovery Research Oncology, Viale Pasteur 10, 20014 (MI), Nerviano, Italy. [email protected]

PMID: 14741263
DOI: 10.1016/j.bmcl.2003.11.045

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.

MeSH terms

Cell Adhesion / drug effects*
Cells, Cultured
Combinatorial Chemistry Techniques
Extracellular Matrix / metabolism
Humans
Integrin alphaVbeta3 / antagonists & inhibitors*
Molecular Structure
Niacin / analogs & derivatives*
Niacin / chemical synthesis*
Niacin / pharmacology
Phenols / chemistry*
Phenols / pharmacology
Propionates / chemistry*
Propionates / pharmacology
Receptors, Vitronectin / metabolism
Structure-Activity Relationship
Vitronectin / pharmacology

Substances

Integrin alphaVbeta3
Phenols
Propionates
Receptors, Vitronectin
Vitronectin
Niacin
propionic acid