Nerviano Medical Sciences S.r.l.

Pharmacia & Upjohn Company

Pfizer Italia S.r.l.

Claudio Dalvit

Brian J Stockman

Nicola Mongelli

Paolo Polucci

Fabio Zuccotto

Francesco Casuscelli

Elena Casale

Elena Ardini

Kathleen A Farley

Maria Magdalena Flocco

Gianpaolo Fogliatto

Marina Veronesi

Maria Flocco

The present invention relates to [1,2,4]triazolo[1,5-c]pyrimidine derivatives of formula (I) which inhibit the activity of Heat Shock Protein Hsp90. The compounds of the invention are therefore useful in treating proliferative diseases such as cancer and neurodegenerative diseases. The present invention also provides processes for preparing these compounds, methods of treating diseases and the pharmaceutical compositions comprising these compounds. 

[1,2,4]triazolo [1,5-c]pyrimidine derivatives as Hsp90 modulators

A method of identifying a ligand to a target molecule that includes: providing a reference compound that interacts with the target molecule; collecting a 1DH nuclear magnetic resonance spectrum of the reference compound in the presence of the target molecule; providing a plurality of test samples, each test sample including at least one test compound; collecting a 1DH nuclear magnetic resonance spectrum of the reference compound in the presence of each test sample and the target molecule; comparing the spectrum of the reference compound in the presence of the target molecule to the spectrum of the reference compound in the presence of each test sample and the target molecule to determine a change in one or more of the reference compound resonances; and identifying at least one test compound that interacts with the target molecule, wherein the test compound displaces the reference compound.

[object Object]

High-Throughput Screening (HTS) of large compound libraries is the method of drug-lead discovery. It is now well accepted that for a functional assay, quality is more important than quantity. A biochemical NMR method originally proposed by Percival and Withers (Biochemistry, 1992, 31, 498&#x2013;505) is extended to the screening of Ser/Thr kinases. The method requires the presence of a CF(or CF) moiety on the substrate and utilizesF NMR spectroscopy for the detection of the starting and enzymatically modified substrates. Experiments can be performed in real time or in an endpoint assay format using protein and substrate concentrations comparable to the ones used by other HTS techniques. Application of this technique to the phosphorylation of a substrate by the protein Ser/Thr kinase AKT1 is presented.

Fluorine NMR spectroscopy for biochemical screening

A method for developing a library of compounds, the compound library, a method for identifying ligands for target molecules, and a method for identifying lead chemical templates, which, for example, can be used in drug discovery and design are provided. Certain embodiments of these methods include the use of NMR spectroscopy.

Methods for creating a compound library and identifying lead chemical templates and ligands for target molecules

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Milan, Italy

Claudio Dalvit