Newron Pharmaceuticals S.p.a.

Novozymes A/s

Zach System

Francesco Ponzini

Renato Canevotti

Patricia Salvati

Elena Barbanti

Laura Faravelli

Maurizio Paiocchi

Lise Munch Mikkelsen

Marco Villa

Roberto Bisaccia

Aldo Belli

The conversion of a peptide aldehyde to a hydrosulfite adduct can be used to increase the aqueous solubility in the purification of the peptide aldehydes. Advantageously, this hydrosulfite adduct is itself effective as a subtilisin inhibitor and stabilizer and it can also stabilize a second enzyme if present. The hydrosulfite adduct is effective as a subtilisin inhibitor, and it maintains its inhibitory and stabilizing effect in a liquid detergent during storage. Thus, use of the hydrosulfite adduct can avoid the cost and time of converting it back to the peptide aldehyde and subsequent drying of the peptide aldehyde can be saved, and this can avoid the inconvenience of handling the peptide aldehyde in powder form or as a highly diluted aqueous solution.

Stabilized subtilisin composition

A process for obtaining therapeutically active 2-[4-(3- and 2-(fluorobenzyloxy)benzylamino]propanamides, and their salts with pharmaceutically acceptable acids with high purity degree, in particular, with a content of dibenzyl derivatives impurities lower than 0.03%, preferably lower than 0.01% by weight. The process is carried out by submitting the Schiff bases intermediates 2-[4-(3- and 2-fluorobenzyloxy)benzylideneamino]propanamides to a reduction reaction with a reducing agent selected from sodium borohydride and potassium borohydride in an appropriate amount of an organic solvent selected from C-Clower alkanols, allowing the formation and presence during a substantial position of the reduction reaction course of a suspension of the Schiff base into the saturated solution of the Schiff base into the same organic solvent.

High purity 2-[4-(3- or 2-fluorobenzyloxy)benzylamino] propanamides and methods of use thereof

A process for obtaining therapeutically active 2-[4-(3- and 2-(fluorobenzyloxy)benzylamino]-propanamides and their salts with pharmaceutically acceptable acids with a high degree of purity, i.e. with a content of dibenzyl derivatives impurities lower than 0.03% by weight. The process is carried out by submitting a Schiff base intermediate to a reduction reaction with a reducing agent in an amount of organic solvent to allow the formation (and presence during a substantial portion of the reduction reaction) of a suspension of the Schiff base.

High purity 2-[4-(3- OR 2-fluorobenzyloxy)benzylamino]propanamides and methods of use thereof

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Chignolo d'Isola, Italy

Francesco Ponzini