Helsinn Healthcare Sa

Other

Alessio Venturini

Roberta Cannella

Luca Fadini

Valentino J Stella

Peter Manini

Claudio Pietra

Claudio Giuliano

Emanuela Lovati

Injectable dosages and formulations of fosnetupitant and pharmaceutically acceptable salts thereof are provided that are efficacious, chemically stable and physiologically balanced for safety and efficacy.

Physiologically balanced injectable formulations of fosnetupitant

Disclosed are compounds including phosphate and N-oxide prodrugs of the NK1 antagonist netupitant, useful in the prevention and/or treatment of diseases including emesis induced by chemotherapy. Also disclosed are methods of making a di-tert-butyl (chloromethyl) phosphate useful in the manufacture of such prodrugs by reacting a dialkylphosphate salt with an acid to obtain the corresponding ester of phosphoric acid, reacting the ester with a quaternary ammonium hydroxide base to form a monobasic salt, and reacting the monobasic salt with chloroiodomethane to form the corresponding chloromethyl dialkyl phosphate.

Process for the synthesis of substituted chloromethyl dialkylphosphates

Fosnetupitant chloride hydrochloride having improved stability, characterized by the following chemical structure: 

Fosnetupitant chloride hydrochloride having improved stability

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK) receptor. The compounds have the general formula (I): 

Substituted piperaziniums for the treatment of emesis

Disclosed is a solution comprising the chloride hydrochloride salt of 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium (fosnetupitant) and palonosetron hydrochloride in combination with dexamethasone and its application in methods for preventing acute and delayed nausea and vomiting in a human patient receiving highly emetogenic cancer chemotherapy.

Solution comprising the chloride hydrochloride salt of 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-IUM-(fosnetupitant) and palonosetron hydrochloride in combination with dexamethasone as a neurokinin receptor modulator

The present invention provides crystalline forms of the chloride monohydrochloride salt of fosnetupitant, methods of making the crystalline forms, and pharmaceutical dosage forms that make use of the crystalline forms.

Crystalline forms of fosnetupitant

Compounds and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK) receptor, based on 4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)3yridine-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium and pharmaceutically acceptable salts thereof.

4-(5-(2-(3,5-bis(trifluoromethyl)phenyl)-N,2-dimethylpropanamido)-4-(o-tolyl)pyridin-2-yl)-1-methyl-1-((phosphonooxy)methyl)piperazin-1-ium as a neurokinin receptor modulator

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Varese, Italy

Alessio Venturini