Helsinn Healthcare Sa

Angelo Guainazzi

Claudio Pietra

Claudio Giuliano

Silvina Garcia Rubio

Antoine Daina

Mauro Perseghini

Marielle Martinez-Loi

The new compound 3-(1-(2,3-dichloro-4-methoxyphenyl)ethyl)-1-methyl-1-(1,3,3-trimethylpiperidin-4-yl)urea monohydrochloride salt has a high capability to permeate through the blood-brain barrier and to display, at central nervous system level, a consistent ghrelin agonist activity; the compound is effective in the treatment and/or prevention of a medical condition mediated by the ghrelin receptor in the central nervous system. In particular, in experimental tests, the compound has shown high efficacy in the treatment of neurotoxic damage, with a useful combined pattern of neuroprotective effects both at central and peripheral level. The compound is further useful in the treatment of conditions which require a reduction of the heart rate. The compound is pharmacologically active at low to moderate doses, thus showing a favourable therapeutic index.

Centrally-active ghrelin agonist and medical uses thereof

The new compound 3-(1-(2,3-dichloro-4-methoxyphenyl) ethyl)-1-methyl-1-(1,3, 3-trimethylpiperidin-4-yl)urea monohydrochloride salt has a high capability to permeate through the blood-brain barrier and to display, at central nervous system level, a consistent ghrelin agonist activity; the compound is effective in the treatment and/or prevention of a medical condition mediated by the ghrelin receptor in the central nervous system. In particular, in experimental tests, the compound has shown high efficacy in the treatment of neurotoxic damage, with a useful combined pattern of neuroprotective effects both at central and peripheral level. The compound is further useful in the treatment of conditions which require a reduction of the heart rate. The compound is pharmacologically active at low to moderate doses, thus showing a favourable therapeutic index.

Provided are various embodiments relating to fumarate salt of (R)-3-(1-(2,3-dichloro-4-(pyrazin-2-yl)phenyl)-2,2,2-trifluoroethyl)-1-methyl-1-(1-methylpiperidin-4-yl) urea, and methods of producing and using the same to treat conditions and disorders associated with an increase of ghrelin level, such as food abuse, alcohol addiction, and other disorders (e.g., Prader-Willi syndrome). Also provided are various embodiments relating to crystalline HM04 free base, different crystalline forms of HM04 fumarate salt, and methods of producing the same.

Fumarate salt of (R)-3-(1-(2,3-dichloro-4-(pyrazin-2-yl)phenyl)-2,2,2-trifluoroethyl)-1-methyl-1-(1-methylpiperidin-4-yl)urea, methods of preparation, and uses thereof

Fumarate salt of (R)-3-(1-(2,3-dichloro-4-(pyrazin-2-yl)phenyl)-2,2,2- trifluoroethyl)-1-methyl-1-(1-methylpiperidin-4-yl) urea, methods of preparation, and uses thereof

Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the ghrelin receptor. The compounds have the general Formula I: or pharmaceutically acceptable salts thereof.

Growing community of inventors

Iselin, NJ, United States of America

Angelo Guainazzi