Abstract: The invention concerns the use of compounds represented by formula (I) as inotropic agents. The compounds of formula (I), which include, as preferred, 1-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-3-methyl-3-[(4R)-1-methyl-3,3-dimethyl-4-piperidyl]-urea and its hydrochloride salt, are herein reported to have a significant inotropic activity on cardiomyocytes from both normal and myocardial infarction-induced heart failure animal models, which makes them useful for treating cardiovascular patients in need thereof. Differently from known inotropic agents, the present compounds are effective on cardiomyocyte contractility without influencing calcium mobilization. Accordingly, they are advantageously free from adverse effects caused by increased calcium concentrations, such as increased oxygen demand, tachycardia, arrhythmia, ischemia, etc. Overall, a new, safe and effective inotropic treatment is thus made available.

Abstract: The invention concerns the use of compounds represented by formula (I) as inotropic agents. The compounds of formula (1), which include, as preferred, 1-[(1S)-1-(2,3-dichloro-4-methoxyphenyl)ethyl]-3-methyl-3-[(4R)-1-methyl-3,3-dimethyl-4-piperidyl]-urea and its hydrochloride salt, are herein reported to have a significant inotropic activity on cardiomyocytes from both normal and myocardial infarction-induced heart failure animal models, which makes them useful for treating cardiovascular patients in need thereof. Differently from known inotropic agents, the present compounds are effective on cardiomyocyte contractility without influencing calcium mobilization. Accordingly, they are advantageously free from adverse effects caused by increased calcium concentrations, such as increased oxygen demand, tachycardia, arrhythmia, ischemia, etc. Overall, a new, safe and effective inotropic treatment is thus made available.

Abstract: 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.

Abstract: 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.

Abstract: The invention concerns the use of compounds represented by formula (I) as inotropic agents. The compounds of formula (I), which include, as preferred, 1-[(1S)-1-(2,3-dichloro-4-methoxyphenypethyl]-3-methyl-3-[(4R)-1-methyl-3,3-dimethyl-4-piperidyl]-urea and its hydrochloride salt, are herein reported to have a significant inotropic activity on cardiomyocytes from both normal and myocardial infarction-induced heart failure animal models, which makes them useful for treating cardiovascular patients in need thereof. Differently from known inotropic agents, the present compounds are effective on cardiomyocyte contractility without influencing calcium mobilization. Accordingly, they are advantageously free from adverse effects caused by increased calcium concentrations, such as increased oxygen demand, tachycardia, arrhythmia, ischemia, etc. Overall, a new, safe and effective inotropic treatment is thus made available.

Abstract: 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.

Abstract: An organic Rankine cycle system with cascade cycles provided with a first organic Rankine cycle which operates at high temperature, in which a first organic working fluid carries out a heat exchange with a hot source fluid and a second organic Rankine cycle which operates at a temperature lower than the temperature of the first organic Rankine cycle and in which a second organic working fluid carries out a heat exchange with the same hot source. The evaporator of the first organic Rankine cycle is fed by the entire flow rate of the hot source fluid, while the evaporator and the preheater of the second organic Rankine cycle are fed by a first partial flow of the hot source fluid, the remaining second partial flow of the hot source fluid being used to partially carry out the preheating of the organic working fluid of the first organic Rankine cycle.

Abstract: 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.

Abstract: A cascade organic Rankine cycle plant comprising a hot source, at least a first high temperature organic Rankine cycle and a second low temperature organic Rankine cycle, said cycles comprising at least one preheater, at least one vaporizer, at least one turbine, at least one condenser, wherein the hot source first supplies a vaporizer of the high temperature cycle, then the vaporizer of the low temperature cycle and finally it is divided into two flows which supply a first preheater of the high temperature cycle and a preheater of the low temperature cycle. The first high-temperature organic Rankine cycle comprises a further vaporizer operating at an intermediate pressure between the vaporizer pressure of the high temperature cycle and the vaporizer pressure of the low temperature cycle.

Abstract: An organic Rankine cycle system with cascade cycles provided with a first organic Rankine cycle which operates at high temperature, in which a first organic working fluid carries out a heat exchange with a hot source fluid and a second organic Rankine cycle which operates at a temperature lower than the temperature of the first organic Rankine cycle and in which a second organic working fluid carries out a heat exchange with the same hot source. The evaporator of the first organic Rankine cycle is fed by the entire flow rate of the hot source fluid, while the evaporator and the preheater of the second organic Rankine cycle are fed by a first partial flow of the hot source fluid, the remaining second partial flow of the hot source fluid being used to partially carry out the preheating of the organic working fluid of the first organic Rankine cycle.

Abstract: 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.

Abstract: Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor.

Abstract: 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.

Abstract: A cascade organic Rankine cycle plant comprising a hot source, at least a first high temperature organic Rankine cycle and a second low temperature organic Rankine cycle, said cycles comprising at least one preheater, at least one vaporizer, at least one turbine, at least one condenser, wherein the hot source first supplies a vaporizer of the high temperature cycle, then the vaporizer of the low temperature cycle and finally it is divided into two flows which supply a first preheater of the high temperature cycle and a preheater of the low temperature cycle. The first high-temperature organic Rankine cycle comprises a further vaporizer operating at an intermediate pressure between the vaporizer pressure of the high temperature cycle and the vaporizer pressure of the low temperature cycle.

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

Abstract: 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.

Abstract: Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor.

Abstract: 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.

Abstract: 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.

Abstract: Disclosed are compounds, compositions and methods for the prevention and/or treatment of diseases which are pathophysiologically mediated by the neurokinin (NK1) receptor.