Details for Patent: 9,861,630

Title:	1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine as a compound with combined serotonin reuptake, 5-HT.sub.3 and 5-HT.sub.1A activity for the treatment of cognitive impairment
Abstract:	1-[2-(2,4-dimethylphenylsulphanyl)phenyl)]piperazine exhibits potent activity on SERT, 5-HT.sub.3 and 5-HT.sub.1A and may as such be useful for the treatment of cognitive impairment, especially in depressed patients.
Inventor(s):	Faldt; Andre (Ishoj, DK), Lopez de Diego; Heidi (N.ae butted.rum, DK), Holm; Rene (Jyllinge, DK)
Assignee:	H. Lundbeck A/S (Valby, DK)
Filing Date:	Aug 10, 2017
Application Number:	15/674,043
Claims:	1. A method of alleviating a symptom or complication of depression or major depressive disorder, or delaying progression of depression or major depressive disorder, comprising: administering to a patient in need thereof a pharmaceutical composition comprising a hydrobromide salt of a 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine selected from the group consisting of 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt alpha form, 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt beta form, 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt gamma form, 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt hemihydrate, 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt ethyl acetate solvate, and mixtures thereof, wherein said method alleviates a symptom or complication of depression or major depressive disorder, or delays the progression of depression or major depressive disorder, in said patient. 2. The method of claim 1, wherein said hydrobromide salt of 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt alpha form. 3. The method of claim 2, wherein the hydrobromide salt of 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt alpha form characterized by an XRPD pattern as shown in FIG. 2. 4. The method of claim 2, wherein the 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt alpha form is characterized by XRPD peaks at 5.85, 9.30, 17.49, and 18.58+/-0.10.degree. 2.theta.. 5. The method of claim 1, wherein said hydrobromide salt of 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt beta form. 6. The method of claim 5, wherein the hydrobromide salt of 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt beta form characterized by an XRPD pattern as shown in FIG. 3. 7. The method of claim 5, wherein the 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt beta form is characterized by XRPD peaks at 6.89, 9.73, 13.78, and 14.62+/-0.10.degree. 2.theta.. 8. The method of claim 1, wherein said hydrobromide salt of 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt gamma form. 9. The method of claim 8, wherein the hydrobromide salt of 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt gamma form characterized by an XRPD pattern as shown in FIG. 4. 10. The method of claim 8, wherein the 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt gamma form is characterized by XRPD peaks at 11.82, 16.01, 17.22, and 18.84+/-0.10.degree. 2.theta.. 11. The method of claim 1, wherein said hydrobromide salt of 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt hemihydrate. 12. The method of claim 11, wherein the hydrobromide salt of 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt hemihydrate characterized by an XRPD pattern as shown in FIG. 5. 13. The method of claim 11, wherein the 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine hydrobromide salt hemihydrate is characterized by XRPD peaks at 10.69, 11.66, 15.40, and 17.86+/-0.10.degree. 2.theta.. 14. The method of claim 1, wherein said hydrobromide salt of 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine is 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt ethyl acetate solvate. 15. The method of claim 14, wherein the 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine hydrobromide ethyl acetate solvate is characterized by XRPD peaks at 8.29, 13.01, 13.39, and 16.62+/-0.10.degree. 2.theta.. 16. The method of claim 1, wherein the hydrobromide salt of 1-[2-(2,4-dimethylphenyl sulfanyl)-phenyl]piperazine is a mixture of 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt ethyl acetate solvate and 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine hydrobromide salt alpha form characterized by an XRPD pattern as shown in FIG. 6.