Disubstituted piperidine derivatives for the treatment of depression

Abstract

The present invention relates to the field of pharmacy, and in particular to compounds of formula (I) as pharmaceutically active compounds. Compounds of formula (I) have been proven for the first time to be particularly useful for the treatment of depression and eating disorders related to depression, or diseases with depressive pathology as well as for the treatment of appetite related side effects of antidepressants and antipsychotics.

Description

[0001] Univerza v Ljubljani, et al. July 16, 2025 U74685PC Disubstituted piperidine derivatives for the treatment of depression Technical Field The present invention relates to the field of pharmacy, and in particular to compounds of formula (I) as pharmaceutically active compounds. The compounds of formula (I) have been proven for the first time to be particularly useful for the treatment of depression and eating disorders related to depression or diseases with depressive pathology, as well as for the treatment of appetite related side effects of antidepressants and antipsychotics. Background Art Major depressive disorder (MDD) is a debilitating disease characterised by depressed mood, anhedonia, impaired cognitive function (including memory acquisition, consolidation, and retrieval, as well as concentration), disturbed appetite, and sleep disturbances. These characteristics are spread across four areas, including emotional, motivational, cognitive, and physiological domains, therefore MDD is a complex disease to diagnose and treat (Bains N, Abdijadid S Major Depressive Disorder.2023. Treasure Island (FL): StatPearls Publishing; Ménard C, Hodes GE, Russo SJ. Pathogenesis of depression: Insights from human and rodent studies. Neuroscience. 2016.3;321:138-162; Otte C, Gold SM, Penninx BW, Pariante CM, Etkin A, Fava M, Mohr DC, Schatzberg AF. Major depressive disorder. Nat Rev Dis Primers.2016 Sep 15; 2:16065). Also supporting this statement is the fact that MDD’s aetiology and pathogenesis are very poorly understood, especially regarding MDD associated with impaired cognitive function seen in treatment resistant depression (TRD) (Dean J, Keshavan M. The neurobiology of depression: An integrated view. Asian J Psychiatr. 2017 Jun; 27:101-111). It is however known that many factors play a role in the development of MDD, including genetic, neurological, hormonal and neuroendocrinological factors (Kim YK, Na KS, Myint AM, Leonard BE. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Jan 4; 64:277-84; Penner-Goeke S, Binder EB. Epigenetics and depression. Dialogues Clin Neurosci. 2019 Dec;21(4):397-405; Thériault RK, Perreault ML. Hormonal regulation of circuit function: sex, systems and depression. Biol Sex Differ. 2019 Feb 28;10(1):12). The WHO reported that people who have suffered from traumatic experiences or adverse life events are more prone to develop MDD (Vitriol V, Cancino A, Weil K, Salgado C, Asenjo MA, Potthoff S. Depression and psychological trauma: an overview integrating current research and specific evidence of studies in the treatment of depression in public mental health services in chile. Depress Res Treat.2014; 2014:608671), highlighting the role of environmental factors in the aetiology of depression. Moreover, MDD is ranked as the leading cause of disability worldwide, and it is estimated that only 55% of patients respond to current treatment options available (Kennedy SH, Ceniti AK. Unpacking Major Depressive Disorder: From Classification to Treatment Selection. Can J Psychiatry. 2018 May;63(5):308-313; Ménard C, Hodes GE, Russo SJ. Pathogenesis of depression: Insights from human and rodent studies. Neuroscience. 2016 May 3; 321:138-162, Papakostas GI, Jackson WC, Rafeyan R, Trivedi MH. Inadequate Response to Antidepressant Treatment in Major Depressive Disorder. J Clin Psychiatry.2020 May 19;81(3): OT19037COM5). Based on this, understanding MDD, and creating better antidepressant treatment regimens is of paramount importance. In addition, approximately 50% of individuals with MDD experience a reduction in appetite due to their condition, and about 30% of these patients suffer from weight loss related to their depression ( Simmons, W. K., Burrows, K., Avery, J. A., Kerr, K. L., Taylor, A., Bodurka, J., Potter, W., Teague, T. K. & Drevets, W. C. 2020. Appetite changes reveal depression subgroups with distinct endocrine, metabolic, and immune states. Molecular Psychiatry, 25, 1457-1468.). From this, a subset of MDD patients exhibit appetite loss without significant weight changes. This subtype can benefit from the orexigenic effects of the compound, improving their overall nutritional intake and potentially alleviating some depressive symptoms. A subset of patients with MDD, particularly those with atypical features, often experience significant weight gain as a symptom of their condition ( Mills, J. G., Thomas, S. J., Larkin, T. A., Pai, N. B. & Deng, C. 2018. Problematic eating behaviours, changes in appetite, and weight gain in Major Depressive Disorder: The role of leptin. Journal of Affective Disorders, 240, 137-145.). The paradoxical nature of the above findings suggests some congruence regarding the use of this compound in typical and atypical types of depression. Many current antidepressants and antipsychotics are linked to weight gain, which significantly contributes to patient non-compliance ( Fava, M.2000. Weight gain and antidepressants. Journal of Clinical Psychiatry, 61 Suppl 11, 37-41.). New drugs are needed that could address this issue by offering antidepressant benefits without the associated weight gain. Summary of Invention The invention generally relates to compounds of formula (I), optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment of depression. As demonstrated in the Examples, compounds of formula (I) have shown unexpected efficacy and positive effects in a genetic rat model of depression. Especially, compounds of formula (I) have shown unexpected efficacy and positive effects on appetite in a genetic rat model of depression. This is the first proven use of these compounds in the treatment of depression or a disease or disorder with depressive pathology, such as eating disorders related to depression, as well as for the treatment of appetite related side effects of antidepressants and antipsychotics. The present invention can be summarized by the following items: 1. A compound of formula (I) wherein the piperidine ring is 1,3- or 1,4-disubstituted and the substituents are: wherein R1is: H, CH3, CH3CH2, CH3(CH2)2, (CH3)2CH, OH, OCH3, OCH2CH3, O(CH2)2CH3, OCF3, F, Cl, Br, CF3, NH2, NO2, N(CH3)2, N(CH3CH2)2, NHCH3, NHCH2CH3, COOH, COOCH3, COOCH2CH3, CONH2, CONHCH3, CONHCH2CH3, COCH3, or COCH2CH3; Y is: H, CH3, CH2CH3, (CH2)2CH3, (CH2)3CH3, (CH2)2OCH3, (CH2)3OCH3, (CH2)2NHCH3, (CH2)2N(CH3)2, or (CH2)3N(CH3)2; X is: CO, or SO2 wherein R2is: H, CH3, CH3CH2, CH3(CH2)2, (CH3)2CH, OH, OCH3, OCH2CH3, O(CH2)2CH3, OCF3, F, Cl, Br, CF3, NH2, NO2, N(CH3)2, N(CH3CH2)2, NHCH3, NHCH2CH3, COOH, COOCH3, COOCH2CH3, CONH2, CONHCH3, CONHCH2CH3, COCH3, or COCH2CH3; optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment of depression or a disease or disorder with depressive pathology, such as an eating disorder related to depression, or for use in the treatment of an appetite related side effect of an antidepressant or antipsychotic.Compound for use according to item 1, wherein preferably . 3. Compound for use according to item 1, wherein . 4. Compound for use according to item 1, wherein W is . 5. Compound for use according to item 1 or 2, wherein R1is H. 6. Compound for use according to item 1 or 2, wherein R1is CH3. 7. Compound for use according to item 1 or 2, wherein R1is CH3CH2. 8. Compound for use according to item 1 or 2, wherein R1is CH3(CH2)2. 9. Compound for use according to item 1 or 2, wherein R1is (CH3)2CH. 10. Compound for use according to item 1 or 2, wherein R1is OH. 11. Compound for use according to item 1 or 2, wherein R1is OCH3. 12. Compound for use according to item 1 or 2, wherein R1is OCH2CH3. 13. Compound for use according to item 1 or 2, wherein R1is O(CH2)2CH3. 14. Compound for use according to item 1 or 2, wherein R1is OCF3. 15. Compound for use according to item 1 or 2, wherein R1is F. 16. Compound for use according to item 1 or 2, wherein R1is Cl. 17. Compound for use according to item 1 or 2, wherein R1is Br. 18. Compound for use according to item 1 or 2, wherein R1is CF3. 19. Compound for use according to item 1 or 2, wherein R1is NH2. 20. Compound for use according to item 1 or 2, wherein R1is NO2. 21. Compound for use according to item 1 or 2, wherein R1is N(CH3)2. 22. Compound for use according to item 1 or 2, wherein R1is N(CH3CH2)2. 23. Compound for use according to item 1 or 2, wherein R1is NHCH3. 24. Compound for use according to item 1 or 2, wherein R1is NHCH2CH3. 25. Compound for use according to item 1 or 2, wherein R1is COOH. 26. Compound for use according to item 1 or 2, wherein R1is COOCH3. 27. Compound for use according to item 1 or 2, wherein R1is COOCH2CH3. 28. Compound for use according to item 1 or 2, wherein R1is CONH2. 29. Compound for use according to item 1 or 2, wherein R1is CONHCH3. 30. Compound for use according to item 1 or 2, wherein R1is CONHCH2CH3. 31. Compound for use according to item 1 or 2, wherein R1is COCH3. 32. Compound for use according to item 1 or 2, wherein R1is COCH2CH3. 33. Compound for use according to any one of items 1 to 32, wherein Y is H. 34. Compound for use according to any one of items 1 to 32, wherein Y is CH3. 35. Compound for use according to any one of items 1 to 32, wherein Y is CH2CH3. 36. Compound for use according to any one of items 1 to 32, wherein Y is (CH2)2CH3. 37. Compound for use according to any one of items 1 to 32, wherein Y is (CH2)3CH3. 38. Compound for use according to any one of items 1 to 32, wherein Y is (CH2)2OCH3. 39. Compound for use according to any one of items 1 to 32, wherein Y is (CH2)3OCH3. 40. Compound for use according to any one of items 1 to 32, wherein Y is (CH2)2NHCH3. 41. Compound for use according to any one of items 1 to 32, wherein Y is (CH2)2N(CH3)2. 42. Compound for use according to any one of items 1 to 32, wherein Y is or (CH2)3N(CH3)2. 43. Compound for use according to any one of items 1 to 42, wherein X is CO. 44. Compound for use according to any one of items 1 to 42, wherein X is SO2. 45. Compound for use according to any one of items 1 to 44, wherein Z is . 46. Compound for use according to any one of items 1 to 44, wherein Z is . 47. Compound for use according to any one of items 1 to 46, wherein R2is H. 48. Compound for use according to any one of items 1 to 46, wherein R2is CH3. 49. Compound for use according to any one of items 1 to 46, wherein R2is CH3CH2. 50. Compound for use according to any one of items 1 to 46, wherein R2is CH3(CH2)2. 51. Compound for use according to any one of items 1 to 46, wherein R2is (CH3)2CH. 52. Compound for use according to any one of items 1 to 46, wherein R2is OH. 53. Compound for use according to any one of items 1 to 46, wherein R2is OCH3. 54. Compound for use according to any one of items 1 to 46, wherein R2is OCH2CH3. 55. Compound for use according to any one of items 1 to 46, wherein R2is O(CH2)2CH3. 56. Compound for use according to any one of items 1 to 46, wherein R2is OCF3. 57. Compound for use according to any one of items 1 to 46, wherein R2is F. 58. Compound for use according to any one of items 1 to 46, wherein R2is Cl. 59. Compound for use according to any one of items 1 to 46, wherein R2is Br. 60. Compound for use according to any one of items 1 to 46, wherein R2is CF3. 61. Compound for use according to any one of items 1 to 46, wherein R2is NH2. 62. Compound for use according to any one of items 1 to 46, wherein R2is NO2. 63. Compound for use according to any one of items 1 to 46, wherein R2is N(CH3)2. Compound for use according to any one of items 1 to 46, wherein R2is N(CH3CH2)2. Compound for use according to any one of items 1 to 46, wherein R2is NHCH3. Compound for use according to any one of items 1 to 46, wherein R2is NHCH2CH3. Compound for use according to any one of items 1 to 46, wherein R2is COOH. Compound for use according to any one of items 1 to 46, wherein R2is COOCH3. Compound for use according to any one of items 1 to 46, wherein R2is COOCH2CH3. Compound for use according to any one of items 1 to 46, wherein R2is CONH2. Compound for use according to any one of items 1 to 46, wherein R2is CONHCH3. Compound for use according to any one of items 1 to 46, wherein R2is CONHCH2CH3. Compound for use according to any one of items 1 to 46, wherein R2is COCH3. Compound for use according to any one of items 1 to 46, wherein R2is COCH2CH3. Compound for use according to item 1, wherein the compound is selected from the group consisting of: N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2- sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-3- nitrobenzenesulfonamide; 3-amino-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)benzenesulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-4- methylbenzenesulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-4- nitrobenzenesulfonamide; 4-amino-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)benzenesulfonamide; N-(4-(N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)sulfamoyl)phenyl)acetamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)benzenesulfonamide; methyl 2-(N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)sulfamoyl)benzoate; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-4-methoxy-N-(2- methoxyethyl)benzenesulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-4-fluoro-N-(2- methoxyethyl)benzenesulfonamide; 2-(N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)sulfamoyl)-N-methylbenzamide; N-(3-(N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)sulfamoyl)phenyl)acetamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-1- sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-7-methoxy-N-(2-methoxyethyl)naphthalene- 2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-7-(cyanomethoxy)-N-(3- methoxypropyl)naphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(3-methoxypropyl)naphthalene-2- sulfonamide; N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2- sulfonamide; N-((1-(3-fluorobenzyl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2- sulfonamide; N-((1-(4-cyanobenzyl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene- 2-sulfonamide; N-((1-(3-cyanobenzyl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene- 2-sulfonamide; N-((1-(4-(dimethylamino)benzyl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-N-methylnaphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-N-ethylnaphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-N-propylnaphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-N-butylnaphthalene-2-sulfonamide; N-((1-(3-methylbenzyl)piperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-(2-chloro-4-fluorobenzyl)piperidin-3-yl)methyl)naphthalene-2- sulfonamide; N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-(4-cyanobenzyl)piperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)-N-methylnaphthalene-2- sulfonamide; N-((1-benzylpiperidin-4-yl)methyl)-N-(3-methoxypropyl)naphthalene-2- sulfonamide; N-((1-benzylpiperidin-4-yl)methyl)-N-(2-methoxyethyl)naphthalene-2- sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-4-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-4-yl)methyl)-N-(3- methoxypropyl)naphthalene-2-sulfonamide; N-((1-benzylpiperidin-4-yl)methyl)naphthalene-2-sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- (dimethylamino)ethyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)-1-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-6-methoxy-N-(2- methoxyethyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-3- methylbenzamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-6-methoxy-2- naphthamide; 6-bromo-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-2- naphthamide; 6-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methylcarbamoyl)naphthalen-2- yl acetate N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)-1-naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-6-methoxy-N-(2-methoxyethyl)-2- naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-6-bromo-N-(2-methoxyethyl)-2- naphthamide; 6-(((1-benzylpiperidin-3-yl)methyl)(2-methoxyethyl)carbamoyl)naphthalen-2-yl acetate; N-((1-benzylpiperidin-3-yl)methyl)-N-(3-methoxypropyl)-2-naphthamide; N-((1-benzylpiperidin-4-yl)methyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-4-yl)methyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-4-yl)methyl)-N-(2-methoxyethyl)-2- naphthamide; N-((1-benzylpiperidin-4-yl)methyl)-N-(3-methoxypropyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-4-yl)methyl)-N-(3-methoxypropyl)-2- naphthamide; 6-bromo-N-((1-(2,3-dihydro-1H-inden-2-yl)-piperidin-3-yl)methyl)-N-(2- methoxyethyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-1-naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)-2-naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-2-naphthamide; N-((1-(2,3-Dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(3-methoxypropyl)- 2-naphthamide; N-((1-Benzylpiperidin-4-yl)methyl)-N-(2-methoxyethyl)-2-naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(2-(dimethylamino)-ethyl)-2-naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(3-(dimethylamino)-propyl)-2- naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(3- (dimethylamino)propyl)-2-naphthamide; N-((1-(2,3-Dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- (methylamino)ethyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-2- naphthamide; N-(2-methoxyethyl)-N-((1-(prop-2-yn-1-yl)piperidin-3-yl)methyl)-2- naphthamide; N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)-2-naphthamide; N-(3-methoxypropyl)-N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)-2-naphthamide; N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)-2-naphthamide; N-(2-methoxyethyl)-N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)-2-naphthamide; N-(3-methoxypropyl)-N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)-2-naphthamide; N-(2-methoxyethyl)-N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)naphthalene-2- sulfonamide; N-(3-methoxypropyl)-N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)naphthalene-2- sulfonamide; N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)naphthalene-2- sulfonamide; N-(2-methoxyethyl)-N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)naphthalene-2- sulfonamide; N-(3-methoxypropyl)-N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)naphthalene-2- sulfonamide; and N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)naphthalene-2- sulfonamide; optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof. 76. Compound for use according to item 1, wherein the compound is N-((1- benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2-sulfonamide, optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof, such as N-((1- benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2-sulfonamide hydrochloride. 77. A compound for use in the treatment of depression or a disease or disorder with depressive pathology, such as an eating disorder related to depression, or for use in the treatment of an appetite related side effect of an antidepressant or antipsychotic, wherein the compound is selected from the group consisting of: N-((1-(pyridin-4-ylmethyl)piperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-((2-methylthiazol-4-yl)methyl)piperidin-3-yl)methyl)naphthalene-2- sulfonamide; N-((1-(benzo[d]thiazol-2-yl)piperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)quinoline-6-carboxamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)furan-2-carboxamide; (E)-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)-3-(4-methoxyphenyl)acrylamide; N-{[1-(2,3-dihydro-1H-inden-2-yl)-3-piperidinyl]methyl}-N-(2-methoxyethyl)-2- thiophenecarboxamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)furan-3-carboxamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)isonicotinamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)nicotinamide; N-{[1-(2,3-dihydro-1H-inden-2-yl)-3-piperidinyl]methyl}-5-methoxy-N-(2- methoxyethyl)-2-furamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)quinoline-6- carboxamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)quinoline-6- carboxamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-2-naphthamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-1-naphthamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-6-bromo-2-naphthamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-6-methoxy-2-naphthamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)quinoline-6-carboxamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-4-hydroxy-7- (trifluoromethyl)quinoline-3-carboxamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-6-hydroxy-2-naphthamide; N-((1-(benzo[d]thiazol-2-yl)piperidin-3-yl)methyl)-2-naphthamide; N-((1-(benzo[d]thiazol-2-yl)piperidin-3-yl)methyl)-6-bromo-2-naphthamide; N-((1-(benzo[d]thiazol-2-yl)piperidin-3-yl)methyl)-6-methoxy-2-naphthamide; N-((1-(benzo[d]thiazol-2-yl)piperidin-3-yl)methyl)quinoline-6-carboxamide; and N-((1-(benzo[d]thiazol-2-ylmethyl)piperidin-3-yl)methyl)-2-naphthamide; optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof. 78. Compound for use according to any one of items 1 to 77, wherein the compound is used in combination with one or more other anti-depressants. 79. The compound for use according to any one of items 1 to 78, for use in the treatment of depression. 80. The compound for use according to item 79, wherein the depression is selected from the group consisting of major depressive disorder (MDD), unipolar depression, treatment-resistant depression, bipolar depression, post-partum depression, anxious depression and dysthymia. 81. The compound for use according to item 79, wherein the depression is major depressive disorder (MDD). 82. The compound for use according to any one of items 1 to 78, for use in the treatment of a disease or disorder with depressive pathology. 83. The compound for use according to item 82, wherein the disease or disorder is selected from the group consisting of anxiety disorders, such as generalized anxiety disorder (GAD), panic disorder, social anxiety disorder, and obsessive- compulsive disorder (OCD), dysthymia (Persistent Depressive Disorder), post- traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), schizophrenia, Parkinson’s disease and Huntington’s disease, eating disorders, such as bulimia nervosa and binge eating disorder, neuropathic pain, fibromyalgia and chronic pain syndrome. 84. The compound for use according to any one of items 1 to 78, for use in the treatment of an eating disorder related to depression. 85. The compound for use according to item 84, wherein the eating disorder related to depression is selected from the group consisting of anorexia nervosa, bulimia nervosa, binge eating disorder and avoidant / restrictive food intake disorder (ARFID). 86. The compound for use according to any one of items 1 to 78, for use in the treatment of an appetite related side effect of an antidepressant or antipsychotic. 87. The compound for use according to item 86, wherein the appetite related side effect is selected from the group consisting of increased appetite, decreased appetite, weight gain, weight loss, change in taste, and metabolic change. 88. The compound for use according to item 86, wherein the appetite related side effect is weight gain. 89. Pharmaceutical composition for use in the treatment of depression, a disease or disorder with depressive pathology, an eating disorder related to depression or an appetite related side effect of antidepressants and antipsychotics, comprising a therapeutically effective amount of a compound of formula (I) as defined in any one of items 1 to 77, and a pharmaceutically acceptable carrier, adjuvant, or vehicle. 90. The pharmaceutical composition for use according to item 89, for use in the treatment of depression. 91. The pharmaceutical composition for use according to item 90, wherein the depression is selected from the group consisting of major depressive disorder (MDD), unipolar depression, treatment-resistant depression, bipolar depression, post-partum depression, anxious depression and dysthymia. 92. The pharmaceutical composition for use according to item 90, wherein the depression is major depressive disorder (MDD). 93. The pharmaceutical composition for use according to item 89, for use in the treatment of a disease or disorder with depressive pathology. 94. The pharmaceutical composition for use according to item 93, wherein the disease or disorder is selected from the group consisting of anxiety disorders, such as generalized anxiety disorder (GAD), panic disorder, social anxiety disorder, and obsessive-compulsive disorder (OCD), dysthymia (Persistent Depressive Disorder), post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), schizophrenia, Parkinson’s disease and Huntington’s disease, eating disorders, such as bulimia nervosa and binge eating disorder, neuropathic pain, fibromyalgia and chronic pain syndrome. 95. The pharmaceutical composition for use according to item 89, for use in the treatment of an eating disorder related to depression. 96. The pharmaceutical composition for use according to item 95, wherein the eating disorder related to depression is selected from the group consisting of anorexia nervos, bulimia nervosa, binge eating disorder and avoidant / restrictive food intake disorder (ARFID). 97. The pharmaceutical composition for use according to item 89, for use in the treatment of an appetite related side effect of an antidepressant or antipsychotic. 98. The pharmaceutical composition for use according to item 97, wherein the appetite related side effect is selected from the group consisting of increased appetite, decreased appetite, weight gain, weight loss, change in taste, and metabolic change. 99. The pharmaceutical composition for use according to item 97, wherein the appetite related side effect is weight gain. 100. Use of a compound of formula (I) as defined in any one of items 1 to 77 in the preparation of a medicament for use in the treatment of depression, a disease or disorder with depressive pathology, an eating disorder related to depression or an appetite related side effect of an antidepressant or antipsychotic. 101. Method of treating depression, a disease or disorder with depressive pathology, an eating disorder related to depression or an appetite related side effect of an antidepressant or antipsychotic in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a compound of formula (I) as defined in any one of items 1 to 77 or a pharmaceutical composition as define in item 88. Brief description of the drawings Figure 1: Immobility time as seen in the Forced Swim Test for assessing behavioral despair and resulting antidepressant-like activity. Comp 30 shows comparable efficacy to the control reference antidepressant, ESC, in reducing behavior despair. FSL CTL- Vehicle control group; ESC 20- escitalopram (20 mg / kg); COMP 30- N-((1-Benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2- sulfonamide (30 mg / kg). **** (p < 0.0001) Figure 2: A) Swimming time as seen in the Forced Swim Test for assessing coping behavior and resulting antidepressant-like activity. Comp 30 shows comparable efficacy to the control antidepressant, ESC, in improving coping behavior. B) Struggling time as seen in the Forced Swim Test for assessing coping behavior and resulting antidepressant-like activity. Comp 30 shows comparable efficacy to the control reference antidepressant, ESC, in improving coping behavior. FSL CTL- Vehicle control group; ESC 20- escitalopram (20 mg / kg); COMP 30- N((1Benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2-sulfonamide (30 mg / kg). **** (p < 0.0001); *** (p = 0.0002) Figure 3: A) Weight gain during the treatment. Rats treated with comp 30 did not exhibit significant weight gain. B) Food consumption during the treatment period. Comp 30 shows appetite-stimulating effect. FSL CTL- Vehicle control group; ESC 20- escitalopram (20 mg / kg); COMP 30- N-((1-Benzylpiperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide (30 mg / kg). Fig 1A: **** (p < 0.0001); * (p = 0.02). Fig 1B: **** (p < 0.0001); ** (p = 0.04); * (p = 0.02). Technical Problem Current antidepressant treatments have several limitations, including limited efficacy, a frequent incidence of intolerable initial and lasting side-effects including metabolic dysregulation and weight gain, a delayed onset of action and treatment resistance in about one third of patients. Side-effects furthermore contribute to reduced patient compliance and could ultimately contribute to treatment failure. Another shortcoming of current drug treatments is the inability to adequately address cognitive and memory impairment, along with anhedonia, which are all common complications of MDD. The importance of finding new compounds with novel mechanisms of action to address these symptoms and / or reduce side-effects and other shortcomings is apparent. Solution to Problem The above problem is solved by the present inventors based on the surprising finding that compounds of formula (I) show excellent efficacy in genetic rat model of depression. The present invention thus provides in a first aspect a compound of formula (I) wherein the piperidine ring is 1,3- or 1,4-disubstituted and the substituents are: R1is: H, CH3, CH3CH2, CH3(CH2)2, (CH3)2CH, OH, OCH3, OCH2CH3, O(CH2)2CH3, OCF3, F, Cl, Br, CF3, NH2, NO2, N(CH3)2, N(CH3CH2)2, NHCH3, NHCH2CH3, COOH, COOCH3, COOCH2CH3, CONH2, CONHCH3, CONHCH2CH3, COCH3, or COCH2CH3 Y is: H, CH3, CH2CH3, (CH2)2CH3, (CH2)3CH3, (CH2)2OCH3, (CH2)3OCH3, (CH2)2NHCH3, (CH2)2N(CH3)2, or (CH2)3N(CH3)2 X is: CO, or SO2 R2is: H, CH3, CH3CH2, CH3(CH2)2, (CH3)2CH, OH, OCH3, OCH2CH3, O(CH2)2CH3, OCF3, F, Cl, Br, CF3, NH2, NO2, N(CH3)2, N(CH3CH2)2, NHCH3, NHCH2CH3, COOH, COOCH3, COOCH2CH3, CONH2, CONHCH3, CONHCH2CH3, COCH3, or COCH2CH3; optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof, for use in the treatment of depression or a disease or disorder with depressive pathology, such as an eating disorder related to depression, or for use in the treatment of an appetite related side effect of an antidepressant or antipsychotic. Particular embodiments of the compound of formula (I) have been described in the summary of the invention, and the respective disclosure applies mutatis mutandis. The term "depression" as used herein includes major depressive disorder (MDD), including single and recurrent episodes, unipolar depression, treatment-resistant depression, bipolar depression, anxious depression, and dysthymia (also referred to as dysthymic disorder). In addition, the broad term "depression" includes any major depressive disorder, dysthymic disorder, mood disorder due to medical illness with depressive features, mood disorders due to medical illness with major depressive-like episodes, substance-induced mood disorders with depressive features, and depressive disorders not otherwise specified according to the diagnostic criteria of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders, 5th edition, 2013. Non-limiting examples of depression include major depressive disorder (MDD), unipolar depression, treatment-resistant depression, bipolar depression, post-partum depression, anxious depression and dysthymia. A “disease or disorder with depressive pathology” as referred to herein is meant a medical condition where depression is a significant component or symptom. Non- limiting examples of such diseases or disorders include anxiety disorders, such as generalized anxiety disorder (GAD), panic disorder, social anxiety disorder, and obsessive-compulsive disorder (OCD), dysthymia (Persistent Depressive Disorder), post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), schizophrenia, Parkinson’s disease and Huntington’s disease, eating disorders, such as bulimia nervosa and binge eating disorder, neuropathic pain, fibromyalgia and chronic pain syndrome. Eating disorders related to depression include, but are not limited to, anorexia nervosa, bulimia nervosa, binge eating disorder and Avoidant / Restrictive Food Intake Disorder (ARFID). Antidepressants and antipsychotic have a range of known side effects, which can vary depending on the specific medication and the individual taking it. Common side effects of antidepressants and antipsychotic are appetite related side effects, including, but not limiting to, increased appetite, decreased appetite, weight gain, weight loss, changes in taste, and metabolic changes, such as increased blood sugar levels and altered lipid profiles, which can contribute to weight gain and increase the risk of developing metabolic syndrome and diabetes. Antidepressants are typically used to treat depression or disorder related to depression, including, but not limited to, major depressive disorder (MDD), anxiety disorders, such as generalized anxiety disorder (GAD), panic disorder, social anxiety disorder, and obsessive-compulsive disorder (OCD), dysthymia (Persistent Depressive Disorder), post-traumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), post-partum depression, schizophrenia, Parkinson’s disease and Huntington’s disease, eating disorders, such as bulimia nervosa and binge eating disorder, neuropathic pain, fibromyalgia and chronic pain syndrome. Known antidepressants include, but are not limited to, selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), sertraline (Zoloft), and citalopram (Celexa), serotonin and norepinephrine reuptake inhibitors (SNRIs), such as venlafaxine (Effexor), duloxetine (Cymbalta), and desvenlafaxine (Pristiq), tricyclic antidepressants (TCAs), such as amitriptyline (Elavil), nortriptyline (Pamelor), and imipramine (Tofranil), monoamine oxidase inhibitors (MAOIs), such as phenelzine (Nardil) and tranylcypromine (Parnate), atypical antidepressants, such as bupropion (Wellbutrin), mirtazapine (Remeron), and trazodone, and newer antidepressants, such as vortioxetine (Trintellix) and vilazodone (Viibryd). Additional information on antidepressants is also provide further below. Antipsychotics are typically used to treat conditions such as schizophrenia, bipolar disorder, and other serious mental health conditions. They are divided into two main classes: typical (or first-generation) antipsychotics and atypical (or second-generation) antipsychotics. Known antipsychotics include, but are not limited to, typical antipsychotics, such as haloperidol (Haldol), chlorpromazine (Thorazine), and fluphenazine (Prolixin), and atypical antipsychotics, such as risperidone (Risperdal), quetiapine (Seroquel), olanzapine (Zyprexa), aripiprazole (Abilify), and clozapine (Clozaril). The term “treatment” includes therapeutic treatments, prophylactic treatments, and applications in which one reduces the risk that a subject will develop a disease or disorder as mentioned herein, or in which one reduces a side effect of an antidepressant or antipsychotic. The treatment may thus be ameliorative, curative or prophylactic. The therapeutic treatment does not require the complete curing of a disease or disorder, or side effect, and encompasses embodiments in which one reduces symptoms. The prophylactic treatment does not require the 100% elimination of the possibility of an event. Rather, it denotes that the likelihood of the occurrence of the event has been reduced in the presence of the compound of the present invention. A compound of formula (I) may form stable acid or basic salts, and in such cases administration of a compound as a salt may be appropriate, and pharmaceutically acceptable salts may be made by conventional methods. Examples of salts derived from pharmaceutically-acceptable inorganic bases include aluminum, ammonium, calcium, copper, ferric, ferrous, lithium, magnesium, manganic, manganous, potassium, sodium, zinc and the like. Salts derived from pharmaceutically-acceptable organic bases include salts of primary, secondary and tertiary amines, including substituted amines, cyclic amines, naturally-occurring amines and the like. Examples of pharmaceutically acceptable acid addition salts include those derived from inorganic acids like hydrochloric, hydrobromic, nitric, carbonic, monohydrogencarbonic, phosphoric, monohydrogenphosphoric, dihydrogenphosphoric, sulfuric, monohydrogensulfuric, hydroiodic, or phosphorous acids and the like, as well as the salts derived from relatively nontoxic organic acids like acetic, propionic, isobutyric, malonic, salicyclic, ascorbic, benzoic, succinic, suberic, fumaric, mandelic, phthalic, o-glycerophosphoric, benzenesulfonic, p- tolylsulfonic, citric, tartaric, methanesulfonic, and the like. Also included are salts of amino acids such as argininate and the like, and salts of organic acids like glucuronic or galactunoric acids and the like (see, for example, Berge, S. M., et al, "Pharmaceutical Salts", Journal of Pharmaceutical Science, 1977, 66, 1-19). A preferred pharmaceutically-acceptable salt is the hydrochloride salt. Particular pharmaceutically acceptable salts of compounds of formula (I) are the hydrochloride salts. A non-limiting example of a hydrochloride salt of a compound of formula (I) is N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2- sulfonamide hydrochloride. It will be appreciated by those skilled in the art that the compounds of formula (I) can exists as stereoisomers (for example, optical (+ and −), geometrical (cis and trans) and conformational isomers (axial and equatorial). All such stereoisomers are included in the scope of the present invention. It will be appreciated by those skilled in the art that the compounds of the invention can contain a chiral center. The compounds may thus exist in the form of two different optical isomers (i.e. (+) or (−) enantiomers). All such enantiomers and mixtures thereof including racemic mixtures are included within the scope of the invention. The single optical isomer or enantiomer can be obtained by method well known in the art, such as chiral HPLC, enzymatic resolution and chiral auxiliary. It is also to be understood that compounds of the invention and salts thereof can exist in solvated as well as unsolvated forms such as, for example, hydrated forms. The present invention further provides a pharmaceutical composition for the treatment of depression, comprising a therapeutically effective amount of a compound of formula (I) as defined herein, optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and a pharmaceutically acceptable carrier, adjuvant, or vehicle Examples of pharmaceutical compositions include any solid (tablets, pills, capsules, granules etc.) or liquid (solutions, suspensions or emulsions) composition. In a preferred embodiment, the pharmaceutical compositions are in oral form, either solid or liquid. Suitable dose forms for oral administration may be tablets, capsules, syrups or solutions and may contain conventional excipients known in the art such as binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone: fillers, for example lactose, sugar, maize starch, calcium phosphate, sorbitol or glycine; tabletting lubricants, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycollate or microcrystalline cellulose; or pharmaceutically acceptable wetting agents such as sodium lauryl sulfate. The solid oral compositions may be prepared by conventional methods of blending, filling, or tableting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantities of fillers. Such operations are conventional in the art. The tablets may for example be prepared by wet or dry granulation and optionally coated according to methods well known in normal pharmaceutical practice, in particular with an enteric coating. The pharmaceutical compositions may also be adapted for parenteral administration, such as sterile solutions, suspensions or lyophilized products in the appropriate unit dosage form. Adequate excipients can be used, such as bulking agents, buffering agents or surfactants. The mentioned formulations will be prepared using standard methods such as those described or referred to in the European and US Pharmacopoeias and similar reference texts. Administration of the compound of formula (I) or the pharmaceutical composition as described herein may be by any suitable method, such as intravenous infusion, oral preparations, and intraperitoneal and intravenous administration. Oral administration is preferred because of the convenience for the patient and the potential chronic character of the disease to be treated. The dose, frequency and way of use are dependent from several factors, which are further dependent also from the active pharmaceutical ingredient used, its pharmacokinetic properties and patient’s condition. Generally, a therapeutic effective amount of a compound of formula (I) will depend on the relative efficacy of the compound chosen, the severity of the disorder being treated and the weight of the sufferer. However, active compounds will typically be administered once or more times a day for example 1, 2, 3 or 4 times daily, with typical total daily doses in the range of from 0.1 to 1000 mg / kg / day. For example, a compound of the present invention, such as N-((1-benzylpiperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide, may be administered at a dose of 30 mg / kg twice a day, preferably one dose of 30 mg / kg in the morning and a second dose of 30 mg / kg in the evening. The compound of formula (I) and the pharmaceutical composition described herein may be used alone or with other drug(s) to provide a combination therapy. The other drug(s) may form part of the same composition or be provided as a separate composition for administration at the same time or at different time. Particularly, the other drug(s) may be one or more other anti-depressants. Unless otherwise specified, the term "anti-depressant" means any drug used to treat depression. Appropriate examples include but are not limited to, monoamine oxidase inhibitors such as phenelzine, tranylcypromine, moclobemide; tricyclics such as imipramine, amitriptyline, desipramine, nortriptyline, doxepin, protriptyline, trimipramine, clomipramine, amoxapine; tetracyclic antidepressants such as maprotiline; noncyclic agents such as nomifensine; triazolopyridines such as trazodone; serotonin reuptake inhibitors such as fluoxetine, sertraline, paroxetine, citalopram, escitalopram, fluvoxamine; serotonin receptor antagonists such as nefazodone; serotonin noradrenergic reuptake inhibitors such as venlafaxine, milnacipran; noradrenergic and specific serotonergic agents such as mirtazapine; noradrenaline reuptake inhibitors such as reboxetine; atypical antidepressants such as bupropion; natural products such as kava-kava, and St. John's Wort.; dietary supplements such as S-adenosylmethionine; neuropeptides such as thyrotropin- releasing hormone; compounds targeting neuropeptide receptors such as neurokinin receptor antagonists; and hormones such as triiodothyronine. Usual first-line antidepressant treatment regimens often include one of the following: escitalopram, fluoxetine, imipramine, bupropion, venlafaxine, and sertraline. The compound of formula (I) and the pharmaceutical composition described herein may be administer to any subject in need of treatment. The subject may be a human or non-human mammal, such as dog, cat, horse, cow, pig, sheep, goat, monkey, rat, mouse, rabbit, guinea pig etc. Preferably, the subject is a human. The invention further provides the use of the compound of formula (I) as defined herein, optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof, as the active ingredient for the preparation of a medicament for the treatment of depression, a disease or disorder with depressive pathology, an eating disorder related to depression or an appetite related side effect of an antidepressant or antipsychotic in a subject in need thereof. The invention further provides a method of treating depression, a disease with depressive pathology, an eating disorder related to depression or an appetite related side effect of an antidepressant or antipsychotic in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of formula (I) as defined herein, optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof, or a pharmaceutical composition described herein. It should be understood that all details provided in the context of the compound for use equally apply to the aspects of use of manufacture and method of treatment. Compounds of formula (I) can be prepared using modified synthetic procedure described in the literature (such as in Košak U. et al. Tetrahedron Lett.2014, 55, 2037– 2039; Brus B. et al. J. Med. Chem.2014, 57, 8167–8179; Košak U. et al. Sci. Rep. 2016, 6, 39495; Košak U. et al. Bioorg. Med. Chem. 2017, 25, 633–645; Zakošek Pipan M. et al. Sci. Rep.2021, 11, 18098). Having generally described this invention, a further understanding can be obtained by reference to the following examples, which are provided herein for purposes of illustration only, and are not intended to be limiting unless otherwise specified. Examples EXAMPLE 1: Synthesis of N-((1-benzylpiperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide hydrochloride STEP 1: Synthesis of 1-benzoylpiperidine-3-carboxylic acid To a 4-L round-bottomed flask equipped with a stirring bar, piperidine-3-carboxylic acid (100 g, 0.774 mol, 1.0 equiv.) was added. THF (600 mL) was added and the resulting suspension was stirred. H2O (800 mL) was added, and after all piperidine-3-carboxylic acid dissolved, the solution was cooled to 0 °C. K2CO3 (536 g, 3.878 mol, 5.0 equiv.) were added portionwise. A solution of benzoyl chloride (90 mL, 0.774 mol, 1.0 equiv.) in THF (200 mL) was then added dropwise. The reaction mixture was allowed to warm to room temperature, stirred for 24 hours, transferred into a 2-L separating funnel and washed with ethyl acetate (3 × 1 L). The aqueous phase was transferred into a 5-L beaker equipped with a stirring bar, stirred, cooled to 0 °C, and adjusted to pH 1-2 with 6 M aqueous HCl solution. A white solid precipitated and the suspension was stirred at 0 °C for 2 hours. The white precipitate was then collected in a Büchner funnel under suction filtration, washed with H2O (3 × 500 mL) and dried in a drying oven at 80 °C to constant mass to produce 169 g of 1-benzoylpiperidine-3-carboxylic acid. Product appearance: white solid Yield: 93% Melting point: 171–175 °C TLC: 0.53 (CH3CN-CH3OH-H2O = 3 / 1 / 1, v / v / v) IR (ATR): 2865, 2563, 1709, 1584, 1564, 1464, 1277, 1212, 929, 861, 791, 729, 632, 572 cm-1.1H NMR (400 MHz, DMSO-d6): δ = 1.45–1.69 (3 H, m), 1.96–2.00 (1 H, m), 2.42–2.46 (1 H, m), 3.00–3.17 (2 H, m), 3.45–3.63 (1 H, m), 4.13–4.43 (1 H, m), 7.37–7.52 (5 H, m), 12.44 (1 H, bs).13C NMR (100 MHz, DMSO-d6): δ = 23.63, 24.40, 26.79, 40.63, 41.54, 43.41, 47.29, 48.72, 48.72, 126.64, 128.33, 129.32, 136.24, 169.14, 174.24 HRMS (ESI+): m / z calculated for C13H16NO3 [M+H]+: 234.1130; found: 231.1129. STEP 2: Synthesis of 1-benzoyl-N-(2-methoxyethyl)piperidine-3-carboxamide To a 4-L round-bottomed flask equipped with a stirring bar, 1-benzoylpiperidine-3- carboxylic acid (169 g, 0.725 mol, 1.0 equiv.) was added followed by CH2Cl2 (3 L). The resulting suspension was stirred and cooled to 0 °C. (CH3CH2)3N (202 mL, 1.449 mol, 2.0 equiv.) was added dropwise. After all the solid dissolved, O-(benzotriazol-1-yl)- N,N,N’,N’-tetramethyluronium tetrafluoroborate (TBTU) (233 g, 0.725 mol, 1.0 equiv.) was added in two equal portions. After 1 hour, 2-methoxyethylamine (125 mL, 1.449 mol, 2.0 equiv.) was added dropwise via a dropping funnel. The reaction mixture was allowed to warm to room temperature, stirred for 24 h and then divided up into 3 portions of approximately 1 L. Every portion was transferred into a 2-L separating funnel, washed with H2O (2 × 1 L), 0.5 M aqueous HCl solution (2 × 1 L) followed by saturated aqueous NaHCO3 solution (2 × 1 L), and dried over anhydrous Na2SO4. All dried organic phases were pooled and evaporated, to produce 186 g of 1-benzoyl-N- (2-methoxyethyl)piperidine-3-carboxamide. Product appearance: colorless oil Yield: 86 % HRMS (ESI+): m / z calculated for C16H23N2O3 [M+H]+: 291.1709; found: 291.1707. STEP 3: Synthesis of N-((1-benzylpiperidin-3-yl)methyl)-2-methoxyethan-1-amine To a 1-L tree-neck round-bottomed flask equipped with a stirring bar and a reflux condenser, LiAlH4 (14.200 g, 0.374 mol, 3.5 equiv.) was added under an argon atmosphere. Dry THF (ca.450 mL) was added with a double-tipped needle. A solution of 1-benzoyl-N-(2-methoxyethyl)piperidine-3-carboxamide (31 g, 0.107 mol, 1.0 equiv.) in dry THF (ca. 150 mL) was added with a double-tipped needle, and the reaction mixture was refluxed for 3.5 hours. The mixture was then cooled to 0 °C and the excess hydride was decomposed by dropwise addition of H2O (14.2 mL) followed by 15% aqueous NaOH solution (14.2 mL) and then H2O (42.6 mL). The suspension was allowed to warm to room temperature, stirred for 12 h then filtered under suction. The white precipitate was washed thoroughly with THF (5 × 200 mL). This reaction was performed in the same way 5 more times to use up all of compound 1-benzoyl-N- (2-methoxyethyl)piperidine-3-carboxamide. Filtrates of all 6 reactions were pooled together and evaporated to produce 156 g of N-((1-benzylpiperidin-3-yl)methyl)-2- methoxyethan-1-amine. Product appearance: slightly golden liquid Yield: 93 % HRMS (ESI+): m / z calculated for C16H27N2O [M+H]+: 263.2123; found: 263.2128. STEP 4: Synthesis of N-((1-benzylpiperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide To a 2-L round-bottomed flask containing N-((1-benzylpiperidin-3-yl)methyl)-2- methoxyethan-1-amine (156 g, 0.595 mol, 1.0 equiv.), CH2Cl2 (1.5 L) was added. A stirring bar was added to the resulting solution, which was then stirred and cooled to 0 °C. (CH3CH2)3N (83 mL, 0.595 mol, 1.0 equiv.) was added dropwise. After 30 minutes, naphthalene-2-sulfonyl chloride (135 g, 0.595 mol, 1.0 equiv.) was added portion-wise. The reaction mixture was allowed to warm up to room temperature, stirred for 24 hours and divided up into 2 portions of approximately 1 L. Every portion was transferred into a 2-L separating funnel, washed with H2O (1 L), followed by 1 M aqueous NaOH solution (1 L), and dried over anhydrous Na2SO4. Both dried organic phases were pooled together and evaporated, to produce 256 g of N-((1- benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2-sulfonamide as a slightly golden oil. An analytically pure sample was obtained by purifying via flash column chromatography using CH2Cl2-H3COH (30:1, v / v) as the eluent. The rest of N- ((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2-sulfonamide was used in the next step without further purification. Product appearance (analytically pure sample): colorless oil Yield: 95% TLC: Rf = 0.57 (CH2Cl2-CH3OH = 10:1, v / v) IR (ATR): 2928, 2803, 1452, 1333, 1154, 1115, 1072, 983, 883, 859, 817, 732, 699, 650, 615 cm-11H NMR (400 MHz, CDCl3): δ = 0.95–1.04 (1 H, m), 1.54 (1 H, bs), 1.66–1.74 (3 H, m), 1.98 (2 H, bs), 2.76 (2 H, d, J = 30.4 Hz), 3.06–3.16 (2 H, m), 3.21 (3 H, s), 3.30 (2 H, t, J = 6.3 Hz), 3.45–3.48 (4 H, m), 7.23–7.30 (5 H, m), 7.59–7.66 (2 H, m), 7.76 (1 H, dd, J1 = 8.6 Hz, J2 = 1.8 Hz), 7.89–7.97 (3 H, m), 8.38 (1 H, d, J = 1.4 Hz).13C NMR (100 MHz, CDCl3): δ = 24.54, 28.21, 34.82, 48.04, 53.21, 53.89, 57.60, 58.66, 63.44, 71.10, 122.52, 126.85, 127.39, 127.78, 128.05, 128.36, 128.56, 129.07, 129.11, 129.14, 132.07, 134.59, 136.40, 138.25. HRMS (ESI+): m / z calculated for C26H33N2O3S [M+H]+: 453.2212; found: 453.2209. STEP 5: Synthesis of N-((1-benzylpiperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide hydrochloride To a 2-L round-bottomed flask containing N-((1-benzylpiperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide (128 g, 0.282 mol, 1.0 equiv.), CH3OH (640 mL) was added. A stirring bar was added to the resulting solution, which was then stirred, agitated with a stream of argon for 30 min, and cooled to 0 °C.2 M HCl solution in (CH3CH2)2O (156 mL, 0.310 mol, 1.1 equiv.) was added with a double-tipped needle. The reaction mixture was allowed to warm up to room temperature, stirred for 24 hours and evaporated. CH3OH (240 mL) was added to the residue, followed by a stirring bar. The solution was stirred and (CH3CH2)2O (1.5 L) was added slowly. A white solid precipitated and the suspension was stirred at room temperature for 3 hours. The white precipitate was then collected in a Büchner funnel under suction filtration and washed with (CH3CH2)2O (2 × 500 mL). This reaction was performed in the same way with the rest of N-((1-benzylpiperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide (128 g). The white solid from both batches were pooled together and dried in a desiccator in vacuo at room temperature in the presence of crushed NaOH to constant mass to produce 192 g of N-((1- benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2-sulfonamide hydrochloride. The mother liquids from both crystallizations were pooled together and evaporated to produce 84 g of impure N-((1-benzylpiperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide hydrochloride. Product appearance: slightly golden oil Yield: 69% EXAMPLE 2: Synthesis of N-((1-benzylpiperidin-3-yl)methyl)-7-methoxy-N-(2- methoxyethyl)naphthalene-2-sulfonamide STEP 1: Synthesis of N-((1-benzylpiperidin-3-yl)methyl)-7-methoxy-N-(2- methoxyethyl)naphthalene-2-sulfonamide N-((1-benzylpiperidin-3-yl)methyl)-2-methoxyethanamine (0.073 g, 0.278 mmol, 1.0 equiv.) was dissolved in CH2Cl2 (15 mL) at room temperature. The solution was stirred and cooled to 0 °C. (CH3CH2)3N (38.8 µL, 0.278 mmol, 1.0 equiv.) was added dropwise, followed by naphthalene-2-sulfonyl chloride (0.071 g, 0.278 mmol, 1.0 equiv.). The reaction mixture was stirred at room temperature for 24 h, transferred into a separating funnel and washed with water (15 mL). The organic phase was dried over anhydrous Na2SO4, and evaporated. The crude product was purified by flash column chromatography using CH2Cl2-MeOH (20:1, v / v) as the eluent to produce 0.124 g of N-((1-benzylpiperidin-3-yl)methyl)-7-methoxy-N-(2-methoxyethyl)naphthalene-2- sulfonamide. Product appearance: orange oil Yield: 92 % TLC: Rf = 0.29 (CH2Cl2-CH3OH = 20:1, v / v) IR (ATR): 2932, 2803, 1626, 1596, 1508, 1454, 1439, 1392, 1336, 1254, 1216, 1155, 1123, 1074, 1027, 987, 954, 916, 885, 842, 744, 717 cm–11H NMR (400 MHz, CDCl3): δ = 0.97–1.06 (1 H, m), 1.50–1.60 (1 H, m), 1.65–1.80 (3 H, m), 1.94–2.04 (2 H, m), 2.71–2.77 (1 H, m), 2.81–2.87 (1 H, m), 3.06–3.18 (2 H, m), 3.24 (3 H, s), 3.32 (2 H, t, J = 6.0 Hz), 3.46–3.52 (4 H, m), 3.95 (3 H, s), 7.24–7.32 (7 H, m), 7.64 (1 H, dd, J1 = 8.6 Hz, J2 = 2.2 Hz), 7.79 (1 H, d, J = 8.8 Hz), 7.86 (1 H, d, J = 8.8 Hz), 8.29 (1 H, d, J = 1.6 Hz).13C NMR (100 MHz, CDCl3): δ = 24.49, 28.16, 34.79, 48.07, 53.27, 53.83, 55.29, 57.55, 58.58, 63.28, 71.11, 106.56, 120.23, 121.50, 126.77, 126.91, 127.98, 128.76, 129.01, 129.14, 130.06, 133.45, 136.69, 138.18, 158.54. HRMS (ESI+): m / z calculated for C27H35N2O4S [M+H]+: 483.2318; found 483.2323. EXAMPLE 3: Synthesis of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N- (2-(dimethylamino)ethyl)-2-naphthamide dihydrochloride STEP 1: Synthesis of 1-benzoyl-N-(2-(dimethylamino)ethyl)piperidine-3-carboxamide To a 500-mL round-bottomed flask equipped with a stirring bar, 1-benzoylpiperidine- 3-carboxylic acid (17.000 g, 72.876 mmol, 1.0 equiv.) and CH2Cl2 (350 mL) were added. (CH3CH2)3N (20.205 mL, 145.754 mmol, 2.0 equiv.) was added dropwise, followed by TBTU (23.400 g, 72.876 mmol, 1.0 equiv.). After 30 min, N,N- dimethylethylenediamine (15.900 mL, 145.754 mmol, 2.0 equiv.) was added dropwise, and the reaction mixture was stirred for 18 h. The reaction mixture was transferred into a 1 L separating funnel and washed with saturated aqueous NaHCO3 (2 × 150 mL), H2O (2 × 150 mL) followed by saturated aqueous NaCl solution (150 mL), and dried over anhydrous Na2SO4 and evaporated, to produce 27.190 g of 1-benzoyl-N-(2- (dimethylamino)ethyl)piperidine-3-carboxamide. Product appearance: golden-yellow oil TLC: Rf = 0.19 (CH2Cl2-CH3OH = 9:1, v / v) HRMS (ESI+): m / z calculated for C17H26N3O2: 304.2025; found: 304.2018. STEP 2: Synthesis of N1-((1-benzylpiperidin-3-yl)methyl)-N2,N2-dimethylethane-1,2- diamine To a 500-mL tree-neck round-bottomed flask equipped with a stirring bar and a reflux condenser, LiAlH4 (4.378 g, 115.359 mmol, 5.0 equiv.) was added under an argon atmosphere. Anhydrous THF (ca.120 mL) was added with a double-tipped needle. A solution of 1-benzoyl-N-(2-(dimethylamino)ethyl)piperidine-3-carboxamide (7.000 g, 23.072 mmol, 1.0 equiv.) in anhydrous THF (ca. 60 mL) was added with a double- tipped needle, and the reaction mixture was refluxed for 3 h. The mixture was then cooled to 0 °C and the excess hydride was decomposed by dropwise addition of H2O (4.378 mL) followed by 15% aqueous NaOH (4.378 mL) and then H2O (13.134 mL). After vigorous stirring for 1 h at room temperature, the mixture was filtered under suction and the white precipitate was washed thoroughly with THF (5 × 60 mL). The combined filtrates were evaporated to produce 4.239 g of N1-((1-benzylpiperidin-3- yl)methyl)-N2,N2-dimethylethane-1,2-diamine. Product appearance: colorless oil TLC: Rf = 0.04 (CH2Cl2-CH3OH = 9:1, v / v + 0.3% (CH3CH2)3N) HRMS (ESI+): m / z calculated for C17H30N3 [M+H]+: 276.2440; found: 276.2439 STEP 3: Synthesis of tert-butyl ((1-benzylpiperidin-3-yl)methyl)(2- (dimethylamino)ethyl)carbamate CH2Cl2 (150 mL) and a stirring bar were added to N1-((1-benzlpiperidin-3-il)metil)- dimetiletan-1,2-diaminom (4.239 g, 15.390 mmol, 1.0 equiv.) in a 250-mL round- bottomed flask. (CH3CH2)3N (2.133 mL, 15.390 mmol, 1.0 equiv.) was added dropwise, and the reaction mixture was cooled to 0 °C. A solution of Boc2O (3.359 g, 15.390 mmol, 1.0 equiv) in CH2Cl2 (20 mL) was added dropwise, and the reaction mixture was allowed to warm to r.t. and then stirred for 18 h. The reaction mixture was transferred into a 500-mL separating funnel and washed with H2O (150 mL), sat. aq NaHCO3 (150 mL), dried over anhydrous Na2SO4, and evaporated. The residue was purified by flash column chromatography using CH2Cl2-CH3OH (9:1, v / v) as the eluent to produce 3.190 g of tert-butyl ((1-benzylpiperidin-3-yl)methyl)(2- (dimethylamino)ethyl)carbamate. Product appearance: slightly golden-yellow oil Yield: 37% (from 1-benzoylpiperidine-3-carboxylic acid) TLC: Rf = 0.42 (CH2Cl2-CH3OH = 9:1, v / v) IR (ATR): 2972, 2933, 2766, 1690, 1455, 1416, 1365, 1247, 1156, 1096, 1068, 1025, 886, 863, 773, 739, 698 cm-11H NMR (400 MHz, CDCl3): δ = 0.85–0.97 (1 H, m), 1.38 (9 H, s), 1.47–1.54 (1 H, m), 1.59–1.66 (3 H, m), 1.81–1.94 (2 H, m), 2.20 (3 H, s), 2.21 (3 H, s), 2.31 (1 H, t, J = 7.4 Hz), 2.38 (1 H, t, J = 7.0 Hz), 2,72 (2 H, bs), 3.02–3.06 (2 H, m), 3.11–3.27 (2 H, m), 3.45 (2 H, s), 7.17–7.26 (5 H, m)13C NMR (100 MHz, CDCl3): δ = 24.81, 28.32, 28.52, 35.61, 36.03, 45.43, 45.57, 45.67, 50.84, 51.25, 53.93, 54.13, 56.81, 57.51, 57.70, 58.06, 63.50, 79.20, 79.28, 126.82, 126.86, 128.06, 129.06, 129.13, 138.09, 138.20, 155.55 HRMS (ESI+): m / z calculated for C22H38N3O2 [M+H]+: 376.2964; found: 376.2972. STEP 4: Synthesis of tert-butyl (2-(dimethylamino)ethyl)(piperidin-3- ylmethyl)carbamate To a 250-mL round-bottomed flask with a stirring bar, tert-butyl ((1-benzylpiperidin-3- yl)methyl)(2-(dimethylamino)ethyl)carbamate (3.190 g, 8.494 mmol, 1.0 equiv.) and CH3OH (70 mL) were added at room temperature. The resulting solution was stirred and agitated with a stream of argon for 15 min. Pd(OH)2 on carbon (20 wt.%) (0.320g, 10% mass of tert-butyl ((1-benzylpiperidin-3-yl)methyl)(2- (dimethylamino)ethyl)carbamate) was added, followed by cyclohexene (8.150 mL, 84.942 mmol, 10.0 equiv.). The resulting suspension was refluxed under an atmosphere of argon for 15 h, then filtered through a pad of Celite, and evaporated, to produce 2.410 g of tert-butyl (2-(dimethylamino)ethyl)(piperidin-3-ylmethyl)carbamate. Product appearance: slightly yellow oil Yield: 97% TLC: Rf = 0.09 (CH2Cl2-CH3OH = 9:1, v / v + 0.3% (CH3CH2)3N) IR (ATR): 3368, 2978, 1671, 1560, 1477, 1405, 1368, 1313, 1251, 1159, 1042, 1015, 649 cm-11H NMR (400 MHz, CDCl3): δ = 0.80–0.94 (1 H, m), 1.02–1.14 (1 H, m), 1.44 (9 H, s), 1.49–1.75 (3 H, m), 1.81–1.91 (1 H, m), 2.23 (6 H, s), 2.36–2.44 (2 H, m), 2.53–2.62 (0.5 H, m), 2.72–2.76 (0.5 H, m), 2.84–3.10 (4 H, m), 3.16–3.31 (2 H, m) HRMS (ESI+): m / z calculated for C15H32N3O2 [M+H]+: 286.2495; found: 286.2487. STEP 5: Synthesis of tert-butyl ((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3- yl)methyl)(2-(dimethylamino)ethyl)carbamate 1H-inden-2(3H)-one, NaBH(OAc)3, AcOH,1,2-dichloroethane, room temperature,under argon, 18 h To a 100-mL round-bottomed flask with a stirring bar, tert-butyl (2- (dimethylamino)ethyl)(piperidin-3-ylmethyl)carbamate (1.920 g, 6.727 mmol, 1.0 equiv.) and 1,2-dichloroethane (50 mL) were added at room temperature. The resulting solution was stirred and agitated with a stream of argon for 15 min. NaBH(OAc)3 (4.277 g, 20.181 mmol, 3.0 equiv.), 1H-inden-2(3H)-one (0.889 g, 6.727 mmol, 1.0 equiv.) and acetic acid (0.577 mL, 10.091 mmol, 1.5 equiv.) were added, and the resulting suspension was stirred under an atmosphere of argon for 18 h. The reaction mixture was opened to the air and quenched with saturated aqueous NaHCO3 solution (50 mL). The mixture was transferred into a 250-mL separating funnel, and CH2Cl2 (50 mL) was added. The separating funnel was shaken vigorously and the organic phase was separated, dried over anhydrous Na2SO4, and evaporated. The residue was purified by flash column chromatography using CH2Cl2-CH3OH (9:1, v / v) as the eluent, to produce 1.870 g tert-butyl ((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3- yl)methyl)(2-(dimethylamino)ethyl)carbamate. Product appearance: slightly golden-yellow oil Yield: 69% (from tert-butyl ((1-benzylpiperidin-3-yl)methyl)(2- (dimethylamino)ethyl)carbamate) TLC: Rf = 0.11 (CH2Cl2-CH3OH = 9:1, v / v) IR (ATR): 2934, 2766, 1690, 1461, 1416, 1390, 1365, 1249, 1156, 1099, 1023, 937, 888, 863, 771, 742 cm-11H NMR (400 MHz, CDCl3): δ = 0.87–1.01 (1 H, m), 1.44 (9 H, s), 1.60–1.83 (4 H, m), 1.92–1.97 (2 H, m), 2.24 (6 H, s), 2.38–2.46 (2 H, m), 2.86–2.96 (4 H, m), 3.01–3.15 (5 H, m), 3.24 (1 H, t, J = 7.2 Hz), 3.30 (1 H, t, J = 7.4 Hz), 7.08–7.14 (4 H, m)13C NMR (100 MHz, CDCl3): δ = 24.80, 24.89, 28.33, 28.68, 35.69, 36.02, 36.81, 37.02, 45.43, 45.55, 45.64, 50.88, 51.45, 52.11, 56.16, 56.43, 56.82, 57.52, 67.19, 79.33, 124.25, 126.27, 141.35, 141.39, 155.51, 155.62 HRMS (ESI+): m / z calculated for C14H40N3O2 [M+H]+: 402.3121; found: 402.3115 STEP 6: Synthesis of N1-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N2,N2- dimethylethane-1,2-diamine tri(2,2,2-trifluoroacetate) To a 50-mL round-bottomed flask equipped with a stirring bar, tert-butyl ((1-(2,3- dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)(2-(dimethylamino)ethyl)carbamate (1.870 g, 4.656 mmol) and CH2Cl2 (20 mL) were added at room temperature. The resulting solution was stirred and TFA (16.045 mL, 209.542 mmol, 46 equiv.) was added dropwise. After 2 h, the reaction mixture was evaporated. The residue was co- evaporated with CH2Cl2 (2 × 30 mL), followed by n-hexane (2 × 30 mL). (CH3CH2)2O (30 mL) was added to the oily residue, and the flask was placed in an ultrasonic bath for 15 min. During this time, the oily residue transformed into a white solid. The flask was removed from the ultrasonic bath and the precipitate was allowed to settle to the bottom of the flask. The supernatant was removed, (CH3CH2)2O (30 mL) was added, and the flask was placed back in the ultrasonic bath for 1 min. The flask was removed from the ultrasonic bath and the precipitate was allowed to settle to the bottom of the flask. The supernatant was removed, (CH3CH2)2O (30 mL) was added again, and this procedure was repeated two more times. After the final supernatant was removed, the solid residue was dried at reduced pressure to produce 3.020 g of N1-((1-(2,3-dihydro- 1H-inden-2-yl)piperidin-3-yl)methyl)-N2,N2-dimethylethane-1,2-diamine tri(2,2,2- trifluoroacetate). Product appearance: white solid Yield: 99% TLC: Rf = 0.08 (CH2Cl2-CH3OH = 9:1, v / v) IR (ATR): 2674, 1664, 1476, 1418, 1174, 1118, 1001, 973, 830, 798, 776, 748, 719 cm-11H NMR (400 MHz, MeOD): δ = 1.36–1.50 (1 H, m), 1.84–1.94 (1 H, m), 2.03–2.11 (2 H, m), 2.39–2.49 (1 H, m), 2.87–3.03 (8 H, m), 3.15 (2 H, bd, J = 6.4 Hz), 3.27 (2 H, dd, J = 16.0, 8.0 Hz), 3.41–3.49 (2 H, m), 3.56–3.65 (5 H, m), 3.87 (1 H, bd, J = 11.6 Hz), 4.10 (1 H, p, J = 8.2 Hz), 7.22–7.29 (4 H, m), NH exchanged HRMS (ESI+): m / z calculated for C19H32N3 [M+H]+: 302.2596; found: 302.2591 STEP 7: Synthesis of (±)-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- (dimethylamino)ethyl)-2-naphthamide To a 250-mL round-bottomed flask with a stirring bar, N1-((1-(2,3-dihydro-1H-inden-2- yl)piperidin-3-yl)methyl)-N2,N2-dimethylethane-1,2-diamine tri(2,2,2-trifluoroacetate) (2.418 g, 3.757 mmol, 1.0 equiv.) and CH2Cl2 (150 mL) were added. The resulting suspension reaction mixture was stirred and cooled to 0 °C. (CH3CH2)3N (2.095 mL, 15.028 mmol, 4.0 equiv.) was added dropwise, followed by 2-naphtoyl chloride (0.716 g, 3.757 mmol, 1.0 equiv.) and the reaction mixture was allowed to warm to room temperature and then stirred for 94 h. The reaction mixture was transferred into a 500- mL separating funnel and washed with H2O (150 mL), saturated aqueous NaHCO3 (150 mL), dried over anhydrous Na2SO4, and evaporated. The residue was purified by flash column chromatography using CH2Cl2-CH3OH-(CH3CH2)3N (120:10:1, v / v / v) as the eluent to produce 1.172 g of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3- yl)methyl)-N-(2-(dimethylamino)ethyl)-2-naphthamide. Product appearance: golden-brown oil Yield: 68% TLC: Rf = 0.14 (CH2Cl2-CH3OH-(CH3CH2)3N = 150:10:1, v / v / v)1H NMR (400 MHz, DMSO-d6, 80 °C): δ = 0.95 (1 H, bs), 1.43–1.51 (1 H, m), 1.59– 1.67 (2 H, m), 1.81 (1 H, bs), 1.98–2.09 (7 H, m), 2.70–2.83 (4 H, m), 2.96–3.21 (6 H, m), 3.35–3.45 (4 H, m), 7.09–7.20 (4 H, m), 7.41–7.43 (1 H, m), 7.55–7.59 (2 H, m), 7.87 (1 H, s), 7.94–7.98 (3 H, m) HRMS (ESI+): m / z calculated for C31H40N3O [M+H]+: 470.3171; found: 470.3180 STEP 8: Synthesis of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- (dimethylamino)ethyl)-2-naphthamide dihydrochloride To a 100 mL round-bottomed flask equipped with a stirring bar, N-((1-(2,3-dihydro-1H- inden-2-yl)piperidin-3-yl)methyl)-N-(2-(dimethylamino)ethyl)-2-naphthamide (1.172 g, 2.572 mmol, 1.0 equiv.) and CH3OH (60 mL) were added at room temperature. The solution was stirred and agitated with a stream of argon for 15 min and then cooled to 0 °C. Then a 2 M solution of HCl in (CH3CH2)2O (5.150 mL, 10.288 mmol, 4.0 equiv.) was added dropwise with a glass syringe. After 15 min, the reaction mixture was allowed to warm to room temperature and stirred for an additional 90 min. After evaporation of the solvent, (CH3CH2)2O (50 mL) was added to the oily residue, and the flask was placed in an ultrasonic bath until the oily residue transformed into a white solid. The flask was removed from the ultrasonic bath, and the precipitate was allowed to settle to the bottom of the flask. The supernatant was removed, (CH3CH2)2O (60 mL) was added, and the flask was placed back in the ultrasonic bath for 1 min. This procedure was repeated three times, and the solid residue was dried at reduced pressure to produce 1.335 g of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3- yl)methyl)-N-(2-(dimethylamino)ethyl)-2-naphthamide dihydrochloride. Product appearance: white solid Yield: 98% EXAMPLE 4: Synthesis of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N- (2-methoxyethyl)-2-naphthamide STEP 1: Synthesis of tert-butyl ((1-benzylpiperidin-3-yl)methyl)(2- methoxyethyl)carbamate 23 2 3 2 2,to room temperature, 20 hTo a 250-mL round-bottomed flask equipped with a stirring bar, 1-benzoylpiperidine- 3-carboxylic acid (2.883 g, 12.359 mmol, 1.0 equiv.) and CH2Cl2 (160 mL) were added. (CH3CH2)3N (3.446 mL, 24.719 mmol, 2.0 equiv.) was added dropwise, followed by TBTU (3.969 g, 12.359 mmol, 1.0 equiv.). After 30 min, 2-methoxyethylamine (2.125 mL, 24.719 mmol, 2.0 equiv.) was added dropwise, and the reaction mixture was stirred for 22 h. The reaction mixture was transferred into a 500-mL separating funnel and washed with H2O (2 × 200 mL), 0.5 M aqueous HCl solution (2 × 200 mL), saturated aqueous NaHCO3 solution (2 × 200 mL) followed by saturated aqueous NaCl solution (200 mL), and dried over anhydrous Na2SO4 and evaporated, to produce 3.756 g of 1-benzoyl-N-(2-methoxyethyl)piperidine-3-carboxamide as a colorless oil. To a 250-mL tree-neck round-bottomed flask equipped with a stirring bar and a reflux condenser, LiAlH4 (2.455 g, 64.679 mmol, 5.0 equiv. calculated according to raw 1- benzoyl-N-(2-methoxyethyl)piperidine-3-carboxamide) was added under an argon atmosphere. Anhydrous THF (ca.120 mL) was added with a double-tipped needle. A solution of 1-benzoyl-N-(2-methoxyethyl)piperidine-3-carboxamide (3.756 g) in anhydrous THF (ca.40 mL) was added with a double-tipped needle, and the reaction mixture was refluxed for 3 h. The mixture was then cooled to 0 °C and the excess hydride was decomposed by dropwise addition of H2O (2.455 mL) followed by 15% aqueous NaOH solution (2.455 mL) and then H2O (7.365 mL). After vigorous stirring for 1 h at room temperature, the mixture was filtered under suction and the white precipitate was washed thoroughly with THF (5 × 60 mL). The combined filtrates were evaporated to produce 2.794 g of N-((1-benzylpiperidin-3-yl)methyl)-2-methoxyethan- 1-amine as a slightly golden liquid. CH2Cl2 (50 mL) and a stirring bar were added to N-((1-benzylpiperidin-3-yl)methyl)-2-methoxyethan-1-amine (2.794 g) in a 100-mL round-bottomed flask. (CH3CH2)3N (1.484 mL, 10.648 mmol, 1.0 equiv. calculated according to N-((1-benzylpiperidin-3-yl)methyl)-2-methoxyethan-1-amine) was added dropwise, and the reaction mixture was cooled to 0 °C. A solution of Boc2O (2.324 g, 10.648 mmol, 1.0 equiv.) in CH2Cl2 (10 mL) was added dropwise, and the reaction mixture was allowed to warm to room temperature. and then stirred for 20 h. The reaction mixture was transferred into a 100-mL separating funnel and washed with H2O (30 mL), dried over anhydrous Na2SO4, and evaporated. The residue was purified by flash column chromatography using CH2Cl2-CH3OH, first 30:1 (v / v) then 10:1 (v / v) as the eluent to produce 3.484 g of tert-butyl ((1-benzylpiperidin-3-yl)methyl)(2- methoxyethyl)carbamate. Product appearance: slightly golden oil Yield: 78 % TLC: Rf = 0.53 (CH2Cl2-CH3OH = 10:1, v / v) IR (ATR): 2973, 2929, 1690, 1412, 1364, 1244, 1158, 1116, 867, 738, 698, 560 cm-11H NMR (400 MHz, CDCl3): δ = 0.88–1.01 (1 H, m), 1.43 (9 H, s), 1.51–1.58 (1 H, m), 1.62–1.72 (3 H, m), 1.88–1.96 (2 H, m), 2.74–2.79 (2 H, m), 3.11–3.15 (2 H, m), 3.24– 3.36 (5 H, m), 3.39–3.49 (4 H, m), 7.21–7.38 (5 H, m).13C NMR (100 MHz, CDCl3): δ = 24.85, 28.32, 28.51, 35.54, 36.02, 47.03, 51.31, 51.89, 53.94, 54.15, 57.72, 58.05, 58.73, 63.54, 70.83, 71.03, 79.21, 79.32, 126.76, 126.80, 126.85, 128.03, 129.05, 129.10, 138.15, 138.35, 155.59 HRMS (ESI+): m / z calculated for C21H35N2O3 [M+H]+: 363.2648; found: 363.2638 STEP 2: Synthesis of tert-butyl (2-methoxyethyl)(piperidin-3-ylmethyl)carbamate To a 250 mL round-bottomed flask with a stirring bar, tert-butyl ((1-benzylpiperidin-3- yl)methyl)(2-methoxyethyl)carbamate (4.137 g, 11.412 mmol, 1.0 equiv.) and CH3OH (160 mL) were added at room temperature. The resulting solution was stirred and agitated with a stream of argon for 30 min. Pd(OH)2 on carbon (20 wt %) (0.828g, 20% mass of tert-butyl ((1-benzylpiperidin-3-yl)methyl)(2-methoxyethyl)carbamate) was added, followed by cyclohexene (11.571 mL, 114.122 mmol, 10.0 equiv.). The resulting suspension was refluxed under an atmosphere of argon for 17 h then filtered through a pad of Celite and evaporated to produce 3.015 g of tert-butyl (2- methoxyethyl)(piperidin-3-ylmethyl)carbamate. Product appearance: colorless oil Yield: 97 % TLC: Rf = 0.44 (CH2Cl2-CH3OH-(CH3CH2)3N = 20:2:1, v / v)1H NMR (400 MHz, CDCl3): δ = 1.00−1.14 (1 H, m), 1.37−1.49 (10 H, m), 1.60−1.80 (5 H, m), 2.25−2.37 (1 H, m), 2.51−2.58 (1 H, m), 2.95−3.00 (2 H, m), 3.13−3.25 (1 H, m), 3.28−3.38 (5 H, m), 3.44−3.52 (2 H, m). HRMS (ESI+): m / z calculated for C14H29N2O3 [M+H]+: 273.2178; found: 273.2174. STEP 3: Synthesis of 1H-inden-2(3H)-one A mixture of pyridinium chlorochromate (6.426 g, 29.811 mmol, 2.0 equiv.) and silica gel (6.426 g, 70−230 mesh) was ground to a fine powder using a pestle and mortar. The light-orange mixture was added to a 250 mL round-bottomed flask with a stirring bar, and CH2Cl2 (80 mL) was added. The resulting orange suspension was stirred at room temperature, and 2-indanol (2.000 g, 14.905 mmol, 1.0 equiv.) was added in small portions. After 130 min, the resulting dark-brown suspension was diluted with (CH3CH2)2O (60 mL) and filtered under suction through a Büchner funnel layered with silica gel (70−230 mesh) and Celite. The dark-brown precipitate was washed thoroughly with (CH3CH2)2O (3 × 20 mL). The combined filtrates were evaporated. The residue was purified by flash column chromatography using (CH3CH2)2O-petroleum ether (1:4, v / v) as the eluent, to produce 1.302 g of 1H-inden-2(3H)-one. Product appearance: slightly yellow solid Yield: 66 % TLC: Rf = 0.46 ((CH3CH2)2O-petroleum ether = 1:1, v / v) Melting point: 51−53 °C1H NMR (400 MHz, CDCl3): δ = 3.58 (4 H, s), 7.21−7.32 (4 H, m). STEP 4: Synthesis of tert-butyl ((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3- yl)methyl)(2-methoxyethyl)carbamate To a 100mL round-bottomed flask with a stirring bar, tert-butyl (2- methoxyethyl)(piperidin-3-ylmethyl)carbamate (1.094 g, 4.016mmol, 1.0 equiv.) and 1,2-dichloroethane (50 mL) were added at room temperature. The resulting solution was stirred and agitated with a stream of argon for 15 min. NaBH(OAc)3 (1.596 g, 7.530 mmol, 1.875 equiv.), 1H-inden-2(3H)-one (0.531 g, 4.018 mmol, 1.0 equiv.), and acetic acid (0.230 mL,4.018 mmol, 1.0 equiv.) were added, and the resulting suspension was stirred under an atmosphere of argon for 72 h. The reaction mixture was opened to the air and quenched with saturated aqueous NaHCO3 solution (50 mL). The mixture was transferred into a 250 mL separating funnel, and CH2Cl2 (20 mL) was added. The separating funnel was shaken vigorously, and the organic phase was separated, dried over anhydrous Na2SO4, and evaporated. The residue was purified by flash column chromatography using CH2Cl2-CH3OH (30:1, v / v) as the eluent to produce 1.292 g of amine tert-butyl ((1-(2,3-dihydro-1H-inden-2-yl)piperidin- 3-yl)methyl)(2-methoxyethyl)carbamate. Product appearance: slightly golden oil Yield: 83 % TLC: Rf = 0.50 (CH2Cl2-CH3OH = 10:1, v / v) IR (NaCl): 2930, 2359, 1692, 1463, 1414, 1365, 1170, 1117, 1010, 867, 743, 526 cm-11H NMR (400 MHz, DMSO-d6, 60°C): δ = 0.90−0.99 (1 H, m), 1.40 (9 H, s), 1.56−1.67 (2 H, m), 1.77−1.88 (2 H, m), 2.01−2.07 (1 H, m), 2.73−2.81 (4 H, m), 2.95−3.02 (2 H, m), 3.10 (2 H, d, J = 6.90 Hz), 3.14−3.15 (3 H, m), 3.25 (3 H, s), 3.28−3.31 (1 H, m), 3.41−3.44 (2 H, m), 7.07−7.12 (2 H, m), 7.15−7.19 (2 H, m).13C NMR (100 MHz, DMSO-d6, 60°C): δ = 24.08, 27.70, 27.85, 35.92, 36.02, 46.29, 51.18,54.95, 57.67, 66.13, 78.09, 123.76, 125.78, 141.04, 141.10, 154.52. HRMS (ESI+): m / z calculated for C23H37N2O3 [M+H]+: 389.2804; found: 389.2798. STEP 5: Synthesis of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-2- methoxyethan-1-amine To a 100 mL round-bottomed flask equipped with a stirring bar, tert-butyl ((1-(2,3- dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)(2-methoxyethyl)carbamate (1.203 g, 3.096mmol, 1.0 equiv.) and CH2Cl2 (50 mL) were added at room temperature. The resulting solution was stirred and TFA (2.371 mL, 30.960 mmol, 10.0 equiv.) was added dropwise. After 22 h, the reaction mixture was evaporated. The residue was co evaporated with CH2Cl2 (2 × 40 mL), followed by n-hexane (2 × 50 mL). (CH3CH2)2O (50 mL) was added to the oily residue, and the flask was placed in an ultrasonic bath for 15 min. During this time, the oily residue transformed into a white solid. The flask was removed from the ultrasonic bath, and the precipitate was allowed to settle to the bottom of the flask. The supernatant was removed, (CH3CH2)2O (30 mL) was added, and the flask was placed back in the ultrasonic bath for 1 min. The flask was removed from the ultrasonic bath, and the precipitate was allowed to settle to the bottom of the flask. The supernatant was removed, (CH3CH2)2O (30 mL) was added again, and this procedure was repeated two more times. After the final supernatant was removed, the solid residue was dried at reduced pressure. Water (15 mL) and a stirring bar were added, and the resulting solution was cooled to 0°C and adjusted to pH 12 with 1M aqueous NaOH. The mixture was transferred into a 50 mL separating funnel, extracted with CH2Cl2 (2 × 30 mL), dried over anhydrous Na2SO4, and evaporated to produce 0.750 g of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-2-methoxyethan-1- amine. Product appearance: slightly brown oil Yield: 84 % TLC: Rf = 0.38 (CH2Cl2-CH3OH-(CH3CH2)3N = 40:10:1, v / v)1H NMR (400 MHz, CDCl3): δ = 0.90−1.00 (1 H, m), 1.57−1.83 (6 H, m), 1.94−2.01 (1H, m), 2.55 (2 H, d, J = 6.40 Hz), 2.77 (2 H, t, J = 5.15 Hz), 2.89−2.98 (3 H, m), 3.03−3.21 (4 H, m), 3.36 (3 H, s), 3.50 (2 H, t, J = 5.14 Hz), 7.11−7.19 (4 H, m). HRMS (ESI+): m / z calculated for C18H29N2O [M+H]+: 289.2280; found: 289.2273. STEP 6: Synthesis of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)-2-naphthamide To a 50 mL round-bottomed flask with a stirring bar, 2-naphthoic acid (0.423g, 2.457 mmol, 1.0 equiv.) and CH2Cl2(20 mL) were added at room temperature. The resulting suspension was stirred, and (CH3CH2)3N (0.685mL, 4.914 mmol, 2.0 equiv.) was added dropwise. The solution was stirred for 5 min before O-(benzotriazol-1-yl)- N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU; 0.789 g, 2.457 mmol, 1.0 equiv.) was added in small portions. After 30 min, a solution of N-((1-(2,3-dihydro-1H- inden-2-yl)piperidin-3-yl)methyl)-2-methoxyethan-1-amine (0.709 g, 2.458 mmol, 1.0 equiv.) in CH2Cl2 (10 mL) was added dropwise, and the reaction mixture was stirred for 19 h. The solvent was evaporated, the residue dissolved in ethyl acetate (60 mL), transferred into a 250 mL separating funnel, and washed with H2O (2 × 50 mL) and then aqueous saturated NaHCO3 solution (50 mL), and dried over anhydrous Na2SO4and evaporated. The residue was purified by flash column chromatography using CH2Cl2-MeOH (20:1, v / v) as the eluent and then precipitated from (CH3CH2)2O to produce 0.391 g of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)-2-naphthamide. Product appearance: white solid Yield: 36 % TLC: Rf = 0.48 (CH2Cl2-CH3OH = 10:1, v / v) Melting point: 54−57 °C IR (KBr): 3546, 3209, 2929, 2144, 1622, 1487, 1418, 1301, 1112, 827, 748, 482 cm-11H NMR (400 MHz, DMSO-d6, 60°C): δ = 0.93 (1 H, bs), 1.44−1.46 (1 H, m), 1.63 (2 H, bs), 1.98 (2 H, bs), 2.67−2.79 (4 H, m), 2.95−3.00 (2 H, m), 3.15 (3 H, s), 3.23 (2 H, bs), 3.44 (6 H, bd), 7.08−7.13 (2 H, m), 7.16−7.21 (2 H, m), 7.40−7.43 (1 H, m), 7.54−7.60 (2 H, m), 7.88 (1 H, s), 7.94−7.98 (3 H, m).13C NMR (100 MHz, DMSO-d6, 60°C): δ = 24.00, 27.85, 34.24, 35.84, 35.90, 51.01, 54.68, 57.75,65.98, 69.28, 123.75, 123.80, 124.06, 125.44, 125.79, 126.25, 126.43,127.27, 127.53, 127.79, 131.93, 132.47, 134.25, 141.14, 141.16, 170.76. HRMS (ESI+): m / z calculated for C29H35N2O2 [M+H]+: 443.2699; found: 443.2696. EXAMPLE 5 Synthesis of N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide STEP1: Synthesis of tert-butyl (1-(4-fluorobenzyl)piperidin-3-yl)methyl(2- methoxyethyl)carbamate Tert-butyl (2-methoxyethyl)(piperidin-3-ylmethyl)carbamate (0.207 g, 0.760 mmol, 1.0 equiv.) was dissolved in 1,2-dichloroethane (20 mL) at room temperature. The solution was stirred and agitated with a stream of argon for 15 min. NaBH(OAc)3 (0.302 g, 1.425 mmol, 1.875 equiv.), 4-fluorobenzaldehide (81.6 µL, 0.760 mmol, 1.0 equiv.) and AcOH (43.5 µL, 0.760 mmol, 1.0 equiv.) were added, and the resulting suspension was stirred under an atmosphere of argon for 24 h. The reaction mixture was opened to the air and quenched with saturated aqueous NaHCO3 solution (40 mL). The mixture was transferred into a separating funnel, and CH2Cl2 (20 mL) was added. The separating funnel was shaken vigorously, and the organic phase was separated, dried over anhydrous Na2SO4, and evaporated. The crude product was purified by flash column chromatography using CH2Cl2-MeOH (25:1, v / v) as the eluent to produce 0.229 g of tert-butyl (1-(4-fluorobenzyl)piperidin-3-yl)methyl(2- methoxyethyl)carbamate. Product appearance: slightly golden oil Yield: 79 % TLC: Rf = 0.36 (CH2Cl2-CH3OH = 10:1, v / v) IR (ATR): 2930, 1689, 1509, 1464, 1413, 1365, 1345, 1220, 1155, 1116, 1090, 1073, 824 cm–11H NMR (400 MHz, CDCl3): δ = 0.87–1.00 (1 H, m), 1.37–1.46 (10 H, m), 1.62–1.74 (3 H, m), 1.86–1.94 (2 H, m), 2.71–2.74 (2 H, m), 3.12 (2 H, bs), 3.24–3.49 (9 H, m), 6.97 (2 H, t, J = 8.60 Hz), 7.23–7.27 (2 H, m).13C NMR (100 MHz, CDCl3): δ = 24.87, 28.36, 28.54, 35.59, 36.08, 47.11, 51.37, 51.94, 53.92, 54.15, 57.64, 58.06, 58.81, 62.74, 70.92, 71.11, 79.32, 79.40, 114.87 (d,2J = 21.3 Hz), 130.48 (d,3J = 8.1 Hz), 134.01 (d,4J = 2.9 Hz), 155.64, 161.88 (d,1J = 244.3 Hz). HRMS (ESI+): m / z calculated for C21H34N2O3F [M+H]+: 381.2553; found 381.2557. STEP 2: Synthesis of N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)-2-methoxyethan-1- amine di(2,2,2-trifluoroacetate) Tert-butyl (1-(4-fluorobenzyl)piperidin-3-yl)methyl(2-methoxyethyl)carbamate (0.183 g, 0.481 mmol, 1.0 equiv.) was dissolved in CH2Cl2 (15 mL) at room temperature. The solution stirred and TFA (0.736 mL, 9.62 mmol, 20.0 equiv.) was added dropwise. After 24 h, the reaction mixture was evaporated. The residue was co-evaporated with Et2O (3 × 15 mL) to produce 0.230 g of N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)-2- methoxyethan-1-amine di(2,2,2-trifluoroacetate). Product appearance: slightly golden oil Yield: 94 % HRMS (ESI+): m / z calculated for C16H26N2OF [M+H]+: 281.2029; found 281.2046. STEP 3: Synthesis of N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)-2-methoxyethan-1-amine di(2,2,2- trifluoroacetate) (0.219 g, 0.431 mmol, 1.0 equiv.) was dissolved in CH2Cl2 (22 mL) at room temperature. The solution was stirred and cooled to 0 °C. (CH3CH2)3N (0.180 mL, 1.293 mmol, 3.0 equiv.) was added dropwise, followed by naphthalene-2-sulfonyl chloride (0.098 g, 0.431 mmol, 1.0 equiv.). The reaction mixture was stirred at room temperature for 24 h, transferred into a separating funnel and washed with water (20 mL). The organic phase was dried over anhydrous Na2SO4, and evaporated. The crude product was purified by flash column chromatography using CH2Cl2-MeOH (28:1, v / v) as the eluent to produce 0.146 g of N-((1-(4-fluorobenzyl)piperidin-3- yl)methyl)-N-(2-methoxyethyl)naphthalene-2-sulfonamide. Product appearance: slightly golden oil Yield: 72 % TLC: Rf = 0.37 (CH2Cl2-CH3OH = 15:1, v / v) IR (ATR): 2930, 1508, 1335, 1219, 1154, 1129, 1116, 1095, 1073, 819, 751, 729, 651 cm–11H NMR (400 MHz, CDCl3): δ = 0.95–1.04 (1 H, m), 1.50–1.53 (1 H, m), 1.64–1.76 (3 H, m), 1.94–1.99 (2 H, m), 2.66–2.80 (2 H, m), 3.11 (2 H, d, J = 7.5 Hz), 3.21 (3 H, s), 3.28–3.33 (2 H, m), 3.41–3.47 (4 H, m), 6.95–7.00 (2 H, m), 7.22–7.25 (2 H, m), 7.59– 7.67 (2 H, m), 7.76 (1 H, dd, J1= 8.7 Hz, J2= 1.9 Hz), 7.89–7.97 (3 H, m), 8.37–8.38 (1 H, m).13C NMR (100 MHz, CDCl3): δ = 24.58, 28.26, 34.87, 48.14, 53.27, 53.86, 57.55, 58.71, 62.53, 71.18, 114.88 (d,2J = 21.3 Hz), 122.56, 127.47, 127.84, 128.42, 128.63, 129.17, 129.20, 130.52 (d,3J = 8.1 Hz), 132.13, 134.03 (d,4J = 2.9 Hz), 134.66, 136.44, 161.89 (d,1J = 245.0 Hz). HRMS (ESI+): m / z calculated for C26H32N2O3SF [M+H]+: 471.2118; found 471.2129. EXAMPLE 6: Synthesis of 3-amino-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3- yl)methyl)-N-(2-methoxyethyl)benzenesulfonamide STEP 1: Synthesis of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-2- methoxyethanamine di(2,2,2-trifluoroacetate) To a 100 mL round-bottomed flask equipped with a stirring bar, tert-butyl ((1-(2,3- dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)(2-methoxyethyl)carbamate (1.203 g, 3.096mmol, 1.0 equiv.) and CH2Cl2 (50 mL) were added at room temperature. The resulting solution was stirred and TFA (2.371 mL, 30.960 mmol, 10.0 equiv.) was added dropwise. After 22 h, the reaction mixture was evaporated. The residue was co evaporated with CH2Cl2 (2 × 40 mL), followed by n-hexane (2 × 50 mL). (CH3CH2)2O (50 mL) was added to the oily residue, and the flask was placed in an ultrasonic bath for 15 min. During this time, the oily residue transformed into a white solid. The flask was removed from the ultrasonic bath, and the precipitate was allowed to settle to the bottom of the flask. The supernatant was removed, (CH3CH2)2O (30 mL) was added, and the flask was placed back in the ultrasonic bath for 1 min. The flask was removed from the ultrasonic bath, and the precipitate was allowed to settle to the bottom of the flask. The supernatant was removed, (CH3CH2)2O (30 mL) was added again, and this procedure was repeated two more times. After the final supernatant was removed, the solid residue was dried at reduced pressure to produce 1.589 g of N-((1-(2,3-dihydro- 1H-inden-2-yl)piperidin-3-yl)methyl)-2-methoxyethanamine di(2,2,2-trifluoroacetate). Product appearance: white solid Yield: 99% STEP 2: Synthesis of N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)-3-nitrobenzenesulfonamide N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-2-methoxyethanamine di(2,2,2-trifluoroacetate) (0.396 g, 0.767 mmol, 1.0 equiv.) was dissolved in CH2Cl2 (50 mL) and cooled to 0 °C. The reaction mixture was stirred and (CH3CH2)3N (0.321 mL, 2.300 mmol, 3.0 equiv.) was added dropwise. After 15 min, 3-nitrobenzenesulfonyl chloride (0.170 g, 0.767 mmol, 1.0 equiv.) was added, and the reaction mixture was allowed to warm up to room temperature, and then stirred for 24 h. The reaction mixture was transferred into a separating funnel, washed with water (50 mL), followed by saturated aqueous NaHCO3 solution (50 mL), dried over anhydrous Na2SO4, and evaporated. The crude product was purified by flash column chromatography using CH2Cl2-CH3OH (20:1, v / v) as the eluent to produce 0.145 g of N-((1-(2,3-dihydro-1H- inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-3-nitrobenzenesulfonamide. Product appearance: orange oil Yield: 40 % TLC: Rf = 0.27 (CH2Cl2-CH3OH = 20:1, v / v) IR (ATR): 2932, 2847, 2812, 1687, 1531, 1459, 1349, 1274, 1198, 1161, 1118, 1070, 993, 928, 878, 766, 745, 710 cm–11H NMR (400 MHz, CDCl3): δ = 0.94–1.05 (1 H, m), 1.54–1.64 (1 H, m), 1.71–1.79 (3 H, m), 1.95–2.09 (2 H, m), 2.82–2.97 (4 H, m), 3.01–3.09 (2 H, m), 3.12–3.16 (2 H, m), 3.17 (3 H, s), 3.32-3.45 (4 H, m), 3.52–3.61 (1 H, m), 7.11–7.18 (4 H, m), 7.69 (1 H, t, J = 8.2 Hz), 8.15 (1 H, ddd, J1= 7.8 Hz, J2= 1.8 Hz, J3= 1.0 Hz), 8.37 (1 H, ddd, J1= 7.8 Hz, J2= 2.2 Hz, J3= 1.2 Hz), 8.67 (1 H, t, J = 1.8 Hz).13C NMR (100 MHz, CDCl3): δ = 24.67, 28.36, 34.36, 36.79, 36.99, 47.36, 52.07, 52.10, 55.75, 58.60, 67.09, 69.91, 122.33, 124.24, 124.27, 126.26, 126.31, 126.64, 130.05, 132.76, 141.36, 141.39, 142.19, 148.04. HRMS (ESI+): m / z calculated for C24H32N3O5S [M+H]+: 474.2063; found: 474.2055. STEP 3: Synthesis of 3-amino-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3- yl)methyl)-N-(2-methoxyethyl)benzenesulfonamide N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-3- nitrobenzenesulfonamide (0.120 g, 0.253 mmol, 1.0 equiv.) was dissolved in a mixture of THF and MeOH (1:1, v / v, 15 mL) and cooled to 0 °C. NiCl2 × 6H2O (0.241 g, 1.014 mmol, 4.0 equiv.) and NaBH4 (0.173 g, 4.573 mmol, 18.0 equiv.) were added, and the resulting suspension was stirred at 0 °C for 2 h, then allowed to warm up to room temperature, and stirred for an additional 16 h. The solvent was evaporated and CH2Cl2 (15 mL) was added to the residue. The precipitated solid was filtered under suction, and washed with CH2Cl2 (3 x 5 mL). Combined filtrates were evaporated, and the crude product purified by flash column chromatography using CH2Cl2-MeOH (20:1, v / v) as the eluent to produce 0.064 g of 3-amino-N-((1-(2,3-dihydro-1H-inden-2- yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)benzenesulfonamide Product appearance: pale brown solid Yield: 57 % TLC: Rf = 0.23 (CH2Cl2-CH3OH = 20:1, v / v) IR (ATR): 3458, 3375, 2931, 2849, 2811, 1627, 1597, 1484, 1450, 1313, 1276, 1151, 1114, 1082, 990, 923, 888, 865, 734 cm–11H NMR (400 MHz, CDCl3): δ = 0.93 (1 H, qd, J1 = 11.8 Hz, J2 = 3.1 Hz), 1.53–1.63 (1 H, m), 1.66–1.74 (3 H, m), 1.91–1.99 (2 H, m), 2.81–2.97 (4 H, m), 3.00–3.15 (5 H, m), 3.24–3.28 (2 H, m), 3.27 (3 H, s), 3.48–3.52 (2 H, m), 4.00 (2 H, bs), 6.77 (1 H, ddd, J1 = 8.0 Hz, J2 = 2.3 Hz, J3 = 1.0 Hz,), 7.08 (1 H, t, J = 1.8 Hz), 7.10–7.17 (5 H, m), 7.22 (1 H, t, J = 7.8 Hz).13C NMR (100 MHz, CDCl3): δ = 24.73, 28.42, 34.82, 36.80, 36.92, 48.06, 52.18, 53.51, 55.89, 58.63, 67.12, 71.18, 112.73, 116.38, 118.49, 124.21, 124.23, 126.18, 126.21, 129.75, 139.91, 141.45, 147.19. HRMS (ESI+): m / z calculated for C24H34N3O3S [M+H]+: 444.2321; found 444.2312. EXAMPLE 7: Synthesis of N-((1-benzylpiperidin-3-yl)methyl)naphthalene-2- sulfonamide STEP 1: Synthesis of 1-benzoylpiperidine-3-carboxamide To a 500-mL round-bottomed flask equipped with a stirring bar, nipecotamide (10.000 g, 78.020 mmol, 1.0 equiv) and THF (260 mL) were added. The suspension was cooled to 0 °C and Et3N (10.875 mL, 78.020 mmol, 1.0 equiv.) was added drop-wise. A solution of benzoyl chloride (9.049 mL, 78.020 mmol, 1.0 equiv.) in THF (30 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature and then stirred for 22 h. The solvent was evaporated, the residue dissolved in H2O (200 mL) and transferred into a 500-mL separating funnel, and washed with CH2Cl2 (3 × 300 mL). The combined organic phases were dried over anhydrous Na2SO4, and evaporated, to produce 17.809 g of 1-benzoylpiperidine-3-carboxamide. Product appearance: slightly yellow solid Yield: 98 % TLC: Rf = 0.58 (CH2Cl2-CH3OH = 5:1, v / v) Melting point: 171–173 °C IR (ATR): 3339, 3139, 2938, 2360, 1670, 1617, 1442, 1271, 1102, 936, 855, 670, 577 cm–11H NMR (400 MHz, CDCl3): δ = 0.93 (1 H, qd, J1 = 11.8 Hz, J2 = 3.1 Hz), 1.53–1.63 (1 H, m), 1.66–1.74 (3 H, m), 1.91–1.99 (2 H, m), 2.81–2.97 (4 H, m), 3.00–3.15 (5 H, m), 3.24–3.28 (2 H, m), 3.27 (3 H, s), 3.48–3.52 (2 H, m), 4.00 (2 H, bs), 6.77 (1 H, ddd, J1 = 8.0 Hz, J2 = 2.3 Hz, J3 = 1.0 Hz,), 7.08 (1 H, t, J = 1.8 Hz), 7.10–7.17 (5 H, m), 7.22 (1 H, t, J = 7.8 Hz).13C NMR (100 MHz, CDCl3): δ = 23.98, 24.80, 27.54, 27.79, 41.59, 41.60, 42.23, 43.99, 47.33, 49.35, 126.61, 128.36, 129.32, 136.20, 169.01, 174.52, 174.64. HRMS (ESI+): m / z calculated for C13H17N2O2 [M+H]+: 233.1290; found: 233.1296. STEP 2: Synthesis of (1-benzylpiperidin-3-yl)methanamine To a 250-mL tree-neck round-bottomed flask equipped with a stirring bar and a reflux condenser, LiAlH4 (2.879 g, 75.863 mmol, 5.0 equiv) was added under an argon atmosphere. Anhydrous THF (ca.150 mL) was added with a double-tipped needle. Then 1-benzoylpiperidine-3-carboxamide (3.524 g, 15.171 mmol, 1.0 equiv) was added in small portions over 1 h, and the reaction mixture was refluxed for 3 h. The mixture was then cooled to 0 °C and the excess hydride was decomposed by dropwise addition of H2O (2.879 mL) followed by 15% aqueous NaOH (2.879 mL) and then H2O (8.637 mL). After vigorous stirring for 1 h at room temperature, the mixture was filtered under suction and the white precipitate was washed thoroughly with THF (5 × 60 mL). The combined filtrates were evaporated, to produce 3.085 g of (1-benzylpiperidin-3- yl)methanamine. Product appearance: slightly golden liquid Yield: 99 % HRMS (ESI+): m / z calculated for C13H21N2 [M+H]+: 205.1705; found 205.1710. STEP 3: Synthesis of N-((1-benzylpiperidin-3-yl)methyl)naphthalene-2-sulfonamide (1-benzylpiperidin-3-yl)methanamine (1.551 g, 7.591 mmol, 1.0 equiv.) was dissolved in CH2Cl2 (60 mL) at room temperature. The solution was stirred and cooled to 0 °C. (CH3CH2)3N (1.058 mL, 7.591 mmol, 1.0 equiv.) was added dropwise, followed by naphthalene-2-sulfonyl chloride (1.721 g, 7.591 mmol, 1.0 equiv.). The reaction mixture was stirred at room temperature for 24 h, transferred into a separating funnel and washed with water (60 mL). The organic phase was dried over anhydrous Na2SO4, and evaporated. The crude product was purified by flash column chromatography using CH2Cl2-MeOH (20:1, v / v) as the eluent to produce 1.288 g of N-((1- benzylpiperidin-3-yl)methyl)naphthalene-2-sulfonamide. Product appearance: white solid Yield: 43 % TLC: Rf = 0.43 (CH2Cl2-CH3OH = 10:1, v / v) IR (ATR): 3062, 2938, 2816, 2769, 1467, 1452, 1328, 1159, 1068, 972, 817, 759, 701, 658, 640, 614 cm–11H NMR (400 MHz, CDCl3): δ = 1.02–1.11 (1 H, m), 1.45–1.55 (1 H, m), 1.60–1.71 (2 H, m), 1.76–1.90 (2 H, m), 2.09–2.15 (1 H, m), 2.52–2.67 (2 H, m), 2.85–2.97 (2 H, m), 3.38–3.46 (2 H, m), 5.20 (1 H, bs), 7.22–7.31 (5 H, m), 7.59–7.67 (2 H, m), 7.78 (1 H, dd, J1= 8.7 Hz, J2= 1.9 Hz), 7.90–7.97 (3 H, m), 8.41 (1 H, t, J = 0.9 Hz).13C NMR (100 MHz, CDCl3): δ = 24.07, 28.06, 35.36, 47.02, 53.78, 57.14, 63.23, 122.23, 126.95, 127.41, 127.80, 128.11, 128.26, 128.60, 129.05, 129.12, 129.38, 132.03, 134.62, 136.64, 137.77. HRMS (ESI+): m / z calculated for C23H27N2O2S [M+H]+: 395.1793; found 395.1784. EXAMPLE 8: Synthesis of N-((1-benzylpiperidin-3-yl)methyl)-N-methylnaphthalene- 2-sulfonamide STEP 1: Synthesis of N-((1-benzylpiperidin-3-yl)methyl)-N-methylnaphthalene-2- sulfonamide N-((1-benzylpiperidin-3-yl)methyl)naphthalene-2-sulfonamide (0.105 g, 0.266 mmol, 1.0 equiv.) was dissolved in CH3CN (10 mL) at room temperature under an atmosphere of argon. Cs2CO3 (0.130 g, 0.399 mmol, 1.5 equiv.), NaI (catalytic amount), and CH3I (69.1 µL, 0.399 mmol, 1.5 equiv.) were added dropwise, and the resulting suspension was stirred at 60 °C for 1 h. The reaction mixture was evaporated, and the residue suspended in CH2Cl2 (15 mL), transferred into a separating funnel, and washed with water (15 mL) followed by saturated aqueous NaHCO3 solution (15 mL), dried over anhydrous Na2SO4, and evaporated. The crude product was purified by flash column chromatography using CH2Cl2-MeOH (24:1, v / v) as the eluent to produce 0.076 g of N-((1-benzylpiperidin-3-yl)methyl)-N-methylnaphthalene-2- sulfonamide. Product appearance: white solid Yield: 70 % TLC: Rf = 0.29 (CH2Cl2-CH3OH = 20:1, v / v) IR (ATR): 2937, 2809, 1453, 1334, 1155, 1132, 1070, 960, 889, 740, 653 cm–11H NMR (400 MHz, CDCl3): δ = 1.00–1.10 (1 H, m), 1.66–1.77 (3 H, m), 1.82–2.04 (3 H, m), 2.74 (4 H, s), 2.84–2.97 (3 H, m), 3.43–3.60 (2 H, m), 7.21–7.25 (1 H, m), 7.30 (4 H, d, J = 4.4 Hz), 7.60–7.67 (2 H, m), 7.74 (1 H, dd, J1= 8.6, J2= 1.8 Hz), 7.90– 7.99 (3 H, m), 8.34–8.35 (1 H, s).13C NMR (100 MHz, CDCl3): δ = 24.48, 28.12, 34.20, 35.23, 53.78, 57.68, 63.38, 122.63, 126.88, 127.43, 127.81, 128.08, 128.53, 128.60, 120.09, 129.17, 132.11, 134.33, 134.63, 138.13. HRMS (ESI+): m / z calculated for C24H29N2O2S [M+H]+409.1950; found 409.1939. EXAMPLE 9: Synthesis of N-((1-benzylpiperidin-4-yl)methyl)-N-(3- methoxypropyl)naphthalene-2-sulfonamide To a 250-mL round-bottomed flask equipped with a stirring bar, isonipecotic acid (10.000 g, 77.425 mmol, 1.0 equiv) was added. THF (80 mL), H2O (80 mL) and K2CO3 (53.504 g, 387.121 mmol, 5.0 equiv) were added, and the mixture was cooled to 0 °C. A solution of benzoyl chloride (8.980 mL, 77.425 mmol, 1.0 equiv) in THF (35 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature and then stirred for 24 h. The reaction mixture was transferred into a 500-mL separating funnel and washed with EtOAc (3 × 150 mL). The aqueous phase was cooled to 0 °C and adjusted to pH 1-2 with 6 M aqueous HCl. The white precipitate was collected in a Büchner funnel under suction filtration, and then dried in vacuo at room temperature in the presence of NaOH, P2O5 and silica gel to constant mass to produce 15.369 g of 1-benzoylpiperidine-4-carboxylic acid. Product appearance: white solid Yield: 85 % TLC: Rf = 0.55 (MeCN-H2O-MeOH = 3:1:1) Melting point: 118–122 °C IR (ATR): 2857, 2359, 1730, 1612, 1447, 1207, 1169, 1014, 791, 731, 707, 628, 577 cm–11H NMR (400 MHz, DMSO-d6): δ = 1.49 (2 H, bs), 1.83 (2 H, bd, J = 45.68 Hz), 2.52– 2.57 (1 H, m), 3.01 (2 H, bd, J = 52.08 Hz), 3.52 (1 H, bs), 4.31 (1 H, bs), 7.34–7.46 (5 H, m), 12.32 (1 H, bs).13C NMR (100 MHz, DMSO-d6): δ = 27.62, 28.24, 40.06, 40.74, 46.38, 126.61, 128.38, 129.31, 136.23, 168.96, 175.48. HRMS (ESI+): m / z calculated for C13H16NO3 [M+H]+: 234.1130; found 231.1125. STEP 2: Synthesis of 1-benzoyl-N-(3-methoxypropyl)piperidine-4-carboxamide To a 250-mL round-bottomed flask equipped with a stirring bar, 1-benzoylpiperidine- 4-carboxylic acid (3.201 g, 13.723 mmol, 1.0 equiv.) and CH2Cl2 (180 mL) were added. Et3N (3.824 mL, 27.446 mmol, 2.0 equiv.) was added dropwise, followed by TBTU (4.406 g, 13.723 mmol, 1.0 equiv.). After 30 min, 2-methoxyethylamine (2.355 mL, 27.446 mmol, 2.0 equiv.) was added drop-wise, and the reaction mixture was stirred for 23 h. The reaction mixture was transferred into a 500-mL separating funnel and washed with H2O (2 × 200 mL), 0.5 M aqueous HCl (2 × 200 mL), saturated aqueous NaHCO3 solution (2 × 200 mL) followed by saturated NaCl solution (200 mL), dried over anhydrous Na2SO4, and evaporated to produce 3.711 g of 1-benzoyl-N-(3- methoxypropyl)piperidine-4-carboxamide. Product appearance: white solid. Yield: 89 % HRMS (ESI+): m / z calculated for C16H23N2O3 [M+H]+: 291.1709; found 291.1703. STEP 3: Synthesis of N-((1-benzylpiperidin-4-yl)methyl)-3-methoxypropan-1-amine To a 250-mL tree-neck round-bottomed flask equipped with a stirring bar and a reflux condenser, LiAlH4 (2.425 g, 63.900 mmol, 5.0 equiv.) was added under an argon atmosphere. Anhydrous THF (ca.120 mL) was added with a double-tipped needle. A solution of 1-benzoyl-N-(3-methoxypropyl)piperidine-4-carboxamide (3.711 g, 12.191 mmol, 1.0 equiv.) in anhydrous THF (ca. 40 mL) was added with a double-tipped needle, and the reaction mixture was refluxed for 2 h. The mixture was then cooled to 0 °C, and the excess hydride was decomposed by dropwise addition of H2O (2.425 mL) followed by 15% aq NaOH (2.425 mL) and then H2O (7.275 mL). After vigorous stirring for 1 h at room temperature, the mixture was filtered under suction and the white precipitate was washed thoroughly with THF (5 × 60 mL). The combined filtrates were evaporated to produce 2.833 g of N-((1-benzylpiperidin-4-yl)methyl)-3- methoxypropan-1-amine. Product appearance: slightly golden liquid. Yield: 84 % HRMS (ESI+): m / z calculated for C16H27N2O [M+H]+: 263.2123; found 263.2120. STEP 4: Synthesis of N-((1-benzylpiperidin-4-yl)methyl)-N-(3- methoxypropyl)naphthalene-2-sulfonamide

[0002] N-((1-benzylpiperidin-4-yl)methyl)-3-methoxypropan-1-amine (0.175 g, 0.633 mmol, 1.0 equiv.) was dissolved in CH2Cl2 (30 mL) at room temperature. The solution was stirred and cooled to 0 °C. (CH3CH2)3N (88.2 µL, 0.633 mmol, 1.0 equiv.) was added dropwise, followed by naphthalene-2-sulfonyl chloride (0.144 g, 0.633 mmol, 1.0 equiv.). The reaction mixture was stirred at room temperature for 24 h, transferred into a separating funnel and washed with water (30 mL). The organic phase was dried over anhydrous Na2SO4, and evaporated. The crude product was purified by flash column chromatography using CH2Cl2-MeOH (32:1, v / v) as the eluent to produce 0.254 g of N-((1-benzylpiperidin-4-yl)methyl)-N-(3-methoxypropyl)naphthalene-2-sulfonamide. Product appearance: white solid Yield: 86 % TLC: Rf = 0.37 (CH2Cl2-CH3OH = 15:1, v / v) IR (ATR): 2921, 2804, 2757, 1452, 1334, 1267, 1196, 1152, 1114, 1073, 990, 880, 858, 735, 699, 651, 615 cm–11H NMR (400 MHz, CDCl3): δ = 1.24–1.33 (2 H, m), 1.64–1.71 (3 H, m), 1.76–1.83 (2 H, m), 1.93–1.99 (2 H, m), 2.89 (2 H, d, J = 10.2 Hz), 3.04 (2 H, d, J = 6.9 Hz), 3.23– 3.26 (5 H, m), 3.34 (2 H, t, J = 6.0 Hz), 3.51 (2 H, s), 7.23–7.31 (5 H, m), 7.59–7.66 (2 H, m), 7.77 (1 H, dd, J1= 8.6 Hz, J2= 1.8 Hz), 7.89–7.98 (3 H, m), 8.37 (1 H, d, J = 1.5 Hz.13C NMR (100 MHz, CDCl3): δ = 29.04, 29.92, 34.81, 46.60, 53.11, 54.63, 58.51, 63.12, 69.73, 122.50, 126.84, 127.38, 127.76, 128.05, 128.34, 128.52, 129.04, 129.08, 129.19, 132.06, 134.55, 136.34, 138.23. HRMS (ESI+): m / z calculated for C27H35N2O3S [M+H]+467.2368; found 467.2359. EXAMPLE 10: Synthesis of N-(2-methoxyethyl)-N-((1-(prop-2-yn-1-yl)piperidin-3- yl)methyl)-2-naphthamide STEP 1: Synthesis of tert-butyl (2-methoxyethyl)((1-(prop-2-yn-1-yl)piperidin-3- yl)methyl)carbamate Tert-butyl (2-methoxyethyl)(piperidin-3-ylmethyl)carbamate (1.030 g, 3.781 mmol, 1.0 equiv.) was dissolved in acetone (60 mL) at room temperature. The solution was stirred and Cs2CO3 (1.232 g, 3.781 mmol, 1.0 equiv.) was added, followed by propargyl bromide (0.408 mL, 3.781 mmol, 80 wt. % solution in toluene, 1.0 equiv.). The reaction mixture was protected from the light by wrapping the flask with aluminum foil. After 24 h, the reaction mixture was evaporated, and ethyl acetate (60 mL) was added to the residue. The suspension was transferred into a separating funnel and extracted with water (60 mL) followed by saturated aqueous NaHCO3 solution (60 mL), dried over anhydrous Na2SO4, and evaporated. The crude product was purified by flash column chromatography using CH2Cl2-CH3OH (20:1, v / v) as the eluent to produce 0.819 g of tert-butyl (2-methoxyethyl)((1-(prop-2-yn-1-yl)piperidin-3- yl)methyl)carbamate. Product appearance: slightly golden oil Yield: 70 % TLC: Rf = 0.44 (CH2Cl2-CH3OH = 10:1, v / v) IR (ATR): 3247, 2974, 2930, 2808, 1686, 1412, 1365, 1158, 1115, 866, 772, 656, 618 cm–11H NMR (400 MHz, CDCl3): δ = 0.87–1.00 (1 H, m), 1.43–1.48 (9 H, m), 1.61–1.76 (3 H, m), 1.97–2.05 (2 H, m), 2.21–2.26 (2 H, m), 2.81–2.83 (2 H, m), 3.09–3.22 (2 H, m), 3.30–3.52 (9 H, m).13C NMR (100 MHz, CDCl3): δ = 24.33, 24.72, 27.60, 27.98, 28.38, 35.37, 35.98, 47.21, 51.17, 51.96, 52.56, 56.29, 56.55, 58.84, 71.05, 71.19, 79.58, 79.64, 155.67. HRMS (ESI+): m / z calculated for C17H31N2O3 [M+H]+: 311.2335; found: 311.2326. STEP 2: Synthesis of 2-methoxy-N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)ethanamine dihydrochloride Tert-butyl 2-methoxyethyl((1-(prop-2-ynyl)piperidin-3-yl)methyl)carbamate (0.819 g, 2.638 mmol, 1.0 equiv.) was dissolved in CH3OH (40 mL) at room temperature. The solution was stirred and agitated with a stream of argon for 15 min, and then cooled to 0 °C. A solution 2 M HCl in (CH3CH2)2O (13.191 mL, 26.380 mmol, 10 equiv.) was added dropwise, then allowed to warm to room temperature, and stirred for 24 h. The reaction mixture was evaporated, and (CH3CH2)2O (50 mL) was added to the oily residue obtained. The flask was placed in an ultrasonic bath for 15 min. During this time, the oily residue transformed into a solid. The flask was removed from the ultrasonic bath and the precipitate was allowed to settle to the bottom of the flask. The supernatant was removed, (CH3CH2)2O (50 mL) was added, and the flask was placed back in the ultrasonic bath for 1 min. The flask was removed from the ultrasonic bath and the precipitate was allowed to settle to the bottom of the flask. The supernatant was removed, (CH3CH2)2O (50 mL) was added again, and this procedure was repeated two more times. After the final supernatant was removed, the solid residue was dried at reduced pressure to produce 0.701 g of crude 2-methoxy-N-((1-(prop-2- ynyl)piperidin-3-yl)methyl)ethanamine dihydrochloride. Product appearance: white solid Yield: 94 % HRMS (ESI+): m / z calculated for C12H23N2O [M+H]+: 211.1810; found: 211.1814 STEP 3: Synthesis of N-(2-methoxyethyl)-N-((1-(prop-2-yn-1-yl)piperidin-3-yl)methyl)- 2-naphthamide 2-methoxy-N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)ethanamine dihydrochloride (0.106 g, 0.374 mmol, 1.0 equiv.) was dissolved in CH2Cl2 and cooled to 0 °C. The reaction mixture was stirred and (CH3CH2)3N (0.157 mL, 1.123 mmol, 3.0 equiv.) was added dropwise. After 15 min, 2-naphthoyl chloride (0.072 g, 0.374 mmol, 1.0 equiv.) was added, and the reaction mixture was allowed to warm up to room temperature, and then stirred for 24 h. The reaction mixture was transferred into a separating funnel, washed with water, followed by saturated aqueous NaHCO3 solution, dried over anhydrous Na2SO4, and evaporated. The crude product was purified by flash column chromatography using CH2Cl2-CH3OH (20:1, v / v) as the eluent to produce 0.130 g of N-(2-methoxyethyl)-N-((1-(prop-2-yn-1-yl)piperidin-3-yl)methyl)-2-naphthamide. Product appearance: colorless oil Yield: 96 % TLC: Rf = 0.43 (CH2Cl2-CH3OH = 10:1, v / v) IR (ATR): 3235, 2929, 2808, 1622, 1476, 1421, 1288, 1194, 1115, 1071, 900, 823, 757 cm–11H NMR (400 MHz, CDCl3): δ = 0.83 (1 H, dd, J1 = 217.1 Hz, J2 = 7.0 Hz), 1.47–2.93 (9 H, m), 3.18–3.54 (7 H, m), 3.51 (2 H, d, J = 28.2 Hz), 3.69–3.78 (2 H, m), 7.43–7.49 (3 H, m), 7.80–7.84 (4 H, m).13C NMR (100 MHz, CDCl3): δ = 24.49, 24.68, 27.57, 27.93, 35.00, 35.12, 44.75, 47.07, 47.26, 47.56, 48.03, 48.66, 52.18, 52.70, 53.80, 55.78, 56.47, 58.70, 70.21, 70.44, 73.10, 78.39, 78.86, 124.18, 126.12, 126.23, 126.39, 126.65, 127.59, 128.08, 128.12, 132.48, 133.16, 134.02, 172.08, 172.33. HRMS (ESI+): m / z calculated for C23H29N2O2 [M+H]+: 365.2229; found: 365.2221. Example 11: Biological evaluation In vivo activity 1. Procedures 1.1. Forced Swim Test The Forced Swim Test (FST) is a well-described behavioural test in rodents, commonly used to detect the antidepressant activity of novel compounds. In particular, it has demonstrated predictive validity of antidepressant activity in humans. In this test, rodents are forced to swim in a water-filled cylinder for 5 minutes, without the possibility to escape, inducing behavioural despair (observed as depressive-like behaviour), which is alleviated by antidepressants. Depressive-like behaviour is characterised by increased immobility (i.e., just sufficient movement to keep the head above the water), when compared to swimming (escape-directed) or climbing (struggling) behaviour. Whereas the original FST described by Porsolt (Porsolt RD, Le Pichon M, Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature.1977 Apr 21;266(5604):730-2.) is an acute test, with an induction swim to induce learned behavioural despair, followed by three drug administrations within 24 hours and finally the test swim, the FST has been refined (inducing deeper water depth and distinguishing immobility, swimming and struggling behaviour) to detect the antidepressant activity of serotonin reuptake inhibitors (Lucki I. The forced swimming test as a model for core and component behavioral effects of antidepressant drugs. Behav Pharmacol. 1997 Nov;8(6-7):523-32). Furthermore, the Flinder’s Sensitive Line rat is a genetic model of depression, displaying spontaneous depressive-like behaviour in the FST without the conditioning swim, and also displaying antidepressive-like activity following chronic and not acute administration of the antidepressant, similar to antidepressant activity in humans. Thus the FST using FSL rats represent a better translational model of human antidepressant activity. We followed a previously published method (Liebenberg, N; Harvey, BH.; Brand, L; Brink, CB. Antidepressant-like properties of phosphodiesterase type 5 inhibitors and cholinergic dependency in a genetic rat model of depression. Behavioural Pharmacology 21(5-6): p 540-547,). Briefly, animals were placed in an inescapable Perspex® cylinder (18 cm (diameter) x 60 cm (height)), filled with 30 cm of water at a temperature of 25 ± 1 °C for 7 min. During the first minute of the test, air might be trapped in the animal’s fur, increasing buoyancy. Also, by the start of the 7thminute, some animals might have reached full immobility. Consequently, the middle 5 minutes of the test were analysed and scored, using randomly assigned codes, to ensure unbiased scoring. The tests were scored with respect to immobility, swimming, and struggling behaviours. 1.2. Study Layout and Treatment Groups Rats were randomized into three groups (n = 12 each), receiving via oral gavage for 15 days either vehicle control (code: FSL CTL), the 20 mg / kg / day escitalopram (an SSRI antidepressant) as a positive control (code: ESC 20), or 30 mg / kg twice daily of the test compound, N-((1-Benzylpiperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide (code: COMP 30). 1.3. Weight assessment methods Weight monitoring in preclinical studies is crucial for evaluating the effects of treatment on general health in animal models. The following describes our method for assessing weight and food consumption in rats over the treatment period: Rats were housed in groups of three per cage to ensure consistent measurement of food intake and body weight. Both the body weight of the rats and the amount of food consumed were recorded daily from the first day (Day 1) to the last day (Day 16) of the treatment period. The measurements were taken at the same time each day to maintain consistency. To assess the impact of the treatment on weight and food consumption, we calculated the percentage increase in these parameters from the start to the end of the treatment period. The following equation was used to calculate the percentage increase: Equation 1: Percentage Increase Formula 100 Where: TotalEND is the total body weight or total food consumption at the end of the treatment period (day 16), and TotalSTART is the total body weight or total food consumption at the start of the treatment period (day 1). 2. Results 2.1. Forced Swim Test 2.1.1. Immobility During the FST, increased immobility behaviour can be associated with increased depression-like behaviour interpreted as behaviour akin to despair in human depression. Data from the three groups can be found in Error! Reference source not found.. Significantly increased immobility, or pronounced depressive-like behaviour, was evident in FSL vs control Flinders Resistant Line rats, confirming the validity of the model. Subsequent studies compared drug treatment in FSL vs vehicle treated FSL rats. Results from Brown-Forsythe Welch ANOVA tests with Dunnett’s T3 multiple comparisons test, with individual variances computed for each comparison, provided the following regarding immobility behaviour. Firstly, there were statistically significant differences between the control group and ESC 20 (t21.52 = 5.66, p < 0.0001), with the ESC 20 group presenting with significantly decreased immobility behaviour (antidepressant-like activity). Secondly, there were also statistically significant differences between the control group and COMP 30, with the latter presenting with significantly decreased immobility behaviour (t22 = 7.423, p < 0.0001) and hence antidepressant-like activity. No statistically significant differences were found between the ESC 20 and COMP 30 groups (t21.5 = 2.307, p = 0.0888). As mentioned earlier, increased time spent immobile in the FST relates to depression- like behaviour and Error! Reference source not found. represents immobility data obtained during the FST. When comparing the results from the control group with the ESC 20 group, the antidepressant-like effects of the positive control are confirmed by a lower recorded time spent immobile, translating to decreased depression-like behaviour. Similar antidepressant-like activity is also seen for the COMP 30 group. This confirms the claim that the novel compound (COMP 30) possesses significant antidepressant-like characteristics. 2.1.2. Swimming and Struggling During the FST, decreased swimming and struggling behaviour can be associated with depression-like behaviour, relating to deficits in coping strategies in human depression. Data from the three groups can be found in Figures 2A and 2B. There were statistically significant differences between the control group and ESC 20 (positive control group) regarding swimming (t21.17 = 5.743, p < 0.0001) and struggling (t21.97 = 5.502, p < 0.0001), with the ESC 20 group presenting with significantly increased swimming and struggling behaviour. Secondly, there were also statistically significant differences between the control group and COMP 30, with the latter presenting with significantly increased swimming (t17.75 = 6.293, p < 0.0001) and struggling (t19.03 = 5.158, p = 0.0002) behaviour. Increased time spent swimming and struggling in the FST, as seen in Figures 2A and 2B, relate to antidepressant-like activity. Again, when comparing the results from the control group with the positive control group (ESC 20), the antidepressant-like effects of the positive control group are confirmed by a higher recorded times spent swimming and struggling, translating to decreased depression-like behaviour. Similar antidepressant-like activity is also seen for the COMP 30 group. This confirms that the test compound N-((1-Benzylpiperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide (COMP 30) possesses significant escape- directed behaviours associated with antidepressant-like activity. 2.1.3. Weight assessment results FSL rats treated with ESC 20 demonstrated significant weight gain compared to the FSL CTL rats (p = 0.02). This indicates a possible undesirable side effect commonly associated with antidepressant treatments, even selective serotonin reuptake inhibitors (SSRI) i.e., weight gain (Alonso‐Pedrero et al., 2019, Harvey and Bouwer, 2000, Bouwer and Harvey, 1996). In contrast, rats treated with COMP 30 did not exhibit significant weight gain compared to the FSL CTL rats; rather, rats receiving COMP 30 gained significantly less weight versus the FSL CTL rats (p < 0.0001) and versus ESC 20 (p < 0.0001). This result suggests that COMP 30 may have therapeutic potential in mitigating antidepressant-associated weight gain, and possibly depression-related weight gain. Analysis of food consumption during the treatment period (Figure 3B)showed that ESC 20 rats consumed significantly more food than the FSL CTL group (p = 0.02). Similarly, COMP 30 rats had a significantly higher food intake compared to FSL CTL rats (p < 0.0001) and versus ESC 20 (p = 0.04). This suggests that COMP 30 could be effective in addressing depression-related loss of appetite.

Claims

Claims 1. A compound of formula (I)wherein the piperidine ring is 1,3- or 1,4-disubstituted and the substituents are:wherein R1is: H, CH3, CH3CH2, CH3(CH2)2, (CH3)2CH, OH, OCH3, OCH2CH3, O(CH2)2CH3, OCF3, F, Cl, Br, CF3, NH2, NO2, N(CH3)2, N(CH3CH2)2, NHCH3, NHCH2CH3, COOH, COOCH3, COOCH2CH3, CONH2, CONHCH3, CONHCH2CH3, COCH3, or COCH2CH3; Y is: H, CH3, CH2CH3, (CH2)2CH3, (CH2)3CH3, (CH2)2OCH3, (CH2)3OCH3, (CH2)2NHCH3, (CH2)2N(CH3)2, or (CH2)3N(CH3)2; X is: CO, or SO2wherein R2is: H, CH3, CH3CH2, CH3(CH2)2, (CH3)2CH, OH, OCH3, OCH2CH3, O(CH2)2CH3, OCF3, F, Cl, Br, CF3, NH2, NO2, N(CH3)2, N(CH3CH2)2, NHCH3, NHCH2CH3, COOH, COOCH3, COOCH2CH3, CONH2, CONHCH3, CONHCH2CH3, COCH3, or COCH2CH3; optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof,for use in the treatment of depression or a disease or disorder with depressive pathology, such as an eating disorder related to depression, or for use in the treatment of an appetite related side effect of an antidepressant or antipsychotic.

2. Compound for use according to claim 1, whereinpreferably.

3. Compound for use according to claim 1 or 2, wherein R1is H.

4. Compound for use according to claim 1, wherein5. Compound for use according to claim 1, wherein W is.

6. Compound for use according to any one of claims 1 to 5, wherein Y is (CH2)2OCH3.

7. Compound for use according to any one of claims 1 to 5, wherein Y is (CH2)2NHCH3.

8. Compound for use according to any one of claims 1 to 7, wherein X is CO.

9. Compound for use according to any one of claims 1 to 7, wherein X is SO2.

10. Compound for use according to any one of claims 1 to 9, wherein Z is.

11. Compound for use according to any one of claims 1 to 9, wherein Z is.

12. Compound for use according to any one of claims 1 to 11, wherein R2is H.

3. Compound for use according to claim 1, wherein the compound is selected from the group consisting of : N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2- sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-3- nitrobenzenesulfonamide; 3-amino-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)benzenesulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-4- methylbenzenesulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-4- nitrobenzenesulfonamide; 4-amino-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)benzenesulfonamide; N-(4-(N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)sulfamoyl)phenyl)acetamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)benzenesulfonamide; methyl 2-(N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)sulfamoyl)benzoate; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-4-methoxy-N-(2- methoxyethyl)benzenesulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-4-fluoro-N-(2- methoxyethyl)benzenesulfonamide; 2-(N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)sulfamoyl)-N-methylbenzamide;N-(3-(N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)sulfamoyl)phenyl)acetamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-1- sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-7-methoxy-N-(2-methoxyethyl)naphthalene- 2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-7-(cyanomethoxy)-N-(3- methoxypropyl)naphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(3-methoxypropyl)naphthalene-2- sulfonamide; N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2- sulfonamide; N-((1-(3-fluorobenzyl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2- sulfonamide; N-((1-(4-cyanobenzyl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene- 2-sulfonamide; N-((1-(3-cyanobenzyl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene- 2-sulfonamide; N-((1-(4-(dimethylamino)benzyl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-N-methylnaphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-N-ethylnaphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-N-propylnaphthalene-2-sulfonamide; N-((1-benzylpiperidin-3-yl)methyl)-N-butylnaphthalene-2-sulfonamide; N-((1-(3-methylbenzyl)piperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-(2-chloro-4-fluorobenzyl)piperidin-3-yl)methyl)naphthalene-2- sulfonamide; N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)naphthalene-2-sulfonamide;N-((1-(4-cyanobenzyl)piperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-(4-fluorobenzyl)piperidin-3-yl)methyl)-N-methylnaphthalene-2- sulfonamide; N-((1-benzylpiperidin-4-yl)methyl)-N-(3-methoxypropyl)naphthalene-2- sulfonamide; N-((1-benzylpiperidin-4-yl)methyl)-N-(2-methoxyethyl)naphthalene-2- sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-4-yl)methyl)-N-(2- methoxyethyl)naphthalene-2-sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-4-yl)methyl)-N-(3- methoxypropyl)naphthalene-2-sulfonamide; N-((1-benzylpiperidin-4-yl)methyl)naphthalene-2-sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- (dimethylamino)ethyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)-1-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-6-methoxy-N-(2- methoxyethyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-3- methylbenzamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-6-methoxy-2- naphthamide; 6-bromo-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-2- naphthamide; 6-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methylcarbamoyl)naphthalen-2- yl acetate N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)-1-naphthamide;N-((1-benzylpiperidin-3-yl)methyl)-6-methoxy-N-(2-methoxyethyl)-2- naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-6-bromo-N-(2-methoxyethyl)-2- naphthamide; 6-(((1-benzylpiperidin-3-yl)methyl)(2-methoxyethyl)carbamoyl)naphthalen-2-yl acetate; N-((1-benzylpiperidin-3-yl)methyl)-N-(3-methoxypropyl)-2-naphthamide; N-((1-benzylpiperidin-4-yl)methyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-4-yl)methyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-4-yl)methyl)-N-(2-methoxyethyl)-2- naphthamide; N-((1-benzylpiperidin-4-yl)methyl)-N-(3-methoxypropyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-4-yl)methyl)-N-(3-methoxypropyl)-2- naphthamide; 6-bromo-N-((1-(2,3-dihydro-1H-inden-2-yl)-piperidin-3-yl)methyl)-N-(2- methoxyethyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-1-naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)-2-naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-2-naphthamide; N-((1-(2,3-Dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(3-methoxypropyl)- 2-naphthamide; N-((1-Benzylpiperidin-4-yl)methyl)-N-(2-methoxyethyl)-2-naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(2-(dimethylamino)-ethyl)-2-naphthamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(3-(dimethylamino)-propyl)-2- naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(3- (dimethylamino)propyl)-2-naphthamide;N-((1-(2,3-Dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- (methylamino)ethyl)-2-naphthamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2-methoxyethyl)-2- naphthamide; N-(2-methoxyethyl)-N-((1-(prop-2-yn-1-yl)piperidin-3-yl)methyl)-2- naphthamide; N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)-2-naphthamide; N-(3-methoxypropyl)-N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)-2-naphthamide; N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)-2-naphthamide; N-(2-methoxyethyl)-N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)-2-naphthamide; N-(3-methoxypropyl)-N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)-2-naphthamide; N-(2-methoxyethyl)-N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)naphthalene-2- sulfonamide; N-(3-methoxypropyl)-N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)naphthalene-2- sulfonamide; N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)naphthalene-2- sulfonamide; N-(2-methoxyethyl)-N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)naphthalene-2- sulfonamide; N-(3-methoxypropyl)-N-((1-(prop-2-ynyl)piperidin-3-yl)methyl)naphthalene-2- sulfonamide; and N-((1-(prop-2-ynyl)piperidin-4-yl)methyl)naphthalene-2- sulfonamide; optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

14. Compound for use according to claim 1, wherein the compound is N-((1- benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)naphthalene-2-sulfonamide, optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

5. A compound for use in the treatment of depression or a disease or disorder with depressive pathology, such as an eating disorder related to depression, or for use in the treatment of an appetite related side effect of an antidepressant or antipsychotic, wherein the compound is selected from the group consisting of: N-((1-(pyridin-4-ylmethyl)piperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-((2-methylthiazol-4-yl)methyl)piperidin-3-yl)methyl)naphthalene-2- sulfonamide; N-((1-(benzo[d]thiazol-2-yl)piperidin-3-yl)methyl)naphthalene-2-sulfonamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)quinoline-6-carboxamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)furan-2-carboxamide; (E)-N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)-3-(4-methoxyphenyl)acrylamide; N-{[1-(2,3-dihydro-1H-inden-2-yl)-3-piperidinyl]methyl}-N-(2-methoxyethyl)-2- thiophenecarboxamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)furan-3-carboxamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)isonicotinamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)-N-(2- methoxyethyl)nicotinamide; N-{[1-(2,3-dihydro-1H-inden-2-yl)-3-piperidinyl]methyl}-5-methoxy-N-(2- methoxyethyl)-2-furamide; N-((1-(2,3-dihydro-1H-inden-2-yl)piperidin-3-yl)methyl)quinoline-6- carboxamide; N-((1-benzylpiperidin-3-yl)methyl)-N-(2-methoxyethyl)quinoline-6- carboxamide;N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-2-naphthamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-1-naphthamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-6-bromo-2-naphthamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-6-methoxy-2-naphthamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)quinoline-6-carboxamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-4-hydroxy-7- (trifluoromethyl)quinoline-3-carboxamide; N-((1-(benzo[d]oxazol-2-yl)piperidin-3-yl)methyl)-6-hydroxy-2-naphthamide; N-((1-(benzo[d]thiazol-2-yl)piperidin-3-yl)methyl)-2-naphthamide; N-((1-(benzo[d]thiazol-2-yl)piperidin-3-yl)methyl)-6-bromo-2-naphthamide; N-((1-(benzo[d]thiazol-2-yl)piperidin-3-yl)methyl)-6-methoxy-2-naphthamide; N-((1-(benzo[d]thiazol-2-yl)piperidin-3-yl)methyl)quinoline-6-carboxamide; and N-((1-(benzo[d]thiazol-2-ylmethyl)piperidin-3-yl)methyl)-2-naphthamide; optionally in the form of a stereoisomer, such as enantiomer, or a mixture of at least two stereoisomers, such as at least two enantiomers, or a pharmaceutically acceptable salt, hydrate or solvate thereof.

16. The compound for use according to any one of claims 1 to 15, for use in the treatment of depression.

17. The compound for use according to any one of claims 1 to 15, for use in the treatment of a disease or disorder with depressive pathology.

18. The compound for use according to any one of claims 1 to 15, for use in the treatment of an eating disorder related to depression.

19. The compound for use according to any one of claims 1 to 15, for use in the treatment of an appetite related side effect of an antidepressant or antipsychotic.

20. Pharmaceutical composition for use in the treatment of depression or a disease or disorder with depressive pathology, such as an eating disorder related to depression, or for use in the treatment of an appetite related side effect of an antidepressant or antipsychotic, comprising a therapeuticallyeffective amount of a compound of formula (I) as defined in any one of claims 1 to 15, and a pharmaceutically acceptable carrier, adjuvant, or vehicle.

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