Combination of an alpha2-adrenergic receptor subtype C (alpha-2C) antagonist and a norepinephrine reuptake inhibitor for the treatment of sleep apnea

Abstract

The present invention relates to the combination of a noradrenaline reuptake inhibitor and an alpha2-adrenergic receptor subtype C (alpha-2C) antagonist, in particular a substituted heterocyclic carboxamide of formula (I), for the treatment and / or prevention of sleep-related breathing disorders, preferably obstructive sleep apnea and central sleep apnea and snoring.

Description

[Technical field]

[0001] The present invention relates to a combination of an alpha2-adrenergic receptor subtype C (alpha-2C) antagonist, in particular a substituted heterocyclic carboxamide of formula (I), with a norepinephrine (noradrenaline) reuptake inhibitor for the treatment and / or prevention of sleep-related breathing disorders, preferably obstructive and central sleep apnea and snoring. [Background technology]

[0002] 2. Background of the Invention Obstructive sleep apnea (OSA) is a sleep-related respiratory disorder characterized by repeated episodes of upper airway obstruction. When breathing, the patency of the upper airway is ensured by the interplay of two opposing forces. The dilator action of the upper airway musculature opposes the negative intraluminal pressure that constricts the lumen. The active contraction of the diaphragm and other accessory respiratory muscles generates a negative pressure in the airway and thus constitutes the driving force of breathing. The stability of the upper airway is substantially determined by the coordination and contraction properties of the dilator muscles of the upper airway.

[0003] Upper airway collapse in OSA is thought to occur at sleep onset due to a decrease in the activity of several upper airway dilator muscles, resulting in an inability to maintain the anatomically vulnerable airway open. However, several upper airway dilator muscles, including the genioglossus, the most important of the upper airway dilator muscles and innervated by the hypoglossal nerve, can increase their activity during sleep in response to respiratory stimuli, potentially countering some of these changes at sleep onset. OSA patients were observed to have apnea intervals with only 25-40% higher genioglossus activity compared to sleep periods with frequent obstructive apneas (Jordan AS, White DP, Lo YL, et al. Airway dilator muscle activity and lung volume during stable breathing in obstructive sleep apnea. Sleep 2009, 32(3):361-8). Noradrenaline is one of the most potent neuromodulators of hypoglossal motoneuron activity (Horner RL Neuromodulation of hypoglossal motoneurons during sleep. Respir Physiol Neurobiol 2008, 164(1-2):179-196). It is believed that a reduction in noradrenergic drive leads to a sleep-dependent reduction in hypoglossal motoneuron excitability, which in turn leads to a reduction in upper airway dilator muscle activity, particularly genioglossus muscle activity.

[0004] Alpha 2C-adrenergic receptors regulate the release of noradrenaline from central noradrenergic neurons, and they are autoreceptors involved in the presynaptic feedback inhibition of noradrenaline (Hein Let et al., Two functionally distinct alpha 2-adrenergic receptors regulate sympathetic neurotransmission Nature 1999, 402(6758):181-184). Increasing the activity of hypoglossal motoneurons via alpha 2c-adrenergic receptor antagonism can stabilize the upper airways and protect them from collapse and obstruction. In addition, snoring can also be suppressed by mechanisms of stabilization of the upper airways (Horner RL Neuromodulation of hypoglossal motoneurons during sleep.Respir Physiol Neurobiol 2008, 164 (1-2):179-196).

[0005] In simple snoring, there is no obstruction of the upper airway. The narrowing of the upper airway increases the inhalation and exhalation flow rates. This, together with the relaxed muscles, causes the soft tissues of the mouth and throat to flap in the airflow. This slight vibration produces the typical snoring sound.

[0006] Obstructive snoring (upper airway resistance syndrome, severe snoring, hypopnea syndrome) is caused by recurrent partial obstruction of the upper airway during sleep. This leads to an increase in airway resistance and therefore an increase in the work of breathing with significant intrathoracic pressure fluctuations. The development of negative intrathoracic pressure during inspiration can thereby reach values ​​that result from complete airway obstruction in OSA. The pathophysiological effects on the heart, circulation and sleep quality are the same as in obstructive sleep apnea. The etiology is probably the same as in OSA. Obstructive snoring is often a precursor to OSA (Hollandt JH et al., Upper airway resistance syndrome (UARS)-obstructive snoring. HNO 2000, 48(8):628-634).

[0007] Central sleep apnea (CSA) occurs as a result of impaired brain function or respiratory control. CSA is characterized by a lack of drive to breathe during sleep, resulting in repeated periods of insufficient or absent ventilation and impaired gas exchange. CSA has several manifestations. These include highly induced periodic breathing, idiopathic CSA (ICSA), opiate-induced central apnea, obesity hypoventilation syndrome (OHS), and Cheyne-Stokes respiration (CSB). Although the exact triggering mechanisms involved in the various types of CSA can be quite different, an unstable ventilatory drive during sleep is the main underlying feature (Eckert DJ et al., Central sleep apnea:Pathophysiology and treatment. Chest 2007, 131(2):595-607).

[0008] US2018 / 0235934A1 describes a method for treating disorders such as obstructive sleep apnea using an agent for promoting hypoglossal motoneuron excitability. As an agent for promoting hypoglossal motoneuron excitability, a disinhibitor and / or stimulator of central noradrenergic neurons is described. In some embodiments, the disinhibitor of central noradrenergic neurons is an alpha2-adrenergic receptor antagonist such as yohimbine or an alpha2-adrenergic receptor subtype A (alpha-2A) antagonist or an alpha2-adrenergic receptor subtype C (alpha-2C) antagonist. The alpha2-adrenergic receptor antagonist is selected from the group consisting of atipamezole, MK-912, RS-79948, RX821002, [3H]2-methoxy-idazoxan and JP-1302.

[0009] Alpha 2C-adrenergic receptors belong to the family of G-protein-coupled receptors. Besides the different alpha 1-adrenergic receptors, there are three different alpha 2-adrenergic receptor subtypes (alpha 2A, alpha 2B and alpha 2C). They are involved in mediating several diverse physiological effects in various tissues upon stimulation by endogenous catecholamines (epinephrine, norepinephrine) derived either from the synapse or from the blood. Alpha 2-adrenergic receptors play an important physiological role mainly in the cardiovascular and central nervous systems. Alpha 2A- and alpha 2C-adrenergic receptors are the main autoreceptors involved in the presynaptic feedback inhibition of noradrenaline in the central nervous system. The potency and affinity of noradrenaline at alpha 2C-adrenergic receptors is higher than that for alpha 2A-adrenergic receptors. Alpha2C-adrenergic receptors inhibit noradrenaline release when endogenous concentrations of noradrenaline are low, whereas alpha2A-adrenergic receptors inhibit noradrenaline release when endogenous concentrations of noradrenaline are high. (Uys MM et al., Therapeutic Potential of Selectively Targeting α2C-Adrenoceptor in Cognition, Depression, and Schizophrenia-New Developments and Future Perspective. Frontiers in Psychiatry 2017 Aug 14;8:144. doi:10.3389 / fpsyt.2017.00144.eCollection 2017).

[0010] An additional mechanism for increasing the level of endogenous noradrenaline is through inhibition of the norepinephrine transporter (NET). The norepinephrine transporter is located in the plasma membrane of noradrenergic neurons, where it regulates the uptake of norepinephrine (NE) released into the synapse. Reuptake of NE by NET proteins is the primary mechanism by which the biological effects of NE at the synapse are terminated. Norepinephrine reuptake inhibitors increase the synaptic availability of NE (Zhou J Norepinephrine transporter inhibitors and their therapeutic potential.Drugs Future 2004 Dec;29(12):1235-1244).

[0011] Noradrenaline reuptake inhibitors have been described in the literature as drugs for the treatment of depression and attention-deficit / hyperactivity disorder (Kent JMSNaRIs, NaSSAs, and NaRIs: new agents for the treatment of depression. Lancet 2000 Mar 11;355(9207):911-8, Kratochvil CJ, et al. Atomoxetine: a selective noradrenaline reuptake inhibitor for the treatment of attention-deficit / hyperactivity disorder. Expert Opin Pharmacother 2003 Jul;4(7):1165-74) WO2018 / 200775 and WO2019 / 152475 describe compositions for the treatment of conditions associated with pharyngeal airway muscle collapse while a subject is in a non-fully conscious state, such as sleep apnea and snoring, comprising the administration of a norepinephrine reuptake inhibitor (NRI) and a muscarinic receptor antagonist. Arylpiperazines as α2-adrenergic receptor subtype C (alpha-2C) antagonists, and their preparation and use as medicines are known from WO03 / 082866A1, where it is disclosed that the compounds are useful for treating disorders such as stress-propagated disorders, Parkinson's disease, depression, schizophrenia, attention deficit hyperactivity disorder, post-traumatic stress disorder, obsessive-compulsive disorder, Tourette's syndrome, blepharospasm or other focal dystonia, temporal lobe epilepsy with psychosis, drug-induced psychosis, Huntington's disease, disorders caused by fluctuations in the level of sex hormones, panic disorder, Alzheimer's disease or mild cognitive impairment.Nothing is disclosed about the use of these compounds in the treatment of sleep-related breathing disorders, preferably obstructive and central sleep apnea and snoring.

[0012] WO2021089683 describes substituted heterocyclic carboxamides as inhibitors of the adrenergic receptor ADRA2C and their use for the treatment and / or prevention of diseases, in particular for the treatment and / or prevention of dyspnea, including sleep-induced dyspnea such as central and obstructive sleep apnea, snoring, etc. [Prior art documents] [Patent documents]

[0013] [Patent Document 1] US Patent Application Publication No. 2018 / 0235934 [Patent Document 2] International Publication No. 2018 / 200775 [Patent Document 3] International Publication No. 2019 / 152475 [Patent Document 4] WO 03 / 082866 [Patent Document 5] International Publication No. 2021089683 [Non-patent literature]

[0014] [Non-Patent Document 1] Jordan AS, White DP, Lo YL et al. Sleep 2009, 32(3):361-8 [Non-Patent Document 2] Horner RLRespir Physiol Neurobiol 2008, 164(1-2):179-196 [Non-Patent Document 3] Hein Let et al., Nature 1999, 402(6758):181-184 [Non-Patent Document 4] Horner RLRespir Physiol Neurobiol 2008, 164(1-2):179-196 [Non-Patent Document 5] Hollandt JH et al., HNO 2000, 48(8):628-634 [Non-Patent Document 6] Eckert DJ et al., Chest 2007, 131(2):595-607 [Non-Patent Document 7] Uys MM et al., Frontiers in Psychiatry 2017 Aug 14;8:144.doi:10.3389 / fpsyt.2017.00144.eCollection 2017 [Non-Patent Document 8] Zhou J, Drugs Future 2004 Dec;29(12):1235-1244 [Non-Patent Document 9] Kent JM, Lancet 2000 Mar 11;355(9207):911-8 [Non-Patent Document 10] Kratochvil CJ et al. Expert Opin Pharmacother 2003 Jul;4(7):1165-74 Summary of the Invention [Problem to be solved by the invention]

[0015] The current gold standard treatment for OSA patients is continuous positive airway pressure (CPAP). The positive airflow pressure generated by the airflow turbine pump splint opens the upper airway and reverses all potential causes of pharyngeal collapse, thereby preventing hypopnea, apnea, and sleep fragmentation. Unfortunately, up to 50% of OSA patients cannot tolerate CPAP for long periods of time (M. Kohler, D. Smith, V. Tippett et al., Thorax 2010 65(9):829-32:Predictors of long-term compliance with continuous positive airway press). Thus, there remains a need to find effective therapeutic agents for the treatment and / or prevention of sleep-related breathing disorders, such as obstructive sleep apnea. Thus, the object of the present invention is to provide an effective therapeutic agent for the treatment and / or prevention of sleep-related breathing disorders, such as obstructive sleep apnea, central sleep apnea, and snoring.

[0016] Surprisingly, it has now been found that the combination of α2-adrenergic receptor subtype C (alpha-2C) antagonist and noradrenaline reuptake inhibitor synergistically inhibits the collapsibility of upper airway, and is therefore suitable for the manufacture of a medicament for use in the treatment and / or prevention of sleep-related breathing disorders, preferably obstructive and central sleep apnea and snoring.It has been found that the synergistic effect of the combination of α2-adrenergic receptor subtype C (alpha-2C) antagonist and noradrenaline reuptake inhibitor allows the dose of each treatment to be reduced. [Means for solving the problem]

[0017] The present invention relates to a compound represented by formula (I) [ka]

[0018] [During the ceremony, X represents S, N or O; Y represents N, S or O; where, when X represents S, Y represents N; wherein when X represents O, Y represents N; Z represents CR4, O or NR4; wherein when X represents N and Y represents N, then Z represents O; where X represents S, Z represents CR4 or NR4, R1 represents a 5- or 6-membered heteroaryl, phenyl; wherein the 5-6-membered heteroaryl may be substituted with 1-2 substituents independently selected from the group consisting of (C1-C4)-alkyl, (C1-C4)-alkoxy, halogen; wherein (C1-C4)-alkyl may be up to trisubstituted by halogen, wherein (C1-C4)-alkoxy is optionally up to trisubstituted by halogen; wherein phenyl may be substituted with 1-2 substituents independently selected from the group consisting of (C1-C4)-alkyl, (C3-C5)-cycloalkyl, (C1-C4)-alkoxy, cyano, hydroxy, halogen; wherein (C1-C4)-alkyl may be up to trisubstituted by halogen, R2 represents hydrogen, (C1-C4)-alkyl; wherein (C1-C4)-alkyl may be up to trisubstituted by halogen, or together with the carbon atom to which R2 is attached, forms a (C3-C4)-cycloalkyl ring, R3 represents hydrogen, (C1-C4)-alkyl, wherein (C1-C4)-alkyl may be up to trisubstituted by halogen, R4 in CR4 represents hydrogen, (C1-C4)-alkyl, (C3-C4)-cycloalkyl, phenyl, halogen; wherein (C1-C4)-alkyl may be up to trisubstituted by halogen, and phenyl may be optionally substituted by halogen, In NR4, hydrogen, (C1-C4)-alkyl, (C3-C4)-cycloalkyl, phenyl; wherein (C1-C4)-alkyl may be up to trisubstituted by halogen, and phenyl may be optionally substituted by halogen, R5 represents hydrogen, (C1-C4)-alkyl, (C1-C4)-alkoxy or halogen; R6 represents a group of formula a), b), c), d), e), f) or g); [ka]

[0019] where *** indicates a bond to the adjacent piperidine ring, R7 represents hydrogen, (C1-C4)-alkyl, (C3-C4)-cycloalkyl, (C1-C4)-alkoxy, (C3-C4)-cycloalkoxy, phenyl; wherein (C1-C4)-alkyl may be substituted by (C3-C4)-cycloalkyl, (C1-C4)-alkoxy, (C3-C4)-cycloalkoxy or up to trisubstituted by halogen, wherein (C1-C4)-alkoxy is optionally substituted by (C3-C4)-cycloalkyl and up to trisubstituted by halogen, where (C3-C4)-cycloalkyl may be optionally substituted by mono-, di- or trifluoromethyl and up to disubstituted by halogen, wherein (C1-C4)-alkoxy is optionally substituted by (C3-C4)-cycloalkyl and up to trisubstituted by halogen, wherein (C3-C4)-cycloalkyl may be mono- or disubstituted by halogen, wherein (C3-C4)-cycloalkoxy is optionally up to disubstituted by halogen, where R8 represents hydrogen or fluorine; where R9 represents hydrogen, (C1-C4)-alkyl, (C1-C4)-alkoxy, halogen; wherein (C1-C4)-alkyl may be substituted by (C1-C4)-alkoxy, n represents 0 or 1; m represents 0, 1 or 2; p represents 0, 1 or 2, and q represents 0, 1 or 2. Compound and Combination noradrenaline reuptake inhibitors, and salts, solvates and solvates of the salts thereof. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] The compounds of the present invention are compounds of formula (I) and the salts, solvates and solvates of the salts thereof, compounds of the formulae encompassed by formula (I) and described below and the salts, solvates and solvates of the salts thereof, if the compounds are not already salts, solvates and solvates of the salts thereof, compounds of the formulae encompassed by formula (I) and described below and the salts, solvates and solvates of the salts thereof, and compounds encompassed by formula (I) and listed below as examples and the salts, solvates and solvates of the salts thereof.

[0021] Compounds of the invention also include the N-oxides and S-oxides of compounds of formula (I) and their salts, solvates and solvates of the salts.

[0022] Preferred in the present invention salt are physiologically acceptable salts of the compounds according to the invention. Also included are salts which are not themselves suitable for pharmaceutical applications but which can be used, for example, for the isolation, purification or storage of the compounds of the invention.

[0023] Suitable pharma- ceutically acceptable salts of the compounds of the invention are, for example, acid addition salts of compounds of the invention having a sufficiently basic nitrogen atom in the chain or ring, for example, acid addition salts with inorganic acids or "mineral acids", such as, for example, hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, sulfamic acid, bisulfuric acid, phosphoric acid or nitric acid, for example, formic acid, acetic acid, acetoacetic acid, pyruvic acid, trifluoroacetic acid, propionic acid, butyric acid, hexanoic acid, heptanoic acid, undecanoic acid, lauric acid, benzoic acid, salicylic acid, 2-(4-hydroxybenzoyl)benzoic acid, camphoric acid, cinnamic acid, cyclopentanepropionic acid, digluconic acid, 3-hydroxy-2-naphthoic acid, nicotinic acid, pamoic acid. , pectinic acid, 3-phenylpropionic acid, pivalic acid, 2-hydroxyethanesulfonic acid, itaconic acid, trifluoromethanesulfonic acid, dodecylsulfuric acid, ethanesulfonic acid, benzenesulfonic acid, paratoluenesulfonic acid, methanesulfonic acid, 2-naphthalenesulfonic acid, naphthalenedisulfonic acid, camphorsulfonic acid, citric acid, tartaric acid, stearic acid, lactic acid, oxalic acid, malonic acid, succinic acid, malic acid, adipic acid, alginic acid, maleic acid, fumaric acid, D-gluconic acid, mandelic acid, ascorbic acid, glucoheptanoic acid, glycerophosphoric acid, aspartic acid, sulfosalicylic acid or thiocyanic acid.

[0024] Further suitable pharma- ceutically acceptable salts of the sufficiently acidic compounds of the present invention include alkali metal salts, e.g., sodium or potassium salts, alkaline earth metal salts, e.g., calcium, magnesium or strontium salts, or aluminum salts or zinc salts, or ammonium salts derived from ammonia or primary, secondary or tertiary amines having 1 to 20 carbon atoms, e.g., ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylaminoethanol, diethylaminoethanol, tris(hydroxymethyl)aminomethane, procaine, dibenzylamine, N-methyl ... and ammonium salts derived from ammonium ion having 1 to 20 carbon atoms, such as tetramethylammonium, tetraethylammonium, tetra(n-propyl)ammonium, tetra(n-butyl)ammonium, N-benzyl-N,N,N-trimethylammonium, choline or benzalkonium.

[0025] Those skilled in the art will further recognize that acid addition salts of the claimed compounds can be prepared via any of a number of known methods by reacting the compounds with a suitable inorganic or organic acid. Alternatively, alkali metal and alkaline earth metal salts of acidic compounds of the invention are prepared by reacting the compounds of the invention with a suitable base via a variety of known methods.

[0026] The present invention includes all possible salts of the compounds of the present invention, either as a single salt or as any mixture of said salts in any ratio.

[0027] When compounds are referred to herein as salt forms with the corresponding bases or acids, particularly in the experimental sections for the synthesis of intermediates and examples of the present invention, the exact stoichiometry of said salt forms obtained by the respective preparation and / or purification processes is in most cases unknown. Unless otherwise specified, the term "hydrochloride", "trifluoroacetate", "sodium salt", or "xHCl", "xCF3COOH", "xNa + Suffixes of chemical names or structural formulae relating to salts, such as ", for example, refer to the salt form, without specifying the stoichiometry of this salt. This also applies if the synthetic intermediates or example compounds or salts thereof are obtained as solvates, for example hydrates, by the described preparation and / or purification process.

[0028] solvate are described in the present invention as forms of the compounds according to the invention which form complexes in the solid or liquid state by coordination with solvent molecules. Hydrates are specific forms of solvates in which the coordination is with water. Preferred solvates in the present invention are hydrates.

[0029] Depending on their structure, the compounds of the present invention can exist in different stereoisomeric forms, i.e. in the form of configurational isomers or, if appropriate, as conformational isomers (enantiomers and / or diastereomers, including the case of atropisomers). The present invention therefore encompasses enantiomers and diastereomers, as well as their respective mixtures. From such mixtures of enantiomers and / or diastereomers, it is possible to isolate stereoisomerically homogeneous components in known manner. For this purpose, it is preferred to use chromatographic methods, in particular HPLC chromatography on achiral or chiral separation phases. In the case of carboxylic acids as intermediates or final products, it is also possible to separate via diastereomeric salts using chiral amine bases.

[0030] In the present invention, the term "enantiomerically pure" is understood to mean the effect that the compound in question is present in an enantiomeric excess of more than 95%, preferably more than 98%, with respect to the absolute configuration of the chiral center. The enantiomeric excess ee is calculated here by evaluating the HPLC analytical chromatogram on a chiral phase using the following formula:

number

[0031] Where compounds of the invention can exist in tautomeric forms, the present invention encompasses all tautomeric forms.

[0032] The present invention also encompasses all suitable isotopic variants of the compounds of the present invention. An isotopic variant of a compound according to the present invention is understood here to mean a compound in which at least one atom in the compound according to the present invention has been replaced by another atom of the same atomic number, but with an atomic mass different from the atomic mass that is usually or predominantly found in nature ("unnatural fraction"). The expression "unnatural fraction" is understood to mean a fraction of such an isotope that is higher than its natural frequency. For the natural frequency of an isotope used in this context, see "Isotopic Compositions of Elements 1997", Pure Appl.Chem., 70(1), 217-235, 1998. Examples of isotopes that can be incorporated into the compounds according to the present invention are hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine and iodine, e.g. 2 H (deuterium), 3 H (tritium), 13 C. 14 C. 15 N, 17 O. 18 O. 32 P, 33 P, 33 S, 34 S, 35 S, 36 S, 18 F, 36Cl, 82 Br, 123 I, 124 I, 129 I and 131 I isotopes. Certain isotopic variants of the compounds according to the invention, particularly those incorporating one or more radioisotopes, may be advantageous, for example, in studying the mechanism of action or distribution of the active ingredient in the body; 3 H or 14 Compounds labeled with C isotopes are suitable for this purpose.In addition, the incorporation of isotopes, such as deuterium, can result in certain therapeutic benefits, such as increased half-life in the body or reduced active doses required, as a result of the greater metabolic stability of the compound; therefore, such modifications of the compounds of the present invention may also possibly constitute preferred embodiments of the present invention.For the treatment and / or prevention of disorders specified herein, the isotopic variants of the compounds of general formula (I) preferably contain deuterium ("deuterium-containing compounds of general formula (I)"). 3 H or 14 Isotopic variations of compounds of general formula (I), into which one or more radioactive isotopes, such as C, are useful, for example, in drug and / or substrate tissue distribution studies. These isotopes are particularly preferred because of their easy incorporation and detectability. 18 F or 11 Positron-emitting isotopes, such as C, can be incorporated into the compounds of general formula (I). These isotopic variants of the compounds of general formula (I) are suitable for use in in vivo imaging applications. 13 C-containing compounds can be used within the scope of preclinical or clinical research in mass spectrometry analysis (HJ Leis et al., Curr. Org. Chem., 1998, 2, 131). Isotopic variants of the compounds of the present invention can be prepared by commonly used methods known to those skilled in the art, for example, by using the corresponding isotopic modifications of the respective reagents and / or starting compounds, by the methods and procedures described in the examples further below.

[0033] Isotopic variants of compounds of general formula (I) can generally be prepared by processes known to those skilled in the art, as described in the schemes and / or examples described herein, by replacing the reagent with an isotopic variant of the reagent, preferably a deuterium-containing reagent. Depending on the desired deuteration site, in some cases, deuterium from DO can be incorporated directly into the compound or into a reagent that can be used to synthesize such a compound (Esaki et al., Tetrahedron, 2006, 62, 10954; Esaki et al., Chem.Eur.J., 2007, 13, 4052). Photochemical deuteration and tritiation methods have also been described (YYLoh et al., Science 10.1126 / science.aap9674(2017)). Another useful reagent for incorporating deuterium into a molecule is deuterium gas. A rapid route for incorporating deuterium is the catalytic deuteration of olefinic bonds (HJ Leis et al., Curr. Org. Chem., 1998, 2, 131; JR Morandi et al., J. Org. Chem., 1969, 34(6), 1889) and acetylenic bonds (NHK Han, J. Am. Chem. Soc., 1952, 74(12), 3018; S. Chandrasekhar et al., Tetrahedron, 2011, 52, 3865). It is also possible to use metal catalysts (i.e., Pd, Pt and Rh) in the presence of deuterium gas for the direct exchange of hydrogen with deuterium in hydrocarbons containing functional groups (JG Atkinson et al., U.S. Pat. No. 3,966,781). A variety of deuteration reagents and synthesis units are commercially available from companies such as, for example, C / D / N Isotopes, Quebec, Canada; Cambridge Isotope Laboratories Inc., Andover, Mass., USA; and CombiPhos Catalysts, Inc., Princeton, NJ, USA.Further information on the prior art regarding deuterium-hydrogen exchange can be found, for example, in Hanzlik et al., J. Org. Chem., 1990, 55, 3992-3997; RP Hanzlik et al., Biochem. Biophys. Res. Commun., 1989, 160, 844; PJ Reider et al., J. Org. Chem., 1987, 52, 3326-3334; M. Jarman et al., Carcinogenesis, 1993, 16(4), 683-688; J. Atzrodt et al., Angew. Chem., Int. Ed. 2007, 46, 7744; K. Matoishi et al., 2000, J. Chem. Soc. Chem. Commun., 1519-1520; K. Kassahun et al., WO2012 / 112363.

[0034] The term "deuterium-containing compound of general formula (I)" is defined as a compound of general formula (I) in which one or more hydrogen atoms are replaced by one or more deuterium atoms, and the abundance of deuterium at all deuteration positions in the compound of general formula (I) is higher than the natural abundance of deuterium (about 0.015%). More specifically, in the deuterium-containing compound of general formula (I), the abundance of deuterium at all deuteration positions in the compound of general formula (I) is higher than 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80% at this or these positions, preferably higher than 90%, 95%, 96% or 97%, and even more preferably higher than 98% or 99%. It will be apparent that the abundance of deuterium at all deuteration positions is independent of the abundance of deuterium at other deuteration positions.

[0035] The selective incorporation of one or more deuterium atoms into the compounds of general formula (I) can have a significant effect on the physicochemical properties (e.g., acidity [A. Streitwiser et al., J. Am. Chem. Soc., 1963, 85, 2759; CL Perrin et al., J. Am. Chem. Soc., 2007, 129, 4490], basicity [CL Perrin et al., J. Am. Chem. Soc., 2003, 125, 15008; CL Perrin in Advances in Physical Organic Synthesis, 2003, 125, 15008], and the like). Chemistry, 44, 144; CL Perrin et al., J. Am. Chem. Soc., 2005, 127, 9641], lipophilicity [B. Testa et al., Int. J. Pharm., 1984, 19(3), 271]) and / or metabolic profile of the molecule can be altered, causing changes in the ratio of parent compound to metabolites or the amount of metabolites produced. Such changes may provide certain therapeutic benefits and are therefore preferred under certain circumstances. Decreased rates of metabolism and metabolic switching that alter the ratio of metabolites have been reported (DJ Kushner et al., Can. J. Physiol. Pharmacol., 1999, 77, 79; AEMutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). These changes in exposure to parent compounds and metabolites can have important consequences with regard to the pharmacodynamics, tolerability and efficacy of deuterium-containing compounds of general formula (I). In some cases, deuterium substitution reduces or eliminates the production of undesirable or toxic metabolites and promotes the production of desired metabolites (e.g., nevirapine: AM Sharma et al., Chem. Res. Toxicol., 2013, 26, 410; Uetrecht et al., Chemical Research in Toxicology, 2008, 21, 9, 1862; efavirenz: AEMutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). In other cases, the primary effect of deuteration is to decrease the rate of systemic clearance. As a result, the biological half-life of the compound is increased. Potential clinical benefits include the ability to maintain similar systemic exposure with reduced peak levels and increased trough levels.This may result in fewer side effects and enhanced efficacy depending on the pharmacokinetic / pharmacodynamic relationship of the particular compound. Indiplon (AJ Morales et al., Abstract 285, The 15th. th North American Meeting of International Society of Xenobiotics, San Diego, CA, October 12-16, 2008), ML-337 (C. J. Wenthur et al., J. Med. Chem., 2013, 56, 5208), and odanacatib (K. Kassahun et al., WO2012 / 112363) are examples of this deuterium effect. Still other cases have been reported where a decrease in the rate of metabolism leads to increased exposure of the drug without changing the rate of systemic clearance (e.g., rofecoxib: F. Schneider et al., Arzneim. Forsch. Drug. Res., 2006, 56, 295; telaprevir: F. Maltais et al., J. Med. Chem., 2009, 52, 7993). Deuterated drugs that exhibit this effect may reduce dosage requirements (e.g., fewer doses or lower doses to achieve the desired effect) and / or may result in a lower metabolic burden.

[0036] Compounds of general formula (I) may have multiple potential attack sites for metabolism. In order to optimize the above effects on physicochemical properties and metabolic profiles, deuterium-containing compounds of general formula (I) can be selected that have one or more specific patterns of deuterium-hydrogen exchange. In particular, the deuterium atoms of deuterium-containing compounds of general formula (I) are bonded to carbon atoms and / or to, for example, cytochrome P. 450 These are located at those positions in the compound of general formula (I) which are the attack sites of metabolic enzymes such as

[0037] The present invention further encompasses prodrugs of the compounds of the present invention. The term "prodrug" as used herein refers to a compound which may itself be biologically active or inactive, but which is converted to a compound of the present invention while present in the body, for example, by metabolic or hydrolytic pathways.

[0038] For purposes of the present invention, unless otherwise stated, the substituents are defined as follows: In the present invention Alkyl is a straight or branched alkyl group having the specified number of carbon atoms. Examples include: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-methylpropyl, tert-butyl, n-pentyl, isopentyl, 1-ethylpropyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,4-dimethylpentyl, 4,4-dimethylpentyl, and 1,4,4-trimethylpentyl.

[0039] In the present invention Alkoxy is a straight or branched chain alkoxy group having the specified number of carbon atoms specified. Examples include: methoxy, ethoxy, n-propoxy, isopropoxy, 1-methylpropoxy, n-butoxy, isobutoxy, and tert-butoxy.

[0040] In the present invention Cycloalkoxy is a cyclic alkoxy group having the specified number of carbon atoms specified. Examples include: cyclopropoxy or cyclobutoxy.

[0041] In the present invention Cycloalkyl or Carbocycleis a monocyclic, polycyclic or spirocyclic, preferably monocyclic or bicyclic, saturated carbocycle having a total of 3 to 8 ring atoms. Monocyclic saturated carbocycles are synonymously referred to as cycloalkyl. Examples include: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclopentenyl, cyclohexadienyl, cycloheptenyl, cycloheptadienyl, spiro[2.3]hexyl, spiro[2.4]heptyl, spiro[2.5]octyl, bicyclo[1.1.1]pentyl, bicyclo[2.2.1]heptyl, bicyclo[4.1.0]heptyl, bicyclo[2.2.2]octyl, tricyclo[3.3.1.13,7]decyl. Monocyclic cycloalkyls having 3 to 5 carbon atoms are preferred. Examples include: cyclopropyl, cyclobutyl or cyclopentyl.

[0042] In the present invention, the 5- or 6-membered heteroaryl is a monocyclic aromatic heterocycle (heteroaromatic) having a total of 5 or 6 ring atoms, containing up to 3 identical or different ring heteroatoms from a series of N, O and / or S, bonded via a ring carbon atom or optionally via a ring nitrogen atom. Examples include: furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl.

[0043] In general, unless otherwise stated, heteroaryl groups include all possible isomeric forms, such as tautomers and positional isomers with respect to the point of attachment to the remainder of the molecule, such that the term pyridyl includes, as non-limiting examples, 2-pyridyl, 3-pyridyl, and 4-pyridyl, or the term thienyl includes 2-thienyl and 3-thienyl.

[0044] In the present invention halogen includes fluorine, chlorine, bromine and iodine, with chlorine or fluorine being preferred.

[0045] When the group in the compound of the present invention is substituted, the group may be mono- or polysubstituted, unless otherwise specified.In the present invention, all groups that appear more than once are defined independently of each other.When the group in the compound of the present invention is substituted, the group may be mono- or polysubstituted, unless otherwise specified.Substitution with one substituent or two identical or different substituents is preferred.

[0046] In the present invention, the term "treatment" or "treating" includes inhibiting, delaying, checking, mitigating, attenuating, limiting, reducing, suppressing, warding off or curing a disease, condition, disorder, injury or health problem, or the onset, course or progression of such a condition and / or symptoms of such a condition. The term "therapy" is understood herein to be synonymous with the term "treatment."

[0047] The terms "prevention", "prophylaxis" and "preclusion" are used interchangeably herein and refer to the avoidance or reduction of the risk of developing, experiencing, suffering from or having a disease, condition, disorder, injury or health problem, or the onset or progression of such a condition and / or symptoms of such a condition.

[0048] The treatment or prevention of a disease, condition, disorder, injury or health problem may be partial or complete.

[0049] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X represents S or N; Y represents N, S or O; where, when X represents S, Y represents N; Z represents CR4, N or O; wherein when X represents N and Y represents N, then Z represents O; where X represents S, Z represents N or CR4, R1 represents pyridinyl, pyrazolyl, thiazolyl, thienyl, or phenyl; wherein pyridinyl is optionally substituted by 1 to 2 mutually independent substituents selected from the group consisting of (C1-C2)-alkyl, fluorine, chlorine, trifluoromethyl, trifluoromethoxy, wherein pyrazolyl is optionally substituted by 1 to 2 mutually independent substituents selected from the group consisting of (C1-C2)-alkyl, fluorine, chlorine, trifluoromethyl, Here, thiazolyl may be substituted with 1 to 2 mutually independent substituents selected from the group consisting of fluorine and chlorine; Here, thienyl may be substituted with 1 to 2 mutually independent substituents selected from the group consisting of fluorine and chlorine; wherein phenyl may be substituted by 1-2 mutually independent substituents selected from the group: (C1-C2)-alkyl, (C3-C4)-cycloalkyl, methoxy, cyano, hydroxy, fluorine, chlorine, trifluoromethyl; R2 represents hydrogen, (C1-C2)-alkyl, or forms a cyclopropyl ring together with the carbon atom to which R2 is attached, R3 represents hydrogen, (C1-C2)-alkyl; R4 represents hydrogen, (C1-C2)-alkyl, (C3-C4)-cycloalkyl, trifluoromethyl, bromine, chlorine, phenyl; wherein the phenyl may be substituted with halogen; R5 represents hydrogen, (C1-C2)-alkyl, methoxy, fluorine; R6 represents a group of formula a), b), c) or e); [ka]

[0050] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7, independently of one another, represent hydrogen, (C1-C4)-alkyl, (C3-C4)-cycloalkyl, (C1-C2)-alkoxy, (C3-C4)-cycloalkoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, phenyl, where (C1-C4)-alkyl may be optionally substituted by methoxy, n-butoxy, cyclopropyl, cyclobutoxy and up to disubstituted by fluorine, wherein methoxy is optionally substituted with cyclopropyl, cyclobutyl, trifluoromethyl; wherein cyclopropyl is optionally substituted with monofluoromethyl, difluoromethyl, or trifluoromethyl; wherein cyclobutyl may be up to disubstituted with fluorine; wherein n-butoxy may be up to disubstituted with fluorine; wherein (C1-C2)-alkoxy may be substituted by cyclopropyl, cyclobutyl, cyclobutoxy, trifluoromethyl, and wherein cyclopropyl and cyclobutyl are optionally up to disubstituted by fluorine; wherein (C3-C4)-cycloalkoxy is optionally up to disubstituted by fluorine, wherein R8 or R'8 independently represent hydrogen or fluorine; where R9 represents hydrogen, (C1-C4)-alkyl, (C1-C2)-alkoxy, methoxyethyl, fluorine, chlorine; n represents 0 or 1, and m represents 1 or 2; q represents 0 or 2. Compound and a noradrenaline reuptake inhibitor selected from the group of norepinephrine selective reuptake inhibitors including atomoxetine, 4-hydroxyatomoxetine, CP-39,332, daredalin, edivoxetine, esreboxetine, lortalamine, nisoxetine, reboxetine, talopram, talsupram, tandamine, amidabutyric acid, and virox; or A noradrenaline reuptake inhibitor selected from the group of nonselective norepinephrine reuptake inhibitors including Amitriptyline, Amoxapine, Bupropion, Ciclazindol, Desipramine, Desvenlafaxine, Dexmethilphenidate, Diethylpropion, Doxepin, Duloxetine, Imipramine, Levomilnacipran, Manifaxine, Maprotiline, Methylphenidate, Milnacipran, Nefazodone, Nortriptyline, Phendimetrazine, Protryptyline, Radafaxine, Tapentadol, Teniloxazine, and Venlafaxine A combination of and salts, solvates and solvates of the salts thereof.

[0051] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected such that the aromatic five-membered ring has the structural formula h), i), j), k) or (r); [ka]

[0052] where * indicates a bond to the carbonyl group, ** indicates a bond to the nitrogen atom of the adjacent piperidine ring, and R1 represents pyridinyl, pyrazolyl, thiazolyl, thienyl, or phenyl; wherein pyridinyl is optionally substituted by 1 to 2 mutually independent substituents selected from the group consisting of (C1-C2)-alkyl, fluorine, chlorine, trifluoromethyl, trifluoromethoxy, wherein pyrazolyl is optionally substituted by 1 to 2 mutually independent substituents selected from the group consisting of (C1-C2)-alkyl, fluorine, chlorine, trifluoromethyl, wherein thiazolyl is optionally substituted with chlorine; wherein thienyl may be substituted with fluorine; wherein phenyl may be substituted by 1-2 mutually independent substituents selected from the group: (C1-C2)-alkyl, (C3-C4)-cycloalkyl, methoxy, cyano, hydroxy, fluorine, chlorine, trifluoromethyl; R2 represents hydrogen or methyl; or forms a cyclopropyl ring together with the carbon atom to which R2 is attached, R3 represents hydrogen, (C1-C2)-alkyl; R4 represents hydrogen, methyl, ethyl, cyclopropyl, trifluoromethyl, bromine, chlorine, or phenyl; wherein the phenyl may be substituted with chlorine; R5 represents hydrogen or fluorine; R6 represents a group of formula a), b'), b''), c'), c'') or e); [ka]

[0053] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7, independently of one another, represent hydrogen, (C1-C4)-alkyl, (C3-C4)-cycloalkyl, (C1-C2)-alkoxy, (C3-C4)-cycloalkoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, phenyl, where (C1-C4)-alkyl may be optionally substituted by methoxy, n-butoxy, cyclopropyl, cyclobutoxy and up to disubstituted by fluorine, wherein methoxy is optionally substituted with cyclopropyl, cyclobutyl, trifluoromethyl; wherein cyclopropyl is optionally substituted with monofluoromethyl, difluoromethyl, or trifluoromethyl; wherein cyclobutyl may be up to disubstituted with fluorine; wherein n-butoxy may be up to disubstituted with fluorine; wherein (C1-C2)-alkoxy may be substituted by cyclopropyl, cyclobutyl, cyclobutoxy, trifluoromethyl, and wherein cyclopropyl and cyclobutyl are optionally up to disubstituted by fluorine; wherein (C3-C4)-cycloalkoxy is optionally up to disubstituted by fluorine, Wherein R9 represents hydrogen, methyl, tert-butyl, methoxy, methoxymethyl, fluorine, or chlorine; n represents 0 or 1, and m represents 1 or 2. Compound and a noradrenaline reuptake inhibitor selected from the group of norepinephrine selective reuptake inhibitors including Atomoxetine, 4-hydroxyatomoxetine, CP-39,332, Daredalin, Edivoxetine, Esreboxetine, Lortalamine, Nisoxetine, Reboxetine, Talopram, Talsupram, Tandamine, Amedalin and Vilox; or A noradrenaline reuptake inhibitor selected from the group of nonselective norepinephrine reuptake inhibitors including Amitriptyline, Amoxapine, Bupropion, Ciclazindol, Desipramine, Desvenlafaxine, Dexmethilphenidate, Diethylpropion, Doxepin, Duloxetine, Imipramine, Levomilnacipran, Manifaxine, Maprotiline, Methylphenidate, Milnacipran, Nefazodone, Nortriptyline, Phendimetrazine, Protryptyline, Radafaxine, Tapentadol, Teniloxazine, and Venlafaxine A combination of and salts, solvates and solvates of the salts thereof.

[0054] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected such that the aromatic five-membered ring has the structural formula h), i), j), k) or (r); [ka]

[0055] where * indicates a bond to the carbonyl group, ** indicates a bond to the nitrogen atom of the adjacent piperidine ring, and R1 represents pyridinyl, pyrazolyl, thiazolyl, thienyl, or phenyl; wherein pyridinyl is optionally substituted by 1 to 2 mutually independent substituents selected from the group consisting of (C1-C2)-alkyl, fluorine, chlorine, trifluoromethyl, trifluoromethoxy, wherein pyrazolyl is optionally substituted by 1 to 2 mutually independent substituents selected from the group consisting of (C1-C2)-alkyl, fluorine, chlorine, trifluoromethyl, wherein thiazolyl is optionally substituted with chlorine; wherein thienyl may be substituted with fluorine; wherein phenyl may be substituted by 1-2 mutually independent substituents selected from the group: (C1-C2)-alkyl, (C3-C4)-cycloalkyl, methoxy, cyano, hydroxy, fluorine, chlorine, trifluoromethyl; R2 represents hydrogen or methyl; or forms a cyclopropyl ring together with the carbon atom to which R2 is attached, R3 represents hydrogen, (C1-C2)-alkyl; R4 represents hydrogen, methyl, ethyl, cyclopropyl, trifluoromethyl, bromine, chlorine, or phenyl; wherein the phenyl may be substituted with chlorine; R5 represents hydrogen or fluorine; R6 represents a group of formula a), b'), b''), c'), c'') or e); [ka]

[0056] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7, independently of one another, represent hydrogen, (C1-C4)-alkyl, (C3-C4)-cycloalkyl, (C1-C2)-alkoxy, (C3-C4)-cycloalkoxy, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, phenyl, where (C1-C4)-alkyl may be optionally substituted by methoxy, n-butoxy, cyclopropyl, cyclobutoxy and up to disubstituted by fluorine, wherein methoxy is optionally substituted with cyclopropyl, cyclobutyl, trifluoromethyl; wherein cyclopropyl is optionally substituted with monofluoromethyl, difluoromethyl, or trifluoromethyl; wherein cyclobutyl may be up to disubstituted with fluorine; wherein n-butoxy may be up to disubstituted with fluorine; wherein (C1-C2)-alkoxy may be substituted by cyclopropyl, cyclobutyl, cyclobutoxy, trifluoromethyl, and wherein cyclopropyl and cyclobutyl are optionally up to disubstituted by fluorine; wherein (C3-C4)-cycloalkoxy is optionally up to disubstituted by fluorine, Wherein R9 represents hydrogen, methyl, tert-butyl, methoxy, methoxymethyl, fluorine, or chlorine; n represents 0 or 1, and m represents 1 or 2. Compound and Atomoxetine combination, and salts, solvates and solvates of the salts thereof.

[0057] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected from the group S, N, O and C to form 1,3-thiazolyl, 1,3-oxazolyl or 1,2,4-oxadiazolyl; R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen or methyl; R4 represents hydrogen, methyl, ethyl or trifluoromethyl; R5 represents hydrogen or fluoro; R6 represents a group of formula a), c') or c''); [ka]

[0058] In the formula, *** indicates a bond to the adjacent piperidine ring, where R7 or R'7 independently of one another represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropyl-methoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutyl-methoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropyl-methoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy or fluoro; n represents 0 or 1; m represents 1. Compound and Combination noradrenaline reuptake inhibitors, and salts, solvates and solvates of the salts thereof.

[0059] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected from the group S, N, O and C to form 1,3-thiazolyl, 1,3-oxazolyl or 1,2,4-oxadiazolyl; R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen or methyl; R4 represents hydrogen, methyl, ethyl or trifluoromethyl; wherein the phenyl is optionally substituted with chloro; R5 represents hydrogen or fluoro; R6 represents a group of formula a), c') or c''); [ka]

[0060] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7 independently of one another represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropyl-methoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutyl-methoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropyl-methoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy or fluoro; n represents 0 or 1; m represents 1. Compound and a noradrenaline reuptake inhibitor selected from the group of norepinephrine selective reuptake inhibitors including atomoxetine, 4-hydroxyatomoxetine, CP-39,332, daredalin, edivoxetine, esreboxetine, lortalamine, nisoxetine, reboxetine, talopram, talsupram, tandamine, amidabutyric acid, and virox; or A noradrenaline reuptake inhibitor selected from the group of nonselective norepinephrine reuptake inhibitors including Amitriptyline, Amoxapine, Bupropion, Ciclazindol, Desipramine, Desvenlafaxine, Dexmethilphenidate, Diethylpropion, Doxepin, Duloxetine, Imipramine, Levomilnacipran, Manifaxine, Maprotiline, Methylphenidate, Milnacipran, Nefazodone, Nortriptyline, Phendimetrazine, Protryptyline, Radafaxine, Tapentadol, Teniloxazine, and Venlafaxine A combination of and salts, solvates and solvates of the salts thereof.

[0061] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected from the group S, N, O and C to form 1,3-thiazolyl, 1,3-oxazolyl or 1,2,4-oxadiazolyl; R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen or methyl; R4 represents hydrogen, methyl, ethyl or trifluoromethyl; wherein the phenyl is optionally substituted with chloro; R5 represents hydrogen or fluoro; R6 represents a group of formula a), c') or c''); [ka]

[0062] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7 independently of one another represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropyl-methoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutyl-methoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropyl-methoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy or fluoro; n represents 0 or 1; m represents 1. Compound and Atomoxetine or 4-hydroxyatomoxetine combinations, and salts, solvates and solvates of the salts thereof.

[0063] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected from the group S, N, O and C to form 1,3-thiazolyl, 1,3-oxazolyl or 1,2,4-oxadiazolyl; R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen or methyl; R4 represents hydrogen, methyl, ethyl or trifluoromethyl; wherein the phenyl is optionally substituted with chloro; R5 represents hydrogen or fluoro; R6 represents a group of formula a), c') or c''); [ka]

[0064] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7 independently of one another represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropyl-methoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutyl-methoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropyl-methoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy or fluoro; n represents 0 or 1; m represents 1. Compound and Atomoxetine combination, and salts, solvates and solvates of the salts thereof.

[0065] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected from the group S, N, O and C to form 1,3-thiazolyl, 1,3-oxazolyl or 1,2,4-oxadiazolyl; R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen or methyl; R4 represents hydrogen, methyl, ethyl or trifluoromethyl; wherein the phenyl is optionally substituted with chloro; R5 represents hydrogen or fluoro; R6 represents a group of formula a), c') or c''); [ka]

[0066] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7 independently of one another represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropyl-methoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutyl-methoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropyl-methoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy or fluoro; n represents 0 or 1; m represents 1. Compound and Reboxetine combination, and salts, solvates and solvates of the salts thereof.

[0067] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected from the group S, N, O and C to form 1,3-thiazolyl, 1,3-oxazolyl or 1,2,4-oxadiazolyl; R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen or methyl; R4 represents hydrogen, methyl, ethyl or trifluoromethyl; wherein the phenyl is optionally substituted with chloro; R5 represents hydrogen or fluoro; R6 represents a group of formula a), c') or c''); [ka]

[0068] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7 independently of one another represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropyl-methoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutyl-methoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropyl-methoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy or fluoro; n represents 0 or 1; m represents 1. Compound and Desipramine combination, and salts, solvates and solvates of the salts thereof.

[0069] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected such that the aromatic five-membered ring has the structural formula h'), [ka]

[0070] R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen; R5 represents hydrogen or fluorine; R6 represents a group of formula a), c') or c''); [ka]

[0071] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7, independently of one another, represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropylmethoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutylmethoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropylmethoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy, fluoro; n represents 0 or 1, and m represents 1. Compound and Combination noradrenaline reuptake inhibitors, and salts, solvates and solvates of the salts thereof.

[0072] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected such that the aromatic five-membered ring has the structural formula h'), [ka]

[0073] R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen; R5 represents hydrogen or fluorine; R6 represents a group of formula a), c') or c''); [ka]

[0074] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7, independently of one another, represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropylmethoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutylmethoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropylmethoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy, fluoro; n represents 0 or 1, and m represents 1. Compound and a noradrenaline reuptake inhibitor selected from the group of norepinephrine selective reuptake inhibitors including atomoxetine, 4-hydroxyatomoxetine, CP-39,332, daredalin, edivoxetine, esreboxetine, lortalamine, nisoxetine, reboxetine, talopram, talsupram, tandamine, amidabutyric acid, and virox; or A noradrenaline reuptake inhibitor selected from the group of nonselective norepinephrine reuptake inhibitors including Amitriptyline, Amoxapine, Bupropion, Ciclazindol, Desipramine, Desvenlafaxine, Dexmethilphenidate, Diethylpropion, Doxepin, Duloxetine, Imipramine, Levomilnacipran, Manifaxine, Maprotiline, Methylphenidate, Milnacipran, Nefazodone, Nortriptyline, Phendimetrazine, Protryptyline, Radafaxine, Tapentadol, Teniloxazine, and Venlafaxine A combination of and salts, solvates and solvates of the salts thereof.

[0075] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected such that the aromatic five-membered ring has the structural formula h'), [ka]

[0076] R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen; R5 represents hydrogen or fluorine; R6 represents a group of formula a), c') or c''); [ka]

[0077] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7, independently of one another, represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropylmethoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutylmethoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropylmethoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy, fluoro; n represents 0 or 1, and m represents 1. Compound and Atomoxetine or 4-hydroxyatomoxetine combinations, and salts, solvates and solvates of the salts thereof.

[0078] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected such that the aromatic five-membered ring has the structural formula h'), [ka]

[0079] R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen; R5 represents hydrogen or fluorine; R6 represents a group of formula a), c') or c''); [ka]

[0080] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7, independently of one another, represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropylmethoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutylmethoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropylmethoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy, fluoro; n represents 0 or 1, and m represents 1. Compound and Atomoxetine combination, and salts, solvates and solvates of the salts thereof.

[0081] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected such that the aromatic five-membered ring has the structural formula h'), [ka]

[0082] R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen; R5 represents hydrogen or fluorine; R6 represents a group of formula a), c') or c''); [ka]

[0083] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7, independently of one another, represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropylmethoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutylmethoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropylmethoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy, fluoro; n represents 0 or 1, and m represents 1. Compound and Reboxetine combination, and salts, solvates and solvates of the salts thereof.

[0084] A further embodiment of the present invention is a compound of formula (I) [During the ceremony, X, Y and Z are selected such that the aromatic five-membered ring has the structural formula h'), [ka]

[0085] R1 is pyridinyl, 2-ethylpyridinyl, 4,6-dimethylpyridinyl, 3,5-difluoropyridinyl, 3-fluoropyridinyl, 4-trifluoromethylpyridinyl, 6-trifluoromethylpyridinyl, 5-chloro-3-fluoropyridinyl, 3-chloro-5-fluoropyridinyl, 3-methylpyridinyl, 4-methylpyridinyl, 6-methylpyridinyl, 3-chloropyridinyl, 5-chloropyridinyl, 6-trifluoromethoxypyridinyl, phenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 3-methoxyphenyl, 4-trifluoromethylphenyl nyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-hydroxyphenyl, 2,5-difluorophenyl, 5-chloro-2-hydroxyphenyl, 5-fluoro-2-methoxyphenyl, 5-chloro-2-fluorophenyl, 2-chloro-5-fluorophenyl, 2-chloro-4-fluorophenyl, 3-cyano-4-fluorophenyl, 2-cyclopropylphenyl, 4-chloro-1-methyl-1H-pyrazolyl, 5-chloro-1,3-thiazolyl, 5-fluoro-2-thienyl; R2 represents hydrogen or methyl; R3 represents hydrogen; R5 represents hydrogen or fluorine; R6 represents a group of formula a), c') or c''); [ka]

[0086] where *** indicates a bond to the adjacent piperidine ring, where R7 or R'7, independently of one another, represent hydrogen, methyl, ethyl, n-propyl, isopropyl, tert-butyl, 2-fluoroethyl, cyclopropyl, cyclobutyl, cyclopropylmethyl, methoxy, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, difluoromethoxy, 3,3-difluorocyclobutylmethoxy, cyclobutylmethoxy, cyclopropylmethoxy, cyclopropylmethoxymethyl, cyclobutyloxymethyl, 3-fluorobutyloxymethyl, 3,3-difluorocyclobutylmethoxymethyl, 2,2,2-trifluoroethoxy, 2,2,2-trifluoroethoxymethyl, 2,2-difluorocyclopropylmethoxy, cyclobutyloxy, 3,3-difluorocyclobutyloxy, fluoromethylcyclopropylmethoxy, difluoromethylcyclopropylmethoxy, trifluoromethylcyclopropylmethoxy, fluoro; n represents 0 or 1, and m represents 1. Compound and Desipramine combination, and salts, solvates and solvates of the salts thereof.

[0087] A preferred embodiment of the present invention is the compound of formula (I) N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(3,4-dihydroisoquinolin-2(1H)-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoro 2-[3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(fluoromethyl)-[ 1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoro-pyridin-2-yl)methyl] methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-4-(trifluoromethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide Boxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-(difluoromethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-ethyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide amide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[3-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(5 -chloro-2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[4-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(3-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(4-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-N -methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-[(5-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl] N-[(3-chloro-5-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethoxy)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-(4-chlorobenzyl)-2- [(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-5-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(4-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-(2-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3S)-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole 1,4'-bipiperidine-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(trifluoromethyl)[1,4'-bipiperidine] N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(3,3-difluorocyclobutyl ) methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(1S)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(1R)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-3-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,2,4-oxadiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'S)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazetyl)azetyl] azepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl [1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(5-fluoro-2-thienyl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(fluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-({[1-(difluoromethyl)cyclo, propyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(trifluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3,3-dimethyl[1,4'-bipiperidine]-1'-yl )-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N- [(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclobutyloxy)methyl]-[1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][ 1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-ethoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{4-[(3R)-3-methylpiperidin-1-yl]azepan-1-yl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(6-methylpyridin-3-yl)methyl]-1,3-thiazole-5-carboxamide, N-benzyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[3-fluorobutyl]oxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-(3-{[(3,3-difluorocyclobutyl)methoxy]methyl aryl}[1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-4-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2,2,2-trifluoroethoxy)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4,6 -Dimethylpyridin-3-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4-chloro-1-methyl-1H-pyrazol-5-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methoxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2,5-difluorobenzyl) -2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-hydroxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(2R)-2-phenylpropyl]-1,3-thiazole-5-carboxamide, N-(4-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-Thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-(3-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-4-fluorophenyl )-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-cyano-4-fluorophenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl ]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-benzyl-N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-cyclopropylphenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-chlorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(1R)-1-(4-methylphenyl)ethyl]-1,3-thiazole-5-carboxamide, N-(2-ethylpyridin-4-yl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl) methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-isopropyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4S)-4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4R)-4-methylazepan-1-yl)piperidine Lysin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3S)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3R)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, 2-{3-[(2,2-difluoro 2-[3-(cyclobutyloxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)oxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-(5-chloro-2-fluorobenzyl)-2-[(3R)-3'-fluoro-3-methyl[1, 4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl [1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-(2-chlorophenyl)-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5 -carboxamide, 4-bromo-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-propyl[1,4'-bipiperidine]-1'-yl)-1,3-Thiazole-5-carboxamide, 4-cyclopropyl-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3S)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3R)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[(3S)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N -[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, formate-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2-fluoroethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-([1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl )cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(3S)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl] ethyl]-1,3-thiazole-5-carboxamide, 2-[4-(3R)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-phenyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide. and a combination of noradrenaline reuptake inhibitors, and salts, solvates and solvates of the salts thereof.

[0088] A preferred embodiment of the present invention is the compound of formula (I) N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(3,4-dihydroisoquinolin-2(1H)-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoro 2-[3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(fluoromethyl)-[ 1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoro-pyridin-2-yl)methyl] methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-4-(trifluoromethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide Boxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-(difluoromethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-ethyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide amide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[3-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(5 -chloro-2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[4-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(3-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(4-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-N -methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-[(5-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl] N-[(3-chloro-5-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethoxy)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-(4-chlorobenzyl)-2- [(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-5-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(4-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-(2-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3S)-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole 1,4'-bipiperidine-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(trifluoromethyl)[1,4'-bipiperidine] N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(3,3-difluorocyclobutyl ) methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(1S)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(1R)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-3-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,2,4-oxadiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'S)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazetyl)azetyl] azepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl [1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(5-fluoro-2-thienyl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(fluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-({[1-(difluoromethyl)cyclo, propyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(trifluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3,3-dimethyl[1,4'-bipiperidine]-1'-yl )-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N- [(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclobutyloxy)methyl]-[1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][ 1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-ethoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{4-[(3R)-3-methylpiperidin-1-yl]azepan-1-yl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(6-methylpyridin-3-yl)methyl]-1,3-thiazole-5-carboxamide, N-benzyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[3-fluorobutyl]oxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-(3-{[(3,3-difluorocyclobutyl)methoxy]methyl aryl}[1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-4-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2,2,2-trifluoroethoxy)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4,6 -Dimethylpyridin-3-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4-chloro-1-methyl-1H-pyrazol-5-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methoxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2,5-difluorobenzyl) -2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-hydroxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(2R)-2-phenylpropyl]-1,3-thiazole-5-carboxamide, N-(4-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-Thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-(3-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-4-fluorophenyl )-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-cyano-4-fluorophenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl ]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-benzyl-N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-cyclopropylphenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-chlorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(1R)-1-(4-methylphenyl)ethyl]-1,3-thiazole-5-carboxamide, N-(2-ethylpyridin-4-yl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl) methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-isopropyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4S)-4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4R)-4-methylazepan-1-yl)piperidine Lysin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3S)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3R)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, 2-{3-[(2,2-difluoro 2-[3-(cyclobutyloxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)oxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-(5-chloro-2-fluorobenzyl)-2-[(3R)-3'-fluoro-3-methyl[1, 4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl [1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-(2-chlorophenyl)-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5 -carboxamide, 4-bromo-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-propyl[1,4'-bipiperidine]-1'-yl)-1,3-Thiazole-5-carboxamide, 4-cyclopropyl-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3S)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3R)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[(3S)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N -[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, formate-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2-fluoroethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-([1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl )cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(3S)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl] ethyl]-1,3-thiazole-5-carboxamide, 2-[4-(3R)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-phenyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide. and a noradrenaline reuptake inhibitor selected from the group of norepinephrine selective reuptake inhibitors including atomoxetine, 4-hydroxyatomoxetine, CP-39,332, daredalin, edivoxetine, esreboxetine, lortalamine, nisoxetine, reboxetine, talopram, talsupram, tandamine, amidabutyric acid, and virox; or A noradrenaline reuptake inhibitor selected from the group of nonselective norepinephrine reuptake inhibitors including Amitriptyline, Amoxapine, Bupropion, Ciclazindol, Desipramine, Desvenlafaxine, Dexmethilphenidate, Diethylpropion, Doxepin, Duloxetine, Imipramine, Levomilnacipran, Manifaxine, Maprotiline, Methylphenidate, Milnacipran, Nefazodone, Nortriptyline, Phendimetrazine, Protryptyline, Radafaxine, Tapentadol, Teniloxazine, and Venlafaxine A combination of and salts, solvates and solvates of the salts thereof.

[0089] A preferred embodiment of the present invention is the compound of formula (I) N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(3,4-dihydroisoquinolin-2(1H)-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoro 2-[3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(fluoromethyl)-[ 1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoro-pyridin-2-yl)methyl] methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-4-(trifluoromethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide Boxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-(difluoromethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-ethyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide amide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[3-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(5 -chloro-2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[4-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(3-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(4-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-N -methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-[(5-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl] N-[(3-chloro-5-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethoxy)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-(4-chlorobenzyl)-2- [(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-5-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(4-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-(2-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3S)-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole 1,4'-bipiperidine-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(trifluoromethyl)[1,4'-bipiperidine] N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(3,3-difluorocyclobutyl ) methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(1S)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(1R)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-3-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,2,4-oxadiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'S)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazetyl)azetyl] azepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl [1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(5-fluoro-2-thienyl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(fluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-({[1-(difluoromethyl)cyclo, propyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(trifluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3,3-dimethyl[1,4'-bipiperidine]-1'-yl )-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N- [(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclobutyloxy)methyl]-[1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][ 1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-ethoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{4-[(3R)-3-methylpiperidin-1-yl]azepan-1-yl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(6-methylpyridin-3-yl)methyl]-1,3-thiazole-5-carboxamide, N-benzyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[3-fluorobutyl]oxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-(3-{[(3,3-difluorocyclobutyl)methoxy]methyl aryl}[1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-4-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2,2,2-trifluoroethoxy)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4,6 -Dimethylpyridin-3-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4-chloro-1-methyl-1H-pyrazol-5-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methoxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2,5-difluorobenzyl) -2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-hydroxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(2R)-2-phenylpropyl]-1,3-thiazole-5-carboxamide, N-(4-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-Thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-(3-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-4-fluorophenyl )-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-cyano-4-fluorophenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl ]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-benzyl-N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-cyclopropylphenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-chlorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(1R)-1-(4-methylphenyl)ethyl]-1,3-thiazole-5-carboxamide, N-(2-ethylpyridin-4-yl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl) methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-isopropyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4S)-4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4R)-4-methylazepan-1-yl)piperidine Lysin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3S)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3R)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, 2-{3-[(2,2-difluoro 2-[3-(cyclobutyloxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)oxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-(5-chloro-2-fluorobenzyl)-2-[(3R)-3'-fluoro-3-methyl[1, 4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl [1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-(2-chlorophenyl)-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5 -carboxamide, 4-bromo-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-propyl[1,4'-bipiperidine]-1'-yl)-1,3-Thiazole-5-carboxamide, 4-cyclopropyl-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3S)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3R)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[(3S)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N -[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, formate-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2-fluoroethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-([1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl )cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(3S)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl] ethyl]-1,3-thiazole-5-carboxamide, 2-[4-(3R)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-phenyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide. and Atomoxetine or 4-hydroxyatomoxetine combinations, and salts, solvates and solvates of the salts thereof.

[0090] A preferred embodiment of the present invention is the compound of formula (I) N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(3,4-dihydroisoquinolin-2(1H)-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoro 2-[3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(fluoromethyl)-[ 1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoro-pyridin-2-yl)methyl] methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-4-(trifluoromethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide Boxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-(difluoromethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-ethyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide amide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[3-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(5 -chloro-2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[4-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(3-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(4-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-N -methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-[(5-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl] N-[(3-chloro-5-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethoxy)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-(4-chlorobenzyl)-2- [(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-5-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(4-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-(2-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3S)-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole 1,4'-bipiperidine-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(trifluoromethyl)[1,4'-bipiperidine] N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(3,3-difluorocyclobutyl ) methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(1S)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(1R)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-3-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,2,4-oxadiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'S)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazetyl)azetyl] azepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl [1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(5-fluoro-2-thienyl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(fluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-({[1-(difluoromethyl)cyclo, propyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(trifluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3,3-dimethyl[1,4'-bipiperidine]-1'-yl )-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N- [(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclobutyloxy)methyl]-[1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][ 1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-ethoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{4-[(3R)-3-methylpiperidin-1-yl]azepan-1-yl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(6-methylpyridin-3-yl)methyl]-1,3-thiazole-5-carboxamide, N-benzyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[3-fluorobutyl]oxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-(3-{[(3,3-difluorocyclobutyl)methoxy]methyl aryl}[1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-4-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2,2,2-trifluoroethoxy)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4,6 -Dimethylpyridin-3-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4-chloro-1-methyl-1H-pyrazol-5-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methoxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2,5-difluorobenzyl) -2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-hydroxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(2R)-2-phenylpropyl]-1,3-thiazole-5-carboxamide, N-(4-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-Thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-(3-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-4-fluorophenyl )-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-cyano-4-fluorophenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl ]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-benzyl-N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-cyclopropylphenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-chlorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(1R)-1-(4-methylphenyl)ethyl]-1,3-thiazole-5-carboxamide, N-(2-ethylpyridin-4-yl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl) methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-isopropyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4S)-4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4R)-4-methylazepan-1-yl)piperidine Lysin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3S)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3R)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, 2-{3-[(2,2-difluoro 2-[3-(cyclobutyloxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)oxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-(5-chloro-2-fluorobenzyl)-2-[(3R)-3'-fluoro-3-methyl[1, 4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl [1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-(2-chlorophenyl)-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5 -carboxamide, 4-bromo-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-propyl[1,4'-bipiperidine]-1'-yl)-1,3-Thiazole-5-carboxamide, 4-cyclopropyl-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3S)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3R)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[(3S)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N -[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, formate-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2-fluoroethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-([1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl )cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(3S)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl] ethyl]-1,3-thiazole-5-carboxamide, 2-[4-(3R)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-phenyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide. and Atomoxetine combination, and salts, solvates and solvates of the salts thereof.

[0091] A preferred embodiment of the present invention is the compound of formula (I) N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(3,4-dihydroisoquinolin-2(1H)-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoro 2-[3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(fluoromethyl)-[ 1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoro-pyridin-2-yl)methyl] methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-4-(trifluoromethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide Boxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-(difluoromethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-ethyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide amide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[3-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(5 -chloro-2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[4-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(3-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(4-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-N -methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-[(5-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl] N-[(3-chloro-5-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethoxy)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-(4-chlorobenzyl)-2- [(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-5-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(4-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-(2-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3S)-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole 1,4'-bipiperidine-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(trifluoromethyl)[1,4'-bipiperidine] N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(3,3-difluorocyclobutyl ) methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(1S)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(1R)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-3-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,2,4-oxadiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'S)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazetyl)azetyl] azepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl [1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(5-fluoro-2-thienyl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(fluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-({[1-(difluoromethyl)cyclo, propyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(trifluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3,3-dimethyl[1,4'-bipiperidine]-1'-yl )-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N- [(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclobutyloxy)methyl]-[1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][ 1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-ethoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{4-[(3R)-3-methylpiperidin-1-yl]azepan-1-yl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(6-methylpyridin-3-yl)methyl]-1,3-thiazole-5-carboxamide, N-benzyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[3-fluorobutyl]oxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-(3-{[(3,3-difluorocyclobutyl)methoxy]methyl aryl}[1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-4-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2,2,2-trifluoroethoxy)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4,6 -Dimethylpyridin-3-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4-chloro-1-methyl-1H-pyrazol-5-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methoxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2,5-difluorobenzyl) -2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-hydroxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(2R)-2-phenylpropyl]-1,3-thiazole-5-carboxamide, N-(4-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-Thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-(3-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-4-fluorophenyl )-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-cyano-4-fluorophenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl ]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-benzyl-N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-cyclopropylphenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-chlorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(1R)-1-(4-methylphenyl)ethyl]-1,3-thiazole-5-carboxamide, N-(2-ethylpyridin-4-yl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl) methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-isopropyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4S)-4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4R)-4-methylazepan-1-yl)piperidine Lysin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3S)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3R)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, 2-{3-[(2,2-difluoro 2-[3-(cyclobutyloxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)oxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-(5-chloro-2-fluorobenzyl)-2-[(3R)-3'-fluoro-3-methyl[1, 4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl [1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-(2-chlorophenyl)-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5 -carboxamide, 4-bromo-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-propyl[1,4'-bipiperidine]-1'-yl)-1,3-Thiazole-5-carboxamide, 4-cyclopropyl-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3S)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3R)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[(3S)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N -[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, formate-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2-fluoroethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-([1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl )cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(3S)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl] ethyl]-1,3-thiazole-5-carboxamide, 2-[4-(3R)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-phenyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide. and Reboxetine combination, and salts, solvates and solvates of the salts thereof.

[0092] A preferred embodiment of the present invention is the compound of formula (I) N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(3,4-dihydroisoquinolin-2(1H)-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoro 2-[3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(fluoromethyl)-[ 1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoro-pyridin-2-yl)methyl] methyl]-4-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-4-(trifluoromethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-5-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide Boxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-(difluoromethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-ethyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide amide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[3-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(5 -chloro-2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[4-(trifluoromethyl)benzyl]-1,3-thiazole-5-carboxamide, N-[(5-chloro-3-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(3-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(4-methylpyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-2-yl)methyl]-N -methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-[(5-chloropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl] N-[(3-chloro-5-fluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-{[6-(trifluoromethoxy)pyridin-2-yl]methyl}-1,3-thiazole-5-carboxamide, N-(4-chlorobenzyl)-2- [(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-5-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(4-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-(2-methylbenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3S)-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(difluoromethyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole 1,4'-bipiperidine-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(fluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(trifluoromethyl)[1,4'-bipiperidine] N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(trifluoromethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(3,3-difluorocyclobutyl)methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(3,3-difluorocyclobutyl ) methoxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(1S)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(1R)-1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-3-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,2,4-oxadiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, ent-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R),(3'S)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazetyl)azetyl] azepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-(4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl)ethyl]-2-[(3R)-3-methyl [1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(5-fluoro-2-thienyl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(fluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[3-({[1-(difluoromethyl)cyclo, propyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[1-(trifluoromethyl)cyclopropyl]methoxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3,3-dimethyl[1,4'-bipiperidine]-1'-yl )-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N- [(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclobutyloxy)methyl]-[1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][ 1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-ethoxy[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{4-[(3R)-3-methylpiperidin-1-yl]azepan-1-yl}-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(6-methylpyridin-3-yl)methyl]-1,3-thiazole-5-carboxamide, N-benzyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-({[3-fluorobutyl]oxy}methyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-(3-{[(3,3-difluorocyclobutyl)methoxy]methyl aryl}[1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3-fluoropyridin-4-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2,2,2-trifluoroethoxy)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4,6 -Dimethylpyridin-3-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(4-chloro-1-methyl-1H-pyrazol-5-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-methoxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2,5-difluorobenzyl) -2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-hydroxybenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(2R)-2-phenylpropyl]-1,3-thiazole-5-carboxamide, N-(4-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-Thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-(3-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-fluorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-chloro-4-fluorophenyl )-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-cyano-4-fluorophenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-(pyridin-3-ylmethyl)-1,3-thiazole-5-carboxamide, N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl ]-N-(pyridin-4-ylmethyl)-1,3-thiazole-5-carboxamide, N-benzyl-N-methyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(2-cyclopropylphenyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-(3-chlorobenzyl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-N-[(1R)-1-(4-methylphenyl)ethyl]-1,3-thiazole-5-carboxamide, N-(2-ethylpyridin-4-yl)-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3S)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-(methoxymethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-{(3S)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{(3R)-3-[(cyclobutyloxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl) methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-isopropyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4S)-4-methylazepan-1-yl)piperidin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[4-((4R)-4-methylazepan-1-yl)piperidine Lysin-1-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3S)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-{(3R)-3-[(2,2,2-trifluoroethoxy)methyl][1,4'-bipiperidine]-1'-yl}-1,3-thiazole-5-carboxamide, 2-{3-[(2,2-difluoro 2-[3-(cyclobutyloxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(3,3-difluorocyclobutyl)oxy][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide3-Thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-4-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-oxazole-4-carboxamide, N-(5-chloro-2-fluorobenzyl)-2-[(3R)-3'-fluoro-3-methyl[1, 4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclopropylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl][1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-{3-[(cyclopropylmethoxy)methyl [1,4'-bipiperidine]-1'-yl}-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(2,5-difluorophenyl)ethyl]-2-[(3R)-3'-fluoro-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-(2-chlorophenyl)-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5 -carboxamide, 4-bromo-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-propyl[1,4'-bipiperidine]-1'-yl)-1,3-Thiazole-5-carboxamide, 4-cyclopropyl-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3S)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole, N-[(3,5-difluoropyridin-2-yl)methyl]-2-((3R)-3-ethoxy[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[(3S)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[(3R)-3-(cyclobutylmethoxy)[1,4'-bipiperidine]-1'-yl]-N -[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, formate-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[3-(2-fluoroethyl)[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-([1,4'-bipiperidine]-1'-yl)-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[1-(3,5-difluoropyridin-2-yl )cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-4-ethyl-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(3S)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl] ethyl]-1,3-thiazole-5-carboxamide, 2-[4-(3R)-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-(3-phenyl[1,4'-bipiperidine]-1'-yl)-1,3-thiazole-5-carboxamide, 2-[4-(1,1-difluoro-5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)-3-fluoropiperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide. and desipramine combination, and salts, solvates and solvates of the salts thereof.

[0093] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R*)-3-(methoxymethyl)[1,4'-bipiperidine] a compound of formula (I) selected from the group consisting of N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and a combination of noradrenaline reuptake inhibitors, and salts, solvates and solvates of the salts thereof.

[0094] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R*)-3-(methoxymethyl)[1,4'-bipiperidine] a compound of formula (I) selected from the group consisting of N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and a noradrenaline reuptake inhibitor selected from the group of norepinephrine selective reuptake inhibitors including atomoxetine, 4-hydroxyatomoxetine, CP-39,332, daredalin, edivoxetine, esreboxetine, lortalamine, nisoxetine, reboxetine, talopram, talsupram, tandamine, amidabutyric acid, and virox; or A noradrenaline reuptake inhibitor selected from the group of nonselective norepinephrine reuptake inhibitors including Amitriptyline, Amoxapine, Bupropion, Ciclazindol, Desipramine, Desvenlafaxine, Dexmethilphenidate, Diethylpropion, Doxepin, Duloxetine, Imipramine, Levomilnacipran, Manifaxine, Maprotiline, Methylphenidate, Milnacipran, Nefazodone, Nortriptyline, Phendimetrazine, Protryptyline, Radafaxine, Tapentadol, Teniloxazine, and Venlafaxine A combination of and salts, solvates and solvates of the salts thereof.

[0095] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R*)-3-(methoxymethyl)[1,4'-bipiperidine] a compound of formula (I) selected from the group consisting of N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and Atomoxetine or 4-hydroxyatomoxetine combinations, and salts, solvates and solvates of the salts thereof.

[0096] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R*)-3-(methoxymethyl)[1,4'-bipiperidine] a compound of formula (I) selected from the group consisting of N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and Atomoxetine combination, and salts, solvates and solvates of the salts thereof.

[0097] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R*)-3-(methoxymethyl)[1,4'-bipiperidine] a compound of formula (I) selected from the group consisting of N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and Reboxetine combination, and salts, solvates and solvates of the salts thereof.

[0098] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R*)-3-(methoxymethyl)[1,4'-bipiperidine] a compound of formula (I) selected from the group consisting of N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and Desipramine combination, and salts, solvates and solvates of the salts thereof.

[0099] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and Combination noradrenaline reuptake inhibitors, and salts, solvates and solvates of the salts thereof.

[0100] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and a noradrenaline reuptake inhibitor selected from the group of norepinephrine selective reuptake inhibitors including atomoxetine, 4-hydroxyatomoxetine, CP-39,332, daredalin, edivoxetine, esreboxetine, lortalamine, nisoxetine, reboxetine, talopram, talsupram, tandamine, amidabutyric acid, and virox; or A noradrenaline reuptake inhibitor selected from the group of nonselective norepinephrine reuptake inhibitors including Amitriptyline, Amoxapine, Bupropion, Ciclazindol, Desipramine, Desvenlafaxine, Dexmethilphenidate, Diethylpropion, Doxepin, Duloxetine, Imipramine, Levomilnacipran, Manifaxine, Maprotiline, Methylphenidate, Milnacipran, Nefazodone, Nortriptyline, Phendimetrazine, Protryptyline, Radafaxine, Tapentadol, Teniloxazine, and Venlafaxine A combination of and salts, solvates and solvates of the salts thereof.

[0101] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and a combination of noradrenaline reuptake inhibitors, which are atomoxetine, reboxetine, or desipramine. and salts, solvates and solvates of the salts thereof.

[0102] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and a combination of atomoxetine or 4-hydroxyatomoxetine, and salts, solvates and solvates of the salts thereof.

[0103] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and atomoxetine in combination, and salts, solvates and solvates of the salts thereof.

[0104] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and reboxetine in combination, and salts, solvates and solvates of the salts thereof.

[0105] Another preferred embodiment of the present invention comprises: N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and desipramine combination, and salts, solvates and solvates of the salts thereof.

[0106] In a possible subgroup of compounds of formula I, X, Y and Z are selected such that the aromatic five-membered ring has the structural formula h), i), j), k) or (r); [ka]

[0107] where * indicates the bond to the carbonyl group, ** indicates the bond to the nitrogen atom of the adjacent piperidine ring, and R4 represents hydrogen, methyl, ethyl, cyclopropyl, trifluoromethyl, bromine, chlorine, or phenyl; wherein the phenyl may be substituted by chlorine. and salts, solvates and solvates of the salts thereof.

[0108] In a possible subgroup of compounds of formula I, X, Y and Z are selected such that the aromatic five-membered ring has structural formula (h) or i); [ka]

[0109] where * indicates the bond to the carbonyl group, ** indicates the bond to the nitrogen atom of the adjacent piperidine ring, and R4 represents hydrogen, methyl, ethyl, cyclopropyl, trifluoromethyl, bromine, chlorine, or phenyl; wherein the phenyl may be substituted by chlorine. and salts, solvates and solvates of the salts thereof.

[0110] In a possible subgroup of compounds of formula I, X represents S; Y represents N; and Z represents C; wherein in the resulting group of formula (h): [ka]

[0111] wherein * indicates a bond to the carbonyl group and ** indicates a bond to the N atom of the adjacent piperidine ring; R4 represents hydrogen or chloro; and salts, solvates and solvates of the salts thereof.

[0112] In another possible subgroup of compounds of formula I, R1 represents pyridinyl or phenyl; wherein pyridinyl is optionally substituted with 1 or 2 substituents independently selected from the group: methyl, ethyl, fluoro, chloro, trifluoromethyl and trifluoromethoxy; wherein phenyl is optionally substituted with 1 or 2 substituents independently selected from the group consisting of methyl, cyclopropyl, methoxy, cyano, hydroxy, fluoro, chloro and trifluoromethyl; and salts, solvates and solvates of the salts thereof.

[0113] In another possible subgroup of compounds of formula I, R1 represents 3,5-difluoropyridin-2-yl.

[0114] In another possible subgroup of compounds of formula I, R2 represents hydrogen; or forms a cyclopropyl ring together with the carbon atom to which R2 is attached, and salts, solvates and solvates of the salts thereof.

[0115] In another possible subgroup of compounds of formula I, R6 represents a group of formula a), [ka]

[0116] In the formula, *** represents a bond to the adjacent piperidine ring. and R7 represents hydrogen; R'7 represents methyl, ethyl, n-propyl, iso-propyl, ethoxy, methoxymethyl, monofluoromethyl, difluoromethyl, trifluoromethyl, 3,3-difluorocyclobutylmethoxy, 2,2,2-trifluoroethoxymethyl, cyclopropylmethyl, 1-fluoromethylcyclopropylmethoxymethyl, 1-difluoromethylcyclopropylmethoxymethyl, 1-trifluoromethylcyclopropylmethoxymethyl, cyclobutylmethoxy, cyclopropylmethoxy, cyclobutyloxymethyl, cyclopropylmethoxymethyl, 3,3-difluorocyclobutylmethoxymethyl, 3-fluorobutyloxymethyl, 2.2-difluorocyclopropylmethoxy, cyclobutyloxy, 3.3-difluorocyclobutyloxy, 2-fluoroethyl, cyclopropyl, cyclobutyl, 2-methoxyethyl or tert-butyl; or R7 and R'7 are bonded to each other and together with the carbon atom to which they are attached form a cyclopropyl ring; and salts, solvates and solvates of the salts thereof.

[0117] In another possible subgroup of compounds of formula I, R6 represents a group of formula a), [ka]

[0118] where *** indicates a bond to the adjacent piperidine ring, and R7 represents hydrogen; R'7 represents methyl; or R7 and R'7 are bonded to each other and together with the carbon atom to which they are attached form a cyclopropyl ring; and salts, solvates and solvates of the salts thereof.

[0119] In another possible subgroup of compounds of formula I, n is 1.

[0120] In a further possible subgroup of compounds of formula I, m is 1.

[0121] In yet another possible subgroup of compounds of formula I, p is 1.

[0122] In yet another possible subgroup of compounds of formula I, q is 2.

[0123] In a further possible subgroup of compounds of formula I, the compounds are N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, 2-[4-(5-azaspiro[2.5]octan-5-yl)piperidin-1-yl]-N-[(3,5-difluoropyridin-2-yl)methyl]-1,3-thiazole-5-carboxamide, N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R* 4-chloro-N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide or N-[1-(3,5-difluoropyridin-2-yl)cyclopropyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, and salts, solvates and solvates of the salts thereof.

[0124] A preferred compound of formula (I) is N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidin]-1'-yl]-1,3-thiazole-5-carboxamide, and salts, solvates and solvates of the salts thereof.

[0125] The compounds of formula (I), their preparation and their action as selective inhibitors of the adrenergic receptor ADRA2C or for the treatment and / or prevention of sleep-induced dyspnea, such as central and obstructive sleep apnea, snoring (primary and obstructive snoring), dysphagia, peripheral and cardiovascular disorders, including diabetic microangiopathy and peripheral vascular disorders, and central nervous system, including neurodegenerative and neuroinflammatory disorders, are generally disclosed in WO2021089683A1, in particular said compounds are an explicit part of the description of the present invention and are incorporated herein by reference.

[0126] The term effective amount as used herein refers to an amount of a combination of a compound of formula (I) and a noradrenaline reuptake inhibitor effective for the treatment and / or prevention of sleep-related breathing disorders, preferably obstructive and central sleep apnea and snoring.

[0127] The present invention relates to the combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor for use in a method for the treatment and / or prevention of respiratory disorders, sleep-related respiratory disorders, obstructive sleep apnea, central sleep apnea and snoring.

[0128] The present invention also relates to the use of a combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor for the production of a medicament for the treatment and / or prevention of respiratory disorders, sleep-related respiratory disorders, obstructive sleep apnea, central sleep apnea and snoring.

[0129] Furthermore, the present invention relates to the use of one or more noradrenaline reuptake inhibitors in combination with one or more alpha2-adrenergic receptor subtype C (alpha-2C) antagonists for the preparation of a pharmaceutical composition for treating sleep-related breathing disorders.

[0130] A further subject of the present invention is the use of a combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor together with one or more other active compounds in a method for the treatment and / or prevention of sleep-related breathing disorders, preferably obstructive and central sleep apnea and snoring.

[0131] A further subject of the present invention is a medicament comprising at least one combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor, in combination with one or more inert, non-toxic, pharma- ceutical suitable excipients, for use in a method for the treatment and / or prevention of sleep-related breathing disorders, preferably obstructive and central sleep apnea and snoring.

[0132] The present invention further relates to a medicament comprising at least one combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor in combination with one or more other active compounds and with one or more inert, non-toxic, pharma- ceutical suitable excipients for use in a method for the treatment and / or prevention of sleep-related breathing disorders, preferably obstructive and central sleep apnea and snoring.

[0133] The present invention is also a method for the treatment and / or prevention of sleep-related breathing disorders by systemically and / or locally administering a therapeutically effective amount of a medicament comprising at least one combination of a compound of formula (I) and a noradrenaline reuptake inhibitor, or at least one combination of a compound of formula (I) and a noradrenaline reuptake inhibitor according to the present invention in combination with an inert, non-toxic, pharma- ceutically acceptable excipient.

[0134] The combination of the compound of formula (I) and a noradrenaline reuptake inhibitor according to the invention can be used alone or, if necessary, in combination with one or more other pharmacologically active substances, provided that the combination does not result in undesirable and unacceptable side effects. Preferred examples of combinations suitable for the purpose of treating sleep-related breathing disorders, preferably obstructive and central sleep apnea and snoring, include: Respiratory stimulants, for example and preferably theophylline, doxapram, nikethamide or caffeine; psychostimulants, for example and preferably modafinil or armodafinil; Amphetamine and amphetamine derivatives, for example and preferably amphetamine, methamphetamine or methylphenidate; Serotonin reuptake inhibitors, for example and preferably fluoxetine, paroxetine, citalopram, escitalopram, sertraline or fluvoxamine; 5-HT2 receptor antagonists and serotonin reuptake inhibitors, such as, preferably, trazodone; Serotonin precursors, for example and preferably L-tryptophan; noradrenergic and specific serotonergic antidepressants, for example and preferably mirtazapine; Tricyclic antidepressants, for example and preferably amitriptyline, protriptyline, doxepin, trimipramine, imipramine, clomipramine or desipramine; Muscarinic receptor antagonists, for example and preferably oxybutynin or (R)-oxybutynin; GABA receptor agonists, for example, preferably baclofen; Glucocorticoids, for example and preferably fluticasone, budesonide, beclomethasone, mometasone, tixocortol or triamcinolone; · Cannabinoid receptor agonists; Carboanhydrase inhibitors, for example and preferably acetazolamide, methazolamide or diclophenamide; Opioid and benzodiazepine receptor antagonists, for example and preferably flumazenil, naloxone or naltrexone; cholinesterase inhibitors, for example and preferably neostigmine, pyridostigmine, physostigmine, donepezil, galantamine or rivastigmine; an appetite suppressant, for example and preferably sibutramine, opiramate, phentermine, a lipase inhibitor or a cannabinoid receptor antagonist; Mineralocorticoid receptor antagonist.

[0135] A preferred subject of the present invention is a medicament comprising a combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor in combination with one or more further active compounds selected from the group consisting of muscarinic receptor antagonists, 5-HT2 receptor antagonists and serotonin reuptake inhibitors, mineralocorticoid receptor antagonists, diuretics, corticosteroids.

[0136] A preferred subject of the present invention is a medicament comprising a combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor for the treatment and / or prevention of respiratory disorders, sleep-related respiratory disorders, obstructive sleep apnea, central sleep apnea and snoring.

[0137] A preferred subject of the present invention is the combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor, and a combination comprising one or more other active compounds selected from the group consisting of muscarinic receptor antagonists, 5-HT2 receptor antagonists and serotonin reuptake inhibitors, mineralocorticoid receptor antagonists, diuretics, corticosteroids, for use in a method for the treatment and / or prevention of sleep-related breathing disorders, preferably obstructive and central sleep apnea and snoring.

[0138] Another preferred subject of the invention is a medicament comprising a combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor in combination with one or more further active compounds selected from the group consisting of muscarinic receptor antagonists.

[0139] In one preferred embodiment of the invention, the inventive combination is administered in combination with a muscarinic receptor antagonist, by way of example and preferably oxybutynin or (R)-oxybutynin.

[0140] In one preferred embodiment of the invention, the inventive combination is administered in combination with a muscarinic receptor antagonist, by way of example and preferably (R)-oxybutynin.

[0141] Another preferred subject of the invention is a medicament comprising a combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor in combination with one or more other active compounds selected from the group consisting of 5-HT2 receptor antagonists and serotonin reuptake inhibitors.

[0142] In one preferred embodiment of the invention, the inventive combination is administered in combination with a 5-HT2 receptor antagonist and a serotonin reuptake inhibitor, by way of example and preferably trazodone.

[0143] In one preferred embodiment of the invention, the inventive combination is administered in combination with a mineralocorticoid receptor antagonist, by way of example and preferably spironolactone, eplerenone or finerenone.

[0144] In one preferred embodiment of the invention, the combination of the invention is administered in combination with a diuretic, for example and preferably furosemide, bumetanide, torasemide, bendroflumethiazide, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methyclothiazide, polythiazide, trichlormethiazide, chlorthalidone, indapamide, metolazone, quinethazone, acetazolamide, dichlorphenamide, methazolamide, glycerol, isosorbide, mannitol, amiloride or triamterene.

[0145] In one preferred embodiment of the invention, the compounds of the invention are administered in combination with a corticosteroid, by way of example and preferably prednisone, prednisolone, methylprednisolone, triamcinolone, dexamethasone, betamethasone, beclomethasone, flunisolide, budesonide or fluticasone.

[0146] If necessary, the arylpiperazines of formula (I) according to the invention can also be used in conjunction with the use of one or more medical technical devices or auxiliaries, provided that this does not result in undesirable and unacceptable side effects. Medical devices and auxiliaries suitable for such combined use are, by way of example and preferably: Devices for positive airway pressure ventilation, such as, for example and preferably, CPAP (Continuous Positive Airway Pressure) devices, BiPAP (Bi-Level Positive Airway Pressure) devices and IPPV (Intermittent Positive Airway Pressure Ventilation) devices; · Hypoglossal nerve stimulator; · Intra-oral appliances, such as, preferably, protruding braces; · Disposable nasal valves; Nasal stents.

[0147] The substituted heterocyclic carboxamides of formula (I) and noradrenaline reuptake inhibitors according to the present invention can act systemically and / or locally.To this end, they can be administered in a suitable manner, for example, orally, parenterally, pulmonary, intrapulmonary (inhalation), nasal, intranasal, pharyngeal, lingual, sublingual, buccal, rectal, dermal, transdermal, conjunctival or auricular, or as an implant or stent.

[0148] A further subject of the present invention is a pharmaceutical composition comprising a combination of a compound of formula (I) according to the invention and a noradrenaline reuptake inhibitor for systemic and / or local administration by oral, parenteral, pulmonary, intrapulmonary (inhalation), nasal, intranasal, pharyngeal, lingual, sublingual, buccal, rectal, dermal, transdermal, conjunctival or aural route or as an implant or stent. The preferred administration route is the oral route.

[0149] For these administration routes, the compounds according to the invention can be administered in suitable dosage forms.

[0150] For oral administration, dosage forms which release the compounds according to the invention rapidly and / or in a modified manner and which contain the compounds according to the invention in crystalline and / or amorphous and / or dissolved form are suitable in accordance with the state of the art, e.g. tablets (uncoated or coated tablets, e.g. having a gastric juice-resistant or slow-dissolving or insoluble coating which controls the release of the compounds according to the invention), tablets or films / wafers, films / lyophilisates which disintegrate rapidly in the oral cavity, capsules (e.g. hard or soft gelatin capsules), dragees, granules, pellets, powders, emulsions, suspensions, aerosols or solutions.

[0151] Parenteral administration can be performed by omitting the absorption step (e.g., intravenous, intraarterial, intracardiac, intraspinal or intralumbar administration) or by accompanying absorption (e.g., intramuscular, subcutaneous, intradermal, transdermal or intraperitoneal administration).Dosage forms suitable for parenteral administration include injection and infusion preparations in the form of solutions, suspensions, emulsions, lyophilisates or sterile powders.

[0152] Other routes of administration are suitable, e.g. inhalation formulations (including powder inhalers and nebulizers), nasal drops, solutions or sprays, throat sprays, tablets for lingual, sublingual or buccal administration, tablets, films / wafers or capsules, suppositories, oral or ophthalmic formulations, vaginal capsules, aqueous suspensions (lotions, shakeable mixtures), lipophilic suspensions, ointments, creams, transdermal therapeutic systems (e.g. plasters), milks, pastes, foams, dusting powders, implants or stents.

[0153] Oral administration is preferred.

[0154] The compound according to the present invention can be converted into the dosage form described.This can be carried out by mixing with inert, non-toxic, pharma- ceutically suitable additives in a manner known per se.These additives include carriers (e.g., microcrystalline cellulose, lactose, mannitol), solvents (e.g., liquid polyethylene glycol), emulsifiers and dispersants or wetting agents (e.g., sodium dodecyl sulfate, polyoxysorbitan oleate), binders (e.g., polyvinylpyrrolidone), synthetic and natural polymers (e.g., albumin), stabilizers (e.g., antioxidants such as ascorbic acid), colorants (e.g., inorganic pigments such as iron oxide), and flavor or odor correctors.

[0155] In general, to achieve effective results in oral administration, it has been found to be advantageous to administer amounts of about 0.01 to 100 mg / kg, preferably about 0.1 to 10 mg / kg of body weight. In nasal or pharyngeal administration, the dosage is about 0.01 μg / kg to 1000 μg / kg, preferably about 0.1 to 10 μg / kg of body weight. Nevertheless, it may sometimes be necessary to deviate from said amounts, i.e. depending on the body weight, the route of administration, the individual response to the active substance, the nature of the preparation and the time or interval at which the administration takes place. Thus, while in some cases it may be sufficient to manage below the minimum amounts mentioned above, in other cases the stated upper limit must be exceeded. In the case of administration of larger amounts, it may be advisable to divide these into several individual administrations throughout the day.

[0156] The preferred administrations are the oral route of the compound of formula (I) and the oral route of the noradrenaline reuptake inhibitor.

[0157] For oral administration, dosage forms which release the compounds according to the invention rapidly and / or in a modified manner and which contain the compounds according to the invention in crystalline and / or amorphous and / or dissolved form are suitable in accordance with the state of the art, e.g. tablets (uncoated or coated tablets, e.g. having a gastric juice-resistant or slow-dissolving or insoluble coating which controls the release of the compounds according to the invention), tablets or films / wafers, films / lyophilisates which disintegrate rapidly in the oral cavity, capsules (e.g. hard or soft gelatin capsules), dragees, granules, pellets, powders, emulsions, suspensions, aerosols or solutions. EXAMPLES

[0158] C. Experimental Methods - Combination of α2-Adrenergic Receptor Subtype C (Alpha-2C) Antagonists and Noradrenaline Reuptake Inhibitors The advantageous pharmacological properties of a combination of an α2-adrenergic receptor subtype C (alpha-2C) antagonist and a noradrenaline reuptake inhibitor can be determined by the following method.

[0159] The therapeutic potential of a combination of an alpha2-adrenergic receptor subtype C (alpha-2C) antagonist and a noradrenaline reuptake inhibitor according to the invention in sleep apnea can be evaluated preclinically in a porcine model of obstructive sleep apnea (OSA).

[0160] Using negative pressure it is possible to induce collapse and therefore obstruction of the upper airway in anesthetized spontaneously breathing pigs (Wirth KJ et al., Sleep 36(5)(2013) pp.699-708).

[0161] German Landrace pigs are used for this model. The pigs are anesthetized and the tracheotomy is performed. Two tracheal cannulas are inserted into the trachea, one in the rostral part of the trachea and the other in the caudal part. Using a connecting piece, the rostral cannula is connected to a tube to a negative pressure device and a distal tracheal cannula. The distal tracheal cannula serves for free tracheal breathing and is further connected to a tube with an open end via a connecting piece that bypasses the upper airway. By proper opening and clamping of these tubes, breathing can be switched from nasal breathing to bypassing the upper airway and breathing through the caudal tracheal cannula, connecting the (isolated) upper airway to a negative pressure device and generating airflow in the inspiratory direction.

[0162] At specific time points, the pigs are breathed through a caudal cannula and the collapsibility of the upper airway is tested by applying negative pressures of -50, -100 and -150 cm H2O to the upper airway. This collapses the upper airway, which is manifested as an interruption in airflow and a drop in pressure in the tube system. This test is performed before administration of the test substance and at regular intervals after administration of the test substance. An appropriately effective test substance is able to prevent this collapse of the airway during the inspiratory phase.

[0163] In this swine model of OSA, systemic administration of an alpha-2-adrenergic receptor subtype C (alpha-2C) antagonist of Formula (I), such as N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide, at 0.01 mg / kg administered intraduodenal route inhibited upper airway collapsibility at all negative pressures of -50, -100 and -150 cm head (cm H2O) in all pigs at no time point after intraduodenal administration. At 120 minutes after intraduodenal administration, upper airway collapsibility was suppressed by negative pressures of -50 cm head (cmH2O) and -100 cm head (cmH2O), and at 150 minutes after intraduodenal administration, upper airway collapsibility was suppressed by negative pressure of -50 cm head (cmH2O) ( Tables 1, 2 and 3 and Figure 1(See ). Systemic administration of the norepinephrine reuptake inhibitor atomoxetine, administered as a bolus injection of 20 μg / kg followed by an intravenous infusion of 12.5 μg / kg / h for 4 hours, did not prevent upper airway collapsibility at any time point in all pigs at all negative pressures of -50, -100, and -150 cm head (cm H2O) ( Tables 4, 5 and 6 and Figure 2 (See, for example, US Pat. No. 5,393,141, JP 2002-1136663 A1.) The combination of this non-effective dose of the alpha2-adrenergic receptor subtype C (alpha-2C) antagonist N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide of formula (I), and this non-effective dose of the noradrenaline reuptake inhibitor atomoxetine, inhibited upper airway collapsibility for more than five and a half hours at all negative pressures of -50, -100 and -150 cm head (cmH2O) ( Tables 7, 8 and 9 and Figure 3 (See ).

[0164] Figure 1 : Effect of intraduodenal administration of 0.01 mg / kg of the alpha2-adrenergic receptor subtype C (alpha-2C) antagonist N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide of formula (I) at 0 min on upper airway collapsibility at different negative pressure levels. Percentage of pigs without collapse is shown. Mean values.

[0165] Table 1: Intraduodenal administration of 0.01 mg / kg of the alpha2-adrenergic receptor subtype C (alpha-2C) antagonist N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide of formula (I) at a negative pressure of -50 cm head (cmH2O). [Table 1]

[0166] Table 2: Intraduodenal administration of 0.01 mg / kg of the alpha2-adrenergic receptor subtype C (alpha-2C) antagonist N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide of formula (I) at a negative pressure of -100 cm head (cmH2O). [Table 2]

[0167] Table 3: Intraduodenal administration of 0.01 mg / kg of the alpha2-adrenergic receptor subtype C (alpha-2C) antagonist N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide of formula (I) at a negative pressure of -150 cm head (cmH2O). [Table 3]

[0168] Tables 4, 5 and 6, and Figure 2: Effect of intravenous administration of the noradrenaline reuptake inhibitor atomoxetine at 20 μg / kg bolus injection at 0 min followed by 12.5 μg / kg / h intravenous infusion for 4 h on upper airway collapsibility at different levels of negative pressure. Percentage of pigs without collapse is shown. Mean values.

[0169] Table 4: - Administer atomoxetine, a noradrenaline reuptake inhibitor, as a bolus injection of 20 μg / kg intravenously at a negative pressure of 50 cm head (cmH2O), followed by an intravenous infusion of 12.5 μg / kg / h for 4 hours [Table 4]

[0170] Table 5:-Intravenous administration of the noradrenaline reuptake inhibitor atomoxetine at a bolus injection of 20 μg / kg at a negative pressure of 100 cm head (cmH2O) followed by an intravenous infusion of 12.5 μg / kg / h for 4 hours [Table 5]

[0171] Table 6: -Intravenous administration of the noradrenaline reuptake inhibitor atomoxetine at a bolus injection of 20 μg / kg at a negative pressure of 100 cm head (cmH2O) followed by an intravenous infusion of 12.5 μg / kg / h for 4 hours [Table 6]

[0172] Table 7: A combination of a non-effective dose of N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and a non-effective dose of the noradrenaline reuptake inhibitor atomoxetine prevents upper airway collapse at a negative pressure of -50 cm head (cmH2O) [Table 7]

[0173] Table 8: A combination of a non-effective dose of N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and a non-effective dose of the noradrenaline reuptake inhibitor atomoxetine prevents upper airway collapse at a negative pressure of -100 cm head (cmH2O) [Table 8]

[0174] Table 9: A combination of a non-effective dose of N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and a non-effective dose of the noradrenaline reuptake inhibitor atomoxetine prevents upper airway collapse at a negative pressure of -150 cm head (cmH2O) [Table 9]

[0175] It was found that the combination of the non-effective dose of the adrenergic receptor ADRA2C inhibitor and the non-effective dose of the noradrenaline reuptake inhibitor atomoxetine suppresses upper airway collapsibility with synergistic effectiveness compared with each treatment alone.From the above data, it can be inferred that the combination of the adrenergic receptor ADRA2C inhibitor of formula (I) and the noradrenaline reuptake inhibitor suppresses upper airway collapsibility with synergistic effectiveness compared with each treatment alone, and is therefore suitable for treating sleep-related breathing disorders, preferably obstructive and central sleep apnea and snoring. [Brief description of the drawings]

[0176] [Figure 1] Effect of intraduodenal administration of 0.01 mg / kg of the alpha2-adrenergic receptor subtype C (alpha-2C) antagonist N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide of formula (I) at 0 minutes on upper airway collapsibility at different negative pressure levels. Percentage of pigs without collapse is shown. Mean values. [Diagram 2] Effect of intravenous administration of the noradrenaline reuptake inhibitor atomoxetine at 20 μg / kg bolus injection at 0 min followed by 12.5 μg / kg / h intravenous infusion for 4 h on upper airway collapsibility at different levels of negative pressure. Percentage of pigs without collapse is shown. Mean values. [Diagram 3]Inhibitory effect of a combination of a non-effective dose of N-[(3,5-difluoropyridin-2-yl)methyl]-2-[(3R)-3-methyl[1,4'-bipiperidine]-1'-yl]-1,3-thiazole-5-carboxamide and a non-effective dose of the norepinephrine reuptake inhibitor atomoxetine on upper airway collapsibility.

Claims

1. The following structural formula 【Chemistry 1】 or a salt, solvate, or solvate of the salt thereof; and Combination noradrenaline reuptake inhibitors.

2. the noradrenaline reuptake inhibitor is selected from the group of norepinephrine selective reuptake inhibitors including atomoxetine, 4-hydroxyatomoxetine, CP-39,332, daredalin, edivoxetine, esreboxetine, lortalamine, nisoxetine, reboxetine, talopram, talsupram, tandamine, amedalin, and virox; or 2. The combination of claim 1, wherein the norepinephrine reuptake inhibitor is selected from the group of non-selective norepinephrine reuptake inhibitors including amitriptyline, amoxapine, bupropion, cyclazindol, desipramine, desvenlafaxine, dexmethylphenidate, diethylpropion, doxepin, duloxetine, imipramine, levomilnacipran, manifaxine, maprotiline, methylphenidate, milnacipran, nefazodone, nortriptyline, phendimetrazine, protriptyline, radafaxine, tapentadol, teniloxazine, and venlafaxine.

3. 2. The combination of claim 1, wherein the noradrenaline reuptake inhibitor is atomoxetine, reboxetine, or desipramine.

4. 2. The combination of claim 1, wherein the noradrenaline reuptake inhibitor is atomoxetine.

5. A combination according to any one of claims 1 to 4 for use in a method for the treatment and / or prevention of respiratory disorders, sleep-related respiratory disorders, obstructive sleep apnea, central sleep apnea or snoring.

6. Use of a combination according to any one of claims 1 to 4 for the manufacture of a medicament for the treatment and / or prevention of respiratory disorders, sleep-related respiratory disorders, obstructive sleep apnea, central sleep apnea or snoring.

7. A medicament comprising a combination according to any one of claims 1 to 4 in combination with one or more inert, non-toxic, pharmaceutically suitable excipients.

8. A medicament comprising a combination according to any one of claims 1 to 4 in combination with one or more further active ingredients selected from the group consisting of muscarinic receptor antagonists, 5-HT2 receptor antagonists, serotonin reuptake inhibitors, mineralocorticoid receptor antagonists, diuretics and corticosteroids.

9. The medicament according to claim 7 for the treatment and / or prevention of respiratory disorders, sleep-related respiratory disorders, obstructive sleep apnea, central sleep apnea or snoring.

10. 7. The use according to claim 6, wherein the sleep-related breathing disorder is obstructive sleep apnea and central sleep apnea or snoring.

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