HUE028378T2 - Helyettesített 4,5,6,7-tetrahidro-1H-pirazolo[4,3-c]piridinek, gyógyszerként való alkalmazásuk, és az ezeket tartalmazó gyógyászati készítmények - Google Patents

Description

Description [0001] The invention relates to 4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine compounds of the formula I,

[0002] The compounds of formula I act on the TASK-1 (KCNK3) potassium channel. The compounds are suitable for the treatment of several pathologies and particularly suitable as antiarrhythmic active ingredients, in particular for the treatment and prophylaxis of atrial arrhythmias, for example atrial fibrillation (AF) or atrial flutter.

[0003] Potassium channels are widespread membrane proteins which, owing to their influences on cell membrane potentials, play an important role in many physiological processes. Within the various classes of the potassium channels, a distinction is drawn on the basis of their molecular structure between three large groups which are characterized by the number of transmembrane domains (2, 4 or 6). The group of the potassium channels with four transmembrane segments is delimited from the two others in that their representatives each have two pore domains, which is why these channels are also referred to as K2p channels (Coetzee W.J. et al; Molecular diversity of K+ channels; Ann. New York Acad. Sei. 1999 (868), 233-285). In functional terms, K2p channels are characterized in that the "leak" or "background" currents flow through them, which play an important role for the resting membrane potential and hence the excitability of nerve or muscle cells.

[0004] A family which is of particular interest among the K2P channels is that of the TASK channels (tandem of P domains in a weak inwardly rectifying K+ channel, [TWIK]-related acid-sensitive K+ channels), which include TASK-1, TASK-3, and TASK-5 subtype (D.A. Bayliss, P. Barrett, Trends in Pharmacological Sciences, 2008, 29(11), 566-575). Other terms used in the literature for the underlying genes are KCNK3 or K2P3.1 (TASK-1), KCNK9 or K2P9.1 (TASK-3) and KCNK15 or K2P15.1 (TASK-5). The greatest homology within this family is possessed by the TASK-1 and TASK-3 channels with an amino acid identity of more than 50%. Dimerization of K2P channels forms functional potassium channels with a total of four pore units. The streams which flow through these channels are referred to in the literature as IKso stream. In addition to a homodimerization of, for example, twoTASK-1 or two TASK-3 proteins, heterodimerization of TASK-1 and TASK-3 is also possible in this context (Berg A.P., Talley E.M., Manger J.P., Bayliss D.A.; Motoneurons express Heteromeric TWIK-related acid-sensitive K+ (TASK) Channels containing TASK-1 (KCNK3) and TASK-3 (KCNK9) subunits; J. Neuroscience 2004 (24), 6693 - 6702).

[0005] The TASK channels are notable in particular for their very strong dependence upon the extracellular pH in the physiological range (pK ca. 6,5-7,5). The channels are inhibited at acidic pH and activated at alkaline pH. Owing to this pH dependence, the physiological function of a sensor which translates small changes in the extracellular pH to corresponding cellular signals is ascribed to the TASK channels (Duprat F., Lesage F., Fink M., Reyes R., Heurteaux C., Lazdunski M.; TASK, a human background K+ channel to sense external pH variations near physiological pH; EMBO J. 1997 (16), 5464 - 5471; Patel A.J., Honore E.; Properties and modulation of mammalian 2P domain K+ channels; Trends Neurosci. 2001 (24), 339 - 346).

[0006] TASK-1 knock-out mice show a mild phenotype and have been described and appear generally in good health and show normal breeding behaviour (Journal of Neuroscience (2005), 25(49), 11455-11467).

[0007] TASK-1 is expressed in the brain and also in spinal ganglia and some peripheral tissues, for example pancreas, placenta, uterus, lung, heart, kidney, small intestine and stomach. In addition, TASK-1 has been detected in the chem-osensitive cells of the brainstem and of the carotid bodies, and also the motor neurons of the hypoglossal nerve (Medhurst A.D., Rennie G., Chapman C.G., Meadows H., Duckworth M.D., Kelsell R.E., Glober 1.1., Pangalos M.N.; Distribution analysis of human two pore domain potassium channels in tissues of the central nervous system and periphery; Mol. Brain Res. 2001 (86), 101 - 114).

[0008] Electrical currents which are caused by TASK-1 potassium channels have been detected in motor neurons of the hypoglossal nerve, a motor cranial nerve which possesses the most important function for the maintenance and patency of the upper respiratory pathways, and locus coeruleus. It has been found that TASK-1 channels are involved in respiratory regulation in respiratory neurons of the brainstem, in carotid bodies and in motor neurons of the hypoglossal nerve, and also in neuroepithelial cells of the lung. In the event of inadequate respiration (hypoxia, hindered breathing) and in the event of physical stress, either via a rise in the C02 concentration and the resulting acidosis or via acidic metabolites, there is a lowering of the pH and hence a blockage of the pH-dependent TASK-1 channels. This depolarizes the cells, which leads to the activation of the neurons involved in the respiratory regulation (Buckler K.J., Williams B.A., Honore E.; An oxygen-, acid-and anaesthetic-sensitive TASK-like background potassium channel in rat arterial chem-oreceptor cells; J. Physiol. 2000 (525), 135 - 142; Bayliss D.A., Talley E.M., Sirois J.E., Lei Q.; TASK-1 is a highly modulated pH-sensitive ’leak’ K+ channel expressed in brainstem respiratory neurons; Respiration Physiology 2001 (129), 159-174).

[0009] An increase in the activity of chemosensitive neurons in conjunction with an activation of the motor neurons of the hypoglossal nerve through blockage of the TASK-1 channel can stimulate respiration and simultaneously stabilize the upper airways to protect them from collapse and occlusion. Moreover, snoring can be inhibited by stabilizing the upper airway via an increase in pharyngeal muscle activity. The blockage of the TASK-1 ion channels is therefore useful in the treatment of respiratory disorders, for example of sleep apnea (Brendel, J.; Goegelein, H.; Wirth, K.; Kamm, W., WO 2007/124849).

[0010] In cultivated granulosa cells of the cerebellum, it has been shown that genetic inactivation of TASK channels brings about neuroprotective action (Lauritzen I., Zanzouri M., Honoré E., Duprat F., Ehrengruber M.U., Lazdunski M., Patel A.J.; K+-dependent cerebellar granule neuron apoptosis - Role of Task leak K+ channels; J. Biol. Chem. 2003 (278), 32068-32076). It has also been shown that TASK-1 channels are responsible for programmed cell death (apoptosis) in granulosa cells, and that the cell death can be prevented by blocking the TASK-3. Thus, the development of specific inhibitors oftheTASK-1/3 channels can be useful for the treatment of neurodegenerative disorders (Patel A.J., Lazdunski M., The 2P-domain K+ channels: role in apoptosis and tumorigenesis, Pflügers Arch. 2004 (448), 261-273).

[0011] It has been stated that TASK-1 is relevant for setting the resting membrane potential and balancing neuronal excitability that is expressed on T cells and neurons, and is a key modulator of T cell immunity and neurodegeneration in autoimmune central nervous system inflammation. After induction of experimental autoimmune encephalomyelitis, an experimental model mimicking multiple sclerosis, TASK1 (-/-) mice showed a significantly reduced clinical severity and markedly reduced axonal degeneration compared with wild-type controls. T cells from TASK1 (-/-) mice displayed impaired T cell proliferation and cytokine production, while the immune repertoire is otherwise normal. In addition to these effects on systemic T cell responses, TASK1 exhibits an independent neuroprotective effect which was demonstrated using both a model of acutely prepared brain slices cocultured with activated T cells as well as in vitro cultivation experiments with isolated optic nerves. Preventive blockade of TASK1 significantly ameliorated experimental autoimmune encephalomyelitis after immunization and significantly reduced disease severity and was capable of lowering progressive loss of brain parenchymal volume as assessed by magnetic resonance imaging. Thus TASK-1 blockers are potent compounds useful for the therapy of inflammatory and degenerative central nervous system disorders (Bittner Stefan; Meuth Sven G; Gobel Kerstin; Melzer Nico; Herrmann Alexander M; Simon Ole J; Weishaupt Andreas; Budde Thomas; Bayliss Douglas A; Bendszus Martin; Wiendl Heinz, Brain : ajournai of neurology (2009), 132(Pt9), 2501-16).

[0012] TASK-1, a member of two-pore-domain (K2P) potassium channel family, has emerged as a target for the pharmacological treatment of atrial fibrillation recently. Two-pore-domain (K2P) potassium channels mediate background potassium currents, stabilizing resting membrane potential and expediting action potential repolarization. In the heart, TASK-1 channels have been shown to play a role in cardiac repolarization, (Basic Res Cardiol. 2011 Jan;106(1 ):75-87, Putzke C, Wemhöner K, Sachse FB, Rinné S, Schlichthörl G, Li XT, Jaé L, Eckhardt I, Wischmeyer E, Wulf H, Preisig-Müller R, Daut J, Decher N (2007), Cardiovascular Research, 75: 59-68).

[0013] Atrial fibrillation (AF) and atrial flutter are extremely common cardiac rhythm disorder that causes substantial morbidity and contributes to mortality (Journal of Clinical Invest. 2011 ; 121 (8):2955-2968). Presently available therapeutic approaches have major limitations, including limited efficacy and potentially serious side effects such as malignant ventricular arrhythmia induction or negative inotropic effects. The occurrence of AF increases with age and frequently leads to fatal sequelae such as stroke. The class I and III antiarrhythmics in use at present reduce the rate of recurrence of AF but are used to only a limited extent because of their potential proarrhythmic side effects and limited efficacy. The growing incidence of AF emphasizes the importance of identifying appropriate treatments, particularly drugs, that are safe, effective, and associated with improved clinical outcomes. It has been shown that in atrial fibrillation and flutter reentrant mechanism play an important role in the induction and maintenance of the arrhythmia. Such reentries or reentrant waves occur when the cardiac tissue has a low conduction velocity and, at the same time, short refractory periods. Increasing the myocardial refractory period by prolonging the action potential is an acknowledged mechanism for terminating arrhythmias or for preventing them to develop (T. J. Colatsky et al., Drug Dev. Res. 19, 1990, 129 - 140; "Potassium channels as targets for antiarrhythmicdrug action"). The length of the action potential is essentially determined by the extent of repolarizing K+ currents which flow out of the cells through various K+ channels. TASK-1 constitutes one of those repolarizing potassium currents. Its inhibition prolong the action potential and thereby refractoriness.

[0014] Most of the known class III antiarrhythmics (e.g. dofetilide, E4031 and d-sotalol) block predominantly or exclusively the rapidly activating potassium channel IKr, which can be detected both in cells of the human ventricle and in the atrium. It has emerged that these compounds have an increased proarrhythmic risk at heart rates which are low or normal, and arrhythmias referred to as torsades de pointes have been observed in particular (D. M. Roden, Am. J.

Cardiol. 72, 1993, 44B - 49B; "Current status of class III antiarrhythmic drug therapy"). Apart from this proarrhythmic risk, the therapeutic efficacy of the lKr blockers has been found to decline under the conditions of tachycardia (electrical tachycardie atrial remodelling).

[0015] TASK-1 expression in the human heart has been shown to be restricted to the atria with no or very little expression in the ventricles. A further advantage is that TASK-1 expression is not decreased but even slightly increased in atrial fibrillation patients compared with sinus rhythm patients, by contrast a decreased expression of other atrial K+ channels has been reported in atrial fibrillation patients compared with sinus rhythm patients: see for example Basic. Res. Cardiol. 2003, 98, 137-148, JACC Vol. 37, No. 3, 2001). Thus, TASK-1 is still expressed in the target patient population (Journal of Molecular Medicine 2004, 308-316; European Journal of Physiology 2005, 450, 201-208, WO 2005/016965; Journal of Thoracic and Cardiovascular Surgery 2005).

[0016] In spite of the great physiological significance of the TASK channels, only very few pharmacological modulators of these channels are known to date in the literature.

[0017] It has been stated that an activation of the TASK-1 channel can be achieved by therapeutic concentrations of the inhalative anesthetics halothane and isoflurane (Patel A.J., Honoré E., Lesage F., Fink M., Romey G., Lazdunski M.; Inhalational anesthetics activate two-pore-domain background K+ channels; Nature Neurosci. 1999 (2), 422-426). Furthermore, some Kv1.5 blockers which also inhibit the TASK-1 channel are described in the state of the art (Brendel, J.; Goegelein, H.; Wirth, K.; Kamm, W„ WO 2007/124849, Brendel, J.; Englert, H. C.; Wirth, K.; Wagner, M.; Ruxer, J.-M.; Pilorge, F., WO 2006/136304). A1899, a previously described Kv1.5 blocker (Peukert, S., Brendel, J., Pirard, B., Brueggemann, A., Below, P., Kleemann, H.-W., Hemmerle, H., Schmidt, W.; Identification, Synthesis, and Activity of Novel Blockers of the Voltage-Gated Potassium Channel Kv1.5.; Journal of Medicinal Chemistry (2003), 46(4), 486-498) has been stated to be a TASK-1 blocker (Streit, A. K.; Netter, M. F., Kempf, F., Walecki, M., Rinne, S., Bollepalli, Μ. K.; Preisig-Mueller, R.; Renigunta, V.; Daut, J.; Baukrowitz, T.; Sansom, M. S. P.; Stansfeld, P. J.; Decher, N.. A Specific Two-pore Domain Potassium Channel Blocker Defines the Structure of the TASK-1 Open Pore; Journal of Biological Chemistry (2011 ), 286(16), 13977-13984). Also arachidonamide anandamide (an endogenous ligand of the cannabinoid receptor) and itsmethanandamide homolog have been described as TASK-1 blockers (MaingretF., Patel A. J., Lazdunski M., Honoré E.; The endocannabinoid anandamide is a direct and selective blocker of the background K+ channel TASK-1 ; EMBO J. 2001 (20), 47-54). Doxapram, which is used for the treatment of respiratory disorders has been stated to be a TASK-1 blocker (Cotten J.F., Keshavaprasad B., Laster M.J., Eger E.I., Yost C.S.; The Ventilatory Stimulant Doxapram Inhibits TASK Tandem Pore (K2P) Potassium Channel Function but Does Not Affect Minimum Alveolar Anesthetic Concentration; Anesth. Analg. 2006 (102) 779-785).

[0018] EP 0 086 422 A2 describes some N-acetylated tetrahydro-1H-pyrazolo[4,3-c]pyridine compounds. However no biological activity has been described for these compounds therein.

[0019] Thus, a goal of the present invention is to provide efficient TASK-1 inhibitors suitable for the treatment and prevention of TASK-1 related conditions. The present invention relates to TASK-1 blockers of the formula I wherein

A = (C6-C10)-aryl or a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C.|-C6)-alkyl-, (C.|-C6)-alkyl-0-and (C.|-C6)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = (C6-C10)-aryl or a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, (C1-C6)-alkyl-S-, (C1-C6)-alkyl-0-C(0)- and (C1-C6)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R1 = R5-C(=0)- or (C1-C6)-aikyl-S02-; R2 = H, (C.|-C6)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H, (C-|-C4)-alkyl-; R4 = H, (CrC4)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; R5 = H, (C-pCy-alkyl-, (C3-C6)-cycloalkyl-, (C1-C6)-alkyl-0-, (C1-C6)-alkyl-S-, (C1-C6)-alkyl-0-(C1-C6)-alkyi-, HO-(C1-C6)-alkyl-, (C3-C6)-cycloalkyl-(C.|-Cg)-alkyl-, (C6-C10)-aryl-, (Ce-C^J-aryl-ÎC^CgJ-alkyl-, R7R6N-, heteroar-yl, heteroaryl-ÎC^CgJ-alkyl-, aliphatic heterocycle, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl and 4 to 7 mem- bered aliphatic heterocycles comprising an oxygen atom, and wherein the aliphatic heterocycle may be optionally substituted with 1 to 3 substituents independently selected from the group of F, OH, (C^CgJ-alkyl-O- and (C-pCgJ-alkyl-, and wherein the heteroaryl residues are five- or six-mem bered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-; R6 = H, (C^CgJ-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH or (C-pCgJ-alkyl-O- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H, (C1-C6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine, and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts, and with the proviso if R5 is methyl and R2, R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-ac-etoxyphenyl, 2-chloro-phenyl, 3,4-dichlorophenyl, and with the proviso if R5 is methyl and R2, R3 and R4 are equal to H and X is a phenyl residue, the residue A is not phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethyloxy-phenyl, 3-trifluoromethyl-phenyl, 2-thiophenyl or 4-meth-ylthiophenyl, and with the proviso if R5 is methyl and R2 is methyl and R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl.

[0020] A preferred embodiment of the present invention relates to compounds, wherein A = phenyl or a five- or six-membered heteroaryl selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl or thiophen-3-yl, wherein phenyl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C.|-Cg)-alkyl-, (Ci-Cg)-alkyl-O-and (C1-C6)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein the heteroaryl group is optionally substituted with 1-3 residues selected independently from F, Cl, Br, CN, (Ci-Cg)-alkyl-, (Ci-Cg)-alkyl-O-and (C1-C6)-alkyl-S-, (C.|-Cg)-alkyl-0-C(0)- and (C1-C6)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R1 = R5-C(=0)- or (C1-C6)-alkyi-S02-; R2 = H, (C1-C4)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H,(C1-C2)-alkyl-; R4 = H,(C1-C2)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; R5 = H, (C1-C6)-alkyl-, (C3-C6)-cycloalkyl- (C1-C6)-alkyl-0-, (C1-C6)-alkyl-S-, (C1-C6)-alkyl-0-(C1-C6)-alkyl-, HO-(C.|-Cg)-alkyl-, (C3-Cg)-cycloalkyl-(C.|-Cg)-alkyl-, (C6-C10)-aryl-, (C6-C10)-aryl-(C.|-Cg)-alkyl-, R7R6N-, heteroaryl, heteroaryl-(C1-Cg)-alkyl-, aliphatic heterocycle, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl and 4 to 7 mem- bered aliphatic heterocycles comprising an oxygen atom, and wherein the aliphatic heterocycle may be optionally substituted with 1 to 3 substituents independently selected from the group of F, OH, (C.|-C6)-alkyl-0- and (C1-C6)-alkyl-, and wherein the heteroaryl residues are five-or six-mem bered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-; R6 = H, (C.|-C6)-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH- or (C1-C6)-alkyl-0- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H,(C1-C6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine, and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts.

[0021] Preferred compounds are, wherein A = phenyl, wherein the phenyl residue is optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, (C1-C4)-alkyl-0- and (CrC4)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = a five- or six-membered heteroaryl, selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, wherein the heteroaryl group is optionally substituted with 1-3 residues selected independently from F, Cl, Br, CN, (CrC6)-alkyl-, (CrC6)-alkyl-0-and (C1-C6)-alkyl-S-, (C1-C6)-alkyl-0-C(0)- and (C1-C6)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R1 = R5-C(=0)- or (CrC2)-alkyl-S02-; R2 = H, (Ci-C2)-alkyl-, cyclopropyl-; R3 = H, methyl-; R4 = H, methyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 = H, (C1-C4)-alkyl-, (C3-C6)-cycloalkyl- (C1-C2)-alkyl-0-, (C.|-C2)-alkyl-S-, (C-pC^-alkyl-O-methyl-, HO-(C1-C2)-alkyl-, (C3-C6)-cycloalkyl-(C1-C2)-alkyl-, phenyl, phenyl-(C.|-C2)-alkyl-, R7R6N-, heteroaryl, heteroar-yl-(C1-C4)-alkyl-, aliphatic heterocycle, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl, oxetanyl, tet- rahydrofuranyl, and tetrahydropyranyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents independently selected from the group of F, OH, (C1-C2)-alkyl-0- and (C1-C4)-alkyl-, and wherein the phenyl residue is optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (C1-C4)-alkyl-, (C1-C4)-alkyl-0-CN, (C1-C2)-alkyl-S02- wherein the heteroaryl residues are selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyra-zol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyri-dazin-4-yl, pyrazin-2-yl and pyrazin-3-yl, and wherein the heteroaryl residues are optionally substituted with 1 or 2 rests selected independently from F, Cl, Br, CF3, (C1-C4)-alkyl-, (C1-C4)-alkyl-0-, CN, (C1-C2)-aikyl-S02-; R6 = H, (CrC4)-alkyl-, cyclopropyl, wherein one hydrogen atom of the alkyl group may be replaced by an OH, methoxy or ethoxy residue; and R7 = H, methyl-, ethyl; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts.

[0022] Particularly preferred compounds are, wherein A = phenyl, wherein the phenyl residue is optionally substituted with 1 or 2 rests selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, and (C.|-C2)-alkyl-S-; X = a five- or six-membered heteroaryl, selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C1-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl-S02-; R1 = R5-C(=0)- or (C1-C2)-alkyl-S02-; R2 = H, methyl, ethyl, cyclopropyl; R3 and R4 = H, and R5 = methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert.-butyl, cyclopropyl or cyclobutyl; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts.

[0023] A further preferred embodiment of the present invention relates to compounds, wherein A = a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein the heteroaryl is substituted with 1-3 residues selected independently from F, Cl, Br, CN, (C1-C6)-alkyl-, (C.|-Cg)-alkyl-0-and (C1-C6)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = phenyl, thiophen-2-yl or thiophen-3-yl, wherein these residues are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (Ci-C6)-alkyl-, (C^CgJ-alkyl-O- and (C^CgJ-alkyl-S-, (Ci-Cg)-alkyl-O-C(O)- and (C.|-Cg)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R1 = R5-C(=0)- or (C1-C6)-alkyi-S02-; R2 = H, (C.|-Cg)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H, (C1-C4)-alkyl-; R4 = H,(C1-C4)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; R5 = H, (C1-C6)-alkyl-, (C3-C6)-cycloalkyl- (C1-C6)-alkyl-0-, (C-pCgJ-alkyl-S-, (C1-C6)-alkyl-0-(C1-C6)-alkyl-, HO-(C1-Cg)-alkyl-, (C3-C6)-cycloalkyl-(Ci-C6)-alkyl-, (C6-C10)-aryl-, (C6-C10)-aryl-(C.|-Cg)-alkyl-, R7R6N-, heteroaryl, heteroaryl-(C-|-Cg)-alkyl-, aliphatic heterocycle, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl and 4 to 7 mem- bered aliphatic heterocycles comprising an oxygen atom, and wherein the aliphatic heterocycle may be optionally substituted with 1 to 3 substituents selected from the group of F, OH, (C1-C6)-alkyl-0- and (CrCg)-alkyl-, and wherein the heteroaryl residues are five- or six-membered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, CN, (CrC2)-alkyl-S02-; R6 = H, (C.|-C6)-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH- or (C1-C6)-alkyl-0- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H, (C1-C6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine, and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts, with the proviso that A is not 4-methylthiophenyl if in compounds of formula I R5 is methyl and R2, R3 and R4 are hydrogen and X is phenyl.

[0024] Preferred compounds are, wherein A = 2-pyridyl, 3-pyridyl or4-pyridyl, wherein the pyridyl residues are substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C.|-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, and (C1-C2)-alkyl-S-; X = phenyl, thiophen-2-yl or thiophen-3-yl, wherein these residues are substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C1-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl-S02-; R1 = R5-C(=0)- or (CrC2)-alkyl-S02-; R2 = H, methyl, ethyl, cyclopropyl; R3 and R4 = H; and R5 = H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert.-butyl or wherein R5 = cyclopropyl, cyclobutyl, cyclopentyl or (C3-C6)-cycloalkyl-(C1-C2)-alkyl-; or wherein R5 = (C1-C2)-alkyl-0-, (CrC2)-alkyl-S-, or OCF3, or wherein R5 = (C1-C4)-alkyl-0-methyl-, HO-(CrC2)-alkyl-, or wherein R5 = phenyl or phenylmethyl-, wherein the phenyl residues are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (CrC2)-alkyl-, (CrC2)-alkyl-0-, CN, methyl-S02-; or wherein, R5 = R7R6N-, wherein R6 = H, (C1-C4)-alkyl-, cyclopropyl, wherein one hydrogen atom of the alkyl group may be replaced by an OH, methoxy or ethoxy residue; and R7 = H, methyl-, ethyl; or wherein R5 = heteroaryl, heteroaryl-(C.|-C6)-alkyl-, wherein the heteroaryl residues are selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyra-zol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyri-dazin-4-yl, pyrazin-2-yl and payrazin-3-yl, and wherein the heteroaryl residues are optionally substituted with 1 or 2 rests selected independently from F, Cl, Br, CF3, (CrC4)-alkyl-, (CrC4)-alkyl-0-, CN, (C1-C2)-alkyl-S02-; or wherein R5 = an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl, oxetanyl and tetrahydrofuranyl, tetrahydropyranyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents independently selected from the group of F, OH, (C.|-C2)-alkyl-0- and (C1-C4)-alkyl-; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts.

[0025] A further preferred embodiment of the present invention relates to compounds, wherein A is equal to phenyl, wherein the phenyl residue is optionally substituted with 1-3 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, (CrC4)-alkyl-0-and (C1-C4)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and X is equal to phenyl, wherein the phenyl group is optionally substituted with 1,2 or 3 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, (CrC4)-alkyl-0-, (CrC4)-alkyl-S-, (CrC4)-alkyl-0-C(0)- and (C1-C4)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and R1 = R5-C(=0)- or (C1-C6)-alkyl-S02-; R2 = H, (C.|-C6)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H, (C1-C4)-alkyl-; R4 = H, (C1-C4)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; R5 = H, (CrC6)-alkyl-, (C3-C6)-cycloalkyl- (CrC6)-alkyl-0-, (CrC6)-alkyl-S-, (C1-C6)-alkyl-0-(C1-C6)-alkyl-, HO-(C1-C6)-alkyl-, (C3-C6)-cycloalkyl-(C1-C6)-alkyl-, (C6-C10)-aryl-, (C6-C10)-aryl-(C1-C6)-alkyl-, R7R6N-, heteroar-yl, heteroaryl-(C1-C6)-alkyl-, aliphatic heterocycle, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl and 4 to 7 mem- bered aliphatic heterocycles comprising an oxygen atom, and wherein the aliphatic heterocycle may be optionally substituted with 1 to 3 substituents selected from the group of F, OH, (C.|-C6)-alkyl-0- and (C^Cg^alkyl-, and wherein the heteroaryl residues are five- or six-mem bered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-; R6 = H, (C.|-C6)-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH- or (C1-C6)-alkyl-0- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H,(C1-C6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine, with the proviso if R5 is methyl and R2, R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-acetoxyphenyl, 2-chloro-phenyl, 3,4-dichlorophenyl, and with the proviso if R5 is methyl and R2, R3 and R4 are equal to H and X is a phenyl residue, the residue A is not phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethyloxy-phenyl or 3-trifluoromethyl-phenyl, and with the proviso if R5 is methyl and R2 is methyl and R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl.

[0026] Preferred compounds are, wherein A = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN,(C.|-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3 and (C.|-C2)-alkyl-S-; X = phenyl, wherein the phenyl residue is substituted with 1 or2 residues selected independently from F,CI, Br, CN, (C-j-C^-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C.|-C2)-alkyl-S-, (C.|-C2)-alkyl-0-C(0)- and methyl-S02-, R1 = R5-C(=0)- or methyl-S02-; R2 = H, (C1-C2)-alkyl-, cyclopropyl-; R3 = H, methyl-; R4 = H, methyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 is equal to a heteroaryl or heteroaryl-(C.|-C6)-alkyl-, wherein the heteroaryl residues are selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin- 2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyridazin-4-yl, pyrazin-2-yl and payrazin-3-yl, and wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CF3, methyl, ethyl, methoxy, ethoxy, CN, methyl-S02-, or wherein R5 is equal to H; or wherein R5 is equal to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or (C3-C6)-cycloalkyl-(Ci-C2)-alkyl-, or wherein R5 is equal to (C1-C2)-alkyl-0-, (C1-C2)-alkyl-S-, or wherein R5 is equal to (C1-C4)-alkyl-0-methyl-, HO-(Ci-C2)-alkyl-, or wherein R5 is equal to phenyl- or phenylmethyl-, wherein the phenyl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C1-C2)-alkyl-, (C1-C2)-alkyl-0-, CN, methyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to R7R6N-, wherein R6 = H, (C1-C4)-alkyl-, cyclopropyl-, wherein one hydrogen atom of the alkyl group may be replaced by a hydroxy, methoxy or ethoxy residue and R7 = H, methyl-, ethyl-or wherein R5 is equal to an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, piperidinyl, pyrrolidinyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents selected from the group of F, OH, (C.|-C2)-alkyl-0- and (C1-C4)-alkyl-, and wherein one or more hydrogen atoms of the alkyl groups may be replaced by fluorine; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts.

[0027] Particularly preferred compounds are, wherein A = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3 and (C1-C2)-alkyl-S-; X = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C.|-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl-S02-, R1 = R5-C(=0)-; R2 = H, (C-|-C2)-alkyl-, cyclopropyl-; R3 = H, methyl-; R4 = H, methyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 is equal to (C2-C4)-alkyl, and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts.

[0028] A further embodiment of the present invention are compounds of formula I, wherein A = (C6-C10)-aryl or a five- orsix-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C1-C6)-alkyl-, (C.|-C6)-alkyl-0-and (C.|-C6)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = (C6-C10)-aryl or a five- orsix-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C^-Cg)-alkyl-, (C^-Cg)-alkyl-O-and (C^-Cg)-alkyl-S-, (C^-Cg)-alkyl-O-C(O)- and (C^-Cg)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R1 = R5-C(=0)- or (C1-C6)-alkyl-S02-; R2 = H, (C1-C6)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H,(CrC4)-alkyl-; R4 = H, (C1-C4)-alkyl-; or R3,R4 together form a (C2-C3)-alkylene bridge; and wherein R5 is equal to a heteroaryl or heteroaryl-(C1-C6)-alkyl-, wherein the heteroaryl residues are five- or six-membered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein the heteroaryl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (CrCg)-alkyl-0-, CN, (CrC2)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not pyrimidin-4-yl, pyridine-2-yl, 1-methyl-pyrazol-3-yl or 1-methyl-imidazol-2-yl, or wherein R5 is methyl, with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 2,4-difluorophenyl residue A is not pyridine-3-yl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluorophenyl, 3-cyano-phenyl, 3-methoxy-phenyl, 3-trifluormethoxy-phenyl, 2-fluoro-5-methoxy-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 3-cyanophenyl residue A is not a 4-fluorophenyl residue, and with the proviso if in compounds of formula I R3 is methyl, R2 and R4 are hydrogen and X is a 2,4-difluoro-phenyl residue A is not a 4-fluoro-phenyl, and with the proviso ifin compounds of formula I R2, R3 and R4 are hydrogen and X is phenyl A is not phenyl, 3-trifluoromethyl-phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethyloxy-phenyl, 4-methyl-thiophenyl, 2-thiophenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and A is 4-fluoro-phenyl X is not phenyl, 2-chloro-phenyl, 3,4-dichloro-phenyl, 4-chloro-phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-ethyloxy-phenyl, or 4-acetoxyphenyl, and with the proviso if R5 is methyl and R2 is methyl and R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl, and or wherein R5 is equal to H, (C2-C6)-alkyl, CF3, CF2H, CFH2, wherein one or more hydrogen atoms of the alkyl residue may be replaced by fluorine; or wherein R5 is equal to (C3-C6)-cycloalkyl or (C3-C6)-cycloalkyl-(C1-C4)-alkyl-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not cyclopropyl, or wherein R5 is equal to (C1-C4)-alkyl-0- or (C.|-C4)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to (C1-C4)-alkyl-0-(C1-C2)-alkyl-, FIO-(C1-C4)-alkyl-, or wherein R5 is equal to phenyl-, phenyl-(C.|-C4)-alkyl-, wherein the phenyl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methylsulfonyl-phenyl, 4-methylsulfonyl-phenyl; or wherein R5 is equal to R7R6N-, wherein R6 = FI, (C1-C4)-alkyl-, cyclopropyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH, methoxy or ethoxy residue and R7 = H, (C1-C2)-alkyl-, or wherein R5 is equal to an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, piperidinyl, pyrrolidinyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents selected from the group of F, OFI, (C1-C4)-alkyl-0- and (C1-C4)-alkyl-, and wherein one or more hydrogen atoms of the alkyl groups may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methyl-oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl or 1-methyl-piperidin-4-yl.

[0029] Preferred compounds are, wherein A = phenyl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl or thiophen-3-yl, wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFFI2, methoxy, ethoxy, OCF3 and (C1-C2)-alkyl-S-; X = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C1-C2)-alkyl-S-, (C.|-C2)-alkyl-0-C(0)- and methyl-S02-, or pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFFI2, methoxy, ethoxy, OCF3, (C1-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl-S02-; R1 = R5-C(=0)- or (C1-C2)-alkyl-S02-; R2 = H, (Ci-C2)-alkyl-, cyclopropyl-; R3 = H, (CrC2)-alkyl-; R4 = H, (CrC2)-alkyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 is equal to a heteroaryl or heteroaryl-(Ci-C6)-alkyl-, wherein the heteroaryl residues are selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin-2-yl, pyri-midin-4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyridazin-4-yl, pyrazin-2-yl and payrazin-3-yl, and wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CF3, methyl, ethyl, methoxy, ethoxy, CN, methyl-S02-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not pyrimidin-4-yl, pyridine-2-yl, 1-methyl-pyrazol-3-yl or 1-methyl-imidazol-2-yl, or wherein R5 is methyl, with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 2,4-difluorophenyl residue A is not pyridine-3-yl, 2-fluoro-phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-cyano-phenyl, 3-methoxy-phenyl, 3-trifluormethoxyphe-nyl, 2-fluoro-5-methoxy-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 3-cyanophenyl residue A is not a 4-fluorophenyl residue, and with the proviso if in compounds of formula I R3 is methyl, R2 and R4 are hydrogen and X is a 2,4-difluoro-phenyl residue A is not a 4-fluoro-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is phenyl A is not phenyl, 3-trifluoromethyl-phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethoxy-phenyl, 2-thiophenyl, 4-methylthiophenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and A is 4-fluoro-phenyl X is not 2-chloro-phenyl, 3,4-dichloro-phenyl, 4-chloro-phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-acetoxyphenyl or 4-ethoxy-phenyl, and or wherein R5 is equal to H, (C2-C4)-alkyl, CF3; or wherein R5 is equal to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or (C3-C6)-cycloalkyl-(C1-C2)-alkyl-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not cyclopropyl, or wherein R5 is equal to (Ci-C2)-alkyl-0- or (Ci-C2)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to (Ci-C4)-alkyl-0-methyl-, HO-(C1-C2)-alkyl-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to phenyl-, phenyl-(C.|-C2)-alkyl-, wherein the phenyl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C.|-C2)-alkyl-, (C.|-C2)-alkyl-0-, CN, methyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methylsulfonyl-phenyl, 4-methylsulfonyl-phenyl; or wherein R5 is equal to R7R6N-, wherein R6 = FI, (C1-C4)-alkyl-, cyclopropyl-, wherein one hydrogen atom of the alkyl group may be replaced by a hydroxy, methoxy or ethoxy residue and R7 = H, methyl-, ethyl-or wherein R5 is equal to an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, piperidinyl, pyrrolidinyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents selected from the group of F, OH, (C.|-C2)-alkyl-0- and (C.|-C4)-alkyl-, and wherein one or more hydrogen atoms of the alkyl groups may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methyl-oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl or 1-methyl-piperidin-4-yl. and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts.

[0030] Further preferred compounds are, wherein A is equal to phenyl, wherein the phenyl residue is optionally substituted with 1-3 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, (C1-C4)-alkyl-0- and (C1-C4)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and X is equal to phenyl, wherein the phenyl group is optionally substituted with 1,2 or 3 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, (C1-C4)-alkyl-0-, (CrC4)-alkyl-S-, (C1-C4)-alkyl-0-C(0)- and (C1-C4)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and R1 = R5-C(=0)- or (CrC6)-alkyl-S02-; R2 = H, (Ci-Cg)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H, (C1-C4)-alkyl-; R4 = H, (C1-C4)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; and wherein R5 is equal to a heteroaryl or heteroaryl-(Ci-C6)-alkyl-, wherein the heteroaryl residues are five- or six-membered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein the heteroaryl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not pyrimidin-4-yl, pyridine-2-yl, 1-methyl-pyrazol-3-yl or 1-methyl-imidazol-2-yl, or wherein R5 is methyl, with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 2,4-difluorophenyl residue A is not pyridine-3-yl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluorophenyl, 3-cyano-phenyl, 3-methoxy-phenyl, 3-trifluormethoxy-phenyl, 2-fluoro-5-methoxy-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 3-cyanophenyl residue A is not a 4-fluorophenyl residue, and with the proviso if in compounds of formula I R3 is methyl, R2 and R4 are hydrogen and X is a 2,4-difluoro-phenyl residue A is not a 4-fluoro-phenyl, and with the proviso ifin compounds of formula I R2, R3 and R4are hydrogen and X is phenyl A is not phenyl, 3-trifluoromethyl-phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethyloxy-phenyl, 4-methyl-thiophenyl, 2-thiophenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and A is 4-fluoro-phenyl X is not phenyl, 2-chloro-phenyl, 3,4-dichloro-phenyl, 4-chloro-phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-ethyloxy-phenyl, or 4-acetoxyphenyl, and with the proviso if in compounds of formula I R2 is methyl, R3 and R4 are hydrogen and A is 4-fluoro-phenyl, the residue X is not phenyl, and or wherein R5 is equal to H, (C2-C6)-alkyl, CF3, CF2H, CFH2, wherein one or more hydrogen atoms of the alkyl residue may be replaced by fluorine; or wherein R5 is equal to (C3-C6)-cycloalkyl or (C3-C6)-cycloalkyl-(C1-C4)-alkyl-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not cyclopropyl, or wherein R5 is equal to (C.|-C4)-alkyl-0- or (C^C^-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to (C1-C4)-alkyl-0-(C1-C2)-alkyl-, HO-(C1-C4)-alkyl-, or wherein R5 is equal to phenyl-, phenyl-(C.|-C4)-alkyl-, wherein the phenyl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (CrC6)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methylsulfonyl-phenyl, 4-methylsulfonyl-phenyl; or wherein R5 is equal to R7R6N-, wherein R6 = H, (Ci-C4)-alkyl-, cyclopropyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH, methoxy or ethoxy residue and R7 = H, (C1-C2)-alkyl-or wherein R5 is equal to an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, piperidinyl, pyrrolidinyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents selected from the group of F, OH, (C1-C4)-alkyl-0- and (C1-C4)-alkyl-, and wherein one or more hydrogen atoms of the alkyl groups may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3- methyl-oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl or 1-methyl-piperidin-4-yl. R6 = H, (C.|-Cg)-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH- or (C1-C6)-alkyl-0- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H, (C.|-C6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine.

[0031] Particularly preferred compounds are compounds of formula I, wherein A = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C.|-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3 and (C.|-C2)-alkyl-S-; X = phenyl, wherein the phenyl residue is substituted with 1 or2 residues selected independentlyfrom F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (Ci-C2)-alkyl-S-, (Ci-C2)-alkyi-0-C(0)- and methyl-S02-, R1 = R5-C(=0)- or methyl-S02-; R2 = H, (C.|-C2)-alkyl-, cyclopropyl-; R3 = H, methyl-; R4 = H, methyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 is equal to a heteroaryl or heteroaryl-(C.|-C6)-alkyl-, wherein the heteroaryl residues are selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin-2-yl, pyri-midin-4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyridazin-4-yl, pyrazin-2-yl and payrazin-3-yl, and wherein these residues are optionally substituted with 1 or2 residues selected independentlyfrom F, Cl, Br, CF3, methyl, ethyl, methoxy, ethoxy, CN, methyl-S02-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not pyrimidin-4-yl, pyridine-2-yl, 1-methyl-pyrazol-3-yl or 1-methyl-imidazol-2-yl, or wherein R5 is methyl, with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 2,4-difluorophenyl residue A is not pyridine-3-yl, 2-fluoro-phenyl, 3-fluorophenyl, 4-fluorophenyl, 3-cyano-phenyl, 3-methoxy-phenyl, 3-trifluormethoxyphe-nyl, 2-fluoro-5-methoxy-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 3-cyanophenyl residue A is not a 4- fluorophenyl residue, and with the proviso if in compounds of formula I R3 is methyl, R2 and R4 are hydrogen and X is a 2,4-difluoro-phenyl residue A is not a 4-fluoro-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is phenyl A is not phenyl, 3-trifluoromethyl-phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethoxy-phenyl, 2-thiophenyl, 4-methylthiophenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and A is 4-fluoro-phenyl X is not 2-chloro-phenyl, 3,4-dichloro-phenyl, 4-chloro-phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-ethoxy-phenyl or 4-acetoxyphenyl, and with the proviso if in compounds of formula I R2 is methyl, R3 and R4 are hydrogen and A is 4-fluoro-phenyl, the residue X is not phenyl, and or wherein R5 is equal to H, (C2-C4)-alkyl, CF3; or wherein R5 is equal to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or (C3-C6)-cycloalkyl-(C1-C2)-alkyl-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not cyclopropyl, or wherein R5 is equal to (C1-C2)-alkyl-0- or (C1-C2)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to (C1-C4)-alkyl-0-methyl-, HO-(Ci-C2)-alkyl-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to phenyl-, phenyl-(C1-C2)-alkyl-, wherein the phenyl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C.|-C2)-alkyl-, (C.|-C2)-alkyl-0-, CN, methyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methylsulfonyl-phenyl, 4-methylsulfonyl-phenyl; or wherein R5 is equal to R7R6N-, wherein R6 = H, (C.|-C4)-alkyl-, cyclopropyl-, wherein one hydrogen atom of the alkyl group may be replaced by a hydroxy, methoxy or ethoxy residue and R7 = H, methyl-, ethyl-or wherein R5 is equal to an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, morpholinyl, piperidinyl, pyrrolidinyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents selected from the group of F, OH, (C1-C2)-alkyl-0- and (C1-C4)-alkyl-, and wherein one or more hydrogen atoms of the alkyl groups may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methyl-oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl or 1 -methyl-piperidin-4-yl, and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts.

[0032] Further preferred compounds suitable as TASK-1 inhibitors are compounds of formula I, wherein A = phenyl, wherein the phenyl residue is substituted with 1 or2 residues selected independently from F, Cl, Br, CN, (C.|-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3 and (C1-C2)-alkyl-S-; X = phenyl, wherein the phenyl residue is substituted with 1 or2 residues selected independently from F,CI, Br, CN, (Ci-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C1-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl-S02-, R1 = R5-C(=0)-; R2 = H, (C.|-C2)-alkyl-, cyclopropyl-; R3 = H, methyl-; R4 = H, methyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 is equal to (C2-C4)-alkyl; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts.

[0033] Alkyl radicals have between 1 and 6, preferably between 1 and 4 carbon atoms and may be straight-chain or branched. Alkyl radicals may also be straight-chain or branched if they are substituted or are present in other radicals, for example in an alkyloxy radical (alkoxy radical) or in a fluorinated alkyl radical. Examples of alkyl radicals are methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl and tert-butyl. One or more, for example 1,2, 3, 4, 5, 6, 7, 8, or 9 hydrogen atoms in alkyl radicals may be replaced by fluorine atoms. Preferred fluorinated alkyl radicals are CF3, CF2H and CFH2. Substituted alkyl radicals may be substituted in any positions. Preferred alkyloxy radicals are methoxy and ethoxy. These explanations with respect to alkyl radicals apply correspondingly to alkyl radicals which in the definition of a group in the compounds of the formula I are bonded to two adjacent groups, or linked to two groups, and may be regarded as divalent alkyl radicals (alkanediyl radicals, alkylene radicals), like in the case of the alkyl part of a substituted alkyl group, for example the group (Ci-C6)-alkyloxy-(C1-C6)-alkyl- or the group heteroaryl-(CrC6)-alkyl-, in which groups and likewise in other groups the terminal hyphen denotes the free bond via which the group is bonded, and thus indicates via which subgroup a group composed of subgroups is bonded. Thus, such radicals can also be straight-chain or branched, the bonds to the adjacent groups can be located in any positions and can start from the same carbon atom or from different carbon atoms, and they can be unsubstituted or substituted by fluorine substituents independently of anyothersubstituents. Examples of such divalent alkyl radicals are methylene, 1,1-ethylene, 1,2-ethylene, 1,1-propylene, 1,2-propylene, 2,2-propylene, 1,3-propylene, 1,1-butylene, 1,4-butylene, etc.

[0034] Examples of cycloalkyl radicals having 3 to 6 C atoms are cyclopropyl, cyclobutyl, 1-methylcyclopropyl-, 2-methylcyclopropyl-, cyclobutyl, 2-methylcyclobutyl-, 3-methylcyclobutyl-, cyclopentyl, 2-methylcyclopentyl-, 3-methylcy-clopentyl-, cyclohexyl etc.

[0035] Preferred heteroaryl residues are five orsix-membered rings, comprising 1 to 3 heteroatoms selected from the group N, O and S, wherein a heteroaryl ring preferably comprise only one O or S atom. Preferred heteroaryl groups are 2- thiophenyl, 3-thiophenyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 3-pyridazinyl, 4-pyridazinyl, 3-pyra-zolyl, 4-pyrazolyl, 2-imidazolyl, 4-imidazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothia-zolyl, wherein particularly preferred are 2-pyridyl, 3-pyridyl and 4-pyridyl.

[0036] Preferred heteroaryl residues for the group A are unsubstituted or substituted pyridine-2-yl, pyridine-3-yl, pyri-dine-4-yl, thiophen-2-yl and thiophen-3-yl, particularly preferred are substituted heteroaryl residues.

[0037] Preferred heteroaryl residues for the group X are unsubstituted or substituted pyridine-2-yl, pyridine-3-yl, pyri-dine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl and thiazol-5-yl, particularly preferred are substituted heteroaryl residues.

[0038] Preferred heteroaryl residues for R5 are unsubstituted or substituted pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol- 3- yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyridazin-4-yl, pyrazin-2-yl and payrazin-3-yl.

[0039] The heteroaryl residues may unsubstituted or substituted with one or two substituents. Preferred substituents of the heteroaryl residues are F, Cl, Br, methoxy, ethoxy, methyl, ethyl, NC-, CF30-, CF3.

[0040] A preferred aryl residue is phenyl, wherein one or two hydrogen may be replaced by substituents, preferably selected from the group F, Cl, methoxy, ethoxy, methyl, ethyl, NC-, CF30-, CF3, Chl3-S02-.

[0041] Preferred aliphatic heterocycle are selected from the group of morpholinyl, piperidinyl, pyrrolidinyl, oxetanyl and tetrahydrofuranyl and tetrahydropyranyl, wherein these aliphatic heterocycle may be optionally substituted with 1 or 2 substituents preferably selected independently from the group of F, OH, methoxy, ethoxy, methyl and ethyl.

[0042] If a radical is disubstituted or trisubstituted, the substituents may be identical or different.

[0043] If the compounds of the formula I comprise one or more basic groups or one or more basic heterocycles, the invention also includes the corresponding physiologically acceptable salts including trifluoroacetates, in particular the pharmaceutically acceptable salts. Thus, the compounds of the formula I which have one or more basic, i.e. protonatable, groups or comprise one or more basic heterocyclic rings, can also be used in the form of their physiologically tolerated acid addition salts with inorganic or organic acids, for example as hydrochlorides, phosphates, sulfates, methanesul-fonates, acetates, lactates, maleates, fumarates, malates, gluconates etc. Salts can be obtained from compounds of the formula I by conventional processes, for example by combining with an acid in a solvent or dispersant or else by anion exchange from other salts. The compounds of the formula I may also be deprotonated on an acidic group and be used for example as alkali metal salts, preferably sodium or potassium salts, or as ammonium salts, for example as salts with ammonia or organic amines or amino acids.

[0044] The compounds of the formula I may exist in stereoisomeric forms. The centers of asymmetry which are present may independently of one another have the S configuration or the R configuration. The invention includes all possible stereoisomers, for example enantiomers ordiastereomers, and mixtures of two or more stereoisomeric forms, for example enantiomers and/or diastereomers, in any ratios. The invention thus includes for example enantiomers in enantiopure form, both as levorotatory and as dextrorotatory antipodes, and in the form of mixtures of the two enantiomers in various ratios or in the form of racemates. Individual stereoisomers can be prepared as desired by fractionating a mixture by conventional methods or for example by stereoselective synthesis.

[0045] For the preparation of the compounds of formula I the following methods can be used.

[0046] In the described various chemical processes, the residues A, X, R1, R2, R3, R4, R5, R6 and R7 have the same meaning as in compounds of the formula I, provided that no specific definition of the respective residue is mentioned.

[0047] The preparation of diverse 4,5,6,7-Tetrahydro-1 H-pyrazolo[4,3-c]pyridine intermediates can be done according to Scheme 1 (method A) following a previously described synthesis (EP 0 086 422 A2). The synthesis is applicable to a large variety of different groups A. Thus, starting from commercially available 1-acetyl-4-piperidone 1-(4-Morpholin-4-yl-3,6-dihydro-2H-pyridin-1-yl)-ethanone (enamine 1) is obtained. Thus, morpholine is added to a solution of 1-acetyl- 4- piperidone in the presence of p-toluenesulfonic acid monohydrate (catalytic PTSA). After acylation with commercially available acyl chlorides, followed by acidic aqueous hydrolysis the diketones 2 are obtained and can be subjected to ring-closure with hydrazine hydrate to give the corresponding diverse 4,5,6,7-Tetrahydro-1H-pyrazolo[4,3-c]pyridine intermediates 3.

[0048] The acyl chlorides can alternatively be prepared by standard procedures from the corresponding acids e.g. by reaction with thionyl chloride in the presence of catalytic amounts of DMF (see for example Dalisay, D. S.; Quach, T.;

Nicholas, G. N.; Molinski, T. F., Angewandte Chemie, International Edition, 2009, vol. 48,4367-4371). If A is a heteroaryl than sometimes an alternative synthesis is preferable and can be used as shown in Scheme 1 (method B). Thus starting from commercially available acids the mixed anhydrides are formed by reaction with isobutylchloroformate. 1-Acetyl-4-piperidone 1-(4-Morpholin-4-yl-3,6-dihydro-2H-pyridin-1-yl)-ethanone can be deprotonated with strong bases like lithium hexamethyldisilazide and reacted with the mixed anhydride described above. The diketones 2 are obtained and can be subjected to ring-closure with hydrazine hydrate to give the corresponding diverse 4,5,6,7-Tetrahydro-1 H-pyrazolo[4,3-cjpyridine intermediates 3.

Scheme 2 [0049] R3,R4 substituted intermediates 5 can be accorded similarly as shown in Scheme 2. Thus after acetylation of commercially available or known piperidones N-Acetyl-piperidones 4 are obtained. They can be deprotonated with strong bases like lithium diisopropylamide (LDA) and reacted with mixed anhydrides formed by reaction of aryl or heteroaryl-carbonic acids and isobutylchloroformate as described above. The diketones obtained can be subjected to ring-closure with hydrazine hydrate to give the corresponding R3,R4 substituted 4,5,6,7-Tetrahydro-1H-pyrazolo[4,3-c]pyridine intermediates 5.

[0050] 4,5,6,7-Tetrahydro-1H-pyrazolo[4,3-c]pyridine intermediates can be successfully alkylated with a range of different aryl- and heteroaryl halogenides by heating in the presence of an excess amount of a base like K2C03 in an inert solvent like CH3CN as shown in Scheme 3. The corresponding substituted 4,5,6,7-Tetrahydro-1 H-pyrazolo[4,3-c]pyridine intermediates 6 were found to be TASK-1 blockers.

Scheme 4 [0051] In a different approach (Scheme 4), starting from Boc-protected piperidones, the diketones obtained after deprotonation by a strong base like lithium diisopropylamide and reaction with diverse acyl chlorides can be reacted with substituted benzylhydrazines and subsequently deprotected to give compounds 7 which are intermediates in the synthesis of TASK-1 blockers.

[0052] The group R1 of compounds of formula I can be varied synthetically as shown in Scheme 5. The N-acetyl group can be cleaved by heating an acidic aqueous solution of compounds 6, for example in a mixture of ethanol and 2N aqueous HCI. The corresponding amines 7 can be modified in a variety of ways, for example by acylation as shown in Scheme 6. This can be done by several methods: for example by reaction with carboxylic acids in the presence of 1-hydroxybenzotriazole and EDC (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride) (Nozaki, S. J. Peptide Res. 1999, 54, 162) (method A) or TOTU (0-[(Ethoxycarbonyi) cyanomethylenamino]-N,N,N’,N’-tetramethyluronium tetrafluoroborate) (Knorr, R. et al. Tetrahedron Lett. 1989, 30, 1927) (method D), by reaction with acyl chlorides or alkyl chloroformâtes in the presence of K2C03 in CH3CN (method B), in a "Schotten-Baumann" reaction type by reaction with acyl chlorides in a water-ethyl acetate mixture in the presence of NaHC03 (method C), by reaction with acyl chlorides in the presence of triethylamine in CH2CI2 (method E), or by reaction with acetic anhydride in pyridine (method F). The group R5 may carry protecting groups which can be cleaved off by methods known in the prior art. For example a hydroxyl group in R5 can be protected as a tert-butylether which can be cleaved off by an acid like HCI to give deprotected compounds 14 (Scheme 11). Of course the reaction is broadly applicable and not limited to the exact structure shown in Scheme 11.

Scheme 6

[0053] Alternatively TASK-1 blockers 8 can be obtained by sulfonylation with alkylsulfonyl halogenides ((C1-C6)-alkyl-S02-) in inert solvents like CH2CI2 in the presence of a base like triethylamine as shown in Scheme 7.

Scheme 8 [0054] In another reaction (Scheme 8), reaction of intermediates 7 with diverse isocyanates in an inert solvent for example CH2CI2 leads to formation of ureas 11 which have been found to be TASK-1 blockers.

12

Scheme 9 [0055] In another reaction (Scheme 9), reaction of intermediates 7 with 4-nitrophenylchloroformate leads to intermediates with can be reacted with diverse amines to give ureas 12 which have been found to be TASK-1 blockers and are novel compounds not described before.

Scheme 10 [0056] The aryl or heteroaryl ring A can be modified when substituted by a bromide to give the corresponding nitriles as shown in Scheme 10 by reaction with Zn(CN)2 in the presence of a catalytic amount of tetrakis(triphenylphosphine)pal-ladium (0) (in analogy to Alterman, M.; Anders, H. Journal of Organic Chemistry, 2000 , vol. 65, 23 p. 7984 - 7989). The reaction is not limited to pyridines as drawn in Scheme 10 but is applicable to a range of aryl and heteroaryl systems. The novel compounds 13 which have not been previously described have been found to be TASK-1 blockers.

Scheme 11 A tert-butylether 8 can be cleaved off by an acid like HCI to give deprotected compounds 14 (Scheme 11). The reaction is broadly applicable and not limited to the exact structure shown in Scheme 11.

[0057] The working up and, if desired, the purification of the products and/or intermediates takes place by conventional methods such as extraction, chromatography or crystallization and conventional dryings.

[0058] Owing to the TASK-1-inhibitory properties, the compounds of the formula I and/or their pharmaceutically compatible salts are suitable for the prevention and treatment of disorders which are caused by activation or by an activated TASK-1, and also of disorders in which have TASK-1- related damages appear secondary to another, primary cause.

[0059] The compounds of the formula I, and/or physiologically compatible salts thereof can also be used for the treatment and prevention of disorders where TASK-1 requires only partial inhibition, for example by using a lower dosage, wherein for the treatment and prevention of disorders described below the compounds of formula I includes compounds wherein R5 is methyl and R2, R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, and the residue X is phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-acetoxyphenyl, 2-chloro-phenyl, 3,4-dichlorophenyl, and compounds wherein R5 is methyl and R2, R3 and R4 are equal to H and X is a phenyl residue, and the residue A is phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethyloxy-phenyl, 3-trifluoromethyl-phenyl, 2-thiophenyl or 4-methylthiophenyl, and compounds wherein R5 is methyl and R2 is methyl and R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl and the residue X is phenyl.

[0060] These compounds can be employed to produce medicaments with a TASK-1 channel-blocking effect for the therapy and prophylaxis of TASK-1 channel-mediated diseases. The compounds of the formula I and/or their pharmaceutically acceptable salts can further be used for the therapy or prophylaxis of cardiac arrhythmias, e.g. of arrhythmias that respond to the changes in the shape of the action potential, mainly a prolongation of the action potential, which is induced by TASK-1 blockade.

[0061] The compounds of the formula I and/or their pharmaceutically acceptable salts can be employed for terminating existent atrial fibrillation or flutter to restore the sinus rhythm (cardioversion). In addition, the compounds reduce the susceptibility for a new development of atrial fibrillation events, thus the compounds are suitable for prophylactic treatment by maintenance of sinus rhythm (rhythm control). The substances are devoid of a ventricular proarrhythmic risk (prolongation of the QT-interval and Torsades de pointe arrhythmias).

[0062] The compounds of the formula I and/or their pharmaceutically acceptable salts can be employed for producing a medicament for the treatment and/or prevention of arrhythmias, particularly atrial tachyarrhythmias, atrial fibrillation and atrial flutter.

[0063] The compounds of the formula I and/or their pharmaceutically acceptable salts are further suitable for producing a medicament for the therapy or prophylaxis of sleep-related respiratory disorders, central and obstructive sleep apneas, upper airway resistance syndrome, Cheyne-Stokes respiration, snoring, disrupted central respiratory drive, sudden child death, postoperative hypoxia and apnea, muscle-related respiratory disorders, respiratory disorders after long-term mechanical ventilation (weaning), respiratory disorders during adaptation in high mountains, acute and for respiratory disorders, chronic lung disorders with hypoxia and hypercapnia, chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome.

[0064] The compounds of the formula I and/or their pharmaceutically acceptable salts are further suitable as a respiratory stimulant for the prevention and treatment of respiratory depression associated with anesthesia or procedural sedations for small interventions or for diagnostic purposes, for the treatment and prevention of respiratory depression by opioids in chronic pain treatment e.g. in cancer or palliative care or procedural sedations and/or for weaning from longterm mechanical ventilation.

[0065] The compounds of the formula I and/or their pharmaceutically acceptable salts are further suitable for the treatment and/or prevention of multiple sclerosis and inflammatory and degenerative disorders of the central nervous system.

[0066] The compounds of the invention of the formula I and their pharmaceutically acceptable salts can thus be used on animals, preferably on mammals, and in particular on humans, as pharmaceuticals on their own, in mixtures with one another or in the form of pharmaceutical preparations (pharmaceutical compositions).

[0067] Thus, a further embodiment of the present invention is a pharmaceutical preparation comprising an effective amount of a compound of the formula I and/or of its pharmaceutically acceptable salts, together with pharmaceutically acceptable carriers and additives, alone or in combination with other pharmacological active ingredients or pharmaceuticals. The pharmaceutical preparations usually comprise from 0.1 to 90 percent by weight of the compounds of the formula I and/or their pharmaceutically acceptable salts. The pharmaceutical preparations can be produced in a manner known per se. For this purpose, the compounds of the formula I and/or their pharmaceutically acceptable salts are converted together with one or more solid or liquid pharmaceutical vehicles and/or excipients and, if desired, in combination with other pharmaceutical active ingredients into a suitable dosage form, which can then be used as pharmaceutical in human medicine or veterinary medicine.

[0068] Pharmaceuticals which comprise a compound of the formula I and/or its pharmaceutically acceptable salts can moreover be administered for example orally, intravenously, intramuscular, subcutaneously, nasally, topically, pharyn-geally or by inhalation, and the preferred administration depends on the individual case, for example on the particular manifestation of the disorder. The compounds of theformula I can moreover be used alone ortogetherwith pharmaceutical excipients, in particular both in veterinary and in human medicine. The pharmaceuticals comprise active ingredients of the formula I and/or their pharmaceutically acceptable salts generally in an amount of from 0.01 mg to 1 g per dose unit.

[0069] The skilled worker is familiar on the basis of his expert knowledge with which excipients are suitable for the desired pharmaceutical formulation. Besides solvents, gel formers, suppository bases, tablet excipients and other active substance carriers it is possible to use for example antioxidants, dispersants, emulsifiers, antifoams, masking flavors, preservatives, solubilizers, agents for achieving a depot effect, buffer substances or colorants.

[0070] For a form for oral use, the active compounds are mixed with the additives suitable for this purpose, such as carriers, stabilizers or inert diluents, and converted by conventional methods into suitable presentations such as tablets, coated tablets, two-piece capsules, aqueous, alcoholic or oily solutions. Examples of inert carriers which can be used are gum arabic, magnesia, magnesium carbonate, potassium phosphate, lactose, glucose or starch, especially corn starch. Preparation can take place both as dry and as wet granules. Suitable as oily carriers or as solvents are, for example, vegetable or animal oils such as sunflower oil or fish liver oil. Suitable solvents for aqueous or alcoholic solutions are, for example, water, ethanol or sugar solutions or mixtures thereof. Examples of further excipients, also for other administration forms, are polyethylene glycols and polypropylene glycols.

[0071] Forsubcutaneous, intramuscular or intravenous administration, the active compounds are converted if desired with the substances usual for this purpose, such as solubilizers, emulsifiers or further excipients, into a solution, suspension or emulsion. The compounds of the formula I and/or their pharmaceutically acceptable salts may also be lyophilized and the resulting lyophilizates be used, for example, for producing products for injection or infusion. Examples of suitable solvents are: water, physiological saline or alcohols, for example ethanol, propanol, glycerol, as well as sugar solutions such as glucose or mannitol solutions, or else mixtures of the various solvents mentioned.

[0072] Suitable as pharmaceutical formulation for administration in the form of aerosols or sprays are, for example, solutions, suspensions or emulsions of the active ingredient of the formula I or their pharmaceutically acceptable salts in a pharmaceutically acceptable solvent, such as in particular ethanol or water, or a mixture of such solvents. The formulation may if required also comprise other pharmaceutical excipients such as surfactants, emulsifiers and stabilizers, and a propellant gas. Such a preparation comprises the active ingredient normally in a concentration of about 0.1 to 10, in particular of about 0.3 to 3 percent by weight.

[0073] The dosage of the active ingredient to be administered or of the pharmaceutically acceptable salts thereof depends on the individual case and should be adapted to the circumstances of the individual case as usual for an optimal effect. Thus, it naturally depends on the frequency of administration and on the potency and duration of action of the particular compounds employed for therapy or prophylaxis, but also on the type and severity of the disease to be treated, and on the gender, age, weight and individual response of the human or animal to be treated, and on whether therapy is acute or prophylactic.

[0074] The daily dose of a compound of the formula I and/or its pharmaceutically acceptable salts for a patient weighing about 75 kg is normally at least 0.001 mg/kg to 100 mg/kg of body weight, preferably 0.01 mg/kg to 20 mg/kg. Even higher dosages may also be necessary for acute episodes of the disease, for example in an intensive care unit. Up to 800 mg per day may be necessary. The dose may be in the form of a single dose or be divided into a plurality, for example two, three or four, single doses. Parenteral administration by injection or infusion, for example a continuous intravenous infusion, may also be advantageous, especially in the treatment of acute cases of cardiac arrhythmias, for example in an intensive care unit.

Examples [0075] The following examples illustrate the various embodiments of the present invention and are part of the present invention. 1-(4-Morpholin-4-yl-3,6-dihydro-2H-pyridin-1-yl)-ethanone (1) [0076]

[0077] According to Scheme 1, step 1 : a mixture of morpholine (67.85 g, 0.779 mol), 1-acetyl-4-piperidone (99.95 g, 0.708 mol) and para-toluenesulfonic acid (0.366 g, 2.1 mmol) in toluene (300 ml) was heated in a Dean-Stark trap apparatus for 16 h at reflux. Solvents were evaporated in vacuo to give 149 g of 1-(4-Morpholin-4-yl-3,6-dihydro-2H-pyridin-1-yl)-ethanone (1) which was used in the next step without any further purification. 3- (5-Acetyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl)-benzonitrile (3a) [0078]

[0079] According to Scheme 1, method A: steps 2-3: to a solution of 1-(4-Morpholin-4-yl-3,6-dihydro-2H-pyridin-1-yl)-ethanone (1) (6.35 g, 30.2 mmol) in dry dichloromethane (30 ml) at 0°C was added triethylamine (3.056 g, 30.2 mmol) and after stirring the solution at 0°C for 10 min, 3-cyanobenzoyl chloride (5 g, 30.2 mmol) was added. The mixture was stirred for 45 min at 0°C then the mixture was allowed to warm to room temeperature and stirred overnight. 5% aqueous HCI was added and the mixture was stirred for 2 h. The mixture was extracted with dichloromethane and the organic layer was washed with water, filtered over a short pad of silica gel and evaporated to dryness to give 8 g of 3-(1-Acetyl- 4- oxo-piperidine-3-carbonyl)-benzonitrile (2a) which was used immediately in the next step without purification.

[0080] To a mixture of 3-(1-Acetyl-4-oxo-piperidine-3-carbonyl)-benzonitrile (2a) (8 g, 29.6 mmol) in ethanol (26 ml) at 10 °C hydrazine hydrate (4.44 g, 88.8 mmol) was added slowly within 5 min. The mixture was stirred 3 h and allowed to warm to room temperature overnight. The mixture was concentrated to % of its volume until a precipitate formed. The suspension was stirred for 2 h, cooled down and filtrated. The solid was washed with a small amount of ethanol. A second portion of product precipitated overnight from the filtrate and was pooled with the first portion of solid to give 4.02 g of 3-(5-Acetyl-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl)-benzonitrile (3a) as a solid.

Rt = 1.20 min (LC-method 7). Detected mass: 267.15 [M+H+] 1-[3-(4-Trifluoromethyl-pyridin-2-yl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (3m) [0081]

[0082] According to Scheme 1, method B: to a solution of 4-(trifluoromethyl)-2-pyridinecarboxylic acid (0.42 g, 1.54 mmol) in dry tetrahydrofuran was added N-methylmorpholine (163 mg, 1.62 mmol) and isobutylchloroformate (221 mg, 1.62 mmol) and the mixture was stirred for 30 min at room temperature and the solid was filtered ofF. The filtrate was used in the subsequent reaction.

[0083] To a solution of 1-acetyl-4-piperidone (0.207g, 1.466 mmol) in tetrahydrofuran at 0°C was added dropwise 1 M lithium bis(trimethyldisilazide) in tetrahydrofuran (1.54 mmol, 1.54 ml) and the mixture was stirred for 15 min at 0°C, then the mixture was cooled down to -78°C. The mixed anhydride solution generated above was added to this mixture at -78°C, the mixture was allowed to warm to room temperature and stirred for 90 min. To this mixture at 10 °C was added ethanol (5 ml) and hydrazine hydrate (0.603 g, 7.72 mmol) and the mixture was stirred 16 h at room temperature. The mixture was concentrated and after addition of CH2CI2 and aqueous NaHC03 the mixture was extracted 3 times with CH2CI2, the combined organic layers were washed with brine, dried over NaCI, filtrated and thefiltrate was evaporated to dryness to give 323 mg of 1-[3-(4-Trifluoromethyl-pyridin-2-yl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-eth-anone (3m). The product was used crude in the next reaction steps without further purification.

Rt = 1.61 min (LC-method 1). Detected mass: 311.18 [M+H+] [0084] The examples in the following table were obtained according to Scheme 1, Method A or Method B as specified, from the specified starting compound (SC) (by following a similar procedure as used for the synthesis of (3a); in part the compounds were purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic acid).

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8-Acetyl-8-aza-bicyclo[3.2.1]octan-3-one (4a) [0085]

According to Scheme 2, Step 1 : [0086] A suspension of nortropinone hydrochloride (1 g, 6.187 mmol) in acetic anhydride was stirred at70°Cfor3h. Water was added, the mixture was boiled for 30 min and cooled down to room temperature. CH2CI2 and 1 N aqueous NaOH was added until pH 9 was reached. The mixture was extracted 2 times with CH2CI2, the combined organic layers were dried over Na2S04, filtrated and the solution was evaporated to dryness to give 0.7 g of 8-Acetyl-8-aza-bicyc-lo[3.2.1]octan-3-one (4a).

Rt = 1.76 min (LC-method 2). Detected mass: 168.24 [M+H+] 1-(3-Phenyl-4, 5,11-triaza-tricyclo[6.2.1,0*2,6*]undeca-2(6),3-dien-11-yl)-ethanone (5a) [0087]

According to Scheme 2, Steps 2+3: [0088] To a mixture of 8-Acetyl-8-aza-bicyclo[3.2.1]octan-3-one (4a) (350 mg, 2.1 mmol) in dry tetrahydrofuran at 0°C was added 1 N lithium hexamethyldisilazide (2.2 ml, 2.2 mmol) and after 5 min the mixture was cooled to -78°C.

[0089] To a solution of 3-cyanobenzoic acid (323 mg, 2.2 mmol) and N-methyl-morpholine (232 mg, 2.3 mmol) in tetrahydrofuran was added isobutylchloroformate (300 mg, 2.2 mmol). The mixture was stirred for 5 min at25°C, filtrated and washed with dry tetrahydrofuran. This solution was added dropwise to the -78°C mixture above and the mixture was then allowed to warm to 25°C for 1 h. Solvents were evaporated, CH2CI2 and water were added, the organic layer was dried over Na2S04, filtrated and the solution was evaporated to dryness, redissolved in ethanol (10 ml). Hydrazine hydrate (245 mg, 3.14 mmol) was added and the solution was stirred for 30 min. Solvents were evaporated and the crude product was purified by silica gel chromatography (dichloromethane/methanol 100/0 to 70/30) to give 45 mg of 1-(3-Phenyl-4,5,11-triaza-tricyclo[6.2.1.0*2,6*]undeca-2(6),3-dien-11-yl)-ethanone (5a).

Rt = 1.01 min (LC-method 4). Detected mass: 293.18 [M+H+] 1-[3-(4-Fluoro-phenyl)-4,5,1 1-triaza-tricyclo[6.2.1,0*2,6*]undeca-2(6),3-dien-1 1-yl]-ethanone (5b) [0090]

[0091] 1-[3-(4-Fluoro-phenyl)-4,5,11-triaza-tricyclo[6.2.1.0*2,6*]undeca-2(6),3-dien-11-yl]-ethanone (5b) was obtained by following a similar reaction as used for synthesis of (5a).

Rt = 1.06 min (LC-method 4). Detected mass: 286.18 [M+H+] 3-[5-Acetyl-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (6a) [0092]

According to Scheme 3: [0093] A mixture of 3-(5-Acetyl-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl)-benzonitrile (3a) (0.48 g, 1.8 mmol), 2,4-difluorobenzyl bromide (0.41 g, 1.99 mmol) and K2C03 (498 mg, 3.6 mmol) in 14 ml CH3CN was stirred at 80°C for 16 h. A second portion of 2,4-difluorobenzyl bromide (0.41 g, 1.99 mmol) was added and the mixture was stirred for additional 7h. Water was added, the mixture was extracted 3 times with ethyl acetate, the combined organic layers were dried over MgS04, filtrated and the solution was evaporated to dryness. The crude product was crystallized from 10 ml 2-propanol and dried in vacuo to give 0.364 g of 3-[5-Acetyl-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (6a).

Rt= 1.62 min (LC method 7). Detected mass: 393.15 [M+H+].

[0094] The examples in the following table were obtained according to Scheme 4 by following a similar reaction as used for synthesis of (6a). The corresponding halogenides used (Hal-CH2-X; particularly the corresponding bromides or chlorides) are obvious to the man skilled in the art and were commercially available. Reaction conditions varied slightly by reaction time (1-3 days), temperature (50-80°C). Products were routinely purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic acid).

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1-(2,4-Difluoro-benzyl)-3-(4-fluoro-phenyl)-6-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine, trifluoroacetate salt (7a) [0095]

According to Scheme 4: [0096] To a solution of 1 N lithium hexamethyldisilazide in dry tetrahydrofuran (4.69 ml, 4.69 mmol) at -78°C was added a solution of N-tert-butoxycarbonyl-4-piperidone (1.0 g, 4.69 mmol) in dry diethyl ether (9 ml) dropwise and the mixture was stirred at -78°C for 30 min. A solution of 4-fluorobenzoyl chloride (743 mg, 4.69 mmol) in dry diethyl ether was added. The mixture was allowed to warm to 25°C overnight. Water was added, the solution was extracted 3 times with CH2CI2, the combined organic layers were washed once with brine, dried over Na2S04, filtrated and the solution was evaporated to dryness, redissolved in ethanol (25 ml) and tetrahydrofuran (11 ml), (2,4-Difluoro-benzyl)-hydrazine (731 mg, 4.62 mmol) was added and the mixture was stirred for 10 min at25°C. The mixture was poured on 1 N aqueous NaOH, extracted 3 times with ethyl acetate, the combined organic layers were washed with brine, dried over Na2S04, filtrated and the solution was evaporated to dryness. The residue was dissolved in 4N HCI/dioxane (3 ml, 12 mmol) and stirred for 2 days. Solvents were evaporated and the crude product was purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic acid) to give 257 mg of 1-(2,4-Difluoro-benzyl)-3-(4-fluoro-phenyl)-6-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine, trifluoroacetate salt (7a).

Rt = 1.05 min (LC-method 4). Detected mass: 358.24 [M+H+] 1-Benzyl-3-(4-fluoro-phenyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine; hydrochloride (7b) [0097]

According to Scheme 5:

[0098] A mixture of 1-[1-Benzyl-3-(4-fluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (6e) (6.9 g, 20 mmol), ethanol (73ml) and 10N aqueous HCI (137 ml) was stirred at 80°C for 2h and then overnight at room temperature. The mixture was concentrated in vacuo and the product was filtrated off and washed with a small amount of cold water to give 4.87 g of 1 -Benzyl-3-(4-fluoro-phenyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridine; hydrochloride (7b).

Rt = 1.80 min (LC-method 12). Detected mass: 308.17 [M+H+] [0099] The examples in the following table were obtained according to Scheme 5 by following a similar reaction as used for synthesis of (7b). Reaction conditions varied slightly by reaction time (2 h -3 days), concentration of the aqueous HCI (2-10M) and work-up procedure (sometimes after evaporation of solvents the residue was purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic acid). The free amine was easily obtained by adding aqueous NaHC03 and extracting with 3 times CH2CI2, combining organic layers, drying over Na2S04, filtrating off and evaporating solvents of the filtrate to dryness.

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3-[1-(2,4-Difluoro-benzyl)-5-(3-methyl-oxetane-3-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzoni-trile (8a) [0100]

According to Scheme 6, method A: [0101] To a 10°C cold solution of 3-[1-(2,4-Difluoro-benzyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-ben-zonitrile, trifluoroacetate (7c) (0.055 g, 0.118 mmol) in Ν,Ν-dimethylformamide (2 ml) was added triethylamine (18 μΙ, 0.13 mmol), 1-hydroxybenzotriazole (17 mg, 0.124 mmol), 3-methyl-3-oxetane carboxylic acid (13.8 mg) and finally 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (24 mg, 0.124 mmol). The mixture was allowed to warm to 25°C and stirred for 16 h and purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic acid) to give 38 mg of 3-[1-(2,4-Difluoro-benzyl)-5-(3-methyl-oxetane-3-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyri-din-3-yl]-benzonitrile (8a).

Rt = 1.23 min (LC-method 4). Detected mass: 449.27 [M+H+] 3-[1-(2,4-Difluoro-benzyl)-5-isobutyryl-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (8b) [0102]

According to Scheme 6, method B: [0103] A mixture of 3-[1-(2,4-Difluoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (7c) (0.057 g, 0.163 mmol), K2C03 (45 mg, 0.327 mmol) and isobutyryl chloride (21 mg, 0.196 mmol) in dry CH3CN (1.5 ml) was stirred at 60°C for 1 h. Water was added, the solution was extracted 3 times with CH2CI2, the combined organic layers were washed once with brine, dried over Na2S04, filtrated and the residue was purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic acid) to give 48 mg of 3-[1-(2,4-Difluoro-benzyl)-5-isobutyryl-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (8b).

Rt = 1.18 min (LC-method 1). Detected mass: 421.29 [M+H+] 3-[5-Cyclopropanecarbonyl-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (8c) [0104]

According to Scheme 6, method C: [0105] To a 0°C cold mixture of 3-[1-(2,4-Difluoro-benzyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzoni- trile, hydrochloride salt (7c) (0.050 g, 0.129 mmol), NaHC03 (44 mg, 0.517 mmol), water (2 ml) and ethyl acetate (2 ml) was added cyclopropanecarbonyl chloride (13.5 mg, 0.129 mmol) and the mixture was stirred at 25°C for 16 h. Water was added, the solution was extracted 2 times with ethyl acetate, the combined organic layers were washed once with brine, dried over MgS04, filtrated and purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic acid) to give 21 mg of 3-[5-Cyclopropanecarbonyl-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (8c).

Rt = 4.14 min (LC-method 13). Detected mass: 419.18 [M+H+] 3-[5-(2-tert-Butoxy-acetyl)-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (8d) [0106]

According to Scheme 6, method D:

[0107] To a 0°C cold mixture of 3-[1-(2,4-Difluoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzoni-trile (7c) (0.4 g, 1.142 mmol) and 2-tert-butoxyacetic acid (196 mg, 1.485 mmol) was added N,N-diisopropylethylamine (0.59 g, 4.57 mmol) and TOTU (0-(Cyano(ethoxycarbonyl)methylenamino)-1,1,3,3-tetramethyluronium tetrafluorobo-rate, 562 mg, 1.71 mmol) and the mixture was stirred at 25°C for 1 h. The crude product was purified by reverse phase HPLC (CH3CN/watergradient with 0,1 % trifluoroacetic acid) to give 120mgof3-[5-(2-tert-Butoxy-acetyl)-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (8d).

Rt = 1.34 min (LC-method 4). Detected mass: 465.3 [M+H+] 3-[1-(2,4-Difluoro-benzyl)-5-(3-methyl-3H-imidazole-4-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (8w) [0108]

According to Scheme 6, method E: [0109] A mixture of 3-[1-(2,4-Difluoro-benzyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (7c) (0.04 g, 0.114 mmol), 3-Methyl-3H-imidazole-4-carbonyl chloride (0.083 g, 0.457 mmol) and triethylamine (138 mg, 1.37 mmol) in CH2CI2 was stirred at 25°C for 16 h. The crude product was purified by reverse phase HPLC (CH3CN / water gradient with 0,1 %trifluoroaceticacid)togive43mgof3-[1-(2,4-Difluoro-benzyl)-5-(3-methyl-3H-imidazole-4-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (8w).

Rt = 3.53 min (LC-method 2). Detected mass: 459.24 [M+H+] 1-[1-(2,4-Difluoro-benzyl)-3-(4-fluoro-phenyl)-6-methyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]-ethanone (8z) [0110]

According to Scheme 6, method F: [0111] A mixture of 1-(2,4-Difluoro-benzyl)-3-(4-fluoro-phenyl)-6-methyl-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyrid-ine (7a) (0.53 g, 1.35 mmol), acetic anhydride (5.5 ml) and pyridine (5.5 ml) was stirred at 25°C for 16 h. The mixture was poured on 50 ml water, extracted with 150 ml ethyl acetate , the combined organic layers were washed with 3 times 0,5 N NaOH (50 ml) and once with brine, dried over MgS04, filtrated and evaporated to dryness. The crude product was silica gel chromatography (eluting with heptane / ethyl acetate) to give 156 mg of 1-[1-(2,4-Difluoro-benzyl)-3-(4-fluoro-phenyl)-6-methyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (8z).

Rt = 1.3 min (LC-method 4). Detected mass: 400.22 [M+H+] [0112] The examples in the following table were obtained according to Scheme 6 by following one of the methods described for the synthesis of 8a-8c (Method (A) according to 8a, Method (B) and Method (C) according to 8c). The acylating reagents are obvious to the man skilled in the art and therefore not mentioned.

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3-(4-Fluoro-phenyl)-1-[(R)-1-(4-fluoro-phenyl)-ethyl]-5-methanesulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine, enantiomer 1 (9a)

[0113]

According to Scheme 7: [0114] To a mixture of 3-(4-Fluoro-phenyl)-1-[1-(4-fluoro-phenyl)-ethyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine (enantiomer 1) (7e) (0.120 g, 0.353 mmol) and triethylamine (0.135 ml, 1.06 mmol) in CH2CI2 at 0°C was added meth-anesulfonyl chloride (49 mg, 0.424 mmol) and the mixture was stirred at 25°C for 16 h. The crude product was purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic acid) to give 96 mg of 3-(4-Fluoro-phenyl)-1-[(R)-1-(4-fluorophenyl)-ethyl]-5-methanesulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine (9a).

Rt = 3.58 min (LC-method 8). Detected mass: 418.09 [M+H+] 3-(4-Fluoro-phenyl)-1-[(R)-1-(4-fluoro-phenyl)-ethyl]-5-methanesulfonyl-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridine, enantiomer 2 (9b) [0115]

[0116] 3-(4-Fluoro-phenyl)-1-[(R)-1-(4-fluoro-phenyl)-ethyl]-5-methanesulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-cjpyridine, enantiomer 2 (9b) was obtained starting from 3-(4-Fluoro-phenyl)-1-[1-(4-fluoro-phenyl)-ethyl]-4,5,6,7-tet-rahydro-1 H-pyrazolo[4,3-c]pyridine (enantiomer 2) (7f) by following a similar reaction as used for synthesis of (9a).

Rt = 3.58 min (LC-method 8). Detected mass: 418.09 [M+H+] 3-(3-Cyano-phenyl)-1-(2,4-difluoro-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylicacid isopropylamide (11a)

[0117]

According to Scheme 8: [0118] To a mixture of 3-(1-(2,4-Difluoro-benzyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (7c) (0.060 g, 0.171 mmol) and triethylamine (138 mg, 1.37 mmol) at 0°C was added isopropylisocyanate (17.5 mg, 0.21 mmol) and the mixture was stirred at room temperature for 16 h. The crude product was purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic) to give 19 mg of 3-(3-Cyano-phenyl)-1-(2,4-difluoro-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid isopropylamide (11a).

Rt = 1.16 min (LC-method 1). Detected mass: 436.25 [M+H+] [0119] The examples in the following table were obtained according to Scheme 9 by following a similar reaction as used for synthesis of (11 a).

(continued)

3-(3-Cyano-phenyl)-1-(2,4-difluoro-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid methylamide (12a) [0120]

According to Scheme 9:

[0121] To a mixture of 3-[1-(2,4-Difluoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (7c) (0.060 g, 0.171 mmol) and triethylamine (60 mg, 0.60 mmol) in CH2CI2 at 0°C was added para-nitrophenylchloroformate (38 mg, 0.188 mmol) and the mixture was stirred at 0°C for 45 min. 2 M methylamine in tetrahydrofuran (2ml, 4 mmol) was added and the mixture was stirred for 3 days at room temperature. The crude product was purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic) to give 3.4 mg of 3-(3-Cyano-phenyl)-1-(2,4-difluoro-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid methylamide (12a).

Rt = 1.11 min (LC-method 1). Detected mass: 408.15 [M+H+] [0122] The examples in the following table were obtained according to Scheme 10 by following a similar reaction as used for synthesis of (12a), but at a reaction temperature of 80°C.

(continued)

2-[5-Acetyl-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-isonicotinonitrile (13a) [0123]

According to Scheme 10: [0124] To a solution of Zn(CN)2 (39 mg, 0.335 mmol) and tetrakis(triphenylphosphine)palladium(0) (19 mg, 0.016 mmol) in dry Ν,Ν-dimethylformamide (0.6 ml) at 150°C was slowly added a solution of 1-[3-(4-Bromo-pyridin-2-yl)-1-(2,4-difluoro-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone (6j) (0.15 g, 0.335 mmol) in dry N,N-dimethyl-formamide (1 ml). The mixture was stirred at 150°C for 3 h and then at 25°C for 16 h. The mixture was diluted with methyl-tert-butylether, filtrated over Celite, washed with water, dried over Na2S04, filtrated and evaporated to dryness. The residue was suspended in methanol, and the solid was filtrated off to give 67 mg of 2-[5-Acetyl-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-isonicotinonitrile (13a).

Rt= 1.11 min (LC-method 1). Detected mass: 394.22 [M+H+] [0125] The examples in the following table were obtained according to Scheme 11 by following a similar reaction as described for the synthesis of 13a. Sometimes the products were purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic acid).

3-[1-(2,4-Difluoro-benzyl)-5-(2-hydroxy-acetyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (14a) [0126]

[0127] Asolutionof3-[5-(2-tert-Butoxy-acetyl)-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (8d) (90 mg , 0.193 mmol) and trifluoroacetic acid (221 mg, 1.94 mmol) in CH2CI2 was stirred at 25°C for 1 day. Solvents were evaporated and the residue purified by reverse phase HPLC (CH3CN / water gradient with 0,1 % trifluoroacetic acid) to give 48 mg of 3-[1-(2,4-Difluoro-benzyl)-5-(2-hydroxy-acetyl)-4,5,6,7-tetrahydro-1H-pyrazo-lo[4,3-c]pyridin-3-yl]-benzonitrile (14a).

Rt = 1.19 min (method 4). Detected mass: 409.21 [M+H+] [0128] The following LC methods were used to analyze the exemplary embodiments: Following abbreviations are used: FA: formic acid TFA: trifluoroacetic acid ACN: acetonitrile LC method 1:

Stationary phase: Waters UPLC BEH C18 2,1*50 mm; 1.7μ

Gradient: H20+0.05% FA : ACN+0.035%FA 95:5 (Omin) to 5:95(1.1 min) to 5:95(1,7min) to 95:5 (1.9min) to 95:5 (2min)

Flow: 0.9 mL/min, 55°C LC method 2:

Stationary phase: Waters XBridge C18 4.6*50 mm; 2,5μ

Gradient: H2O+0.1 %FA : AcN+0.1 %FA97:3 (Omin) to 40:60 (3.5 min) to 2:98(4min) to 2:98(5min) to 97:3 (5.2min) to 97:3 (6.5min);

Flow: 1.3 mL/min LC method 3:

Stationary phase: WatersXBridgeCI 8,4,6*50; 2,5μ

Gradient: H20+0.05%TFA : ACN+0.05%TFA 95:5(0min) to 95:5(0.2 min) to 5:95(2,4min) to 5:95(3,2min) to 95:5(3,3min) to 95:5(4,Omin)

Flow: 1.7 mL/min, 40°C LC method 4:

Stationary phase: Waters UPLC BEH C18 2,1*50 mm; 1.7μ

Gradient: H2O+0.1%FA: ACN+0.08%FA 95:5 (Omin) to 5:95(1.1 min) to 5:95(1,7min) to 95:5 (1,8min) to 95:5 (2min)

Flow: 0.9 mL/min, 55°C LC method 5:

Stationary phase: WatersXBridgeCI 8,4,6*50, 2,5μ

Gradient: H2O+0.05%TFA : ACN+0.05%TFA95:5(0min) to 95:5(0.2 min) to 5:95(2,4min) to 5:95(3,5min) to 95:5(3,6min) to 95:5(4,5min)

Flow: 1.7 mL/min, 50°C LC method 6:

Stationary phase: WatersXBridgeCI 8,4,6*50, 2,5μ

Gradient: H20+0.05%TFA : ACN+0.05%TFA95:5(0min) to5:95(2,6 min)to5:95(3,0min)to95:5(3,1 min), to 95:5(4.Omin)

Flow: 1.7 mL/min, 40°C LC method 7:

Stationary phase: Merck Chromolith FastGrad. RP-18e, 50x2mm

Gradient: H20+0.05% TFA : ACN+0.05% TFA 98:2(0 min) to 98:2(0.2 min) to 2:98(2.4 min) to 2:98(3.2 min) to 98:2(3.3 min) to 98:2(4 min)

Flow: 2 mL/min, 50°C LC method 8:

Stationary phase: WatersXBridgeC18,4,6*50,2^

Gradient: H20+0.05%TFA : ACN+0.05%TFA95:5(0min) to95:5(0.3min) to5:95(3.5 min) to5:95(4min)

Flow: 1,3ml/min, 40°C LC method 9:

Stationary phase: Waters UPLC BEH C18 2,1*50 mm; 1.7μ

Gradient: H20+0.05%FA : ACN+0.035%FA 98:2 (Omin) to 5:95(2min) to 5:95(2.6min) to 95:5 (2.7min) to 95:5 (3min)

Flow: 0.9 ml/min 55° LC method 10:

Stationary phase: 0.2μΙ10 X2 0 LunaC18, 3μ

Gradient: 0 min 93%H20 (0.05%TFA)-1 .Omin- 95%ACN; 95%ACN to 1,45min; 7%ACN 1,50min

Flow: 1 ml/min 55°C LC method 11:

Stationary phase: Waters XBridge C18 4.6*50 mm; 2.5μ

Gradient: H2O+0.1 %FA : ACN+0.08%FA 97:3 (Omin) to 40:60 (3.5 min) to 2:98(4min) to 2:98(5min) to 97:3 (5.2min) to 97:3 (6.5min)

Flow: 1.3 ml, 45 °C LC method 12:

Stationary phase: YMC JSphere33*2, 4μ

Gradient: H20+0.05%FA : ACN+0.05%FA 95:5(0min) to 95:5(0.5min) to 5:95(3.5 min) to 5:95(4min)

Flow: 1.3 ml/min, r.t. LC method 13:

Stationary phase: YMC-Pack JSphere H80 33*2.

Gradient: H20+0.05%TFA : CH3OH+0.05%TFA 98:2(1 min)to5:95(5.0min)to5:95(6.25min)

Flow: 1.0 ml/min, r.t. LC method 14:

Stationary phase: YMC-JSphere-ODS-H80 (20 x 2 1 4 μ)

Gradient: Omin 96 % H20 (0.05%TFA) to 95 % CH3CN (2.4min) to 4 % CH3CN (2.45 min)

Flow: 1.0 ml/min, 30°C LC method 15:

Stationary phase: YMC JSphere33*2^.

Gradient: (AcN+0.05% TFA) : H20+0.05% TFA; 5:95(0min)to5:95(0.5min)to95:5(3.5min)to95:5(4min)

Flow: 1.3 ml/min

Determination of the activity on the TASK-1 channel in Xenopus oocytes [0129] Human TASK-1 channels were expressed in Xenopus oocytes. For this purpose, oocytes were isolated from Xenopus laevis and defoliculated. Subsequently, TASK-1-encoding RNA synthesized in vitro was injected into oocytes. After two days of TASK-1 protein expression, TASK-1 currents were measured by two-microelectrode voltage clamp. Data were acquired and analyzed using a TEC-10cx amplifier (NPI Electronic, Tamm, Germany) connected to an ITC-16 interface (Instrutech Corp., Long Island, USA) and Pulse software (HEKA Elektronik, Lambrecht, Germany). Oocytes were clamped to -90 mV and TASK-1 mediated currentswere measured during 500 ms voltage pulses to 40 mV. Oocytes were continuously superfused with ND96 buffer containing: NaCI96 mM, KCI2 mM, CaCI21.8 mM, MgCI21 mM, HEPES 5 mM (pH adjusted to 7.4 with NaOH). All experiments were performed at room temperature.

[0130] Test substances were consecutively added to the bath solution at rising concentrations. Compound effects were calculated as the percentage inhibition of TASK-1 control current before compound application. IC50 values were obtained by fitting the data to the general dose-response equation.

[0131] The following products/compounds were tested in said assay by using the respective form (salt or free base) obtained as in the examples described above and the following activities were measured (IC50 values or inhibition (in %) at 5 μΜ).

(continued)

Investigation of the refractory period and the left-atrial vulnerability in the pig [0132] The compounds were tested for prolongation of the refractory period and antiarrhythmic activity on the atrium of the anesthetized pig as described in the literature (Knobloch et al. 2002. Naunyn-Schmiedberg’s Arch. Pharmacol. 366; 482-487). Here the anti-arrhythmic action relates to the inhibition of the occurrence of episodes of arrhythmias which are induced by a prematurely placed extra-stimulus (S2) in the left atrium (= left-atrial vulnerability). The refractory period values are stated in percent of the basal values 15 minutes after injection. Mean values for the refractory periods are shown from three rates (150, 200 and 250/min). The inhibitory values for the inhibition of episodes of arrhythmias referto 3 measurements (3 timepoints) before administration vs. 3 measurements during thefirst hour after administration of the compounds.

[0133] The action of 3-[5-Acetyl-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile (6a) on the refractory period of the left atrium and antiarrhythmic activity in the anesthetized pig aftera bolus administration of 1 mg/kg is shown in table 1. From the results shown in table 1, it is seen that it was possible to prevent 61 % of the induced arrhythmias.

Claims

1. A compound of the formula I

wherein A = (Cg-Cio)-aryl or a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (Ci-Cg)-alkyl-, (C1-C6)-alkyl-0- and (Ci-Cg)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = (C6-C10)-aryl or a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, (C1-C6)-alkyl-S-, (C1-C6)-alkyi-0-C(0)- and (C1-C6)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R1 = R5-C(=0)- or (CrC6)-alkyl-S02-; R2 = H, (Ci-Cg)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H, (C1-C4)-alkyl-; R4 = H,(C1-C4)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; R5 = H, (C1-C6)-alkyl-, (C3-C6)-cycloalkyl-, (C1-C6)-alkyl-0-, (C1-C6)-alkyl-S-, (C1-C6)-alkyl-0-(C1-C6)-alkyl-, HO-(C.|-Cg)-alkyl-, (C^CgJ-cycloalkyl-fC^CgJ-alkyl-, (C6-C10)-aryl-, (C6-C10)-aryl-(C.|-C6)-alkyl-, R7R6N-, heteroaryl, heteroaryl-fC^Cgl-alkyl-, aliphatic heterocycle, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl and 4 to 7 membered aliphatic heterocycles comprising an oxygen atom, and wherein the aliphatic heterocycle may be optionally substituted with 1 to 3 substituents independently selected from the group of F, OH, (C.|-C6)-alkyl-0- and (C.|-C6)-alkyl-, and wherein the heteroaryl residues are five- or six-membered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (CrCg)-alkyl-, (C1-C6)-alkyl-0-CN, (CrC2)-alkyl-S02-; R6 = H, (C1-C6)-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH or (C-pCg^alkyl-O- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H,(C1-C6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine, and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts, and with the proviso if R5 is methyl and R2, R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-acetoxyphenyl, 2-chloro-phe-nyl, 3,4-dichlorophenyl, and with the proviso if R5 is methyl and R2, R3 and R4 are equal to H and X is a phenyl residue, the residue A is not phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethyloxy-phenyl, 3-trifluoromethyl-phenyl, 2-thiophenyl or 4-methylthiophenyl, and with the proviso if R5 is methyl and R2 is methyl and R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl. 2. A compound according to claim 1, wherein A = phenyl or a five- or six-membered heteroaryl selected from the group consisting of pyridine-2-yl, pyridine- 3- yl, pyridine-4-yl, thiophen-2-yl orthiophen-3-yl, wherein phenyl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C1-C6)-alkyl-, (C1-C6)-alkyl-0- and (C1-C6)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein the heteroaryl group is optionally substituted with 1-3 residues selected independently from F, Cl, Br, CN, (C1-C6)-alkyl-, (C1-C6)-alkyl-0- and (C1-C6)-alkyl-S-, (C1-C6)-alkyl-0-C(0)- and (C1-C6)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine. R1 = R5-C(=0)- or (C1-C6)-alkyl-S02-; R2 = H, (C1-C4)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H,(C1-C2)-alkyl-; R4 = H,(C1-C2)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; R5 = H, (C1-C6)-alkyl-, (C3-C6)-cycloalkyl-, (C1-C6)-alkyl-0-, (C1-C6)-alkyl-S-, (C1-C6)-alkyl-0-(C1-C6)-alkyl-, FIO-(C1-C6)-alkyl-, (C3-C6)-cycloalkyl-(C1-C6)-alkyl-, (C6-C10)-aryl-, (C6-C10)-aryl-(C1-C6)-alkyl-, R7R6N-, heteroaryl, heteroaryl-(C-|-C6)-alkyl-, aliphatic heterocycle, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl and 4 to 7 membered aliphatic heterocycles comprising an oxygen atom, and wherein the aliphatic heterocycle may be optionally substituted with 1 to 3 substituents independently selected from the group of F, OH, (C^CgJ-alkyl-O- and (C^CgJ-alkyl-, and wherein the heteroaryl residues are five- or six-membered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-., R6 = H, (Ci-Cg)-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH- or (C1-C6)-alkyl-0- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H, (C1-C6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine, and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts. 3. A compound according to claim 1 or 2, wherein A = phenyl, wherein the phenyl residue is optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (CrC4)-alkyl-, (CrC4)-alkyl-0- and (CrC4)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = afive-orsix-mem bered heteroaryl, selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine- 4- yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, wherein the heteroaryl group is optionally substituted with 1-3 residues selected independently from F, Cl, Br, CN, (C1-C6)-alkyl-, (C1-C6)-alkyl-0- and (CrC6)-alkyl-S-, (C1-C6)-alkyl-0-C(0)- and (C1-C6)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R1 = R5-C(=0)- or (C1-C2)-alkyl-S02-; R2 = H, (C1-C2)-alkyl-, cyclopropyl-; R3 = H, methyl-; R4 = H, methyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 = H, (C-j-C^-alkyl-, (C3-C6)-cycloalkyl-, (C1-C2)-alkyl-0-, (C1-C2)-alkyl-S-, (C1-C4)-alkyl-0-methyl-, HO-(C1-C2)-alkyl-, (C3-C6)-cycloalkyl-(C1-C2)-alkyl-, phenyl, phenyl-(C1-C2)-alkyl-, R7R6N-, heteroaryl, heter-oaryl-(C1-C4)-alkyl-, aliphatic heterocycle, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl, oxetanyl, tetrahydrofuranyl, and tetrahydropyranyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents independently selected from the group of F, OH, (C1-C2)-alkyl-0- and (C1-C4)-alkyl-, and wherein the phenyl residue is optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (CrC4)-alkyl-, (C1-C4)-alkyi-0-CN, (C1-C2)-alkyl-S02- wherein the heteroaryl residues are selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine- 4- yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol- 5- yl, pyrazol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyri-dazin-3-yl, pyridazin-4-yl, pyrazin-2-yl and pyrazin-3-yl, and wherein the heteroaryl residues are optionally substituted with 1 or 2 rests selected independently from F, Cl, Br, CF3, (C1-C4)-alkyl-, (CrC4)-alkyl-0-, CN, (C1-C2)-alkyl-S02-., R6 = H, (C1-C4)-alkyl-, cyclopropyl, wherein one hydrogen atom of the alkyl group may be replaced by an OH, methoxy or ethoxy residue; and R7 = H, methyl-, ethyl; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts. 4. A compound according to any one of claims 1 to 3, wherein A = phenyl, wherein the phenyl residue is optionally substituted with 1 or 2 rests selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, and (CrC2)-alkyl-S-; X = a five-or six-mem bered heteroaryl, selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine- 4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C1-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl-S02-; R1 = R5-C(=0)- or (C1-C2)-alkyl-S02-; R2 = H, methyl, ethyl, cyclopropyl; R3 and R4 = H, and R5 = methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert.-butyl, cyclopropyl or cyclobutyl; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts. 5. A compound according to any one of claims 1, wherein A = a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein the heteroaryl is substituted with 1-3 residues selected independently from F, Cl, Br, CN, (Ci-C6)-alkyl-, (C1-C6)-alkyi-0-and (C^CgJ-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = phenyl, thiophen-2-yl or thiophen-3-yl, wherein these residues are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C-|-Cg)-alkyl-, (C^-Cg)-alkyl-O-and (C^-Cg)-alkyl-S-, (C^-Cg)-alkyl-O-C(O)- and (C.|-Cg)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R1 = R5-C(=0)- or (C1-C6)-alkyi-S02-; R2 = H, (C1-C6)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H, (C1-C4)-alkyl-; R4 = H, (C1-C4)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; R5 = H, (C.|-C6)-alkyl-, (C3-C6)-cycloalkyl-, (C^CgJ-alkyl-O-, (C^CgJ-alkyl-S-, (C1-C6)-alkyl-0-(C1-C6)-alkyl-, HO-(Ci-Cg)-alkyl-, (C3-C6)-cycloalkyl-(Ci-Cg)-alkyl-, (C6-Ci0)-aryl-, (C6-C10)-aryl-(C1-C6)-alkyl-, R7R6N-, het-eroaryl, heteroaryl-(Ci-C6)-alkyl-, aliphatic heterocycle, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl and 4 to 7 membered aliphatic heterocycles comprising an oxygen atom, and wherein the aliphatic heterocycle may be optionally substituted with 1 to 3 substituents selected from the group of F, OH, (Ci-Cg)-alkyl-O- and (C1-C6)-alkyl-, and wherein the heteroaryl residues are five- or six-membered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyi-0-CN, (C1-C2)-alkyl-S02-; R6 = H, (C.|-Cg)-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH- or (C1-C6)-alkyl-0- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H, (C1-C6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine, and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts, with the proviso that A is not 4-methylthiophenyl if in compounds of formula I R5 is methyl and R2, R3 and R4 are hydrogen and X is phenyl. 6. A compound according to claim 5, wherein A = 2-pyridyl, 3-pyridyl or 4-pyridyl, wherein the pyridyl residues are substituted with 1 or 2 residues selected independently from F, Cl, Br, ON, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, and (C1-C2)-alkyl-S-; X = phenyl, thiophen-2-yl or thiophen-3-yl, wherein these residues are substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (Ci-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C^C^-alkyl-S-, (C.|-C2)-alkyl-0-C(0)- and methyl-S02-; R1 = R5-C(=0)- or (C1-C2)-alkyl-S02-; R2 = H, methyl, ethyl, cyclopropyl; R3 and R4 = H; and R5 = H, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or tert.-butyl or wherein R5 = cyclopropyl, cyclobutyl, cyclopentyl or (C3-C6)-cycloalkyl-(Ci-C2)-alkyl-; or wherein R5 = (C1-C2)-alkyl-0-, (C1-C2)-alkyl-S-, or OCF3, or wherein R5 = (C1-C4)-alkyl-0-methyl-, HO-(C1-C2)-alkyl-or wherein R5 = phenyl or phenylmethyl-, wherein the phenyl residues are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (C1-C2)-alkyl-, (C1-C2)-alkyl-0-, CN, methyl-S02-; or wherein, R5 = R7R6N-, wherein R6 = H, (CrC4)-alkyl-, cyclopropyl, wherein one hydrogen atom of the alkyl group may be replaced by an OH, methoxy or ethoxy residue; and R7 = H, methyl-, ethyl; or wherein R5 = heteroaryl, heteroaryl-(C.|-Cg)-alkyl-, wherein the heteroaryl residues are selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine- 4- yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol- 5- yl, pyrazol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyri-dazin-3-yl, pyridazin-4-yl, pyrazin-2-yl and payrazin-3-yl, and wherein the heteroaryl residues are optionally substituted with 1 or 2 rests selected independently from F, Cl,

Br, CF3, (C1-C4)-alkyl-, (C1-C4)-alkyl-0-, CN, (C1-C2)-alkyl-S02-; or wherein R5 = an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl, oxetanyl and tetrahydrofuranyl, tetrahydropyranyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents independently selected from the group of F, OH, (C1-C2)-alkyl-0- and (C1-C4)-alkyl-; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts. 7. A compound according to claim 1, wherein A is equal to phenyl, wherein the phenyl residue is optionally substituted with 1-3 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, (C1-C4)-alkyl-0- and (CrC4)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and X is equal to phenyl, wherein the phenyl group is optionally substituted with 1,2 or 3 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, (CrC4)-alkyl-0-, (CrC4)-alkyl-S-, (CrC4)-alkyl-0-C(0)- and (C1-C4)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and R1 = R5-C(=0)- or (CrC6)-alkyl-S02-; R2 = H, (C.|-C6)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H, (C1-C4)-alkyl-; R4 = H, (C1-C4)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; R5 = H, (CrC6)-alkyl-, (C3-C6)-cycloalkyl-, (C1-C6)-alkyl-0-, (C1-C6)-alkyl-S-, (C1-C6)-alkyl-0-(C1-C6)-alkyl-, HO-(C1-C6)-alkyl-, (C3-C6)-cycloalkyl-(C1-C6)-alkyl-, (C6-C10)-aryl-, (C6-C10)-aryl-(C.|-C6)-alkyl-, R7R6N-, heteroaryl, heteroaryl-(Ci-C6)-alkyl-, aliphatic heterocycle, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl and 4 to 7 membered aliphatic heterocycles comprising an oxygen atom, and wherein the aliphatic heterocycle may be optionally substituted with 1 to 3 substituents selected from the group of F, OH, (C.|-C6)-alkyl-0- and (C1-C6)-alkyl-, and wherein the heteroaryl residues are five- or six-membered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyi-0-CN, (C1-C2)-alkyl-S02-; R6 = H, (C.|-C6)-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH- or (C.|-C6)-alkyl-0- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H, (C1-C6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine, with the proviso if R5 is methyl and R2, R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-acetoxyphenyl, 2-chloro-phe-nyl, 3,4-dichlorophenyl, and with the proviso if R5 is methyl and R2, R3 and R4 are equal to H and X is a phenyl residue, the residue A is not phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethyloxy-phenyl, or 3-trifluoromethyl-phenyl, and with the proviso if R5 is methyl and R2 is methyl and R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl. 8. A compound according to claim 7, wherein A = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3and (C1-C2)-alkyl-S-; X = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C.|-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl- so2-, R1 = R5-C(=0)- or methyl-S02-; R2 = H, (C1-C2)-alkyl-, cyclopropyl-; R3 = H, methyl-; R4 = H, methyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 is equal to a heteroaryl or heteroaryl-(C.|-C6)-alkyl-, wherein the heteroaryl residues are selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol- 5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin- 2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyridazin-4-yl, pyrazin-2-yl and pyrazin-3-yl, and wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CF3, methyl, ethyl, methoxy, ethoxy, CN, methyl-S02-, or wherein

R5 is equal to H or wherein R5 is equal to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or (C3-C6)-cycloalkyl-(C.|-C2)-alkyl-, or wherein R5 is equal to (C1-C2)-alkyl-0- or (C1-C2)-alkyl-S-, or wherein R5 is equal to (Ci-C4)-alkyl-0-methyl-, HO-(Ci-C2)-alkyl-, or wherein R5 is equal to phenyl- or phenylmethyl-, wherein the phenyl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C1-C2)-alkyl-, (C1-C2)-alkyl-0-, CN, methyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to R7R6N-, wherein R6 = H, (C1-C4)-alkyl-, cyclopropyl-, wherein one hydrogen atom of the alkyl group may be replaced by a hydroxy, methoxy or ethoxy residue, and R7 = H, methyl-, ethyl-; or wherein R5 is equal to an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, mor-pholinyl, piperidinyl, pyrrolidinyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents selected from the group of F, OH, (C1-C2)-alkyl-0- and (C1-C4)-alkyl-, and wherein one or more hydrogen atoms of the alkyl groups may be replaced by fluorine; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts. 9. A compound according to claim 7, wherein A = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3 and (C1-C2)-alkyl-S-; X = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C4-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C1-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl-S02-, R1 = R5-C(=0)-; R2 = H, (C1-C2)-alkyl-, cyclopropyl-; R3 = H, methyl-; R4 = H, methyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 is equal to (C2-C4)-alkyl, or wherein R5 is equal to methyl, with the proviso if R5 is methyl and R2, R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-acetoxyphenyl, 2-chloro-phe-nyl, 3,4-dichlorophenyl; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts. 10. A compound according to claim 1, wherein A = (C6-C10)-aryl or a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C1-C6)-alkyl-, (C^CgJ-alkyl-O- and (C^CgJ-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = (C6-C10)-aryl or a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C1-C6)-alkyl-, (CrC6)-alkyl-0- and (CrC6)-alkyl-S-, (CrC6)-alkyl-0-C(0)- and (C1-C6)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R1 = R5-C(=0)- or (CrC6)-alkyl-S02-; R2 = H, (Ci-Cg)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H, (C1-C4)-alkyl-; R4 = H, (C1-C4)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; and wherein R5 is equal to a heteroaryl or heteroaryl-(C.|-Cg)-alkyl-, wherein the heteroaryl residues are five- or six-membered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein the heteroaryl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not pyrimidin-4-yl, pyridine-2-yl, 1-methyl-pyrazol-3-yl or 1-methyl-imidazol-2-yl, or wherein R5 is methyl, with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 2,4-difluorophenyl residue A is not pyridine-3-yl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluorophenyl, 3-cyano-phenyl, 3-methoxy-phenyl, 3-trif-luormethoxy-phenyl, 2-fluoro-5-methoxy-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 3-cyanophenyl residue A is not a 4-fluorophenyl residue, and with the proviso ifin compounds of formula I R3 is methyl, R2 and R4 are hydrogen and X is a 2,4-difluoro-phenyl residue A is not a 4-fluoro-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is phenyl A is not phenyl, 3-trifluoromethyl-phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethyloxy-phenyl, 4-acetoxyphenyl, 4-methyl-thiophenyl, 2-thiophenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and A is 4-fluoro-phenyl X is not phenyl, 2-chloro-phenyl, 3,4-dichloro-phenyl, 4-chloro-phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-ethy-loxy-phenyl, and with the proviso if R5 is methyl and R2 is methyl, and R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl, and or wherein R5 is equal to H, (C2-C6)-alkyl, CF3, CF2H, CFH2, wherein one or more hydrogen atoms of the alkyl residue may be replaced by fluorine; or wherein R5 is equal to (C3-C6)-cycloalkyl or (C3-C6)-cycloalkyl-(C1-C4)-alkyl-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not cyclopropyl, or wherein R5 is equal to (C1-C4)-alkyl-0- or (C1-C4)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to (C1-C4)-alkyl-0-(C1-C2)-alkyl-, HO-(C.|-C4)-alkyl-, or wherein R5 is equal to phenyl-, phenyl-(C.|-C4)-alkyl-, wherein the phenyl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methylsulfonyl-phenyl or 4-methylsulfonyl-phenyl; or wherein R5 is equal to R7R6N-, wherein R6 = H, (C1-C4)-alkyl-, cyclopropyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH, methoxy or ethoxy residue and R7 = H, (CrC2)-alkyl-or wherein R5 is equal to an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, mor-pholinyl, piperidinyl, pyrrolidinyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents selected from the group of F, OH, (C.|-C4)-alkyl-0- and (Ci-C4)-alkyl-, and wherein one or more hydrogen atoms of the alkyl groups may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methyl-oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl or 1-methyl-piperidin-4-yl. 11. A compound according to claim 10, wherein A= phenyl, pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl or thiophen-3-yl, wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3 and (C.|-C2)-alkyl-S-; X = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (Ci-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl- so2-, or pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C.|-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl-S02-; R1 = R5-C(=0)- or (C1-C2)-alkyl-S02-; R2 = H, (C.|-C2)-alkyl-, cyclopropyl-; R3 = H, (C.|-C2)-alkyl-; R4 = H, (C1-C2)-alkyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 is equal to a heteroaryl or heteroaryl-(C1-C6)-alkyl-, wherein the heteroaryl residues are selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol- 5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin- 2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyridazin-4-yl, pyrazin-2-yl and payrazin-3-yl, and wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CF3, methyl, ethyl, methoxy, ethoxy, CN, methyl-S02-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not pyrimidin-4-yl, pyridine-2-yl, 1-methyl-pyrazol-3-yl or 1-methyl-imidazol-2-yl, or wherein R5 is methyl, with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 2,4-difluorophenyl residue A is not pyridine-3-yl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluorophenyl, 3-cyano-phenyl, 3-methoxy-phenyl, 3-trif-luormethoxy-phenyl, 2-fluoro-5-methoxy-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 3-cyanophenyl residue A is not a 4-fluorophenyl residue, and with the proviso if in compounds of formula I R3 is methyl, R2 and R4 are hydrogen and X is a 2,4-difluoro-phenyl residue A is not a 4-fluoro-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is phenyl A is not phenyl, 3-trifluoromethyl-phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethoxy-phenyl, 2-thiophenyl, 4-methylthiophenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and A is 4-fluoro-phenyl X is not 2-chloro-phenyl, 3,4-dichloro-phenyl, 4-chloro-phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-ethoxy-phenyl or 4-acetoxyphenyl, and or wherein R5 is equal to H, (C2-C4)-alkyl, CF3; or wherein R5 is equal to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or(C3-C6)-cycloalkyl-(C1-C2)-alkyl-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not cyclopropyl, or wherein R5 is equal to (C1-C2)-alkyl-0- or (C1-C2)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to (C1-C4)-alkyl-0-methyi-, HO-(C.|-C2)-alkyl-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to phenyl-, phenyl-(C.|-C2)-alkyl-, wherein the phenyl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C1-C2)-alkyl-, (C1-C2)-alkyl-0-, CN, methyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methylsulfonyl-phenyl or 4-methylsulfonyl-phenyl; or wherein R5 is equal to R7R6N-, wherein R6 = H, (C1-C4)-alkyl-, cyclopropyl-, wherein one hydrogen atom of the alkyl group may be replaced by a hydroxy, methoxy or ethoxy residue and R7 = H, methyl-, ethyl-or wherein R5 is equal to an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, mor-pholinyl, piperidinyl, pyrrolidinyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents selected from the group of F, OH, (C1-C2)-alkyl-0- and (Ci-C4)-alkyl-, and wherein one or more hydrogen atoms of the alkyl groups may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methyl-oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl or 1 -methyl-piperidin-4-yl, and/or of a stere-oisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts. 12. A compound according to claim 10, wherein A is equal to phenyl, wherein the phenyl residue is optionally substituted with 1,2 or 3 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, (C1-C4)-alkyl-0- and (C1-C4)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and X is equal to phenyl, wherein the phenyl group is optionally substituted with 1,2 or 3 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, (C1-C4)-alkyl-0-, (CrC4)-alkyl-S-, (CrC4)-alkyi-0-C(0)- and (CrC4)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, and R1 = R5-C(=0)- or (C1-C6)-alkyl-S02-; R2 = H, (CrC6)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H, (CrC4)-alkyl-; R4 = H, (C1-C4)-alkyl-; or wherein R3 and R4 together form a (C2-C3)-alkylene bridge; and wherein R5 is equal to a heteroaryl or heteroaryl-(C1-C6)-alkyl-, wherein the heteroaryl residues are five- or six-membered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein the heteroaryl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (C1-C6)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not pyrimidin-4-yl, pyridine-2-yl, 1-methyl-pyrazol-3-yl or 1-methyl-imidazol-2-yl, or wherein R5 is methyl, with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 2,4-difluorophenyl residue A is not pyridine-3-yl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluorophenyl, 3-cyano-phenyl, 3-methoxy-phenyl, 3-trif-luormethoxy-phenyl, 2-fluoro-5-methoxy-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 3-cyanophenyl residue A is not a 4-fluorophenyl residue, and with the proviso if in compounds of formula I R3 is methyl, R2 and R4 are hydrogen and X is a 2,4-difluoro-phenyl residue A is not a 4-fluoro-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is phenyl A is not phenyl, 3-trifluoromethyl-phenyl, 4-fluoro-phenyl, 4-chloro-phenyl, 4-methyl-phenyl, 4-ethyloxy-phenyl, 4-methyl-thiophenyl, 2-thiophenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and A is 4-fluoro-phenyl X is not phenyl, 2-chloro-phenyl, 3,4-dichloro-phenyl, 4-chloro-phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-ethy-loxy-phenyl, 4-acetoxyphenyl, and with the proviso if R5 is methyl and R2 is methyl, and R3 and R4 are equal to H and A is equal to 4-fluoro-phenyl, the residue X is not phenyl, and or wherein R5 is equal to H, (C2-C6)-alkyl, CF3, CF2H, CFH2, wherein one or more hydrogen atoms of the alkyl residue may be replaced by fluorine; or wherein R5 is equal to (C3-C6)-cycloalkyl or (C3-C6)-cycloalkyl-(C1-C4)-alkyl-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not cyclopropyl, or wherein R5 is equal to (C1-C4)-alkyl-0- or (Ci-C4)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to (C1-C4)-alkyl-0-(C1-C2)-alkyl-, HO-(C1-C4)-alkyl-, or wherein R5 is equal to phenyl-, phenyl-(C1-C4)-alkyl-, wherein the phenyl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (Ci-Cg)-alkyl-, (C1-C6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methylsulfonyl-phenyl, 4-methylsulfonyl-phenyl; or wherein R5 is equal to R7R6N-, wherein R6 = H, (C1-C4)-alkyl-, cyclopropyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH, methoxy or ethoxy residue and R7 = H, (C1-C2)-alkyl-, or wherein R5 is equal to an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, mor-pholinyl, piperidinyl, pyrrolidinyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents selected from the group of F, OH, (C1-C4)-alkyl-0- and (C1-C4)-alkyl-, and wherein one or more hydrogen atoms of the alkyl groups may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methyl-oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl or 1-methyl-piperidin-4-yl. R6 = H, (C.|-C6)-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH- or (C.|-C6)-alkyl-0- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H, (CrC6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine. 13. A compound according to claim 12, wherein A = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3 and (C1-C2)-alkyl-S-; X = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C1-C2)-alkyl-S-, (C1-C2)-alkyl-0-C(0)- and methyl-S02-, R1 = R5-C(=0)- or methyl-S02-; R2 = H, (C1-C2)-alkyl-, cyclopropyl-; R3 = H, methyl-; R4 = H, methyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 is equal to a heteroaryl or heteroaryl-(Ci-C6)-alkyl-, wherein the heteroaryl residues are selected from the group consisting of pyridine-2-yl, pyridine-3-yl, pyridine-4-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, thiazol-4-yl, thiazol- 5-yl, isothiazol-3-yl, isothiazol-4-yl, isothiazol-5-yl, pyrazol-3-yl, pyrazol-4-yl, imidazol-2-yl, imidazol-4-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridazin-3-yl, pyridazin-4-yl, pyrazin-2-yl and payrazin-3-yl, and wherein these residues are optionally substituted with 1 or 2 residues selected independently from F, Cl, Br, CF3, methyl, ethyl, methoxy, ethoxy, CN, methyl-S02-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not pyrimidin-4-yl, pyridine-2-yl, 1-methyl-pyrazol-3-yl or 1-methyl-imidazol-2-yl, or wherein R5 is methyl, with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 2,4-difluorophenyl residue A is not pyridine-3-yl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluorophenyl, 3-cyano-phenyl, 3-methoxy-phenyl, 3-trif-luormethoxy-phenyl, 2-fluoro-5-methoxy-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and X is a 3-cyanophenyl residue A is not a 4-fluorophenyl residue, and with the proviso if in compounds of formula I R3 is methyl, R2 and R4 are hydrogen and X is a 2,4-difluoro-phenyl residue A is not a 4-fluoro-phenyl, and with the proviso if in compounds of formula I R2, R3 and R4 are hydrogen and A is 4-fluoro-phenyl X is not 2-chloro-phenyl, 3,4-dichloro-phenyl, 4-chloro-phenyl, 4-fluoro-phenyl, 4-methyl-phenyl, 4-methoxy-phenyl, 4-ethoxy-phenyl or 4-acetoxyphenyl, and or wherein R5 is equal to H, (C2-C4)-alkyl, CF3; or wherein R5 is equal to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or (C3-C6)-cycloalkyl-(C1-C2)-alkyl-, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not cyclopropyl, or wherein R5 is equal to (C1-C2)-alkyl-0- or (C1-C2)-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to (C1-C4)-alkyl-0-methyl-, HO-(C1-C2)-alkyl-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; or wherein R5 is equal to phenyl-, phenyl-(C.|-C2)-alkyl-, wherein the phenyl residues are optionally substituted with 1-3 residues selected independently from F, Cl, Br, CF3, (Cl-C2)-alkyl-, (C1-C2)-alkyl-0-, CN, methyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methylsulfonyl-phenyl, 4-methylsulfonyl-phenyl; or wherein R5 is equal to R7R6N-, wherein R6 = H, (C1-C4)-alkyl-, cyclopropyl-, wherein one hydrogen atom of the alkyl group may be replaced by a hydroxy, methoxy or ethoxy residue and R7 = H, methyl-, ethyl-or wherein R5 is equal to an aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of oxetanyl, tetrahydrofuranyl, tetrahydropyranyl, mor-pholinyl, piperidinyl, pyrrolidinyl, and wherein the aliphatic heterocycle may be optionally substituted with 1 or 2 substituents selected from the group of F, OH, (C1-C2)-alkyl-0- and (C1-C4)-alkyl-, and wherein one or more hydrogen atoms of the alkyl groups may be replaced by fluorine, with the proviso if in compounds of formula I A is a 3-cyanophenyl residue and X a 2,4-difluorophenyl residue R5 is not 3-methyl-oxetan-3-yl, tetrahydrofuran-3-yl, tetrahydropyran-4-yl or 1-methyl-piperidin-4-yl, and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts. 14. A compound according to claim 10, wherein A = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3 and (C1-C2)-alkyl-S-; X = phenyl, wherein the phenyl residue is substituted with 1 or 2 residues selected independently from F, Cl, Br, CN, (C1-C4)-alkyl-, CF3, CF2H, CFH2, methoxy, ethoxy, OCF3, (C.|-C2)-alkyl-S-, (C.|-C2)-alkyl-0-C(0)- and methyl-S02-, R1 = R5-C(=0)-; R2 = H, (C1-C2)-alkyl-, cyclopropyl-; R3 = H, methyl-; R4 = H, methyl-; or wherein R3 and R4 together form an ethylene bridge; and wherein R5 is equal to (C2-C4)-alkyl; and/or of a stereoisomeric form of the compound of the formula I and/or mixtures of these forms, and/or their pharmaceutically acceptable salts. 15. A compound according to claim 1 selected from the group consisting of 3-(3-Cyano-phenyl)-1-(2,4-difluoro-benzyl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid isopropylamide; 3-(4-Fluoro-phenyl)-1-[(S)-1-(4-fluoro-phenyl)-ethyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid ethylamide; 3-(4-Fluoro-phenyl)-1-[(R)- 1-(4-fluoro-phenyl)-ethyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid ethylamide; 3-(4-Fluoro-phe-nyl)-1-[(S)-1-(4-fluoro-phenyl)-ethyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butylamide; 3-(3-Cyano-phenyl)-1-(2,4-difluoro-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid ethylamide; 3-(3-Cyano-phenyl)-1-(2,4-difluoro-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid methylamide; {3-(4-Fluoro-phenyl)-1-[(S)-1-(4-fluoro-phenyl)-ethyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl} -morpholin-4-yl-methanone; {3-(4-Fluoro-phenyl)-1-[(S)-1-(4-fluoro-phenyl)-ethyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-((S)-3-hydroxy-pyrrolidin-1-yl)-methanone; 3-(3-Cyano-phenyl)-1-(2,4-difluoro-benzyl)-1,4,6,7-tet-rahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid dimethylamide; 3-(3-Cyano-phenyl)-1-(2,4-difluoro-benzyl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid (2-hydroxy-ethyl)-methyl-amide; 2-[5-Acetyl-1-(2,4-dif-luoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-isonicotinonitrile; 6-[5-Acetyl-1-(2,4-difluoro-ben-zyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-pyridine-2-carbonitrile; 3-[1-(2,4-Difluoro-benzyl)-5-(2-hy-droxy-acetyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-[5-Acetyl-1-(2,4-difluoro-benzyl)- 4.5.6.7- tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 1-[1-(2,4-Difluoro-benzyl)-3-(3-methyl-pyridin-2-yl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-(4-methoxy-pyridin-2-yl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2-Methyl-thiazol-4-ylmethyl)-3-(3-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-Thiazol-2-ylmethyl-3-(3-trifluoromethyl-phe-nyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-thiophen-2-yl-1,4,6,7-tet-rahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(5-Chloro-thiophen-2-ylmethyl)-3-m-tolyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(5-Chloro-thiophen-2-ylmethyl)-3-(3-trifluoromethyl-phenyl)-1,4,6,7-tet-rahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 3-[5-Acetyl-1-(5-chloro-thiophen-2-ylmethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 1-[3-(3-Chloro-phenyl)-1-(5-chloro-thiophen-2-ylmethyl)-1,4,6,7-tetrahy-dro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[3-(5-Chloro-thiophen-2-yl)-1-(2,4-difluoro-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-thiophen-3-yl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 4-[5-Acetyl-3-(3-trifluoromethyl-phenyl)-4,5,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-1-ylme-thyl]-benzonitrile; 3-{5-Acetyl-1-[1-(4-fluoro-phenyl)-ethyl]-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl}-ben-zonitrile; 1-[1-[Cyclopropyl-(4-fluoro-phenyl)-methyl]-3-(4-fluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin- 5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-(3-trifluoromethoxy-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin- 5-yl]-ethanone; 1-[1-(2,6-Difluoro-benzyl)-3-(4-fluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-eth-anone; 1-{3-(4-Fluoro-phenyl)-1-[1-(4-fluoro-phenyl)-ethyl]-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl}-eth-anone; 1-[3-(4-Fluoro-phenyl)-1-(4-trifluoromethyl-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-eth-anone; 1-[1-(2,4-Difluoro-benzyl)-3-(3-methoxy-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[3-(4-Fluoro-phenyl)-1-(3-trifluoromethyl-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-[1-(4-Fluoro-phenyl)-ethyl]-3-(3-trifluoromethoxy-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-eth-anone; 1-[1-(2,4-Difluoro-benzyl)-3-(4-fluoro-3-methoxy-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 3-[5-Acetyl-1-(2,5-difluoro-benzyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 1-[1-(2,4-Difluoro-benzyl)-3-m-tolyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(6-Chloro-pyrid-in-3-ylmethyl)-3-(3-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[3-(3-Chloro-phenyl)-1-(4-fluoro-2-methyl-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2-Fluoro-ben-zyl)-3-m-tolyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2-Methoxy-benzyl)-3-(3-trifluorome-thyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[3-(3-Chloro-phenyl)-1-(3-methoxy-ben-zyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(4-Chloro-3-fluoro-benzyl)-3-(4-fluoro-phenyl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-(2-fluoro-5-methoxy-phenyl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 5-[5-Acetyl-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-2-fluoro-benzonitrile; 1-[1-(2,4-Difluoro-benzyl)-3-(3-fluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-[(R)-1-(4-Chloro-phenyl)-propyl]-3-(4-fluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-[(S)-1-(4-Chloro-phenyl)-propyl]-3-(4-fluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2-Fluoro-4-methyl-benzyl)-3-(3-trifluoromethyl-phenyl)-1,4,6,7-tetrahy-dro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(4-Chloro-pyridin-3-ylmethyl)-3-(3-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(3-Methyl-pyridin-2-ylmethyl)-3-(3-trifluoromethyl-phenyl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-(4-fluoro-phenyl)-1,4,6,7-tet-rahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(4-Fluoro-benzyl)-3-(6-trifluoromethyl-pyridin-2-yl)-1,4,6,7-tet-rahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-(4-trifluoromethyl-pyridin-2-yl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-(6-trifluoromethyl-pyridin-2-yl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[3-(4-Bromo-pyridin-2-yl)-1-(2,4-difluoro-benzyl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[3-(2-Bromo-pyridin-4-yl)-1-(2,4-difluoro-benzyl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[3-(5-Bromo-pyridin-3-yl)-1-(2,4-difluoro-benzyl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 3-[11-Acetyl-5-(2,4-difluoro-benzyl)-4,5,11-triaza-tricyc- lo[6.2.1.02,6]undeca-2(6),3-dien-3-yl]-benzonitrile; 1-[5-(2,4-Difluoro-benzyl)-3-(4-fluoro-phenyl)-4,5,11-triaza-tri-cyclo[6.2.1.02,6]undeca-2(6),3-dien-11-yl]-ethanone; 1-[1-(6-Chloro-pyridin-3-ylmethyl)-3-m-tolyl-1,4,6,7-tetrahy-dro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(4-Methoxy-pyridin-2-ylmethyl)-3-(3-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(4-Chloro-pyridin-3-ylmethyl)-3-m-tolyl-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(3-Methoxy-pyridin-2-ylmethyl)-3-(3-trifluoromethyl-phenyl)-1,4,6,7-tet-rahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[3-(3-Chloro-phenyl)-1-(3-methyl-pyridin-2-ylmethyl)-1,4,6,7-tet-rahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-[1-(4-Fluoro-phenyl)-ethyl]-3-(6-trifluoromethyl-pyridin-2-yl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-(6-methyl-pyridin-2-yl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[3-(6-Bromo-pyridin-2-yl)-1-(2,4-difluoro-benzyl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-(4-methyl-pyridin-2-yl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[1-(2,4-Difluoro-benzyl)-3-(6-methoxy-pyridin-2-yl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 1-[3-(6-Chloro-5-methoxy-pyridin-2-yl)-1-(2,4-difluoro- benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 3-[1-(2,4-Difluoro-benzyl)-5-(3-methyl-oxetane-3- carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-(1-(2,4-Difluoro-benzyl)-5-isobutyryl- 4.5.6.7- tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-[5-Cyclopropanecarbonyl-1-(2,4-difluoro-benzyl)- 4.5.6.7- tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-[5-(2-tert-Butoxy-acetyl)-1-(2,4-difluoro-benzyl)- 4.5.6.7- tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-(1-(2,4-Difluoro-benzyl)-5-(3-methanesulfonyl-benzoyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; [1-Benzyl-3-(4-fluoro-phenyl)-1,4,6,7-tet-rahydro-pyrazolo[4,3-c]pyridin-5-yl]-(4-fluoro-phenyl)-methanone; [1-Benzyl-3-(4-fluoro-phenyl)-1,4,6,7-tetrahy-dro-pyrazolo[4,3-c]pyridin-5-yl]-(4-methoxy-phenyl)-methanone; [1-Benzyl-3-(4-fluoro-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-phenyl-methanone; 3-[5-Cyclobutanecarbonyl-1-(2,4-difluoro-benzyl)-4,5,6,7-tetrahy-dro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-[5-Cyclopentanecarbonyl-1-(2,4-difluoro-benzyl)-4,5,6,7-tet-rahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-(1-(2,4-Difluoro-benzyl)-5-(4-methanesulfonyl-benzoyl)- 4.5.6.7- tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-(1-(2,4-Difluoro-benzyl)-5-(tetrahydro-pyran-4-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-[1-(2,4-Difluoro-benzyl)-5-(tetrahydro-furan-3-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-(1-(2,4-Difluoro-benzyl)-5-(2-methoxy-acetyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-[1-(2,4-Difluoro-benzyl)-5-(2,2-dimethyl-propionyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-(1-(2,4-Difluoro-benzyl)-5-propionyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-[1-(2,4-Difluoro-benzyl)-5-((S)-2-hy-droxy-propionyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 1-[1-Benzyl-3-(4-fluoro-phenyl)- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-2-phenyl-ethanone; 3-[5-Butyryl-1 -(2,4-difluoro-benzyl)-4,5,6,7-tet-rahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-(1-(2,4-Difluoro-benzyl)-5-(pyridine-2-carbonyl)-4,5,6,7-tet-rahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; compound with trifluoro-acetic acid; 3-(1-(2,4-Difluoro-benzyl)- 5-(3-fluoro-pyridine-4-carbonyl)-4,5,6,7-tetrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; compound with trifluoro-acetic acid; 3-(1-(2,4-Difluoro-benzyl)-5-(pyrimidine-4-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin- 3-yl]-benzonitrile; 3-[1-(2,4-Difluoro-benzyl)-5-(3-methyl-3H-imidazole-4-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazo-lo[4,3-c]pyridin-3-yl]-benzonitrile; 3-(1-(2,4-Difluoro-benzyl)-5-(1-methyl-1 H-pyrazole-3-carbonyl)-4,5,6,7-tetrahy-dro-1H-pyrazolo[4,3-c]pyridin-3-yl]-benzonitrile; 3-(3-Cyano-phenyl)-1-(2,4-difluoro-benzyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid ethyl ester; 1-(1 -(2,4-Difluoro-benzyl)-3-(4-fluoro-phenyl)-6-methyl- 1.4.6.7- tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]-ethanone; 3-(4-Fluoro-phenyl)-1-[(R)-1-(4-fluoro-phenyl)-ethyl]-5- methanesulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine; 3-(4-Fluoro-phenyl)-1-[(S)-1-(4-fluoro-phe- nyl)-ethyl]-5-methanesulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridine; their stereoisomeric forms and/or their pharmaceutically acceptable salts thereof. 16. A medicament comprising a compound of formula I and/or its pharmaceutically acceptable salt according to any one of claims 1 to 15. 17. A compound of formula I or a compound according to any one of claims 1 to 15 and/or their pharmaceutically acceptable salts for use in the treatment or prevention of TASK-1 channel-mediated diseases

wherein A = (C6-C10)-aryl or a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C-|-C6)-alkyl-, (C^CgJ-alkyl-O-and (C^CgJ-alkyl-S-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; X = (C6-C10)-aryl or a five- or six-membered heteroaryl, comprising 1-3 heteroatoms selected from the group N, O and S, wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CN, (C.|-Cg)-alkyl-, (C^CgJ-alkyl-O-and (C^CgJ-alkyl-S-, (C.|-Cg)-alkyl-0-C(0)- and (C1-C6)-alkyl-S02-, wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R1 = R5-C(=0)- or (CrC6)-alkyl-S02-; R2 = H, (C1-C6)-alkyl-, (C3-C6)-cycloalkyl-; R3 = H, (C1-C4)-alkyl-; R4 = H, (C1-C4)-alkyl-; or R3, R4 together form a (C2-C3)-alkylene bridge; R5 = (C1-C6)-alkyl-, (C3-C6)-cycloalkyl-, (C1-C6)-alkyl-0-, (C1-C6)-alkyl-S-, (C1-C6)-alkyl-0-(C1-C6)-alkyl-, HO-(C1-C6)-alkyl-, (C3-C6)-cycloalkyl-(C1-C6)-alkyl-, (C6-C10)-aryl-, (C6-C10)-aryl-(C1-C6)-alkyl-, R7R6N-, heteroaryl, heteroaryl-(C.|-C6)-alkyl-, aliphatic heterocycle, wherein the aliphatic heterocycle is selected from the group of morpholinyl, piperidinyl, pyrrolidinyl and 4 to 7 membered aliphatic heterocycles comprising an oxygen atom, and wherein the aliphatic heterocycle may be optionally substituted with 1 to 3 substituents selected from the group of F, OH, (C1-C6)-alkyl-0- and (C1-C6)-alkyl-, and wherein the heteroaryl residues are five- or six-membered ring systems, comprising 1-3 heteroatoms selected from the group N, O and S, and wherein aryl and heteroaryl are optionally substituted with 1-3 rests selected independently from F, Cl, Br, CF3, (CrC6)-alkyl-, (CrC6)-alkyl-0-, CN, (C1-C2)-alkyl-S02-, and wherein one or more hydrogen atoms of the alkyl moieties may be replaced by fluorine; R6 = H, (C.|-C6)-alkyl-, (C3-C6)-cycloalkyl-, wherein one hydrogen atom of the alkyl group may be replaced by an OH- or (C.|-C6)-alkyl-0- residue, and wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine; R7 = H,(CrC6)-alkyl-; wherein one or more hydrogen atoms of the alkyl group may be replaced by fluorine. 18. A compound of formula I and/or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 15, a medicament according to claim 16 or a compound according to claim 17 for use in the treatment or prevention of arrhythmias, particularly atrial tachyarrhythmias, atrial fibrillation and atrial flutter. 19. A compound of formula I and/or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 15, a medicament according to claim 16 or a compound according to claim 17 for use in the treatment or prevention of sleep-related respiratory disorders, central and obstructive sleep apneas, upper airway resistance syndrome, Cheyne-Stokes respiration, snoring, disrupted central respiratory drive, sudden child death, postoperative hypoxia and apnea, muscle-related respiratory disorders, respiratory disorders after long-term mechanical ventilation (weaning), respiratory disorders during adaptation in high mountains, acute and for respiratory disorders, chronic lung disorders with hypoxia and hypercapnia, chronic obstructive pulmonary disease (COPD) and obesity hypoventilation syndrome; or for use as a respiratory stimulant for the treatment or prevention of respiratory depression associated with anesthesia or procedural sedations for small interventions or for diagnostic purposes, or for use as a respiratory stimulant for the treatment or prevention of respiratory depression by opioids in chronic pain treatment particularly in cancer or palliative care or procedural sedations and/or for weaning from longterm mechanical ventilation; or for use in the treatment or prevention of multiple sclerosis and inflammatory or degenerative disorders of the central nervous system.

Patentansprüche 1. Verbindung der Formel I, wobei

A = (C6-C10)-Aryl oder ein fünf- oder sechsgliedriges Heteroaryl, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, wobei Aryl und Heteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C^CgJ-Alkyl-, (C.|-C6)-Alkyl-0- und (C^CgJ-Alkyl-S- ausgewählte Reste substituiert sind, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; X = (C6-C10)-Aryl oder ein fünf- oder sechsgliedriges Heteroaryl, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, wobei Aryl und Heteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C1-C6)-Alkyl-, (C.|-Cg)-Alkyl-0-, (C.|-C6)-Alkyl-S-, (C.|-C6)-Alkyl-0-C(0)-und (C1-C6)-Alkyl-S02- ausgewählte Reste substituiert sind, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; R1 = R5-C(=0)- oder (C1-C6)-Alkyl-S02-, R2 = H, (C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-; R3 = H, (C1-C4)-Alkyl-, R4 = H, (C1-C4)-Alkyl-, oder wobei R3 und R4 zusammen eine (C2-C3)-Alkylenbrücke bilden; R5 = H, (CrC6)-Alkyl-, (C3-C6)-Cycloalkyl-, (C1-C6)-Alkyl-0-, (CrC6)-Alkyl-S-, (C1-C6)-Alkyl-0-(C1-C6)-alkyl-, HO-(C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-(C1-C6)-alkyl-, (C6-C10)-Aryl-, (C6-C10)-Aryl-(C1-C6)-alkyl-, R7R6N-, Heteroaryl, Heteroaryl-(C1-C6)-alkyl-, aliphatischer Heterocyclus, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, und wobei der aliphatische Heterocyclus aus der Gruppe Morpholinyl, Piperidinyl, Pyrrolidinyl und 4- bis 7-gliedrige aliphatische, ein Sauerstoffatom enthaltende Heterocyclen ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 bis 3 unabhängig voneinander aus der Gruppe F, OH, (Ci-C6)-Alkyl-0- und (Ci-Cg)-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei es sich bei den Heteroarylresten um fünf- oder sechsgliedrige Ringsysteme, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, handelt, und wobei Aryl und Heteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, (C.|-C6)-Alkyl-, (C^CgJ-Alkyl-O-, CN, (C1-C2)-Alkyl-S02- ausgewählte Reste substituiert sind; R6 = H, (C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-, wobei ein Wasserstoffatom der Alkylgruppe durch einen OH- oder (C1-C6)-Alkyl-0-Rest ersetzt sein kann, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppe durch Fluor ersetzt sein können; R7 = H,(C1-C6)-Alkyl-, wobei ein oder mehrere Wasserstoffatome der Alkylgruppe durch Fluor ersetzt sein können; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze, und mit der Maßgabe, dass dann, wenn R5 für Methyl steht und R2, R3 und R4 gleich H sind und A gleich 4-Fluorphenyl ist, der RestX nicht für Phenyl, 4-Fluorphenyl, 4-Chlorphenyl, 4-Methylphenyl, 4-Methoxyphenyl, 4-Acetoxyphenyl, 2-Chlorphenyl, 3,4-Dichlorphenyl steht, und mit der Maßgabe, dass dann, wenn R5 für Methyl steht und R2, R3 und R4 gleich H sind und X für einen Phenylrest steht, der Rest A nicht für Phenyl, 4-Fluorphenyl, 4-Chlorphenyl, 4-Methylphenyl, 4-Ethyloxyphenyl, 3-Trifluorme-thylphenyl, 2-Thiophenyl oder 4-Methylthiophenyl steht, und mit der Maßgabe, dass dann, wenn R5 für Methyl steht und R2 für Methyl steht und R3 und R4 gleich H sind und A gleich 4-Fluorphenyl ist, der Rest X nicht für Phenyl steht. 2. Verbindung nach Anspruch 1, wobei A = Phenyl oder ein fünf- oder sechsgliedriges Heteroaryl ausgewählt aus der Gruppe bestehend aus Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Thiophen-2-yl oder Thiophen-3-yl, wobei Phenyl und Heteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C.|-C6)-Alkyl-, (Ci-C6)-Alkyl-0- und (C1-C6)-Alkyl-S- ausgewählte Reste substituiert sind, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; X = ein fünf- oder sechsgliedriges Heteroaryl, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, wobei die Heteroarylgruppe gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C.|-C6)-Alkyl-, (C.|-C6)-Alkyl-0- und (C1-C6)-Alkyl-S-, (C1-C6)-Alkyl-0-C(0)- und (C.|-Cg)-Alkyl-S02- ausgewählte Reste substituiert ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; R1 = R5-C(=0)- oder (CrC6)-Alkyl-S02-, R2 = H, (C1-C4)-Alkyl-, (C3-C6)-Cycloalkyl-; R3 = H, (C1-C2)-Alkyl-, R4 = H, (C1-C4)-Alkyl-, oder wobei R3 und R4 zusammen eine (C2-C3)-Alkylenbrücke bilden; R5 = H, (C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-, (C1-C6)-Alkyl-0-, (CrC6)-Alkyl-S-, (C1-C6)-Alkyi-0-(C1-C6)-aikyl-, HO-(C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-(C1-C6)-alkyl-, (C6-C10)-Aryl-, (C6-C10)-Aryl-(C1-C6)-alkyl-, R7R6N-, Heteroaryl, Heteroaryl-(C.|-C6)-alkyl-, aliphatischer Heterocyclus, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, und wobei der aliphatische Heterocyclus aus der Gruppe Morpholinyl, Piperidinyl, Pyrrolidinyl und 4- bis 7-gliedrige aliphatische, ein Sauerstoffatom enthaltende Heterocyclen ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 bis 3 unabhängig voneinander aus der Gruppe F, OH, (Ci-Cg)-Alkyl-O- und (C^CgJ-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei es sich bei den Heteroarylresten um fünf- oder sechsgliedrige Ringsysteme, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, handelt, und wobei Aryl und Heteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C^CgJ-Alkyl-, (Ci-Cg)-Alkyl-O-, CN, (C1-C2)-Alkyl-S02- ausgewählte Reste substituiert sind; R6 = H, (C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl, wobei ein Wasserstoffatom der Alkylgruppe durch einen OH- oder (C1-C6)-Alkyl-0-Rest ersetzt sein kann, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppe durch Fluor ersetzt sein können; R7 = H, (C1-C6)-Alkyl-, wobei ein oder mehrere Wasserstoffatome der Alkylgruppe durch Fluor ersetzt sein können; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze. 3. Verbindung nach Anspruch 1 oder 2, wobei A = Phenyl, wobei der Phenylrestgegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C.|-C4)-Alkyl-, (C.|-C4)-Al-kyl-O- und (C1-C4)-Alkyl-S- ausgewählte Reste substituiert ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; X = ein fünf- oder sechsgliedriges Heteroaryl ausgewählt aus der Gruppe bestehend aus Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Thiophen-2-yl, Thiophen-3-yl, Thiazol-2-yl, Thiazol-4-yl, Thiazol-5-yl, wobei die Heteroarylgruppe gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C1-C6)-Alkyl-, (C-pCgJ-Alkyl-O- und (C1-C6)-Alkyl-S-, (C^CgJ-Alkyl-O-CfO)- und (C-pCgJ-Alkyl-SC^- ausgewählte Reste substituiert ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; R1 = R5-C(=0)- oder (C1-C2)-Alkyl-S02-, R2 = H, (C1-C2)-Alkyl-, Cyclopropyl-; R3 = H, Methyl-; R4 = H, Methyl-; oder wobei R3 und R4 zusammen eine Ethylenbrücke bilden; und wobei R5 = H, (CrC4)-Alkyl-, (C3-C6)-Cycloalkyl-, (CrC2)-Alkyl-0-, (CrC2)-Alkyl-S-, (C1-C4)-Alkyl-0-methyl-, HO-(C1-C2)-Alkyl-, (C3-C6)-Cycloalkyl-(C1-C2)-alkyl-, Phenyl, Phenyl-(C1-C2)-alkyl-, R7R6N-, Heteroaryl, Heteroa-ryl-(C.|-C4)-alkyl-, aliphatischer Heterocyclus, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, und wobei der aliphatische Heterocyclus aus der Gruppe Morpholinyl, Piperidinyl, Pyrrolidinyl, Oxetanyl, Tetrahydrofu-ranyl und Tetrahydropyranyl ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 oder 2 unabhängig voneinander aus der Gruppe F, OH, (C1-C2)-Alkyl-0- und (C1-C4)-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei der Phenylrest gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C-j-C^-Alkyl-, (C-|-C4)-Alkyl-0-, CN, (C1-C2)-Alkyl-S02- ausgewählte Reste substituiert ist, wobei die Fleteroarylreste aus der Gruppe bestehend aus Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Thiophen-2-yl, Thiophen-3-yl, Thiazol-2-yl, Thiazol-4-yl, Thiazol-5-yl, lsothiazol-3-yl, lsothiazol-4-yl, lsothiazol-5-yl, Pyrazol-3-yl, Pyrazol-4-yl, lmidazol-2-yl, lmidazol-4-yl, Pyrimidin-2-yl, Pyrimidin-4-yl, Pyrimidin-5-yl, Pyridazin-3-yl, Pyridazin-4-yl, Pyrazin-2-yl und Pyrazin-3-yl ausgewählt sind, und wobei die Heteroarylreste gegebenenfalls durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CF3, (C^C^-Alkyl-, (C1-C4)-Alkyl-0-, CN, (C1-C2)-Alkyi-S02-ausgewähite Reste substituiert sind; R6 = H, (C.|-C4)-Alkyl-, Cyclopropyl, wobei ein Wasserstoffatom der Alkylgruppe durch einen OH-, Methoxy- oder Ethoxyrest ersetzt sein kann; und R7 = H, Methyl-, Ethyl; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze. 4. Verbindung nach einem der Ansprüche 1 bis 3, wobei A = Phenyl, wobei der Phenylrest gegebenenfalls durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C.|-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3 und (C1-C2)-Alkyl-S- ausgewählte Reste substituiert ist; X = ein fünf- oder sechsgliedriges Heteroaryl ausgewählt aus der Gruppe bestehend aus Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Thiophen-2-yl, Thiophen-3-yl, Thiazol-2-yl, Thiazol-4-yl, Thiazol-5-yl, wobei diese Reste gegebenenfalls durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3, (C1-C2)-Alkyl-S-, (C1-C2)-Alkyl-0-C(0)- und Methyl-S02- ausgewählte Reste substituiert sind; R1 = R5-C(=0)- oder (C1-C2)-Alkyl-S02-, R2 = H, Methyl, Ethyl, Cyclopropyl; R3 und R4 = H; und R5 = Methyl, Ethyl, n-Propyl, Isopropyl, n-Butyl, Isobutyl, tert-Butyl, Cyclopropyl oder Cyclobutyl; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze. 5. Verbindung nach einem der Ansprüche 1, wobei A = ein fünf-oder sechsgliedriges Heteroaryl, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, wobei das Heteroaryl durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C^CgJ-Alkyl-, (C.|-Cg)-Alkyl-0- und (CrC6)-Alkyl-S- ausgewählte Reste substituiert ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; X = Phenyl, Thiophen-2-yl oder Thiophen-3-yl, wobei diese Reste gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C.|-Ce)-Alkyl-, (C1-C6)-Al-kyl-O- und (C.|-C6)-Alkyl-S-, (C1-C6)-Alkyl-0-C(0)- und (C.|-Cg)-Alkyl-S02- ausgewählte Reste substituiert sind, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; R1 = R5-C(=0)- oder (CrC6)-Alkyl-S02-, R2 = H, (C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-; R3 = H, (C1-C4)-Alkyl-, R4 = H, (C1-C4)-Alkyl-, oder wobei R3 und R4 zusammen eine (C2-C3)-Alkylenbrücke bilden; R5 = H, (CrC6)-Alkyl-, (C3-C6)-Cycloalkyl-, (C1-C6)-Alkyl-0-, (C1-C6)-Alkyl-S-, (C1-C6)-Alkyl-0-(C1-C6)-alkyl-, HO-(C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-(C1-C6)-alkyl-, (C6-C10)-Aryl-, (Cg-C10)-Aryl-(C1-Cg)-alkyl-, R7R6N-, Heteroaryl, Heteroaryl-(C.|-Cg)-alkyl-, aliphatischer Heterocyclus, wobei ein oder mehrere WasserstofFatome der Alkylgruppierungen durch Fluor ersetzt sein können, und wobei der aliphatische Heterocyclus aus der Gruppe Morpholinyl, Piperidinyl, Pyrrolidinyl und 4- bis 7-gliedrige aliphatische, ein Sauerstoffatom enthaltende Heterocyclen ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 bis 3 aus der Gruppe F, OH, (C.|-Cg)-Alkyl-0- und (C.|-Cg)-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei es sich bei den Heteroarylresten um fünf- oder sechsgliedrige Ringsysteme, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, handelt, und wobei Aryl und Heteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C1-C6)-Alkyl-, (C1-C6)-Alkyl-0-, CN, (C1-C2)-Alkyl-S02- ausgewählte Reste substituiert sind; R6 = H, (C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl, wobei ein Wasserstoffatom der Alkylgruppe durch einen OH- oder (C1-C6)-Alkyi-0-Rest ersetzt sein kann und wobei ein oder mehrere Wasserstoffatome der Alkylgruppe durch Fluor ersetzt sein können; R7 = H,(CrC6)-Alkyl-, wobei ein oder mehrere Wasserstoffatome der Alkylgruppe durch Fluor ersetzt sein können; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze; mit der Maßgabe, dass A nicht für 4-Methylthiophenyl steht, wenn in den Verbindungen der Formel I R5 für Methyl steht und R2, R3 und R4 für Wasserstoff stehen und X für Phenyl steht. 6. Verbindung nach Anspruch 5, wobei A = 2-Pyridyl, 3-Pyridyl oder 4-Pyridyl, wobei die Pyridylreste durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3 und (C1-C2)-Alkyl-S-ausgewählte Reste substituiert sind; X = Phenyl, Thiophen-2-yl oder Thiophen-3-yl, wobei diese Reste durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3, (C1-C2)-Alkyl-S-, (C-|-C2)-Alkyl-0-C(0)- und Methyl-S02- ausgewählte Reste substituiert sind; R1 = R5-C(=0)- oder (C1-C2)-Alkyl-S02-, R2 = H, Methyl, Ethyl, Cyclopropyl; R3 und R4 = H; und R5 = H, Methyl, Ethyl, n-Propyl, Isopropyl, n-Butyl, Isobutyl oder tert-Butyl, oder wobei R5 = Cyclopropyl, Cyclobutyl, Cyclopentyl oder (C3-C6)-Cycloalkyl-(C1-C2)-alkyl-, oder wobei R5 = (C1-C2)-Alkyl-0-, (C1-C2)-Alkyl-S- oder OCF3, oder wobei R5 = (C1-C4)-Alkyl-0-methyl-, HO-(CrC2)-Alkyl-, oder wobei R5 = Phenyl oder Phenylmethyl-, wobei die Phenylreste gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C-j-C^-Alkyl-, (C1-C2)-Alkyl-0-, CN, Methyl-S02- ausgewählte Reste substituiert sind, oder wobei R5 = R7R6N-, wobei R6 = H, (C1-C4)-Alkyl-, Cyclopropyl, wobei ein Wasserstoffatom der Alkylgruppe durch einen OFI-, Methoxy- oder Ethoxyrest ersetzt sein kann, und R7 = H, Methyl-, Ethyl, oder wobei R5 = Fleteroaryl, Fleteroaryl-(Ci-Cg)-alkyl-, wobei die Heteroarylreste aus der Gruppe bestehend aus Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Thiophen-2-yl, Thiophen-3-yl, Thiazol-2-yl, Thiazol-4-yl, Thiazol-5-yl, lsothiazol-3-yl, lsothiazol-4-yl, lsothiazol-5-yl, Pyrazol-3-yl, Pyrazol-4-yl, lmidazol-2-yl, lmidazol-4-yl, Pyrimidin-2-yl, Pyrimidin-4-yl, Pyrimidin-5-yl, Pyridazin-3-yl, Pyridazin-4-yl, Pyrazin-2-yl und Pyrazin-3-yl ausgewählt sind, und wobei die Heteroarylreste gegebenenfalls durch 1 oder2 unabhängig voneinanderaus F, CI, Br, CF3, (C.|-C4)-Alkyl-, (C1-C4)-Alkyl-0-, CN, (C1-C2)-Alkyi-S02-ausgewähite Reste substituiert sind, oder wobei R5 = aliphatischer Heterocyclus, wobei der aliphatische Heterocyclus aus der Gruppe Morpholinyl, Piperidinyl, Pyrrolidinyl, Oxetanyl, Tetrahydrofu-ranyl und Tetrahydropyranyl ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 oder 2 unabhängig voneinanderaus der Gruppe F, OH, (C1-C2)-Alkyl-0- und (C1-C4)-Alkyl- ausgewählte Substituenten substituiert sein kann; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze. 7. Verbindung nach Anspruch 1, wobei A gleich Phenyl ist, wobei der Phenylrest gegebenenfalls durch 1-3 unabhängig voneinanderaus F, CI, Br, CN, (C1-C4)-Alkyl-, (C1-C4)-Al-kyl-O- und (C1-C4)-Alkyl-S- ausgewählte Reste substituiert ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; X gleich Phenyl ist, wobei die Phenylgruppe gegebenenfalls durch 1,2 oder 3 unabhängig voneinander aus F, CI, Br, CN, (C.|-C4)-Alkyl-, (CrC4)-Alkyl-0-, (CrC4)-Alkyl-S-, (CrC4)-Alkyl-0-C(0)- und (Ci-C4)-Alkyl-S02- ausgewählte Reste substituiert ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; R1 = R5-C(=0)- oder (C1-C6)-Alkyl-S02-, R2 = H, (C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-; R3 = H, (C1-C4)-Alkyl-; R4 = H,(C1-C4)-Alkyl-; oder wobei R3 und R4 zusammen eine (C2-C3)-Alkylenbrücke bilden; R5 = H, (CrC6)-Alkyl-, (C3-C6)-Cycloalkyl-, (CrC6)-Alkyl-0-, (CrC6)-Alkyl-S-, (C1-C6)-Alkyl-0-(C1-C6)-alkyl-, HO-(C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-(C1-C6)-alkyl-, (C6-C10)-Aryl-, (C6-C10)-Aryl-(C1-C6)-alkyl-, R7R6N-, Heteroaryl, Heteroaryl-fC^CgJ-alkyl-, aliphatischer Heterocyclus, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, und wobei der aliphatische Heterocyclus aus der Gruppe Morpholinyl, Piperidinyl, Pyrrolidinyl und 4- bis 7-gliedrige aliphatische, ein Sauerstoffatom enthaltende Heterocyclen ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 bis 3 aus der Gruppe F, OH, (C.|-C6)-Alkyl-0- und (C-|-C6)-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei es sich bei den Heteroarylresten um fünf- oder sechsgliedrige Ringsysteme, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, handelt, und wobei Aryl und Heteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C1-C6)-Alkyl-, (C-pC^-Alkyl-O-, CN, (C1-C2)-Alkyl-S02- ausgewählte Reste substituiert sind; R6 = H, (CrC6)-Alkyl-, (C3-C6)-Cycloalkyl-, wobei ein Wasserstoffatom der Alkylgruppe durch einen OH- oder (C^CgJ-Alkyl-O-Rest ersetzt sein kann, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppe durch Fluor ersetzt sein können; R7 = H,(C1-C6)-Alkyl-, wobei ein oder mehrere Wasserstoffatome der Alkylgruppe durch Fluor ersetzt sein können; mit der Maßgabe, dass dann, wenn R5 für Methyl steht und R2, R3 und R4 gleich H sind und A gleich 4-Fluorphenyl ist, der RestX nicht für Phenyl, 4-Fluorphenyl, 4-Chlorphenyl, 4-Methylphenyl, 4-Methoxyphenyl, 4-Acetoxyphenyl, 2-Chlorphenyl, 3,4-Dichlorphenyl steht, und mit der Maßgabe, dass dann, wenn R5für Methyl steht und R2, R3 und R4 gleich H sind und X für einen Phenylrest steht, der Rest A nicht für Phenyl, 4-Fluorphenyl, 4-Chlorphenyl, 4-Methylphenyl, 4-Ethyloxyphenyl oder 3-Trifluor-methylphenyl steht, und mit der Maßgabe, dass dann, wenn R5 für Methyl steht und R2 für Methyl steht und R3 und R4 gleich H sind und A gleich 4-Fluorphenyl ist, der Rest X nicht für Phenyl steht. 8. Verbindung nach Anspruch 7, wobei A = Phenyl, wobei der Phenylrest durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3 und (C-|-C2)-Alkyl-S-ausgewählte Reste substituiert ist; X = Phenyl, wobei der Phenylrest durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3, (C1-C2)-Alkyl-S-, (C.|-C2)-Alkyl-0-C(0)- und Methyl-S02- ausgewählte Reste substituiert ist; R1 = R5-C(=0)- oder Methyl-S02-; R2 = H, (C1-C2)-Alkyl-, Cyclopropyl-; R3 = H, Methyl-; R4 = H, Methyl-; oder wobei R3 und R4 zusammen eine Ethylenbrücke bilden; und wobei R5 gleich einem Heteroaryl oder Heteroaryl-(C1-C6)-Alkyl- ist, wobei die Heteroarylreste aus der Gruppe bestehend aus Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Thiophen-2-yl, Thiophen-3-yl, Thiazol-2-yl, Thiazol-4-yl, Thiazol-5-yl, Iso-thiazol-3-yl, lsothiazol-4-yl, lsothiazol-5-yl, Pyrazol-3-yl, Pyrazol-4-yl, lmidazol-2-yl, lmidazol-4-yl, Pyrimidin-2-yl, Pyrimidin-4-yl, Pyrimidin-5-yl, Pyridazin-3-yl, Pyridazin-4-yl, Pyrazin-2-yl und Pyrazin-3-yl ausgewählt sind, und wobei diese Reste gegebenenfalls durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CF3, Methyl, Ethyl, Methoxy, Ethoxy, CN, Methyl-S02- ausgewählte Reste substituiert sind, oder wobei R5 gleich H ist, oder wobei R5 gleich Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl oder (C3-C6)-Cycloalkyl-(C1-C2)-alkyl- ist, oder wobei R5 gleich (Ci-C2)-Alkyl-0- oder (C.|-C2)-Alkyl-S- ist, oder wobei R5 gleich (Ci-C4)-Alkyl-0-methyl-, HO-(C1-C2)-Alkyl- ist, oder wobei R5 gleich Phenyl- oder Phenylmethyl- ist, wobei die Phenylreste gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C.|-C2)-Alkyl-, (C1-C2)-Alkyl-0-, CN, Methyl-S02- ausgewählte Reste substituiert sind, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, oder wobei R5 gleich R7R6N- ist, wobei R6 = H, (C1-C4)-Alkyl-, Cyclopropyl-, wobei ein Wasserstoffatom der Alkylgruppe durch einen Flydroxy-, Methoxy-oder Ethoxyrest ersetzt sein kann, und R7 = H, Methyl-, Ethyl-, oder wobei R5 gleich einem aliphatischen Fleterocyclus ist, wobei der aliphatische Fleterocyclus aus der Gruppe Oxetanyl, Tetrahydrofuranyl, Tetrahydropyranyl, Morpholinyl, Piperidinyl, Pyrrolidinyl ausgewählt ist, und wobei der aliphatische Fleterocyclus gegebenenfalls durch 1 oder 2 aus der Gruppe F, OFI, (C1-C2)-Alkyl-0- und (C1-C4)-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppen durch Fluor ersetzt sein können; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze. 9. Verbindung nach Anspruch 7, wobei A = Phenyl, wobei der Phenylrest durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2FI, CFFI2, Methoxy, Ethoxy, OCF3 und (C1-C2)-Alkyl-S-ausgewählte Reste substituiert ist; X= Phenyl, wobei der Phenylrest durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2FI, CFFI2, Methoxy, Ethoxy, OCF3, (C1-C2)-Alkyl-S-, (C1-C2)-Alkyl-0-C(0)- und Methyl-S02- ausgewählte Reste substituiert ist; R1 = R5-C(=0)-; R2 = Fl, (C1-C2)-Alkyl-, Cyclopropyl-; R3 = H, Methyl-; R4 = H, Methyl-; oder wobei R3 und R4 zusammen eine Ethylenbrücke bilden; und wobei R5 gleich (C2-C4)-Alkyl ist, oder wobei R5 gleich Methyl ist, mit der Maßgabe, dass dann, wenn R5 für Methyl steht und R2, R3 und R4 gleich Fl sind und A gleich 4-Fluorphenyl ist, der Rest X nicht für Phenyl, 4-Fluorphenyl, 4-Chlorphenyl, 4-Methylphenyl, 4-Methoxyphenyl, 4-Acetoxyphenyl, 2-Chlorphenyl, 3,4-Dichlorphenyl steht; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze. 10. Verbindung nach Anspruch 1, wobei A = (C6-C10)-Aryl oder ein fünf- oder sechsgliedriges Fleteroaryl, enthaltend 1-3 Fleteroatome ausgewählt aus der Gruppe N, O und S, wobei Aryl und Fleteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C^CgJ-Alkyl-, (C.|-C6)-Alkyl-0- und (C1-C6)-Alkyl-S- ausgewählte Reste substituiert sind, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; X = (C6-C10)-Aryl oder ein fünf- oder sechsgliedriges Fleteroaryl, enthaltend 1-3 Fleteroatome ausgewählt aus der Gruppe N, O und S, wobei Aryl und Fleteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C1-C6)-Alkyl-, (C-i-CgJ-Alkyl-O-, (C1-C6)-Alkyl-S-, (C1-C6)-Alkyi-0-C(0)-und (C1-C6)-Alkyl-S02- ausgewählte Reste substituiert sind, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; R1 = R5-C(=0)- oder (C1-C6)-Alkyi-S02-, R2 = H, (CrC6)-Alkyl-, (C3-C6)-Cycloalkyl-; R3 = H, (C1-C4)-Alkyl-, R4 = H, (C1-C4)-Alkyl-, oder wobei R3 und R4 zusammen eine (C2-C3)-Alkylenbrücke bilden; und wobei R5 gleich einem Heteroaryl oder Heteroaryl-(Ci-C6)-Alkyl- ist, wobei es sich bei den Heteroarylresten um fünf- oder sechsgliedrige Ringsysteme, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, handelt, und wobei die Heteroarylreste gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C1-C6)-Alkyl-, (C.|-C6)-Alkyl-0-, CN, (C1-C2)-Alkyl-S02- ausgewählte Reste substituiert sind, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für Pyrimidin-4-yl, Pyridin-2-yl, 1-Methylpyrazol-3-yl oder 1-Methylimida- zol-2-yl steht, oder wobei R5 gleich Methyl ist, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und X für einen 2,4-Difluorphenylrest steht, A nicht für Pyridin-3-yl, 2-Fluorphenyl, 3-Fluorphenyl, 4-Fluorphenyl, 3-Cyanphe-nyl, 3-Methoxyphenyl, 3-Trifluormethoxyphenyl, 2-Fluor-5-methoxyphenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und X für einen 3-Cyanphenylrest steht, A nicht für einen 4-Fluorphenylrest steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R3 für Methyl steht, R2 und R4 für Wasserstoff stehen und X für einen 2,4-Difluorphenylrest steht, A nicht für ein 4-Fluorphenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für WasserstofFstehen und X für Phenyl steht, A nicht für Phenyl, 3-Trifluormethylphenyl, 4-Fluorphenyl, 4-Chlorphenyl, 4-Methylphenyl, 4-Ethylo-xyphenyl, 4-Acetoxyphenyl, 4-Methylthiophenyl, 2-Thiophenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für WasserstofF stehen und A für 4-Fluorphenyl steht, X nicht für Phenyl, 2-Chlorphenyl, 3,4-Dichlorphenyl, 4-Chlorphenyl, 4-Fluorphenyl, 4-Methyl-phenyl, 4-Methoxyphenyl, 4-Ethyloxyphenyl steht, und mit der Maßgabe, dass dann, wenn R5 für Methyl steht und R2 für Methyl steht und R3 und R4 gleich H sind und A gleich 4-Fluorphenyl ist, der Rest X nicht für Phenyl steht, oder wobei R5 gleich H, (C2-C6)-Alkyl, CF3, CF2H, CFH2 steht, wobei ein oder mehrere Wasserstoffatome des Alkylrests durch Fluor ersetzt sein können, oder wobei R5 gleich (C3-C6)-Cycloalkyl oder (C3-C6)-Cycloalkyl-(C.|-C4)-alkyl- ist, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für Cyclopropyl steht, oder wobei R5 gleich (C1-C4)-Alkyl-0- oder (C1-C4)-Alkyl-S- ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, oder wobei R5 gleich (C1-C4)-Alkyi-0-(C1-C2)-aikyl-, HO-(CrC4)-Alkyl- ist, oder wobei R5 gleich Phenyl-, Phenyl-(C1-C4)-alkyl- ist, wobei die Phenylreste gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C.|-C6)-Alkyl-, (C.|-Cg)-Alkyl-0-, CN, (C1-C2)-Alkyl-S02- ausgewählte Reste substituiert sind, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für 3-Methylsulfonylphenyl oder 4-Methylsulfonylphenyl steht, oder wobei R5 gleich R7R6N- ist, wobei R6 = H, (C1-C4)-Alkyl-, Cyclopropyl-, wobei ein Wasserstoffatom der Alkylgruppe durch einen OH-, Methoxy- oder Ethoxyrest ersetzt sein kann, und R7 = H,(C1-C2)-Alkyl-, oder wobei R5 gleich einem aliphatischen Heterocyclus ist, wobei der aliphatische Heterocyclus aus der Gruppe Oxetanyl, Tetrahydrofuranyl, Tetrahydropyranyl, Morpholinyl,

Piperidinyl, Pyrrolidinyl ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 oder 2 aus der Gruppe F, OH, (C1-C4)-Alkyl-0- und (Ci-C4)-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppen durch Fluor ersetzt sein können, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylreststeht, R5 nicht für 3-Methyloxetan-3-yl, Tetrahydrofuran-3-yl, Tetrahydropyran-4-yl oder 1 -Methylpiperidin-4-yl steht. 11. Verbindung nach Anspruch 10, wobei A = Phenyl, Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Thiophen-2-yl oder Thiophen-3-yl, wobei diese Reste gegebenenfalls durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3 und (C1-C2)-AlkylS- ausgewählte Reste substituiert sind; X = Phenyl, wobei der Phenylrest durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (Ci-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3, (C1-C2)-Alkyl-S-, (C1-C2)-Alkyl-0-C(0)- und Methyl-S02- ausgewählte Reste substituiert ist, oder

Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Thiophen-2-yl, Thiophen-3-yl, Thiazol-2-yl, Thiazol-4-yl, Thiazol-5-yl, wobei diese Reste gegebenenfalls durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3, (C1-C2)-Alkyl-S-, (C1-C2)-Alkyl-0-C(0)- und Methyl-S02- ausgewählte Reste substituiert sind; R1 = R5-C(=0)- oder (C1-C2)-Alkyl-S02-, R2 = H, (C.|-C2)-Alkyl-, Cyclopropyl-; R3 = H, (C1-C2)-Alkyl-, R4 = H, (C1-C2)-Alkyl-, oder wobei R3 und R4 zusammen eine Ethylenbrücke bilden; und wobei R5 gleich einem Heteroaryl oder Heteroaryl-(Ci-C6)-Alkyl- ist, wobei die Heteroarylreste aus der Gruppe bestehend aus Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Thiophen-2-yl, Thiophen-3-yl, Thiazol-2-yl, Thiazol-4-yl, Thiazol-5-yl, Iso-thiazol-3-yl, lsothiazol-4-yl, lsothiazol-5-yl, Pyrazol-3-yl, Pyrazol-4-yl, lmidazol-2-yl, lmidazol-4-yl, Pyrimidin-2-yl, Pyrimidin-4-yl, Pyrimidin-5-yl, Pyridazin-3-yl, Pyridazin-4-yl, Pyrazin-2-yl und Pyrazin-3-yl ausgewählt sind, und wobei diese Reste gegebenenfalls durch 1 oder2 unabhängig voneinander aus F, CI, Br, CF3, Methyl, Ethyl, Methoxy, Ethoxy, CN und Methyl-S02 ausgewählte Reste substituiert sind, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylreststeht, R5 nicht für Pyrimidin-4-yl, Pyridin-2-yl, 1-Methylpyrazol-3-yl oder 1-Methylimida-zol-2-yl steht, oder wobei R5 für Methyl steht, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und X für einen 2,4-Difluorphenylreststeht, A nicht für Pyridin-3-yl, 2-Fluorphenyl, 3-Fluorphenyl, 4-Fluorphenyl, 3-Cyanphe-nyl, 3-Methoxyphenyl, 3-Trifluormethoxyphenyl, 2-Fluor-5-methoxyphenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und X für einen 3-Cyanphenylrest steht, A nicht für einen 4-Fluorphenylrest steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R3 für Methyl steht, R2 und R4 für Wasserstoff stehen und X für einen 2,4-Difluorphenylrest steht, A nicht für ein 4-Fluorphenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und X für Phenyl steht, A nicht für Phenyl, 3-Trifluormethylphenyl, 4-Fluorphenyl, 4-Chlorphenyl, 4-Methylphenyl, 4-Ethoxy-phenyl, 2-Thiophenyl, 4-Methylthiophenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und A für 4-Fluorphenyl steht, X nicht für 2-Chlorphenyl, 3,4-Dichlorphenyl, 4-Chlorphenyl, 4-Fluorphenyl, 4-Methylphenyl, 4-Methoxyphenyl, 4-Ethoxyphenyl oder 4-Acetoxyphenyl steht, oder wobei R5 gleich H, (C2-C4)-Alkyl, CF3 ist, oder wobei R5 gleich Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl oder (C3-C6)-Cycloalkyl-(C1-C2)-alkyl- ist, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für Cyclopropyl steht, oder wobei R5 gleich (C1-C2)-Alkyl-0- oder (C1-C2)-Alkyl-S- ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, oder wobei R5 gleich (C1-C4)-Alkyl-0-methyi-, HO-(C1-C2)-Alkyl- ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, oder wobei R5 gleich Phenyl-, Phenyl-(C1-C2)-alkyl- ist, wobei die Phenylreste gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C-j-C^-Alkyl-, (C1-C2)-Alkyl-0-, CN, Methyl-S02- ausgewählte Reste substituiert sind, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für 3-Methylsulfonylphenyl oder 4-Methylsulfonylphenyl steht, oder wobei R5 gleich R7R6N- ist, wobei R6 = H, (C1-C4)-Alkyl-, Cyclopropyl-, wobei ein Wasserstoffatom der Alkylgruppe durch einen Hydroxy-, Methoxy-oder Ethoxyrest ersetzt sein kann, und R7 = H, Methyl-, Ethyl-, oder wobei R5 gleich einem aliphatischen Heterocyclus ist, wobei der aliphatische Heterocyclus aus der Gruppe Oxetanyl, Tetrahydrofuranyl, Tetrahydropyranyl, Morpholinyl, Piperidinyl, Pyrrolidinyl ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 oder 2 aus der Gruppe F, OH, (C1-C2)-Alkyl-0- und (CrC4)-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppen durch Fluor ersetzt sein können, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für 3-Methyloxetan-3-yl, Tetrahydrofuran-3-yl, Tetrahydropyran-4-yl oder 1 -Methylpiperidin-4-yl steht; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze. 12. Verbindung nach Anspruch 10, wobei A gleich Phenyl ist, wobei der Phenylrest gegebenenfalls durch 1,2 oder 3 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, (C1-C4)-Alkyl-0- und (C1-C4)-Alkyl-S- ausgewählte Reste substituiert ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; und X gleich Phenyl ist, wobei die Phenylgruppe gegebenenfalls durch 1,2 oder 3 unabhängig voneinander aus F, CI, Br, CN, (C.|-C4)-Alkyl-, (C1-C4)-Alkyl-0-, (C1-C4)-Alkyl-S-, (C1-C4)-Alkyl-0-C(0)- und (C1-C4)-Alkyl-S02-ausgewählte Reste substituiert ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; und R1 = R5-C(=0)- oder (CrC6)-Alkyi-S02-, R2 = H, (C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-; R3 = H, (C1-C4)-Alkyl-; R4 = H, (C1-C4)-Alkyl-; oder wobei R3 und R4 zusammen eine (C2-C3)-Alkylenbrücke bilden; und wobei R5 gleich einem Heteroaryl oder Heteroaryl-(C1-C6)-alkyl- ist, wobei es sich bei den Heteroarylresten um fünf- oder sechsgliedrige Ringsysteme, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, handelt, und wobei die Heteroarylreste gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C1-C6)-Alkyl-, (C.|-C6)-Alkyl-0-, CN, (C1-C2)-Alkyl-S02- ausgewählte Reste substituiert sind, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für Pyrimidin-4-yl, Pyridin-2-yl, 1-Methylpyrazol-3-yl oder 1-Methylimida- zol-2-yl steht, oder wobei R5 für Methyl steht, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und X für einen 2,4-Difluorphenylrest steht, A nicht für Pyridin-3-yl, 2-Fluorphenyl, 3-Fluorphenyl, 4-Fluorphenyl, 3-Cyanphe-nyl, 3-Methoxyphenyl, 3-Trifluormethoxyphenyl, 2-Fluor-5-methoxyphenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und X für einen 3-Cyanphenylrest steht, A nicht für einen 4-Fluorphenylrest steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R3 für Methyl steht, R2 und R4 für Wasserstoff stehen und X für einen 2,4-Difluorphenylrest steht, A nicht für ein 4-Fluorphenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für WasserstofF stehen und X für Phenyl steht, A nicht für Phenyl, 3-Trifluormethylphenyl, 4-Fluorphenyl, 4-Chlorphenyl, 4-Methylphenyl, 4-Ethylo-xyphenyl, 4-Methylthiophenyl, 2-Thiophenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für WasserstofF stehen und A für 4-Fluorphenyl steht, X nicht für Phenyl, 2-Chlorphenyl, 3,4-Dichlorphenyl, 4-Chlorphenyl, 4-Fluorphenyl, 4-Methylphenyl, 4-Methoxyphenyl, 4-Ethyloxyphenyl oder 4-Acetoxyphenyl steht, und mit der Maßgabe, dass dann, wenn R5 für Methyl steht und R2 für Methyl steht und R3 und R4 für H stehen und A für 4-Fluorphenyl steht, der Rest X nicht für Phenyl steht, oder wobei R5 gleich H, (C2-C6)-Alkyl, CF3, CF2H, CFH2 ist, wobei ein oder mehrere Wasserstoffatome des Alkylrests durch Fluor ersetzt sein können, oder wobei R5 gleich (C3-C6)-Cycloalkyl oder (C3-C6)-Cycloalkyl-(C1-C4)-alkyl- ist, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für Cyclopropyl steht, oder wobei R5 gleich (C1-C4)-Alkyl-0- oder (C1-C4)-Alkyl-S- ist, wobei ein oder mehrere WasserstofFatome der Alkylgruppierungen durch Fluor ersetzt sein können, oder wobei R5 gleich (C1-C4)-Alkyi-0-(C1-C2)-aikyl-, HO-(CrC4)-Alkyl- ist, oder wobei R5 gleich Phenyl-, Phenyl-(C.|-C4)-alkyl- ist, wobei die Phenylreste gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C1-C6)-Alkyl-, (C.|-C6)-Alkyl-0-, CN, (C1-C2)-Alkyl-S02- ausgewählte Reste substituiert sind, und wobei ein oder mehrere WasserstofFatome der Alkylgruppierungen durch Fluor ersetzt sein können, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für 3-Methylsulfonylphenyl, 4-Methylsulfonylphenyl steht, oder wobei R5 gleich R7R6N- ist, wobei R6 = H, (C1-C4)-Alkyl-, Cyclopropyl-, wobei ein Wasserstoffatom der Alkylgruppe durch einen Ohl-, Methoxy- oder Ethoxyrest ersetzt sein kann, und R7 = H, (CrC2)-Alkyl-, oder wobei R5 gleich einem aliphatischen Heterocyclus ist, wobei der aliphatische Heterocyclus aus der Gruppe Oxetanyl, Tetrahydrofuranyl, Tetrahydropyranyl, Morpholinyl, Piperidinyl, Pyrrolidinyl ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 oder 2 aus der Gruppe F, OH, (Ci-C4)-Alkyl-0- und (Ci-C4)-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppen durch Fluor ersetzt sein können, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für 3-Methyloxetan-3-yl, Tetrahydrofuran-3-yl, Tetrahydropyran-4-yl oder 1 -Methylpiperidin-4-yl steht; R6 = H, (C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-, wobei ein Wasserstoffatom der Alkylgruppe durch einen OH- oder (C.|-C6)-Alkyl-0-Rest ersetzt sein kann, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppe durch Fluor ersetzt sein können; R7 = H, (CrC6)-Alkyl-, wobei ein oder mehrere Wasserstoffatome der Alkylgruppe durch Fluor ersetzt sein können. 13. Verbindung nach Anspruch 12, wobei A = Phenyl, wobei der Phenylrest durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3 und (C1-C2)-Alkyl-S-ausgewählte Reste substituiert ist; X = Phenyl, wobei der Phenylrest durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3, (Ci-C2)-Alkyl-S-, (Ci-C2)-Alkyl-0-C(0)- und Methyl-S02- ausgewählte Reste substituiert ist; R1 = R5-C(=0)- oder Methyl-S02-; R2 = H, (C.|-C2)-Alkyl-, Cyclopropyl-; R3 = H, Methyl-; R4 = H, Methyl-; oder wobei R3 und R4 zusammen eine Ethylenbrücke bilden; und wobei R5 gleich einem Heteroaryl oder Heteroaryl-(C.|-C6)-alkyl- ist, wobei die Heteroarylreste aus der Gruppe bestehend aus Pyridin-2-yl, Pyridin-3-yl, Pyridin-4-yl, Thiophen-2-yl, Thiophen-3-yl, Thiazol-2-yl, Thiazol-4-yl, Thiazol-5-yl, Iso-thiazol-3-yl, lsothiazol-4-yl, lsothiazol-5-yl, Pyrazol-3-yl, Pyrazol-4-yl, lmidazol-2-yl, lmidazol-4-yl, Pyrimidin-2-yl, Pyrimidin-4-yl, Pyrimidin-5-yl, Pyridazin-3-yl, Pyridazin-4-yl, Pyrazin-2-yl und Pyrazin-3-yl ausgewählt sind, und wobei diese Reste gegebenenfalls durch 1 oder2 unabhängig voneinander aus F, CI, Br, CF3, Methyl, Ethyl, Methoxy, Ethoxy, CN, Methyl-S02- ausgewählte Reste substituiert sind, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylreststeht, R5 nicht für Pyrimidin-4-yl, Pyridin-2-yl, 1-Methylpyrazol-3-yl oder 1-Methylimida-zol-2-yl steht, oder wobei R5 für Methyl steht, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und X für einen 2,4-Difluorphenylreststeht, A nicht für Pyridin-3-yl, 2-Fluorphenyl, 3-Fluorphenyl, 4-Fluorphenyl, 3-Cyanphe-nyl, 3-Methoxyphenyl, 3-Trifluormethoxyphenyl, 2-Fluor-5-methoxyphenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und X für einen 3-Cyanphenylrest steht, A nicht für einen 4-Fluorphenylrest steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R3 für Methyl steht, R2 und R4 für Wasserstoff stehen und X für einen 2,4-Difluorphenylrest steht, A nicht für ein 4-Fluorphenyl steht, und mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I R2, R3 und R4 für Wasserstoff stehen und A für 4-Fluorphenyl steht, X nicht für 2-Chlorphenyl, 3,4-Dichlorphenyl, 4-Chlorphenyl, 4-Fluorphenyl, 4-Methylphenyl, 4-

Methoxyphenyl, 4-Ethoxyphenyl oder 4-Acetoxyphenyl steht, oder wobei R5 gleich H, (C2-C4)-Alkyl, CF3 ist, oder wobei R5 gleich Cyclopropyl, Cyclobutyl, Cyclopentyl, Cyclohexyl oder (C3-C6)-Cycloalkyl-(C.|-C2)-alkyl- ist, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für Cyclopropyl steht, oder wobei R5 gleich (C^C^-Alkyl-O- oder (C1-C2)-Alkyl-S- ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, oder wobei R5 gleich (C1-C4)-Alkyl-0-methyi-, HO-(C1-C2)-Alkyl- ist, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, oder wobei R5 gleich Phenyl-, Phenyl-(C1-C2)-alkyl- ist, wobei die Phenylreste gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C1-C2)-Alkyl-, (C1-C2)-Alkyl-0-, CN, Methyl-S02- ausgewählte Reste substituiert sind, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylrest steht, R5 nicht für 3-Methylsulfonylphenyl, 4-Methylsulfonylphenyl steht, oder wobei R5 gleich R7R6N- ist, wobei R6 = H, (C1-C4)-Alkyl-, Cyclopropyl-, wobei ein Wasserstoffatom der Alkylgruppe durch einen Hydroxy-, Methoxy-oder Ethoxyrest ersetzt sein kann, und R7 = H, Methyl-, Ethyl-, oder wobei R5 gleich einem aliphatischen Heterocyclus ist, wobei der aliphatische Heterocyclus aus der Gruppe Oxetanyl, Tetrahydrofuranyl, Tetrahydropyranyl, Morpholinyl, Piperidinyl, Pyrrolidinyl ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 oder 2 aus der Gruppe F, OH, (C1-C2)-Alkyl-0- und (C1-C4)-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei ein oder mehrere Wasserstoffatome der Alkylgruppen durch Fluor ersetzt sein können, mit der Maßgabe, dass dann, wenn in Verbindungen der Formel I A für einen 3-Cyanphenylrest steht und X für einen 2,4-Difluorphenylreststeht, R5 nicht für 3-Methyloxetan-3-yl, Tetrahydrofuran-3-yl, Tetrahydropyran-4-yl oder 1 -Methylpiperidin-4-yl steht; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze. 14. Verbindung nach Anspruch 10, wobei A = Phenyl, wobei der Phenylrest durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3 und (C.|-C2)-Alkyl-S-ausgewählte Reste substituiert ist; X= Phenyl, wobei der Phenylrest durch 1 oder 2 unabhängig voneinander aus F, CI, Br, CN, (C1-C4)-Alkyl-, CF3, CF2H, CFH2, Methoxy, Ethoxy, OCF3, (C1-C2)-Alkyl-S-, (C1-C2)-Alkyl-0-C(0)- und Methyl-S02- ausgewählte Reste substituiert ist; R1 = R5-C(=0)-; R2 = H, (C1-C2)-Alkyl-, Cyclopropyl-; R3 = H, Methyl-; R4 = H, Methyl-; oder wobei R3 und R4 zusammen eine Ethylenbrücke bilden; und wobei R5 gleich (C2-C4)-Alkyl ist; und/oder eine stereoisomere Form der Verbindung der Formel I und/oder Mischungen dieser Formen, und/oder deren pharmazeutisch akzeptable Salze. 15. Verbindung nach Anspruch 1, ausgewählt aus der Gruppe bestehend aus 3-(3-Cyanphenyl)-1-(2,4-difluorbenzyl)- 1.4.6.7- tetrahydropyrazolo[4,3-c]pyridin-5-carbonsäureisopropylamid; 3-(4-Fluorphenyl)-1-[(S)-1-(4-fluorphe-nyl)ethyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-carbonsäureethylamid; 3-(4-Fluorphenyl)-1-[(R)-1-(4-fluor-phenyl)ethyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-carbonsäureethylamid; 3-(4-Fluorphenyl)-1-[(S)-1-(4-fluor-phenyl)ethyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-carbonsäure-tert-butylamid; 3-(3-Cyanphenyl)-1-(2,4-difluorbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-carbonsäureethylamid; 3-(3-Cyanphenyl)-1-(2,4-difluor-benzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-carbonsäuremethylamid; {3-(4-Fluorphenyl)-1-[(S)-1-(4-fluor-phenyl)ethyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl}-morpholin-4-yl-methanon; {3-(4-Fluorphenyl)-1-[(S)-1-(4-fluorphenyl)ethyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl}-((S)-3-hydroxypyrrolidin-1-yl)methanon; 3-(3-Cyanphenyl)-1-(2,4-difluorbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-carbonsäuredimethylamid; 3-(3-Cy-anphenyl)-1-(2,4-difluorbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-carbonsäure-(2-hydroxyethyl)methyla-mid; 2-[5-Acetyl-1-(2,4-difluorbenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]isonicotinonitril; 6-[5-Acetyl-1-(2,4-difluorbenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-pyridin-2-carbonitril; 3-[1-(2,4-Difluorben-zyl)-5-(2-hydroxyacetyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[5-Acetyl-1-(2,4-difluorben-zyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 1-[1-(2,4-Difluorbenzyl)-3-(3-methylpyridin-2-yl)- 1.4.6.7- tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(4-methoxy-pyridin-2-yl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2-Methylthiazol-4-ylmethyl)-3-(3-trifluormethylphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-Thiazol-2-ylmethyl-3-(3-trifluormethylphenyl)-1,4,6,7-tetrahy-dropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-thiophen-2-yl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(5-Chlorthiophen-2-ylmethyl)-3-m-tolyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(5-Chlorthiophen-2-ylmethyl)-3-(3-trifluormethylphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin- 5-yl]ethanon; 3-[5-Acetyl-1-(5-chlorthiophen-2-ylmethyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzoni-tril; 1-[3-(3-Chlorphenyl)-1-(5-chlorthiophen-2-ylmethyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[3-(5-Chlorthiophen-2-yl)-1-(2,4-difluorbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-thiophen-3-yl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 4-[5-Acetyl-3-(3-trifluorme-thylphenyl)-4,5,6,7-tetrahydropyrazolo[4,3-c]pyridin-1-ylmethyl]benzonitril; 3-{5-Acetyl-1-[1-(4-fluorphenyl)ethyl]- 4.5.6.7- tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl}benzonitril; 1-[1-[Cyclopropyl-(4-fluorphenyl)methyl]-3-(4-fluor-phenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(3-trifluormethoxyphenyl)- 1.4.6.7- tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,6-Difluorbenzyl)-3-(4-fluorphenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-{3-(4-Fluorphenyl)-1-[1-(4-fluorphenyl)ethyl]-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl}ethanon; 1-[3-(4-Fluorphenyl)-1-(4-trifluormethylbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(3-methoxyphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[3-(4-Fluorphenyl)-1-(3-trifluormethylbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-[1-(4-Fluorphenyl)-ethyl]-3-(3-trifluormethoxyphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(4-fluor-3-methoxyphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 3-[5-Acetyl-1-(2,5-difluorbenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 1-[1-(2,4-Difluorbenzyl)-3-m-to-lyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(6-Chlorpyridin-3-ylmethyl)-3-(3-trifluormethylphe-nyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[3-(3-Chlorphenyl)-1-(4-fluor-2-methylbenzyl)-1,4,6,7- tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2-Fluorbenzyl)-3-m-tolyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyri-din-5-yl]ethanon; 1-[1-(2-Methoxybenzyl)-3-(3-trifluormethylphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[3-(3-Chlorphenyl)-1-(3-methoxybenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(4-Chlor-3-fluorbenzyl)-3-(4-fluorphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(2-fluor-5-methoxyphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 5-[5-Acetyl-1-(2,4-difluorbenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]-2-fluorbenzonitril; 1-[1-(2,4-Difluorbenzyl)- 3-(3-fluorphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(4-trifluormethyl-phenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-[(R)-1-(4-Chlorphenyl)propyl]-3-(4-fluorphenyl)- 1.4.6.7- tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-[(S)-1-(4-Chlorphenyl)propyl]-3-(4-fluorphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2-Fluor-4-methylbenzyl)-3-(3-trifluormethylphenyl)-1,4,6,7-te-trahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(4-Chlorpyridin-3-ylmethyl)-3-(3-trifluormethylphenyl)-1,4,6,7-te-trahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(3-Methylpyridin-2-ylmethyl)-3-(3-trifluormethylphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(4-fluorphenyl)-1,4,6,7-tetrahydropyrazo-lo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(4-Fluorbenzyl)-3-(6-trifluormethylpyridin-2-yl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(4-trifluormethylpyridin-2-yl)-1,4,6,7-tetrahydropyrazolo[4,3-c]py-ridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(6-trifluormethylpyridin-2-yl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin- 5-yl]ethanon; 1-[3-(4-Brompyridin-2-yl)-1-(2,4-difluorbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[3-(2-Brompyridin-4-yl)-1-(2,4-difluorbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[3-(5-Brom-pyridin-3-yl)-1 -(2,4-difluorbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 3-[11 -Acetyl-5-(2,4-difluor-benzyl)-4,5,11-triazatricyclo[6.2.1,02,6]undeca-2(6),3-dien-3-yl]benzonitril; 1-[5-(2,4-Difluorbenzyl)-3-(4-fluorphe-nyl)-4,5,1 1 -triazatricyclo[6.2.1,02,6]undeca-2(6),3-dien-11-yl]ethanon; 1-[1-(6-Chlorpyridin-3-ylmethyl)-3-m-tolyl- 1.4.6.7- tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(4-Methoxypyridin-2-ylmethyl)-3-(3-trifluormethylphe-nyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(4-Chlorpyridin-3-ylmethyl)-3-m-tolyl-1,4,6,7-tetra-hydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(3-Methoxypyridin-2-ylmethyl)-3-(3-trifluormethylphenyl)-1,4,6,7-te-trahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[3-(3-Chlorphenyl)-1-(3-methylpyridin-2-ylmethyl)-1,4,6,7-tetrahy-dropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-[1-(4-Fluorphenyl)ethyl]-3-(6-trifluormethylpyridin-2-yl)-1,4,6,7-tetrahy-dropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(6-methylpyridin-2-yl)-1,4,6,7-tetrahydropyrazo-lo[4,3-c]pyridin-5-yl]ethanon; 1-[3-(6-Brompyridin-2-yl)-1-(2,4-difluorbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyri-din-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(4-methylpyridin-2-yl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 1-[1-(2,4-Difluorbenzyl)-3-(6-methoxypyridin-2-yl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]etha-non; 1-[3-(6-Chlor-5-methoxypyridin-2-yl)-1-(2,4-difluorbenzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]etha-non; 3-[1-(2,4-Difluorbenzyl)-5-(3-methyloxetan-3-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]ben-zonitril; 3-[1-(2,4-Difluorbenzyl)-5-isobutyryl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[5-Cyc-lopropancarbonyl-1-(2,4-difluorbenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[5-(2-tert-Butoxyacetyl)-1-(2,4-difluorbenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[1-(2,4-Difluor-benzyl)-5-(3-methansulfonylbenzoyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; [1-Benzyl-3-(4-fluorphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]-(4-fluorphenyl)methanon; [1-Benzyl-3-(4-fluorphenyl)- 1.4.6.7- tetrahydropyrazolo[4,3-c]pyridin-5-yl]-(4-methoxyphenyl)methanon; [1-Benzyl-3-(4-fluorphenyl)-1,4,6,7-te-trahydropyrazolo[4,3-c]pyridin-5-yl]-phenylmethanon; 3-[5-Cyclobutancarbonyl-1-(2,4-difluorbenzyl)-4,5,6,7-tetra-hydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[5-Cyclopentancarbonyl-1-(2,4-difluorbenzyl)-4,5,6,7-tetrahy-dro-1FI-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[1-(2,4-Difluorbenzyl)-5-(4-methansulfonylbenzoyl)-4,5,6,7-tetra-hydro-1FI-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[1-(2,4-Difluorbenzyl)-5-(tetrahydropyran-4-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[1-(2,4-Difluorbenzyl)-5-(tetrahydrofuran-3-carbonyl)- 4.5.6.7- tetrahydro-1FI-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[1-(2,4-Difluorbenzyl)-5-(2-methoxyacetyl)-4,5,6,7-tetrahydro-1FI-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[1-(2,4-Difluorbenzyl)-5-(2,2-dimethylpropionyl)-4,5,6,7-te-trahydro-1FI-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[1-(2,4-Difluorbenzyl)-5-propionyl-4,5,6,7-tetrahydro-1 H-py-razolo[4,3-c]pyridin-3-yl]benzonitril; 3-[1-(2,4-Difluorbenzyl)-5-((S)-2-hydroxypropionyl)-4,5,6,7-tetrahydro-1 H-py-razolo[4,3-c]pyridin-3-yl]benzonitril; 1-[1-Benzyl-3-(4-fluorphenyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]-2-phenylethanon; 3-[5-Butyryl-1-(2,4-difluorbenzyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3- [1-(2,4-Difluorbenzyl)-5-(pyridin-2-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; Verbindung mit Trifluoressigsäure; 3-[1-(2,4-Difluorbenzyl)-5-(3-fluorpyridin-4-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazo-lo[4,3-c]pyridin-3-yl]benzonitril; Verbindung mit Trifluoressigsäure; 3-[1-(2,4-Difluorbenzyl)-5-(pyrimidin-4-carbo-nyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[1-(2,4-Difluorbenzyl)-5-(3-methyl-3H-imidazol- 4- carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-[1-(2,4-Difluorbenzyl)-5-(1-methyl-1FI- pyrazol-3-carbonyl)-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitril; 3-(3-Cyanphenyl)-1-(2,4-difluor-benzyl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-carbonsäureethylester; 1-[1-(2,4-Difluorbenzyl)-3-(4-fluorphe-nyl)-6-methyl-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridin-5-yl]ethanon; 3-(4-Fluorphenyl)-1-[(R)-1-(4-fluorphe- nyl)ethyl]-5-methansulfonyl-4,5,6,7-tetrahydro-1FI-pyrazolo[4,3-c]pyridin; 3-(4-Fluorphenyl)-1-[(S)-1-(4-fluorphe- nyl)ethyl]-5-methansulfonyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin; deren stereoisomere Formen, und/oder deren pharmazeutisch akzeptable Salze. 16. Medikament, enthaltend eine Verbindung der Formel I und/oder ihr pharmazeutisch akzeptables Salz nach einem der Ansprüche 1 bis 15. 17. Verbindung der Formel I oder Verbindung nach einem der Ansprüche 1 bis 15, und/oder ihre pharmazeutisch akzeptablen Salze zur Verwendung bei der Behandlung oder Prävention von durch den TASK-1-Kanal vermittelten Krankheiten,

wobei A = (C6-C10)-Aryl oder ein fünf- oder sechsgliedriges Heteroaryl, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, wobei Aryl und Heteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C.|-C6)-Alkyl-, (C1-C6)-Alkyl-o- und (C.|-C6)-Alkyl-S- ausgewählte Reste substituiert sind, wobei ein oder mehrere Wasserstoffatome der Alkylgruppierungen durch Fluor ersetzt sein können; X = (C6-C10)-Aryl oder ein fünf- oder sechsgliedriges Heteroaryl, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, wobei Aryl und Heteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CN, (C1-C6)-Alkyl-, (C.|-C6)-Alkyl-0-, (C.|-C6)-Alkyl-S-, (C.|-C6)-Alkyl-0-C(0)- und (C1-C6)-Aikyl-S02- ausgewählte Reste substituiert sind, wobei ein oder mehrere WasserstofFatome der Alkylgruppierungen durch Fluor ersetzt sein können; R1 = R5-C(=0)- oder (C1-C6)-Alkyl-S02-, R2 = H, (CrC6)-Alkyl-, (C3-C6)-Cycloalkyl-; R3 = H, (C1-C4)-Alkyl-, R4 = H, (C1-C4)-Alkyl-, oder wobei R3 und R4 zusammen eine (C2-C3)-Alkylenbrücke bilden; R5 = (C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-, (C1-C6)-Alkyl-0-, (C1-C6)-Alkyl-S-, (C1-C6)-Alkyi-0-(C1-C6)-aikyl-, HO-(C1-C6)-Alkyl-, (C3-C6)-Cycloalkyl-(C1-C6)-alkyl-, (C6-C10)-Aryl-, (C6-C10)-Aryl-(C1-C6)-alkyl-, R7R6N-, Heteroaryl, Heteroaryl-(C1-C6)-alkyl-, aliphatischer Heterocyclus, wobei der aliphatische Heterocyclus aus der Gruppe Morpholinyl, Piperidinyl, Pyrrolidinyl und 4- bis 7-gliedrige aliphatische, ein Sauerstoffatom enthaltende Heterocyclen ausgewählt ist, und wobei der aliphatische Heterocyclus gegebenenfalls durch 1 bis 3 aus der Gruppe F, OH, (C.|-C6)-Alkyl-0- und (C.|-C6)-Alkyl- ausgewählte Substituenten substituiert sein kann, und wobei es sich bei den Heteroarylresten um fünf- oder sechsgliedrige Ringsysteme, enthaltend 1-3 Heteroatome ausgewählt aus der Gruppe N, O und S, handelt, und wobei Aryl und Heteroaryl gegebenenfalls durch 1-3 unabhängig voneinander aus F, CI, Br, CF3, (C1-C6)-Alkyl-, (C1-C6)-Alkyl-0-, CN, (C1-C2)-Alkyl-S02- ausgewählte Reste substituiert sind, wobei ein oder mehrere WasserstofFatome der Alkylgruppierungen durch Fluor ersetzt sein können; R6 = H, (C.|-C6)-Alkyl-, (C3-C6)-Cycloalkyl, wobei ein Wasserstoffatom der Alkylgruppe durch einen OH- oder (C.|-C6)-Alkyl-0-Rest ersetzt sein kann, und wobei ein oder mehrere WasserstofFatome der Alkylgruppe durch Fluor ersetzt sein können; R7 = H, (C1-C6)-Alkyl-, wobei ein oder mehrere WasserstofFatome der Alkylgruppe durch Fluor ersetzt sein können. 18. Verbindung der Formel I und/oder ein pharmazeutisch akzeptables Salz davon nach einem der Ansprüche 1 bis 15, Medikament nach Anspruch 16 oder Verbindung nach Anspruch 17 zur Verwendung bei der Behandlung oder Prävention von Arrhythmien, insbesondere Vorhoftachyarrhythmien, Vorhofflimmern und Vorhofflattern. 19. Verbindung der Formel I und/oder ein pharmazeutisch akzeptables Salz davon nach einem der Ansprüche 1 bis 15, Medikament nach Anspruch 16 oder Verbindung nach Anspruch 17 zur Verwendung bei der Behandlung oder Prävention von schlafbezogenen Atmungsstörungen, zentralen und obstruktiven Schlafapnoen, Widerstandssyndrom der oberen Atemwege, Cheyne-Stokes-Atmung, Schnarchen, gestörtem zentralen Atmungsantrieb, plötzlichem Kindstod, postoperativer Hypoxie und Apnoe, muskelbezogenen Atmungsstörungen, Atmungsstörungen nach langzeitiger mechanischer Beatmung (Beatmungsentwöhnung), Atmungsstörungen während der Anpassung im Hochgebirge, akuten und Atmungsstörungen, chronischen Lungenerkrankungen mit Hypoxie und Hyperkapnie, chronischer obstruktiver Lungenerkrankung ("COPD") und Obesitas-Hypoventilationssyndrom; oder zur Verwendung als Atmungsstimulanz für die Behandlung oder Prävention einer mit Anästhesie oder verfahrensmäßigen Sedierungen für kleine Operationen oder für diagnostische Zwecke assoziierten Atemdepression, oder zur Verwendung als Atmungsstimulanz für die Behandlung oder Prävention von Atemdepression durch Opioide bei der chronischen Schmerzbehandlung, insbesondere bei Krebs oder der palliativen Pflege oder verfahrensmäßigen Sedierungen, und/oder zur Beatmungsentwöhnung von langzeitiger mechanischer Beatmung; oder zur Verwendung bei der Behandlung oder Prävention von multipler Sklerose und entzündlichen oder degene-rativen Erkrankungen des zentralen Nervensystems.

Revendications 1. Composé de formule I,

dans lequel A = un aryle en C6-C10 ou un hétéroaryle à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en CpCg)-, (alkyl en CvC6)-0- et (alkyl en CpCgJ-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; X = un aryle en C6-C10 ou un hétéroaryle à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C1-C6)-, (alkyl en C1-C6)-0-, (alkyl en C.|-C6)-S-, (alkyl en C.|-C6)-0-C(0)- et (alkyl en C.|-C6)-S02-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; R1 = R5-C(=0)- ou (alkyl en C-pC^-SC^- ; R2 = H, (alkyl en CpCg)-, (cycloalkyl en C3-C6)- ; R3 = H, (alkyl en CrC4)-; R4 = H, (alkyl en CrC4)-; ou dans lequel R3 et R4 forment ensemble un pont alkylène en C2-C3 ; R5 = H, (alkyl en CrC6)-, (cycloalkyl en C3-C6)-, (alkyl en CrC6)-0-, (alkyl en CrC6)-S-, (alkyl en CrC6)-0-(alkyl en CpCg)-, HO-(alkyl en CpCg)-, (cycloalkyl en C3-C6)-(alkyl en CpCg)-, (aryl en C6-C10)-, (aryl en C6-C10)-(alkyl en CpCg)-, R7R6N-, hétéroaryle, hétéroaryl-(alkyl en CpCg)-, hétérocycle aliphatique, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, et l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles morpholinyle, pipéridinyle, pyrrolidinyle et hétérocycles aliphatiques à 4 à 7 chaînons comprenant un atome d’oxygène, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 à 3 substituants indépendamment choisis dans le groupe des substituants F, OH, (alkyl en CpCgJ-O-et (alkyl en CpCg)-, et les résidus hétéroaryle étant des systèmes cycliques à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, et l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en CpCg)-, (alkyl en CpCgJ-O-, CN, (alkyl en

Ci-C2)-S02- ; R6 = H, (alkyl en CpCg)-, (cycloalkyl en C3-C6)-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OH ou (alkyl en C.|-Cg)-0-, et un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor ; R7 = H, (alkyl en CrC6)-, un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma- ceutiquement acceptables ; et à condition que si R5 est un méthyle et R2, R3 et R4 sont égaux à H et A est égal à 4-fluorophényle, le résidu X ne soit pas un phényle, 4-fluorophényle, 4-chlorophényle, 4-méthylphényle, 4-méthoxyphényle, 4-acétoxyphényle, 2-chlorophényle, 3,4-dichlorophényle, et à condition que si R5 est un méthyle et R2, R3 et R4 sont égaux à H et X est un résidu phényle, le résidu A ne soit pas un phényle, 4-fluorophényle, 4-chlorophényle, 4-méthylphényle, 4-éthyloxyphényle, 3-trifluorométhylphényle, 2-thiophényle ou 4-méthylthiophényle, et à condition que si R5 est un méthyle et R2 est un méthyle et R3 et R4 sont égaux à H et A est égal à 4-fluorophényle, le résidu X ne soit pas un phényle. 2. Composé selon la revendication 1, dans lequel A = phényle ou un hétéroaryle à cinq ou six chaînons choisi dans le groupe constitué par les hétéroaryles pyridin-2-yle, pyridin-3-yle, pyridin-4-yle, thiophén-2-yle ou thiophén-3-yle, le phényle et l’hétéroaryle étant éventuellement substitués par 1 -3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en CrC6)-, (alkyl en CrC6)-0- et (alkyl en CrC6)-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; X = un hétéroaryle à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, le groupe hétéroaryle étant éventuellement substitué par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en CrC6)-, (alkyl en C.|-C6)-0- et (alkyl en C1-C6)-S-, (alkyl en C.|-C6)-0-C(0)- et (alkyl en C.|-Cg)-S02-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; R1 = R5-C(=0)- ou (alkyl en C.|-C6)-S02- ; R2 = H, (alkyl en C.|-C4)-, (cycloalkyl en C3-C6)- ; R3 = H, (alkyl en CrC2)- ; R4 = H, (alkyl en CrC2)- ; ou dans lequel R3 et R4 forment ensemble un pont alkylène en C2-C3 ; R5 = H, (alkyl en CpCg)-, (cycloalkyl en C3-C6)-, (alkyl en CrC6)-0-, (alkyl en C.|-Cg)-S-, (alkyl en CrC6)-0-(alkyl en CpCg)-, HO-(alkyl en CpCg)-, (cycloalkyl en C3-C6)-(alkyl en CpCg)-, (aryl en C6-C10)-, (aryl en C6-C10)-(alkyl en CpCg)-, R7R6N-, hétéroaryle, hétéroaryl-(alkyl en CpCg)-, hétérocycle aliphatique, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, et l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles morpholinyle, pipéridinyle, pyrrolidinyle et hétérocycles aliphatiques à 4 à 7 chaînons comprenant un atome d’oxygène, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 à 3 substituants indépendamment choisis dans le groupe des substituants F, OH, (alkyl en C^Cgî-O-et (alkyl en CpCg)-, et les résidus hétéroaryle étant des systèmes cycliques à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, et l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en CpCg)-, (alkyl en C.|-Cg)-0-, CN, (alkyl en C.|-C2)-S02- î R6 = H, (alkyl en C-|-C6)-, (cycloalkyl en C3-C6)-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OH- ou (alkyl en C.|-Cg)-0-, et un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor ; R7 = H, (alkyl en CrC6)-, un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma- ceutiquement acceptables. 3. Composé selon la revendication 1 ou 2, dans lequel A = phényle, le résidu phényle étant éventuellement substitué par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en CpC^-, (alkyl en CpC^-O- et (alkyl en CpC^-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; X = un hétéroaryle à cinq ou six chaînons, choisi dans le groupe constitué par les hétéroaryles pyridin-2-yle, pyridin-3-yle, pyridin-4-yle, thiophén-2-yle, thiophén-3-yle, thiazol-2-yle, thiazol-4-yle, thiazol-5-yle, le groupe hétéroaryle étant éventuellement substitué par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C^Cg)-, (alkyl en C1-C6)-0- et (alkyl en C1-C6)-S-, (alkyl en C.|-C6)-0-C(0)- et (alkyl en crC6)-S02-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; R1 = R5-C(=0)- ou (alkyl en C.|-C2)-S02- ; R2 = H, (alkyl en C1-C2)-, cyclopropyl- ; R3 = H, méthyl- ; R4 = H, méthyl- ; ou dans lequel R3 et R4 forment ensemble un pont éthylène ; et dans lequel R5 = H, (alkyl en C.|-C4)-, (cycloalkyl en C3-C6)-, (alkylen 0^03)-0-, (alkylen 0^03)-8-, (alkylen C1-C4)-0-méthyl-, HO-(alkyl en Ci-C2)-, (cycloalkyl en C3-C6)-(alkyl en C1-C2)-, phényle, phényl-(alkyl en 0^03)-, R7R6N-, hétéroaryle, hétéroaryl-(alkyl en C1-C4)-, hétérocycle aliphatique, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, et l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles morpholinyle, pipéridinyle, pyrrolidinyle, oxé-tanyle, tétrahydrofuranyle et tétrahydropyranyle, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 ou 2 substituants indépendamment choisis dans le groupe des substituants F, OH, (alkyl en 0^03)-0- et (alkyl en CrC4)-, et le résidu phényle étant éventuellement substitué par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en C.|-C4)-, (alkyl en C.|-C4)-0-, ON, (alkyl en C1-C2)-S02-, les résidus hétéroaryle étant choisis dans le groupe constitué par les résidus pyridin-2-yle, pyridin-3-yle, pyridin-4-yle, thiophén-2-yle, thiophén-3-yle, thiazol-2-yle, thiazol-4-yle, thiazol-5-yle, isothiazol-3-yle, isothiazol-4-yle, iso-thiazol-5-yle, pyrazol-3-yle, pyrazol-4-yle, imidazol-2-yle, imidazol-4-yle, pyrimidin-2-yle, pyrimidin-4-yle, pyrimidin- 5-yle, pyridazin-3-yle, pyridazin-4-yle, pyrazin-2-yle et pyrazin-3-yle, et les résidus hétéroaryle étant éventuellement substitués par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en C.|-C4)-, (alkyl en C1-C4)-0-, CN, (alkyl en C^-C2)-S02- ] R6 = H, (alkyl en C1-C4)-, cyclopropyle, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OH, méthoxy ou éthoxy ; et R7 = H, méthyl-, éthyle ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma-ceutiquement acceptables. 4. Composé selon l’une quelconque des revendications 1 à 3, dans lequel A = phényle, le résidu phényle étant éventuellement substitué par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C1-C4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3 et (alkyl en C1-C2)-S-; X = un hétéroaryle à cinq ou six chaînons, choisi dans le groupe constitué par les hétéroaryles pyridin-2-yle, pyridin-3-yle, pyridin-4-yle, thiophén-2-yle, thiophén-3-yle, thiazol-2-yle, thiazol-4-yle, thiazol-5-yle, ces résidus étant éventuellement substitués par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C.|-C4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3, (alkyl en C.|-C2)-S-, (alkyl en C.|-C2)-0-C(0)-et méthyl-S02- ; R1 = R5-C(=0)- ou (alkyl en C.|-C2)-S02- ; R2 = H, méthyle, éthyle, cyclopropyle ; R3 et R4=H; et R5 = méthyle, éthyle, n-propyle, isopropyle, n-butyle, isobutyle, tert-butyle, cyclopropyle ou cyclobutyle ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma- ceutiquement acceptables. 5. Composé selon l’une quelconque des revendications 1, dans lequel A = un hétéroaryle à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, l’hétéroaryle étant substitué par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C1-C6)-, (alkyl en C.|-C6)-0- et (alkyl en C^CgJ-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; X = phényle, thiophén-2-yle ou thiophén-3-yle, ces résidus étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C^Cg)-, (alkyl en 0Γ06)-0- et (alkyl en C^CgJ-S-, (alkyl en C.|-C6)-0-C(0)- et (alkyl en C.|-Cg)-S02-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; R1 = R5-C(=0)- ou (alkyl en CrC6)-S02- ; R2 = H, (alkyl en C.|-Cg)-, (cycloalkyl en C3-C6)- ; R3 = H, (alkyl en CrC4)- ; R4 = H, (alkyl en CrC4)- ; ou dans lequel R3 et R4 forment ensemble un pont alkylène en C2-C3 ; R5 = H, (alkyl en C.|-C6)-, (cycloalkyl en C3-C6)-, (alkyl en CrC6)-0-, (alkyl en CrC6)-S-, (alkyl en C1-C6)-0-(alkyl en C.|-C6)-, HO-(alkyl en C.|-C6)-, (cycloalkyl en C3-C6)-(alkyl en C-pCg)-, (aryl en C6-C10)-, (aryl en C6-C10)-(alkyl en C.|-Cg)-, R7R6N-, hétéroaryle, hétéroaryl-(alkyl en CrC6)-, hétérocycle aliphatique, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, et l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles morpholinyle, pipéridinyle, pyrrolidinyle et hétérocycles aliphatiques à 4 à 7 chaînons comprenant un atome d’oxygène, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 à 3 substituants choisis dans le groupe des substituants F, OH, (alkyl en C1-C6)-0- et (alkyl en C1-C6)-, et les résidus hétéroaryle étant des systèmes cycliques à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, et l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en C.|-Cg)-, (alkyl en C.|-Cg)-0-, CN, (alkyl en C^“C2)“S02“ ! R6 = H, (alkyl en C.|-Cg)-, (cycloalkyl en C3-C6)-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OH- ou (alkyl en C^CgJ-O-, et un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor ; R7 = H, (alkyl en 0Γ06)- ; un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma- ceutiquement acceptables ; à condition que A ne soit pas un 4-méthylthiophényle si dans les composés de formule I R5 est un méthyle et R2, R3 et R4 sont l’hydrogène et X est un phényle. 6. Composé selon la revendication 5, dans lequel A = pyrid-2-yle, pyrid-3-yle ou pyrid-4-yle, les résidus pyridyle étant substitués par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en 0Γ04)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3et (alkyl en C-|-C2)-S- ; X = phényle, thiophén-2-yle ou thiophén-3-yle, ces résidus étant substitués par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C1-C4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3, (alkyl en C.|-C2)-S-, (alkyl en C.|-C2)-0-C(0)- et méthyl-S02- ; R1 = R5-C(=0)- ou (alkyl en CrC2)-S02- ; R2 = H, méthyle, éthyle, cyclopropyle ; R3 et R4=H; et R5 = H, méthyle, éthyle, n-propyle, isopropyle, n-butyle, isobutyle ou tert-butyle, ou dans lequel R5 = cyclopropyle, cyclobutyle, cyclopentyle ou (cycloalkyl en C3-C6)-(alkyl en C1-C2)-, ou dans lequel R5 = (alkyl en C.|-C2)-0-, (alkyl en CrC2)-S- ou OCF3, ou dans lequel R5 = (alkyl en Ci-C4)-0-méthyl-, HO-(alkyl en CrC2)-, ou dans lequel R5 = phényle ou phénylméthyl-, les résidus phényle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en CrC2)-, (alkyl en 0Γ02)-0-, CN, méthyl-S02-, ou dans lequel, R5 = R7R6N-, dans lequel R6 = H, (alkyl en C1-C4)-, cyclopropyle, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OH, méthoxy ou éthoxy, et R7 = H, méthyl-, éthyle, ou dans lequel R5 = hétéroaryle, hétéroaryl-(alkyl en CrC6)-, les résidus hétéroaryle étant choisis dans le groupe constitué par les résidus pyridin-2-yle, pyridin-3-yle, pyridin-4- yle, thiophén-2-yle, thiophén-3-yle, thiazol-2-yle, thiazol-4-yle, thiazol-5-yle, isothiazol-3-yle, isothiazol-4-yle, iso-thiazol-5-yle, pyrazol-3-yle, pyrazol-4-yle, imidazol-2-yle, imidazol-4-yle, pyrimidin-2-yle, pyrimidin-4-yle, pyrimidin- 5-yle, pyridazin-3-yle, pyridazin-4-yle, pyrazin-2-yle et pyrazin-3-yle, et les résidus hétéroaryle étant éventuellement substitués par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en C.|-C4)-, (alkyl en C.|-C4)-0-, CN, (alkyl en C.|-C2)-S02-, ou dans lequel R5 = un hétérocycle aliphatique, l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles morpholinyle, pipéridinyle, pyrrolidinyle, oxé-tanyle et tétrahydrofuranyle, tétrahydropyranyle, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 ou 2 substituants indépendamment choisis dans le groupe des substituants F, OFI, (alkyl en C.|-C2)-0- et (alkyl en C.|-C4)- ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma-ceutiquement acceptables. 7. Composé selon la revendication 1, dans lequel A est égal à phényle, le résidu phényle étant éventuellement substitué par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C1-C4)-, (alkyl en C1-C4)-0- et (alkyl en C1-C4)-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor; et X est égal à phényle, le groupe phényle étant éventuellement substitué par 1,2 ou 3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en CrC4)-, (alkyl en CrC4)-0-, (alkyl en C.|-C4)-S-, (alkyl en C1-C4)-0-C(0)- et (alkyl en -04)-002-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor; et R1 = R5-C(=0)- ou (alkyl en CrC6)-S02- ; R2 = H, (alkyl en Ci-C6)-, (cycloalkyl en C3-C6)- ; R3 = H, (alkyl en CrC4)- ; R4 = H, (alkyl en CrC4)-, ou dans lequel R3 et R4 forment ensemble un pont alkylène en C2-C3 ; R5 = H, (alkyl en C^Cg)-, (cycloalkyl en C3-C6)-, (alkyl en C^CgJ-O-, (alkyl en C^CgJ-S-, (alkyl en C.|-C6)-0-(alkyl en C1-C6)-, HO-(alkyl en C1-C6)-, (cycloalkyl en C3-C6)-(alkyl en C1-C6)-, (aryl en C6-C10)-, (aryl en C6-C10)-(alkyl en CrC6)-, R7R6N-, hétéroaryle, hétéroaryl-(alkyl en C-|-C6)-, hétérocycle aliphatique, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, et l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles morpholinyle, pipéridinyle, pyrrolidinyle et hétérocycles aliphatiques à 4 à 7 chaînons comprenant un atome d’oxygène, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 à 3 substituants indépendamment choisis dans le groupe des substituants F, OH, (alkyl en Ci-C6)-0-et (alkyl en C1-C6)-, et les résidus hétéroaryle étant des systèmes cycliques à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, et l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en C-|-C6)-, (alkyl en C.|-C6)-0-, CN, (alkyl en C.|-C2)-S02- ; R6 = H, (alkyl en C^Cg)-, (cycloalkyl en C3-C6)-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OH- ou (alkyl en C-)-C6)-0-, et un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor ; R7 = H, (alkyl en CrC6)-, un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor ; à condition que si R5 est un méthyle et R2, R3 et R4 sont égaux à H et A est égal à 4-fluorophényle, le résidu X ne soit pas un phényle, 4-fluorophényle, 4-chlorophényle, 4-méthylphényle, 4-méthoxyphényle, 4-acétoxyphényle, 2-chlorophényle, 3,4-dichlorophényle, et à condition que si R5 est un méthyle et R2, R3 et R4 sont égaux à H et X est un résidu phényle, le résidu A ne soit pas un phényle, 4-fluorophényle, 4-chlorophényle, 4-méthylphényle, 4-éthyloxyphényleou 3-trifluorométhylphényle, et à condition que si R5 est un méthyle et R2 est un méthyle et R3 et R4 sont égaux à H et A est égal à 4-fluorophényle, le résidu X ne soit pas un phényle. 8. Composé selon la revendication 7, dans lequel A = phényle, le résidu phényle étant substitué par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en CyC^j-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3 et (alkyl en C.|-C2)-S- ; X = phényle, le résidu phényle étant substitué par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C1-C4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3, (alkyl en C1-C2)-S-, (alkyl en C1-C2)-0-C(0)- et méthyl-S02- ; R1 = R5-C(=0)- ou méthyl-S02- ; R2 = H, (alkyl en C.|-C2)-, cyclopropyl- ; R3 = H, méthyl- ; R4 = H, méthyl- ; ou dans lequel R3 et R4 forment ensemble un pont éthylène ; et dans lequel R5 est égal à un hétéroaryle ou hétéroaryl-(alkyl en C-j-Cg)-, les résidus hétéroaryle étant choisis dans le groupe constitué par les résidus pyridin-2-yle, pyridin-3-yle, pyridin-4-yle, thiophén-2-yle, thiophén-3-yle, thiazol-2-yle, thiazol-4-yle, thiazol-5-yle, isothiazol-3-yle, isothiazol-4-yle, iso-thiazol-5-yle, pyrazol-3-yle, pyrazol-4-yle, imidazol-2-yle, imidazol-4-yle, pyrimidin-2-yle, pyrimidin-4-yle, pyrimidin- 5-yle, pyridazin-3-yle, pyridazin-4-yle, pyrazin-2-yle et pyrazin-3-yle, et ces résidus étant éventuellement substitués par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, méthyle, éthyle, méthoxy, éthoxy, CN, méthyl-S02-, ou dans lequel R5 est égal à H, ou dans lequel R5 est égal à cyclopropyle, cyclobutyle, cyclopentyle, cyclohexyle ou (cycloalkyl en C3-C6)-(alkyl en CrC2)-, ou dans lequel R5 est égal à (alkyl en C.|-C2)-0- ou (alkyl en C1-C2)-S-, ou dans lequel R5 est égal à (alkyl en C-pC^-O-méthyl-, HO-(alkyl en C.j-C2)-, ou dans lequel R5 est égal à phényl- ou phénylméthyl-, les résidus phényle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en CrC2)-, (alkyl en CrC2)-0-, CN, méthyl-S02-, et un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, ou dans lequel R5 est égal à R7R6N-, dans lequel R6 = H, (alkyl en C1-C4)-, cyclopropyl-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu hydroxy, méthoxy ou éthoxy, et R7 = H, méthyl-, éthyl-, ou dans lequel R5 est égal à un hétérocycle aliphatique, l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles oxétanyle, tétrahydrofuranyle, tétrahydropy-ranyle, morpholinyle, pipéridinyle, pyrrolidinyle, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 ou 2 substituants choisis dans le groupe des substituants F, OH, (alkyl en CrC2)-0- et (alkyl en C.|-C4)-, et un ou plusieurs atomes d’hydrogène des groupes alkyle pouvant être remplacés par du fluor ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma- ceutiquement acceptables. 9. Composé selon la revendication 7, dans lequel A = phényle, le résidu phényle étant substitué par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C1-C4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3 et (alkyl en C1-C2)-S- ; X = phényle, le résidu phényle étant substitué par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en CrC4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3, (alkyl en C1-C2)-S-, (alkyl en C1-C2)-0-C(0)- et méthyl-S02- ; R1 = R5-C(=0)- ; R2 = H, (alkyl en C.|-C2)-, cyclopropyl- ; R3 = H, méthyl- ; R4 = H, méthyl- ; ou dans lequel R3 et R4 forment ensemble un pont éthylène ; et dans lequel R5 est égal à alkyle en C2-C4, ou dans lequel R5 est égal à méthyle, à condition que si R5 est un méthyle et R2, R3 et R4 sont égaux à H et A est égal à 4-fluorophényle, le résidu X ne soit pas un phényle, 4-fluorophényle, 4-chlorophényle, 4-méthylphényle, 4-méthoxyphényle, 4-acétoxyphényle, 2-chlorophényle, 3,4-dichlorophényle ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma-ceutiquement acceptables. 10. Composé selon la revendication 1, dans lequel A = un aryle en C6-C10 ou un hétéroaryle à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C^Cg)-, (alkyl en C.|-C6)-0- et (alkyl en C^CgJ-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; X = un aryle en C6-C10 ou un hétéroaryle à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C^Cg)-, (alkyl en C^CgJ-O- et (alkyl en C^CgJ-S-, (alkyl en C.|-C6)-0-C(0)- et (alkyl en CrCg)-S02-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; R1 = R5-C(=0)- ou (alkyl en C1-C6)-S02- ; R2 = H, (alkyl en CrC6)-, (cycloalkyl en C3-C6)- ; R3 = H, (alkyl en CrC4)- ; R4 = H, (alkyl en CrC4)-; ou dans lequel R3 et R4 forment ensemble un pont alkylène en C2-C3 ; et dans lequel R5 est égal à un hétéroaryle ou hétéroaryl-(alkyl en CrC6)-, les résidus hétéroaryle étant des systèmes cycliques à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, et les résidus hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en C-j-Cg)-, (alkyl en C-|-Cg)-0-, CN, (alkyl en C-|-C2)-S02-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, à condition que si dans les composés de formule IA est un résidu 3-cyanophényle etX un résidu 2,4-difluorophényle, R5 ne soit pas un pyrimidin-4-yle, pyridin-2-yle, 1-méthylpyrazol-3-yle ou 1-méthyl-imidazol-2-yle, ou dans lequel R5 est un méthyle, à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et X est un résidu 2,4-difluorophényle, A ne soit pas un pyridin-3-yle, 2-fluorophényle, 3-fluorophényle, 4-fluorophényle, 3-cyanophényle, 3-méthoxyphényle, 3-trifluorométhoxyphényle, 2-fluoro-5-méthoxyphényle, et à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et X est un résidu 3-cyanophényle, A ne soit pas un résidu 4-fluorophényle, et à condition que si dans les composés de formule I R3 est un méthyle, R2 et R4 sont l’hydrogène et X est un résidu 2,4-difluorophényle, A ne soit pas un 4-fluorophényle, et à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et X est un phényle, A ne soit pas un phényle, 3-trifluorométhylphényle, 4-fluorophényle, 4-chlorophényle, 4-méthylphényle, 4-éthyloxyphényle, 4-acétoxyphényle, 4-méthylthiophényle, 2-thiophényle, et à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et A est un 4-fluorophényle, X ne soit pas un phényle, 2-chlorophényle, 3,4-dichlorophényle, 4-chlorophényle, 4-fluorophényle, 4-méthylphényle, 4-méthoxyphényle, 4-éthyloxyphényle, et à condition que si R5 est un méthyle et R2 est un méthyle et R3 et R4 sont égaux à H et A est égal à 4-fluorophényle, le résidu X ne soit pas un phényle, ou dans lequel R5 est égal à H, (alkyl en C2-C6)-, CF3, CF2H, CFH2, un ou plusieurs atomes d’hydrogène du alkyle pouvant être remplacés par du fluor, ou dans lequel R5 est égal à cycloalkyle en C3-C6 ou (cycloalkyl en C3-C6)-(alkyl en C1-C4)-, à condition que si dans les composés de formule I A est un résidu 3-cyanophényle et X un résidu 2,4-difluorophényle R5, ne soit pas un cyclopropyle, ou dans lequel R5 est égal à (alkyl en C-|-C4)-0- ou (alkyl en C-|-C4)-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, ou dans lequel R5 est égal à (alkyl en C1-C4)-0-(alkyl en C.|-C2)-, HO-(alkyl en C.|-C4)-, ou dans lequel R5 est égal à phényl-, phényl-(alkyl en C.,-C4)-, les résidus phényle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F,

Cl, Br, CF3, (alkyl en C-pCg)-, (alkyl en C.|-C6)-0-, CN, (alkyl en C.|-C2)-S02-, et un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, à condition que si dans les composés de formule I A est un résidu 3-cyanophényle et X un résidu 2,4-difluorophényle, R5 ne soit pas un 3-méthylsulfonylphényle ou 4-méthylsulfonylphényle, ou dans lequel R5 est égal à R7R6N-, dans lequel R6 = H, (alkyl en CrC4)-, cyclopropyl-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OH, méthoxy ou éthoxy, et R7 = H, (alkyl en CrC2)-, ou dans lequel R5 est égal à un hétérocycle aliphatique, l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles oxétanyle, tétrahydrofuranyle, tétrahydropy-ranyle, morpholinyle, pipéridinyle, pyrrolidinyle, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 ou 2 substituants choisis dans le groupe des substituants F, OH, (alkyl en C.|-C4)-0- et (alkyl en C1-C4)-, et un ou plusieurs atomes d’hydrogène des groupes alkyle pouvant être remplacés par du fluor, à condition que si dans les composés de formule I A est un résidu 3-cyanophényle et X un résidu 2,4-difluorophényle, R5 ne soit pas un 3-méthyloxétan-3-yle, tétrahydrofuran-3-yle, tétrahydropyran-4-yle ou 1 -méthylpipéridin-4-yle. 11. Composé selon la revendication 10, dans lequel A = phényle, pyridin-2-yle, pyridin-3-yle, pyridin-4-yle, thiophén-2-yle ou thiophén-3-yle, ces résidus étant éventuellement substitués par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en CrC4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3 et (alkyl en C1-C2)-S- ; X = phényle, le résidu phényle étant substitué par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C.|-C4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3, (alkyl en C.|-C2)-S-, (alkyl en 0^02)-0-0(0)- et méthyl-S02-, ou pyridin-2-yle, pyridin-3-yle, pyridin-4-yle, thiophén-2-yle, thiophén-3-yle, thiazol-2-yle, thiazol-4-yle, thiazol-5-yle, ces résidus étant éventuellement substitués par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en CrC4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3, (alkyl en C1-C2)-S-, (alkyl en C1-C2)-0-C(0)-et méthyl-S02- ; R1 = R5-C(=0)- ou (alkyl en C.|-C2)-S02- ; R2 = H, (alkyl en C.|-C2)-, cyclopropyl- ; R3 = H, (alkyl en CrC2)-; R4 = H, (alkyl en CrC2)- ; ou dans lequel R3 et R4 forment ensemble un pont éthylène ; et dans lequel R5 est égal à un hétéroaryle ou hétéroaryl-(alkyl en C.|-Cg)-, les résidus hétéroaryle étant choisis dans le groupe constitué par les résidus pyridin-2-yle, pyridin-3-yle, pyridin-4-yle, thiophén-2-yle, thiophén-3-yle, thiazol-2-yle, thiazol-4-yle, thiazol-5-yle, isothiazol-3-yle, isothiazol-4-yle, iso-thiazol-5-yle, pyrazol-3-yle, pyrazol-4-yle, imidazol-2-yle, imidazol-4-yle, pyrimidin-2-yle, pyrimidin-4-yle, pyrimidin- 5-yle, pyridazin-3-yle, pyridazin-4-yle, pyrazin-2-yle et pyrazin-3-yle, et ces résidus étant éventuellement substitués par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, méthyle, éthyle, méthoxy, éthoxy, CN, méthyl-S02-, à condition que si dans les composés de formule I A est un résidu 3-cyanophényle et X un résidu 2,4-difluorophényle, R5 ne soit pas un pyrimidin-4-yle, pyridin-2-yle, 1-méthylpyrazol-3-yle ou 1-méthyl-imidazol-2-yle, ou dans lequel R5 est un méthyle, à condition que si dans les composés deformule IR2, R3 et R4 sont l’hydrogène etX est un résidu 2,4-difluorophényle, A ne soit pas un pyridin-3-yle, 2-fluorophényle, 3-fluorophényle, 4-fluorophényle, 3-cyanophényle, 3-méthoxyphé-nyle, 3-trifluorométhoxyphényle, 2-fluoro-5-méthoxyphényle, et à condition que si dans les composés de formule I R2, R3 et R4sont l’hydrogène et X est un résidu 3-cyanophényle, A ne soit pas un résidu 4-fluorophényle, et à condition que si dans les composés de formule I R3 est un méthyle, R2 et R4 sont l’hydrogène et X est un résidu 2,4-difluorophényle, A ne soit pas un 4-fluorophényle, et à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et X est un phényle, A ne soit pas un phényle, 3-trifluorométhylphényle, 4-fluorophényle, 4-chlorophényle, 4-méthyl-phényle, 4-éthoxyphényle, 2-thiophényle, 4-méthylthiophényle, et à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et A est un 4-fluorophényle, X ne soit pas un 2-chlorophényle, 3,4-dichlorophényle, 4-chlorophényle, 4-fluorophényle, 4-méthylphényle, 4-méthoxy-phényle, 4-éthoxyphényle ou 4-acétoxyphényle, ou dans lequel R5 est égal à H, (alkyl en C2-C4)-, CF3, ou dans lequel R5 est égal à cyclopropyle, cyclobutyle, cyclopentyle, cyclohexyle ou (cycloalkyl en C3-C6)-(alkyl en CVC2)-, à condition que si dans les composés de formule IA est un résidu 3-cyanophényle etX un résidu 2,4-difluorophényle, R5 ne soit pas un cyclopropyle, ou dans lequel R5 est égal à (alkyl en Ci-C2)-0- ou (alkyl en C.|-C2)-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, ou dans lequel R5 est égal à (alkyl en C1-C4)-0-méthyl-, HO-(alkyl en C^-C2)-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, ou dans lequel R5 est égal à phényl-, phényl-(alkyl en CVC2)-, les résidus phényle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en Ci-C2)-, (alkyl en CrC2)-0-, CN, méthyl-S02-, et un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, à condition que si dans les composés de formule IA est un résidu 3-cyanophényle etX un résidu 2,4-difluorophényle, R5 ne soit pas un 3-méthylsulfonylphényle ou 4-méthylsulfonylphényle, ou dans lequel R5 est égal à R7R6N-, dans lequel R6 = H, (alkyl en C1-C4)-, cyclopropyl-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu hydroxy, méthoxy ou éthoxy, et R7 = H, méthyl-, éthyl-, ou dans lequel R5 est égal à un hétérocycle aliphatique, l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles oxétanyle, tétrahydrofuranyle, tétrahydropy-ranyle, morpholinyle, pipéridinyle, pyrrolidinyle, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 ou 2 substituants choisis dans le groupe des substituants F, OH, (alkyl en C.,-C2)-0- et (alkyl en C-j-C^-, et un ou plusieurs atomes d’hydrogène des groupes alkyle pouvant être remplacés par du fluor, à condition que si dans les composés de formule IA est un résidu 3-cyanophényle etX un résidu 2,4-difluorophényle, R5 ne soit pas un 3-méthyloxétan-3-yle, tétrahydrofuran-3-yle, tétrahydropyran-4-yle ou 1-méthylpipéridin-4-yle ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma-ceutiquement acceptables. 12. Composé selon la revendication 10, dans lequel A est égal à phényle, le résidu phényle étant éventuellement substitué par 1,2 ou 3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en CrC4)-, (alkyl en Ci-C4)-0- et (alkyl en CrC4)-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; et X est égal à phényle, le groupe phényle étant éventuellement substitué par 1,2 ou 3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C1-C4)-, (alkyl en ¢^¢4)-0-, (alkyl en C1-C4)-S-, (alkyl en Ci-C4)-0-C(0)- et (alkyl en C1-C4)-S02-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; et R1 = R5-C(=0)- ou (alkyl en C.|-C6)-S02- ; R2 = H, (alkyl en CrC6)-, (cycloalkyl en C3-C6)- ; R3 = H, (alkyl en CrC4)- ; R4 = H, (alkyl en CrC4)-, ou dans lequel R3 et R4 forment ensemble un pont alkylène en C2-C3 ; et dans lequel R5 est égal à un hétéroaryle ou hétéroaryl-(alkyl en C^Cg)-, les résidus hétéroaryle étant des systèmes cycliques à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, et les résidus hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en C-pCg)-, (alkyl en C.|-C6)-0-, CN, (alkyl en C.|-C2)-S02-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, à condition que si dans les composés de formule I A est un résidu 3-cyanophényle et X un résidu 2,4-difluorophényle, R5 ne soit pas un pyrimidin-4-yle, pyridin-2-yle, 1-méthylpyrazol-3-yle ou 1-méthy-limidazol-2-yle, ou dans lequel R5 est un méthyle, à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et X est un résidu 2,4-difluorophényle, A ne soit pas un pyridin-3-yle, 2-fluorophényle, 3-fluorophényle, 4-fluorophényle, 3-cyanophényle, 3-méthoxyphényle, 3-trifluorométhoxyphényle, 2-fluoro-5-méthoxyphényle, et à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et X est un résidu 3-cyanophényle, A ne soit pas un résidu 4-fluorophényle, et à condition que si dans les composés de formule I R3 est un méthyle, R2 et R4 sont l’hydrogène et X est un résidu 2,4-difluorophényle, A ne soit pas un 4-fluorophényle, et à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et X est un phényle, A ne soit pas un phényle, 3-trifluorométhylphényle, 4-fluorophényle, 4-chlorophényle, 4-méthyl-phényle, 4-éthyloxyphényle, 4-méthylthiophényle, 2-thiophényle, et à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et A est un 4-fluorophényle, X ne soit pas un phényle, 2-chlorophényle, 3,4-dichlorophényle, 4-chlorophényle, 4-fluorophényle, 4-méthylphényle, 4-méthoxyphényle, 4-éthyloxyphényle, 4-acétoxyphényle, et à condition que si R5 est un méthyle et R2 est un méthyle et R3 et R4 sont égaux à H et A est égal à 4-fluorophényle, le résidu X ne soit pas un phényle, et ou dans lequel R5 est égal à H, (alkyl en C2-C6)-, CF3, CF2H, CFH2, un ou plusieurs atomes d’hydrogène du résidu alkyle pouvant être remplacés par du fluor, ou dans lequel R5 est égal à cycloalkyle en C3-C6 ou (cycloalkyl en C3-C6)-(alkyl en C.|-C4)-, à condition que si dans les composés de formule I A est un résidu 3-cyanophényle et X un résidu 2,4-difluorophényle, R5 ne soit pas un cyclopropyle, ou dans lequel R5 est égal à (alkyl en C.|-C4)-0- ou (alkyl en C1-C4)-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, ou dans lequel R5 est égal à (alkyl en C1-C4)-0-(alkyl en C.,^)-, HO-(alkyl en C.|-C4)-, ou dans lequel R5 est égal à phényl-, phényl-(alkyl en C.|-C4)-, les résidus phényle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F,

Cl, Br, CF3, (alkyl en CrC6)-, (alkyl en C1-C6)-0-, CN, (alkyl en C1-C2)-S02-, et un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, à condition que si dans les composés de formule IA est un résidu 3-cyanophényle etX un résidu 2,4-difluorophényle, R5 ne soit pas un 3-méthylsulfonylphényle ou 4-méthylsulfonylphényle, ou dans lequel R5 est égal à R7R6N-, dans lequel R6 = H, (alkyl en C1-C4)-, cyclopropyl-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OH, méthoxy ou éthoxy, et R7 = H, (alkyl en ^-ΰ2)-, ou dans lequel R5 est égal à un hétérocycle aliphatique, l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles oxétanyle, tétrahydrofuranyle, tétrahydropy-ranyle, morpholinyle, pipéridinyle, pyrrolidinyle, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 ou 2 substituants choisis dans le groupe des substituants F, OH, (alkyl en Ci-C4)-0- et (alkyl en Ci-C4)-, et un ou plusieurs atomes d’hydrogène des groupes alkyle pouvant être remplacés par du fluor, à condition que si dans les composés de formule IA est un résidu 3-cyanophényle etX un résidu 2,4-difluorophényle, R5 ne soit pas un 3-méthyloxétan-3-yle, tétrahydrofuran-3-yle, tétrahydropyran-4-yle ou 1-méthylpipéridin-4-yle ; R6 = H, (alkyl en C^Cg)-, (cycloalkyl en C3-C6)-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OH- ou (alkyl en C1-C6)-0-, et un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor ; R7 = H, (alkyl en CrC6)-, un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor. 13. Composé selon la revendication 12, dans lequel A = phényle, le résidu phényle étant substitué par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, ON, (alkyl en C1-C4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3 et (alkyl en CrC2)-S- ; X = phényle, le résidu phényle étant substitué par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, ON, (alkyl en C.|-C4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3, (alkylenC.|-C2)-S-,(alkylenC.|-C2)-0-C(0)-etméthyl-S02- ; R1 = R5-C(=0)- ou méthyl-S02- ; R2 = H, (alkyl en C.|-C2)-, cyclopropyl- ; R3 = H, méthyl- ; R4 = H, méthyl- ; ou dans lequel R3 et R4 forment ensemble un pont éthylène ; et dans lequel R5 est égal à un hétéroaryle ou hétéroaryl-(alkyl en C.|-C6)-, les résidus hétéroaryle étant choisis dans le groupe constitué par les résidus pyridin-2-yle, pyridin-3-yle, pyridin-4-yle, thiophén-2-yle, thiophén-3-yle, thiazol-2-yle, thiazol-4-yle, thiazol-5-yle, isothiazol-3-yle, isothiazol-4-yle, iso-thiazol-5-yle, pyrazol-3-yle, pyrazol-4-yle, imidazol-2-yle, imidazol-4-yle, pyrimidin-2-yle, pyrimidin-4-yle, pyrimidin-5-yle, pyridazin-3-yle, pyridazin-4-yle, pyrazin-2-yle et pyrazin-3-yle, et ces résidus étant éventuellement substitués par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, méthyle, éthyle, méthoxy, éthoxy, CN, méthyl-S02-, à condition que si dans les composés de formule IA est un résidu 3-cyanophényle etX un résidu 2,4-difluorophényle, R5 ne soit pas un pyrimidin-4-yle, pyridin-2-yle, 1-méthylpyrazol-3-yle ou 1-méthylimidazol-2-yle, ou dans lequel R5 est un méthyle, à condition que si dans les composés deformule IR2, R3 et R4 sont l’hydrogène et X est un résidu 2,4-difluorophényle, A ne soit pas un pyridin-3-yle, 2-fluorophényle, 3-fluorophényle, 4-fluorophényle, 3-cyanophényle, 3-méthoxyphé-nyle, 3-trifluorométhoxyphényle, 2-fluoro-5-méthoxyphényle, et à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et X est un résidu 3-cyanophényle, A ne soit pas un résidu 4-fluorophényle, et à condition que si dans les composés de formule I R3 est un méthyle, R2 et R4 sont l’hydrogène et X est un résidu 2,4-difluorophényle, A ne soit pas un 4-fluorophényle, et à condition que si dans les composés de formule I R2, R3 et R4 sont l’hydrogène et A est un 4-fluorophényle, X ne soit pas un 2-chlorophényle, 3,4-dichlorophényle, 4-chlorophényle, 4-fluorophényle, 4-méthylphényle, 4-méthoxy-phényle, 4-éthyloxyphényle ou 4-acétoxyphényle, ou dans lequel R5 est égal à H, (alkyl en C2-C4)-, CF3, ou dans lequel R5 est égal à cyclopropyle, cyclobutyle, cyclopentyle, cyclohexyle ou (cycloalkyl en C3-C6)-(alkyl en C1-C2)-, à condition que si dans les composés de formule IA est un résidu 3-cyanophényle et X un résidu 2,4-difluorophényle, R5 ne soit pas un cyclopropyle, ou dans lequel R5 est égal à (alkyl en C-j-C^-O- ou (alkyl en C.|-C2)-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, ou dans lequel R5 est égal à (alkyl en C1-C4)-0-méthyl-, HO-(alkyl en CrC2)-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, ou dans lequel R5 est égal à phényl-, phényl-(alkyl en CA-C2)-, les résidus phényle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F,

Cl, Br, CF3, (alkyl en C1-C2)-, (alkyl en C1-C2)-0-, CN, méthyl-S02-, et un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor, à condition que si dans les composés de formule IA est un résidu 3-cyanophényle et X un résidu 2,4-difluorophényle, R5 ne soit pas un 3-méthylsulfonylphényle, 4-méthylsulfonylphényle, ou dans lequel R5 est égal à R7R6N-, dans lequel R6 = H, (alkyl en C.|-C4)-, cyclopropyl-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OFI, méthoxy ou éthoxy, et R7 = H, méthyl-, éthyl-, ou dans lequel R5 est égal à un hétérocycle aliphatique, l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles oxétanyle, tétrahydrofuranyle, tétrahydropyranyle, morpholinyle, pipéridinyle, pyrrolidinyle, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 ou 2 substituants choisis dans le groupe des substituants F, OH, (alkyl en Ci-C2)-0- et (alkyl en C1-C4)-, et un ou plusieurs atomes d’hydrogène des groupes alkyle pouvant être remplacés par du fluor, à condition que si dans les composés de formule IA est un résidu 3-cyanophényle etX un résidu 2,4-difluorophényle, R5 ne soit pas un 3-méthyloxétan-3-yle, tétrahydrofuran-3-yle, tétrahydropyran-4-yle ou 1-méthylpipéridin-4-yle ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma-ceutiquement acceptables. 14. Composé selon la revendication 10, dans lequel A = phényle, le résidu phényle étant substitué par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C.|-C4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3 et (alkyl en C.|-C2)-S- ; X = phényle, le résidu phényle étant substitué par 1 ou 2 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C1-C4)-, CF3, CF2H, CFH2, méthoxy, éthoxy, OCF3, (alkylen C1-C2)-S-, (alkyl en C1-C2)-0-C(0)-et méthyl-S02- ; R1 = R5-C(=0)- ; R2 = H, (alkyl en C1-C2)-, cyclopropyl- ; R3 = H, méthyl- ; R4 = H, méthyl- ; ou dans lequel R3 et R4 forment ensemble un pont éthylène ; et dans lequel R5 est égal à (alkyl en C2-C4)- ; et/ou une forme stéréoisomère du composé de formule I et/ou mélanges de ces formes, et/ou leurs sels pharma-ceutiquement acceptables. 15. Composé selon la revendication 1 choisi dans le groupe constitué par l’isopropylamide de l’acide 3-(3-cyanophényl)- 1- (2,4-difluorobenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridine-5-carboxylique ; l’éthylamide de l’acide 3-(4-fluoro-phényl)-1-[(S)-1-(4-fluorophényl)éthyl]-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridine-5-carboxylique ; l’éthylamide de l’acide 3-(4-fluorophényl)-1-[(R)-1-(4-fluorophényl)éthyl]-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridine-5-carboxylique ; le tert-butylamide de l’acide 3-(4-fluorophényl)-1-[(S)-1-(4-fluorophényl)éthyl]-1,4,6,7-tétrahydropyrazolo[4,3-c]py-ridine-5-carboxylique ; l’éthylamide de l’acide 3-(3-cyanophényl)-1-(2,4-difluorobenzyl)-1,4,6,7-tétrahydropyrazo-lo[4,3-c]pyridine-5-carboxylique ; le méthylamide de l’acide 3-(3-cyanophényl)-1-(2,4-difluorobenzyl)-1,4,6,7-tétra-hydropyrazolo[4,3-c]pyridine-5-carboxylique ; la {3-(4-fluorophényl)-1-[(S)-1-(4-fluorophényl)éthyl]-1,4,6,7-tétrahy-dropyrazolo[4,3-c]pyridin-5-yl}-morpholin-4-ylméthanone ; la {3-(4-fluorophényl)-1-[(S)-1-(4-fluorophényl)éthyl]- 1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl}-((S)-3-hydroxypyrrolidin-1-yl)méthanone ; le diméthylamide de l’acide 3-(3-cyanophényl)-1-(2,4-difluorobenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridine-5-carboxylique ; le (2-hy-droxyéthyl)méthylamide de l’acide 3-(3-cyanophényl)-1-(2,4-difluorobenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyri-dine-5-carboxylique ; le 2-[5-acétyl-1-(2,4-difluorobenzyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]isonicotinonitrile ; le 6-[5-acétyl-1-(2,4-difluorobenzyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]pyridine- 2- carbonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-(2-hydroxyacétyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3- yl]benzonitrile ; le 3-[5-acétyl-1-(2,4-difluorobenzyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; la 1 -[1 -(2,4-difluorobenzyl)-3-(3-méthylpyridin-2-yl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(4-méthoxypyridin-2-yl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2-méthylthiazol-4-ylméthyl)-3-(3-trifluorométhylphényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-thiazol-2-ylméthyl-3-(3-trifluorométhylphényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5- yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-thiophén-2-yl-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(5-chlorothiophén-2-ylméthyl)-3-m-tolyl-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(5-chlorothiophén-2-ylméthyl)-3-(3-trifluorométhylphényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; le 3-[5-acétyl-1-(5-chlorothiophén-2-ylméthyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; la 1-[3-(3-chlorophényl)-1-(5-chlorothiophén-2-ylméthyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[3-(5-chlorothiophén-2-yl)-1-(2,4-difluorobenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la I- [1-(2,4-difluorobenzyl)-3-thiophén-3-yl-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; le 4-[5-acétyl- 3-(3-trifluorométhylphényl)-4,5,6,7-tétrahydropyrazolo[4,3-c]pyridin-1-ylméthyl]benzonitrile ; le 3-{5-acétyl-1-[1-(4-fluorophényl)éthyl]-4,5,6,7-tétrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl}benzonitrile ; la 1-[1-[cyclopropyl-(4-fluoro-phényl)méthyl]-3-(4-fluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2,4-difluoroben-zyl)-3-(3-trifluorométhoxyphényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2,6-difluoroben-zyl)-3-(4-fluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-{3-(4-fluorophényl)-1-[1-(4-fluorophényl)éthyl]-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl}éthanone ; la 1-[3-(4-fluorophényl)-1-(4-trifluoro-méthylbenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(3-méthoxy-phényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[3-(4-fluorophényl)-1-(3-trifluorométhylben-zyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-[1-(4-fluorophényl)éthyl]-3-(3-trifluorométhoxy-phényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(4-fluoro-3-méthoxy-phényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; le 3-[5-acétyl-1-(2,5-difluorobenzyl)-4,5,6,7-tétra-hydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; la 1-[1-(2,4-difluorobenzyl)-3-m-tolyl-1,4,6,7-tétrahydropyrazo-lo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(6-chloropyridin-3-ylméthyl)-3-(3-trifluorométhylphényl)-1,4,6,7-tétrahydro-pyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[3-(3-chlorophényl)-1-(4-fluoro-2-méthylbenzyl)-1,4,6,7-tétrahydropyra-zolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2-fluorobenzyl)-3-m-tolyl-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2-méthoxybenzyl)-3-(3-trifluorométhylphényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[3-(3-chlorophényl)-1-(3-méthoxybenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5- yl]éthanone ; la 1-[1-(4-chloro-3-fluorobenzyl)-3-(4-fluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5- yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(2-fluoro-5-méthoxyphényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; le 5-[5-acétyl-1-(2,4-difluorobenzyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]-2- fluorobenzonitrile ; la 1-[1-(2,4-difluorobenzyl)-3-(3-fluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5- yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(4-trifluorométhylphényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-[(R)-1-(4-chlorophényl)propyl]-3-(4-fluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-[(S)-1-(4-chlorophényl)propyl]-3-(4-fluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2-fluoro-4-méthylbenzyl)-3-(3-trifluorométhylphényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(4-chloropyridin-3-ylméthyl)-3-(3-trifluorométhylphényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]py-ridin-5-yl]éthanone ; la 1-[1-(3-méthylpyridin-2-ylméthyl)-3-(3-trifluorométhylphényl)-1,4,6,7-tétrahydropyrazo-lo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(4-fluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyri-din-5-yl]éthanone ; la 1-[1-(4-fluorobenzyl)-3-(6-trifluorométhylpyridin-2-yl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyri-din-5-yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(4-trifluorométhylpyridin-2-yl)-1,4,6,7-tétrahydropyrazolo[4,3-c]py-ridin-5-yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(6-trifluorométhylpyridin-2-yl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[3-(4-bromopyridin-2-yl)-1-(2,4-difluorobenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyri-din-5-yl]éthanone ; la 1-[3-(2-bromopyridin-4-yl)-1-(2,4-difluorobenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[3-(5-bromopyridin-3-yl)-1-(2,4-difluorobenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; le 3-[11-acétyl-5-(2,4-difluorobenzyl)-4,5,11-triazatricyclo[6.2.1,02,6]undéca-2(6),3-dién-3-yl]benzonitrile ; la 1-[5-(2,4-difluorobenzyl)-3-(4-fluorophényl)-4,5,11-triazatricyclo[6.2.1.02,6]undéca-2(6),3-dién- II- yl]éthanone ; la 1-[1-(6-chloropyridin-3-ylméthyl)-3-m-tolyl-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5- yl]éthanone ; la 1-[1-(4-méthoxypyridin-2-ylméthyl)-3-(3-trifluorométhylphényl)-1,4,6,7-tétrahydropyrazolo[4,3- c]pyridin-5-yl]éthanone ; la 1-[1-(4-chloropyridin-3-ylméthyl)-3-m-tolyl-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(3-méthoxypyridin-2-ylméthyl)-3-(3-trifluorométhylphényl)-1,4,6,7-tétrahydropyrazolo[4,3- c]pyridin-5-yl]éthanone ; la 1-[3-(3-chlorophényl)-1-(3-méthylpyridin-2-ylméthyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-[1-(4-fluorophényl)éthyl]-3-(6-trifluorométhylpyridin-2-yl)-1 ,4,6,7-tétrahydropyrazo-lo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(6-méthylpyridin-2-yl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[3-(6-bromopyridin-2-yl)-1-(2,4-difluorobenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyri-din-5-yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(4-méthylpyridin-2-yl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 1-[1-(2,4-difluorobenzyl)-3-(6-méthoxypyridin-2-yl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5- yl]éthanone ; la 1-[3-(6-chloro-5-méthoxypyridin-2-yl)-1-(2,4-difluorobenzyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyri-din-5-yl]éthanone ; le 3-[1-(2,4-difluorobenzyl)-5-(3-méthyloxétane-3-carbonyl)-4,5,6,7-tétrahydro-1H-pyrazo-lo[4,3-c]pyridin-3-yl]benzonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-isobutyryl-4,5,6,7-tétrahydro-1H-pyrazolo[4,3-c]py-ridin-3-yl]benzonitrile ; le 3-[5-cyclopropanecarbonyl-1-(2,4-difluorobenzyl)-4,5,6,7-tétrahydro-1h-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; le 3-[5-(2-tert-butoxyacétyl)-1-(2,4-difluorobenzyl)-4,5,6,7-tétrahydro-1H-pyrazolo[4,3- c]pyridin-3-yl]benzonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-(3-méthanesulfonylbenzoyl)-4,5,6,7-tétrahydro-1 H-pyra-zolo[4,3-c]pyridin-3-yl]benzonitrile ; la [1-benzyl-3-(4-fluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]-(4-fluorophényl)méthanone ; la [1-benzyl-3-(4-tluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]-(4-méthoxyphényl)méthanone ; la [1-benzyl-3-(4-fluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]-phénylméthanone ; le 3-[5-cyclobutanecarbonyl-1-(2,4-difluorobenzyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]py-ridin-3-yl]benzonitrile ; le 3-[5-cyclopentanecarbonyl-1-(2,4-difluorobenzyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-(4-méthanesulfonylbenzoyl)-4,5,6,7-tétrahydro-1 H-pyra-zolo[4,3-c]pyridin-3-yl]benzonitrile ; le3-[1-(2,4-difluorobenzyl)-5-(tétrahydropyrane-4-carbonyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-(tétrahydrofurane-3-carbonyl)-4,5,6,7-té-trahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-(2-méthoxyacétyl)-4,5,6,7-tétra-hydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-(2,2-diméthylpropionyl)-4,5,6,7-té-trahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; le3-[1-(2,4-difluorobenzyl)-5-propionyl-4,5,6,7-tétrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-((S)-2-hydroxypropionyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; la 1-[1-benzyl-3-(4-fluorophényl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyri-din-5-yl]-2-phényléthanone ; le 3-[5-butyryl-1-(2,4-difluorobenzyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-(pyridine-2-carbonyl)-4,5,6,7-tétrahydro-1H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; le composé avec de l’acide trifluoroacétique ; le 3-[1-(2,4-difluorobenzyl)-5-(3-fluoropyridine-4-car-bonyl)-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; le composé avec de l’acide trifluoroacétique ; le 3-[1-(2,4-difluorobenzyl)-5-(pyrimidine-4-carbonyl)-4,5,6,7-tétrahydro-1H-pyrazolo[4,3-c]pyridin-3- yl]benzonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-(3-méthyl-3H-imidazole-4-carbonyl)-4,5,6,7-tétrahydro-1H-pyrazo-lo[4,3-c]pyridin-3-yl]benzonitrile ; le 3-[1-(2,4-difluorobenzyl)-5-(1-méthyl-1 H-pyrazole-3-carbonyl)-4,5,6,7-tétra-hydro-1 H-pyrazolo[4,3-c]pyridin-3-yl]benzonitrile ; l’ester éthylique de l’acide 3-(3-cyanophényl)-1-(2,4-difluoroben-zyl)-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridine-5-carboxylique ; la 1-[1-(2,4-difluorobenzyl)-3-(4-fluorophényl)-6-mé-thyl-1,4,6,7-tétrahydropyrazolo[4,3-c]pyridin-5-yl]éthanone ; la 3-(4-fluorophényl)-1-[(R)-1-(4-fluorophényl)éthyl]-5-méthanesulfonyl-4,5,6,7-tétrahydro-1 H-pyrazolo[4,3-c]pyridine ; la 3-(4-fluorophényl)-1-[(S)-1-(4-fluorophé-nyl)éthyl]-5-méthanesulfonyl-4,5,6,7-tétrahydro-1H-pyrazolo[4,3-c]pyridine ; leurs formes stéréoisomères, et/ou leurs sels pharmaceutiquement acceptables. 16. Médicament comprenant un composé de formule I et/ou son sel pharmaceutiquement acceptable selon l’une quelconque des revendications 1 à 15. 17. Composé de formule I ou composé selon l’une quelconque des revendications 1 à 15 et/ou leurs sels pharmaceutiquement acceptables destinés à être utilisés dans le traitement ou la prévention de maladies à médiation par le canal TASK-1, dans lesquels

A = un aryle en C6-C10 ou un hétéroaryle à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C^Cg)-, (alkyl en C.|-C6)-0- et (alkyl en C.|-C6)-S-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; X = un aryle en C6-C10 ou un hétéroaryle à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CN, (alkyl en C1-C6)-, (alkyl en CrC6)-0- et (alkyl en C-|-C6)-S-, (alkyl en C1-C6)-0-C(0)- et (alkyl en c1-c6)-so2-, un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; R1 = R5-C(=0)- ou (alkyl en C.|-C6)-S02- ; R2 = H, (alkyl en C1-C6)-, (cycloalkyl en C3-C6)- ; R3 = H, (alkyl en CrC4)- ; R4 = H, (alkyl en CrC4)-, ou dans lequel R3 et R4 forment ensemble un pont alkylène en C2-C3 ; R5 = (alkyl en C.|-C6)-, (cycloalkyl en C3-C6)-, (alkyl en C.|-C6)-0-, (alkyl en C.|-C6)-S-, (alkyl en C.|-C6)-0-(alkyl en C^Cg)-, HO-(alkyl en C^Cg)-, (cycloalkyl en C3-C6)-(alkyl en 0Γ06)-, (aryl en C6-C10)-, (aryl en C6-C10)-(alkyl en C^Cg)-, R7R6N-, hétéroaryle, hétéroaryl-(alkyl en C^Cg)-, hétérocycle aliphatique, l’hétérocycle aliphatique étant choisi dans le groupe des hétérocycles morpholinyle, pipéridinyle, pyrrolidinyle et hétérocycles aliphatiques à 4 à 7 chaînons comprenant un atome d’oxygène, et l’hétérocycle aliphatique pouvant être éventuellement substitué par 1 à 3 substituants indépendamment choisis dans le groupe des substituants F, OH, (alkyl en C.|-Cg)-0-et (alkyl en C1-C6)-, et les résidus hétéroaryle étant des systèmes cycliques à cinq ou six chaînons, comprenant 1-3 hétéroatomes choisis dans le groupe des hétéroatomes N, O et S, et l’aryle et l’hétéroaryle étant éventuellement substitués par 1-3 résidus indépendamment choisis parmi les résidus F, Cl, Br, CF3, (alkyl en C^Cg)-, (alkyl en C^CgJ-O-, CN, (alkyl en Ci-C2)-S02-, et un ou plusieurs atomes d’hydrogène des entités alkyle pouvant être remplacés par du fluor ; R6 = H, (alkyl en CrC6)-, (cycloalkyl en C3-C6)-, un atome d’hydrogène du groupe alkyle pouvant être remplacé par un résidu OH- ou (alkyl en C^CgJ-O-, et un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor ; R7 = H, (alkyl en C1-C6)-, un ou plusieurs atomes d’hydrogène du groupe alkyle pouvant être remplacés par du fluor. 18. Composé de formule I et/ou sel pharmaceutiquement acceptable de celui-ci selon l’une quelconque des revendications 1 à 15, médicament selon la revendication 16 ou composé selon la revendication 17 destinés à être utilisés dans le traitement ou la prévention d’arythmies, en particulier de tachyarythmies auriculaires, defibrillation auriculaire et de flutter auriculaire. 19. Composé de formule I et/ou sel pharmaceutiquement acceptable de celui-ci selon l’une quelconque des revendications 1 à 15, médicament selon la revendication 16 ou composé selon la revendication 17 destinés à être utilisés dans le traitement ou la prévention de troubles respiratoires liés au sommeil, d’apnées du sommeil centrales et obstructives, du syndrome de résistance des voies aériennes supérieures, de la respiration de Cheyne-Stokes, du ronflement, de la pertubation de la fonction respiratoire centrale, de la mort subite de l’enfant, de l’hypoxie et l’apnée postopératoires, de troubles respiratoires liés aux muscles, de troubles respiratoires après ventilation mécanique prolongée (sevrage), de troubles respiratoires pendant l’adaptation en haute montagne, de troubles respiratoires aigus et, de troubles pulmonaires chroniques avec hypoxie et hypercapnie, d’une bronchopneumopathie chronique obstructive (BPCO) et du syndrome obésité-hypoventilation ; ou destinés à être utilisés comme stimulant respiratoire pour le traitement ou la prévention d’une dépression respiratoire associée à une anesthésie ou à des sédations procédurales pour de petites interventions ou pour de fins de diagnostic, ou destinés à être utilisés comme stimulant respiratoire pour le traitement ou la prévention d’une dépression respiratoire par des opioïdes en traitement de douleur chronique, en particulier dans le cancer ou les soins palliatifs ou les sédations procédurales, et/ou pour le sevrage de la ventilation mécanique prolongée ; ou destinés à être utilisés dans le traitement ou la prévention de la sclérose en plaques et de troubles inflammatoires ou dégénératifs du système nerveux central.

Claims (12)

1. SZABADALMI IGÉNYPONTOK L fîp" (I) álíaláhos fejtei ÿjsg'f&ïi vggyület allét a Mph#eo

   A jeles#|^ (C;iA^io>ariLvag^ egv $ pagl’ i^siô .Ée^ïo^AÉcsQpqîÎ, $n$gfy |-3 hstepalomot tartalmaz N, ö vagy f körébŐkválááztvá, ahoi a* ári|- és fbproariíesoprt aábtt esetbeo 1.-3 Myettesltétt egymástól függetlenül R Ci, Br,. GM, ICi^l-alkiL, |Cj 43s}-aîkiAb es IGí^^siyi-S^éfort Miéből választva, ahol m alkiksoptAk egy vagy ÄL IbdMgáeorap iaorattSBial bslyéítssiíett lehet;; X jeleíttlse: ^Cö~C::e|-sr·)- vagy egy S vagy ő-tagé hetaroaribesoport, ams!y: J.W3· Seteroaiomot tm~ Ättaz N, Ö vagy $. köréből választva, ahol az: aril- és beteroaril-esöpöA átlőtt esetbea 1-3 esspcsrttal helyeoeshett egymástól Ríggetleeü! Fi, Ci Be, CM, (CrCï-XaMÉ, (C3-C^)-aikii-0- es (Cr€s)'Sjkll-S-csopoí1 köréből választva, ahöl az AfkilöSöpösi^í egy vagy több ydtogénatömáa fctmtommal jtelyeöesbeti lebst; Ri jelentése ES-C(~0}- vagy (Ci-Cftl-si&amp;sLiÖs-esögöri; R2:jelentése H, (CrAralkü-, (CrC<.)-dk'oatkfhc8opo«s R3 jelentése II, CCrC4)-aíkH-csoport; R4 jelentése H, (CrOFalkil-esoport; vagy áltól R3 és R4 együtt sgy (CrCijÉ'Sfkiléo látó- alkot; RS jelemé;« H, (CrCihaikik ps-G0}-elkloa|k;ik,: íCr€i|*&amp;ÍRibO-y C€Ok)-aM!-S-, ÍCrCd-aMb Ö:-|C:j-C4)-aliil-, HÖ-CCh-eiMkik (Cf-CiVclkloalkäKCj-CiO-alkU-, (€*€,0>ar»k |€β-€;0>~Μ1-pii-Ctil-alkil-, R7:R#t~, hdeÄrik hetsröarll-|CrC0-alki-, alifás ^terocikhis* alto! az alkllesopoAok egy vágy több felfegéoálöitp lleotótommal ielyetteslÄ lebeg: és .áhöl-az alifás heÍPrüoikltts morlbfMf··,: p|pm4M|. #i 4-2 tagé alifás beteröéikkss koré* bői választott, áspefy tptalrnaz egy ozlgétt betematsmoi ék aboi az alifás beteroe&amp;los adott esetkep 1-3 Csoporttal feelyeaesfteä lehetegymástól äiggetfeoül F,. OH-, {C'ï-iXy-afkU-O- ès t€rC0-Äif-esöpti köréből választva, és ahoi a áfföroaífj matadékoh 5 ;vagÿ .gySrô módszerek, «elyek î~3 heteroatomot tartalmaznak Nf O vagy S köréből választva, és àho! m%&amp;~ totoyupj&amp;mapm adott «satte i^-CKÿMWtf helyettesített egymástól függetlenül ïh Ci Br, CP.?-, (Cj-CVi-alkitt, (€VQi-dkïK>-€bk (CV€:0"alkil~$Oresopert köréből választva; M jelentése 1:¾ fC?-C^aittkiCr ahol ÿz. OH- vagy (CrCeHlkB-O-esaptttak es ahöl az alkileSepett egy vagy Ä hiérogéoáseatk:^^ Miét; feVJelentésefî, CCs4iy^alMl~asöp<ttt; iiæ alkílesöpöft egy «If több itéreglnatorafe fluoratommal hely^tealtetUehet, é$X-agy az (1) áttafánns k%Mi vegyÄ ^mtmmmwéa^ és/vagy ezen alakok keverékei gyögy--é$xsdk:g elfogadható sóik és műd a feltételiek hogy ha R5 jelentése roeticsoport és RI R3 cs» R4 jelentése H és A jelentése 4-Sbot-fenikesoport az X maratték jetaüése mm femh 4-Bnor-feilk 4-klór-íenfk 4-meht-feelk 4-fegfexi-fenlk 4-acetoxiíemk 2-kloí-Rntl~f l^^lhrfeatMsoporí, és Szzal a feltételiek hogy ha R5 jefenfese ntetiesopört és 1¾ S3 és E4 jelentése H és X jelentése feni snarapk, az A marttdék jeietttése eera fenik 4-fieor-IIMk 4-felór-íenil~, 4-nMi-fenlk 4-eíiöRí-fenti, 3~íriíkormeílhfenik 2-tiöfeitth vagy é-atetlltíofenit-csopoff, és sppj a feltételei, Éögy ha RS jelentése nmttíesopöttés R2 jelentése meifesoport és R3 és 14 jelentése H és ÁjeMttése 4>-llö0^feníipöpod,: akkor az X maradék jelentése mm fenilesoporL
2. 2. Egy I. igénypont szerinti yegyülei ahol  jelentése feni- vagy egy 5 vagy h-tagö heieroari-csöptí pifsdïnÆik pizidm-3-tk ptdátn-4-ík tiöfen-2-i- vagy tiofén-3-ibcsoport köréből választva ahöt a feni- és Igteoaatiiesopsrt adott esethet* 1-3 csoporttal helyetfesttei egymástól íhggdlennl F, Ck Br, CN-, (Cj-Cíi-alkU-, (Ch €t,.)-alkif~0- és (C's-kMkihS-csüport köréből választva, ahol az elMlésopttök egy vagy több hídmgénaío«5ja ittettáöttireal helyettesített lehet; X jelentése egy S vagy h-tagn héfemari-esoport. amely 1-3 heteroatomeí iattaíntaz hí, Ö és 5 köré- bő! választva, ahol a hetefoati-est^pört adott esetben 1-3 esopottíal tóyettótett egymástól ülggetlenüi F, Cl, &amp;r, CN-, (Crk)~a&amp;ü-, (Cí-C<;)~oJki 1-0-- és (CrQ,>aíkil-S-, fCrC,}-aikil-0-CfO}- és (G-íVMkil-Sör csopofekőrébőí választva, ahol az afkiasoporíok egy vagy több hidrogénaínntta Rnoratornmal hetyeffesiett lehet; R l jelentése R5-C{~Ö}- vagy {Ci-€6.Hiki-SOrcsoporí: R2 jelentése 1Ç |CfCi)Mki-, tC3-Cs)~eÄalkil-esopnrfc R3 jelentése H, fekkC^-alkil-csoportt R4 jelentése H. (Ci-Ckj-alkil-esoport; vagy ahol R.Î és E4 epött egy (tóCö-alküéa hidat altó; R5 jelentése H, ÍÜ;-€V}-aikíi-·, (C3-C«,hcikJoalkik <C5 •Cj-alkU-ö*·, |CrC^äk|i- Ö-(C; -Csj-alkíK HO'(Cr€&amp;kalkü', (Ci-C.^-cikloalkiHQ'C^Äjh,.$ß6-€*^ati-* (CVOj-alki!-, R2!1ŐM~, heteroarílr, heteíttókí;€$ -CÖ'-síkik.. aíthis betettxttklíss,, stóli az alk besöpörtök egy v agy Äh hidrogénatomja ífaoraitttttttta! bőlyeitosítétt Iahet, és: ahöl s&amp;allfás heterocjfefes piperidinU, pizrobdíaih iés oxipötttömot tóahmaah 4^7 tagi ahlls htórociklus köréből yálasáioíl· amely tartalmaz egy oxigén atöipöi., és ahol μ alifás hdoroeíklus adott esetben 1 -3 csoporttal helyettesített lehet egymástól fhggetlenül F. OH-·. (Cv€;;}-aikil'0- és (CrCtódkíkcsopott köréből választva, és ahol a heteroari rttarsdéfe#; 5 vagy tóagp gyára reodsv:eÄ5 atpelyek 'tó heiteFoatomot tartahnaz-nak N, ü vagy S köréből választva, és ahol az pith és Iteteröarll-esopcal adott esetben 1-3 csoporttal helyettesített egymástól· loggeíleoöl .F« €|: í$r,:€Py\ fCrCiö-aiklI", {CyCai-alkíi-CK CM, (GtóíFtdkíl-SÜrCsoport köréből válásivá; ÄS jelentése H, IC; -C,-O-tóik {GrG*}-cik!oalki1~csoport, ahol az aíhi lesöpör; egy hidrogénatomja helyettesítve lehet Öl'!'- vagy és ahol az alkílesoport egy vagy több hidrogénatomja llaoratornmal helyettesített: lobet; R? jelentése H, {Ci-Cikalkíl-csopott;; abo! az alkllosoport ep vagy több hidrogénatomja J aerators ma! helyettesített lehet, és/vagy az (i) általános képleté vágyóiét satereoizomor aiakía^ésMagy ama alakok keverékeiésdvagy gyógyászati lag dfogadhatö sóik,
3. 3, Egy L vagy 2. igénypont szerinti vegyűlet, ahol A jelentése feoilesoport, ahol a fenti ataradek adÄ estóeo 1-3 csöpoÄl épttpstó! íhggetteiö! F, €|, 8tö CN-. (Cj-CO-alkik (Cj-(.k>a!kil-0 - és (CÇ-Cô-ittklhS-'Csoport köréből választva, ahol az aíkdcsppoH egy vagy Äh hidrogéoattrnga Suoraíommal helyettesített lehet;; Kjelméso ep b vapá-tagá heteroaríi-osopört, piritln-z-lk piríöm-G-dk piíiditt-4-ik tiotótóíh ioÄ-3"il-, tlazol-Mk íiazoi-44í", tiazöl^S-tkosopoít köréből választva, ahol a heteroardl-osopott: adott esetben tó esoprttaí Wyedisielí F, Cb Btt CM··, (C; -Cstókil··, (C:-C;;}'alkii"0- és íCrC6)-alkíí-S-, (CrC^-alkií-O'CÍÖ)« és (CrG.}-aíkií· Sörosoport köréből választva, ahol az alkiicsopöríok egy vap több bídt^getíae|a Ittomtöttttnai helyeiosriett lőhet; Rl jeletttése R5-C(“0;k vagy (CrC-Hlkil-SCF-csoporí.; R2 jelentése H, {CkGy-alkik dklopropíl-csoport; R3 jelentése íi rnetíí-csopott; R4 jeiemése H, metü-csoporí; vagy ahol R3 és M egylRlegy (CrCsNIktléri It&amp;tó alkop és alól ES jelentése II (CrCbb-alklK (CrQbcikfoatksk (CrC2)-atkibÖ-. (CrC,^alkÍES-,: <CrC:Hbkib :ÖM0»eiH· :PO<0r€2|“Ä'iK (CrQH^Ioä&amp;iH^ä-CaEalkti-, .fômb, foaiMCbCybalkib, R7R6bb, heteroari I heteroari MC i -Cibaiki K alifás heteroelklns, äoI sk siyiesopoítékégy vagy több hidrogénatomja Enoratommal belyeifeslteft Äel, és áléi m állás beteröelklns morfidmib,: pijk*idlöll-> pimolidmlb, oxetaniK telmlbdreforäiHb és tetrab idropiranti-csoport köréből választott, és JÉÉ M;-.áÍiÜs'bötéiÉ^W^ »dp# esetbo» 1 vagy 2 csoporttal hefyettesfktí Ebei egymástól föggetle- sub F, OH-, (C ;-€j)~alkü-0- és tCr€4~nlklln;söporí köréből választva, és aböl a ífeítü maradék adott esetbe« 14' csoporttal helyettesített egymástól iiggetieoül Fs CL Br, CFC, (Cj-C^-alkík,: köréből választva. ahöl a heteroarl! maradékok pizldln44bs plrldm44b, giddiP-4-rb, tíoEm~2~ib, tiöiim34b> tlázob 2~íb, tiazob4-ib, tiazoltébrb, Izotiazobldb, izotiazoM^ izotiazobS-íb, plrazoi4-lb, ρεροΜ-ίΕ» Imidazol^-lb, ímidazóMdb;, plramdinbbib,, pltlmidlrH-íi-s piba||Míh4«tb> plddázlsnS-ib, pífl&amp;ats4--li·-- plraxis~2-lb és pímzm-3 41-csoport köréből választott, és abe! a heteroari I maradékok adott esetben !~3 csoporttal h#|?#®é$îettèf£ ^éfyiöástóf. Éiggetíeliti f, CL %, €Fr, tCrCsbalklb, ICrCri-aMkCK CM, (CrCjRalkíPSÖg-osopoft köréből választva, ii jelentése H, (CrCí>alksb, erklopropibesopotí, sbol az alki lesöpört egy Iddrogénafonp kÄ* metökb vagy efoábmaradékkal helyéiíeslteti lelki; és R7 jelentése I L merik etilesoporp ákyggy se 11} általános képied! vegyidet sztemolzcmtér alkfcjia,: és/vagy erem alakok keverékéi ékvagy győgyászatMag elfogadható sóik.
4. 4, Így 1-3 igénypontok bármelyike szériád vegyidet, alól A jelentése lesni áléi a fend maradék adott esetben I vagy 2 Oaopkkl bélyétlésliéP egymástól Ibggetlesild F, CL Br, CM-, (CrGe^áidK CFr, CFjíiy CF.Br.* metoxb, etoxb, C^Fsy éaLCj'-Ciï^alkilsS-osoporî kő-rébôl válásaival K: jelentése egy I vagy ö-tagtl heteroari lesöpört, piridi«44k plrid!n44k piridlmdrik iioíém24k rioíém-34k !iazob24l;~, líazób44b, daápl44bésöpöFt köréből: választva, aboj e^k a maradékok adott esetben 1 Vagy 2 maradékkal helyettesítetek egymástól íaggeílerníi F, CL 8b CN~, (Cr<L)-alksb, CFr, CF?H~, CFHr, metoxb, efoxb, ÖCFr, (CrCC-alklbS-, (CrG}~ alkibCK’(O)· és merik korcsoport köréből választva; Rí. jelentéseR5-C(:::Ob Vanv ißlCi^ÄIrSßMtÄmöife R2 jelentése H, meid, etil, ciklopropil-esoport; R3 és R4 jelentése H, és R5 jelentése KtetiiK étik n-ptepi!-, izopptpil-y n-hatil, rsohotil, tesc-Mnit-, cikloprogi'· vagy eikiolruli lesöpört; és/vagy p'||) általános:: képloti vegyidet sztereoizomer alakja* éslvagy ezen alakok keverékei és/vsgy gyógyászaikig elfogadható sóik.
5. 5. Egy 1. igénypont szerinti vegyidet, ahol A jofeilse egy 5 vagy h-tagi ketefőeríipsopori amely 1-3 betsroatomot tartalmaz M, ö vagy S köréből választva, ahol a heforoaril csoport 1-3 csoporttal helyettesiéit egymástól Rlggetlenill F, O, Br, GM-, (Grt\> alkík éCrQ^alkil-O- és |ßrGs^ä^ikS~esopnrt köréből választva, ahol m alkllesopctink egy vagy t ktdrogeÂonÿa EnotÄtarna! helyettesfteit lehet; X jelentése tens!·, tjbíén-2-il- vagy tiofén-3-ii-, ahol ezek a maradékok sÉ®; esetben 1-3 csoporttal helyettesítettek egy mástól fuggetlcnöl E, Cl, Br, CM, (€r€Á-al!dk tCrC;>)-aikd-G- és <erC*)~aikü~S··, {Cr€6>alkl!-0-C(0)- és {CrCi;)-aikil SOrCSopOit köréből választva, ahol azalkilcsoportok egy vagy Äh hiárügénatemia BeÂtoromal helyettesített lehet; RÍ jelentése RS-€(:::0)- vagy (Ci-Ct;}-aÍkU~SC^^CSCp0ft; E2 jelentése % (CrQKikioÄl^p^ R3 jelentése H, (C;-Cfo~alk O-csoport; R4 jelentése H. (C · -€ í'Hí 1 ki S-c söpört; vagy ahol R3 és 114 együtt egy tprC})»áÍlI:!én hidat alkot; RS jélehiése E, (Ci-C^I-atkil-, (CrGkkoâdoàiMI-ÿ (CrCftEafoií-ö-v 0-jCt-CëlÂir. j|0-(CrCsj-AlK iCECsHikfeaikiHCrCsEalkik (C^CM-eri- fCrCA-öM-v B2MM, heíetearíl, ketenwi-fCi-C^-aikik, alÄieteroeiMes, ahoi azalfciesopoftok egy vagy; Äh hidrogénatomja és ahol az: aillas heteroclklns morfolmlR, píperidiniC, ptfrolídinik és 4-3 tagi aíllichctefocikins köré- Eh! wlsszlstt amely mrtónáz egy osigln atotnot, és aboi az. alifás heieroeiklös adott esethea 1-3 csoporttal helyettesített egymástól Ih^etlenül F» ÖB-, (Ci-C^Ealki-ö·· és tCrCgMlkil-csopoA köréből választva, és atel áfmleroaríl maradékok 5 vagy fotagá gyMmteszerek, ameiyek 1-3 heteÄemot tartalínaz-nak R Ö és S fcőrébSí választva, és ahol asr aril- és |?eíe^rifesöpor5:ök adott esetben 1-3 csoporttal helyettesítettek egymástól íugptfe nöiF,3¾ Br, CFr, (Ci-Cí í-alkil", (CVC^aîkil-O-», tCrCjMkíi-SOrCsoport köréből válasz va; Eá jelentése 1¾ :£CrC*jralkil~, iC's-C^l-clkloalkl besöpört, ahoi M alRfepport egy hidrogén atomja egy OH- vagy :^^s)^tÄceoptÄii helyettesített lehel és afeoias: alfellesoportok egy vagy több hidrogénatomja fXsoratotasnal helyettesített lehet! R 7 jelentésé M, (CrCrRaikR-esopöfí; étói tói aikllesoport egy vagy több hidrogénatomja Rnshdtommal helyettesített: lehet, és/vagy az (i.) MtÆiios képleté vegyidet .satowlasomer üiakp, és/vagy mm alakök keverékei és/vagy gyögyászaíitag elfogadható sóik, azzal $ föltétellel, hogy A jelentése: bent ba μ (I) képlet szerinti vegyidéiben R5 jelentése meíitesopoítés R2,13 és R4 jelentése lÂegénat és X jelentése fenitesoport
6. 6. Egy 5. igénypont szerinti: vegyileg ahol A jelentése t^MiÄ vagy 4-piridlL alsói esaetbe» I vagy 2 esopomal helyettesítettek egymástól függetlenül I·', Ch Br, CN-- (C;-Q}-alkil~, CFr, CFjlE, CPHr. meíoxk etoxk OCFj-, és (Ci -C^-aikil-S-csoport köréből választva;. X jelentésé fotók vagy tsoíé?5-3~il--esepön, ahol égek a maradékok adó« esetben 1 vagy X csoporttal hslyottestettek egymástól függetlenül f, Cl Br, CN-, (CrCO-alkik, CFr, 0¾¾ CFHr, melótól eíoxh OCFr, (CrC2}-alkil-S-, {€,-€.}· aikid}~Ü(0)~ és metiESCB-csopó« köréből választva; Ri jelentése R5~C(~0)~ vagy prC^I-älkikSös^esopost; R| jelentése B, aittih «ttfh ciklí^roptbcsopeft; R3 és le jelentése H; és RS jelentése FI, meid-, etil-, n-propH tóopmpi!-, n-bntil-, izohntil- wgy tere-bmií-eseporl vagy ahol R5 jelentése eikloproplly oiklointlk eikiopentil- vagy |OrCe)-ojktóRíK^rG^tó^»|>«tV vagy ahol 15 jßkntm éC:rCï)-alkïEO-, fEt-Csl-alklI-S-i, vagy OC^E-csoport, vagy ahol R3 jelentése (Os-'C^j-'álklI'-O-nietíl·, BydCt-GB-aikiResoport vagy ahol Rá jelentése fetót- vagy festiImetil-esoport, ëiïsicy! a Äiiött «ssetfeess 1*3 c&amp;<^H3í1%|::feesiy^§fteííek: ©pmásíól feggeí lenül F, CI,Br„ CFrcprCzlalkiK (:Q^s)^ikl~Ö-;, (M-~, meíil-SÓresopört MféÂ^iàsîôv^ vagy ém\, R5 jelentése B?R6N-csoport ahol Ró jelentése B, (CrCp-alkil-, dklopropil-csoport ahol az alk besöpört egy fiiáapéoatoMja OFK ntefegb vagy etosl-esepomal hslyetteshetí lehet; és R 7 jelentése H, metil-, etil-csoport; vagy ahol R5 jelentése heteroariK heteroanHCrCől-aíkil-csoport, ahol a heteroaríl maradékok piridln-l-ll-, phidm-Kd-, pjridin-4-ik rtefert-árth tfe&amp;l-IR, tiazol-2-1-, öazoä-4-tjk tiazobS-lk Izotiazoi-Kk srtá*azoh4-ík Izotiazol-felK gllazol^lfe p!éazöR4-ik koklazoICll-'. imkkzoM-il-, pirhnídin-2-ik pínmidi.o-4-i!-, prtlmiöm~5~iK piridazin-3-ü-, pindazm-4-il··, pirazin~2~i!~ és plrazín-3 dl-csoport köréből választottak. Is áho| a heíeroaril maradékok adod esetben í vagy 2 csoporttal tóyeöesítertek egymástól fúggetkv pil: fe Cl, Br, CFr, éCrCíHMó CN~, (C$-C;RaÍkH-SO»-csöport köréből vá lasztva; vagy ahol RS jelentése egy alifls heterodÄC ahol m alifás heteroeikliss htorfeliail-, pipéridioík pirtoltiiml··,: ogefealF .# tgRahldrofuratsi-, fegilpdiopiraplhesöf őrt köréből választott, és ahol a? aiilyheferociklus adott eseihen I vagy 2 csoporttal hefyeítésf gS ggpig&amp;iél: függetlenül F, ÛHn tCrCîB^klhû- és (CrCii-alkil-'eSoporl: köréből választva; ésfeapaz (í) általános képleti vepüfet sztereo!zomer alakja, és/vagy ezen alakok keverékei és/vagy pópászatöag eltogadhafe sóik, Ί, Így 1, tgéoyponl szerinti vegyidet, ahol Λ jelentése femlcsoperí, ahol a feni! maradék adott esetben KI csoporttal helyettesített egymástól függetlenül F, CL Bt, Cbk (CV€4)-a.!ki!-, {CrC<}-a!kíM> és (CrCC^kiFS-csoport köréből választva, ahol az Ailesoportok egy vagy több hidrpg#atomjs X je leölése feídícsoporg ahol a fend csoport adóit esetben I, 2 vágy ó csoporttal helyettesiéi epmástól ilggeflettül F, Ο, Br, CN-, (CrC,) aik!k (CrQHlkil-O-, (CrCO-Ckil-S-, iCrQ}~alkiFO-CCO)·- és (CrC4}-siktl-SO>~csöpört köréiül választva, altöl az alhlfesoportök egy vagy Äs hldtttgénatomja fítíOtelomthál helpttésitett léhet, és il jélerrtése :R5-C(*€ï)- vagy iCi^sj-alkli-SCl-esoport; R2 jelentése ? L (€rQi}'<dkäS-, (€ j~€Ä }-cikf oaf k i !-C!X>pc>rt; R3 jelentése H. (€rf.\)';dkil-csoport; E4 jelentése H, (€rCO~alkil-esoport; vagy ahol E3 és R4 egyurt «gp C^j-Csi-alfekess írtdat alkot R5 jelentése fi, (C;-C*)-alk Ií-, (Cs-Csi-eikloatkii-, (C<-Cy-alkIl~Ö~, {CírtXfedhit-S-v iCi-Cfd-alkd-0-{C?:-C«}-alkd-, HÖRGrCkMkil-, C^CgpoíkloalkíHCrCfil-alkíl-, (Cs-C^j-arik {C6-C)(iRarii-(CKXHIkií··, R7R6N-, heteroarik heíeroariK€r€a)~aiktk a|l|s heterociklos, ahol M âlkilssegîortofc egy vagy több hldrogmrfemja Eucanfommal helyertesltetf lohet, és émlm alitas hetöroclklus morfèlmik pipersdiojl-, pirsolidME és 4*7 tagú allias heteroelklns köréből választöft, a;nely fealmâz egy oxigén atomot, és ahol az alills botértjoikfe adott esmfeen I *3 csoporttal helyetesiétt egymástól föggetierml f, 011-, (CrCf.l-alkíl-O- és (CrCe)~alkíi-esoport köréből választva, és ahol a heteroártl m&amp;mâêUtk S vagy bongó gyári mndszemk, amelyek 1-3 heteroatomot tartalmaznak N, Ô és § köréből választva, és ahol az ártl- és heferoazIResoport adott esetbe« I -3 csoporttal helyettesített egymástól függetlenül F, Cl, Br, CFr, (CrQ,}~alkil-, (CrCéj-alkíl-O-CN-, |Cí-&amp;}-alktl-SOrtrtoport köréből választva; E b jelentése 1¾ ICrCsl-alklk, |CrC«)-C5kfoalkM~esoport, ahol aZalki lesöpört égy jddíogénaíomja Öff- vagy |CrC^-alkíi-Ö-ésoporttal helyettesített lehet és ahol az hlkllcsoport egy vagy több bkirogénaíomja inomRmmml helyértesitetl: lohet; R 7 jelentése M, (Cj-QO-alkil-csoport; ahol az alkllesoport egy vagy több hidrogénatomja íksor&amp;tomma! helyettesített lehet, azzal a feltételiéi, hogy ha R5 jelentése medksoport és R.2, R3 és R4 jelentése H és A jelentése, 4-ÉííOf-&amp;5tkeso|>ort,: az X maradék jelentése: nem feil-, 4-Rloí-feníj-> d-mtókímtR* 4- metoxi-feníK 4~aeeíoxiCenii--, 2-klór-fenÉl~, 3,4-dikknienií-csoport, és azzal 1 feRéfellét, hogy ha RS jelentése mell! és RR, R3 és R4 jelentése fi és % jelentése egy fell mk radék, az Á rmmáék jelentése nem fenil-, 4-Rnor-feníK 4--kífefenil-, 4-mefíI-fenif~, 4Hetík»á-feaiH vagy 3'-trífí«ormeÉk:felS-csoport, és azzal a feltételiek hogy ha R5 jelentése metllcseport és R2 jelentése nfelésoport és R3 és R4 jelentése II és A jelentésé d-fcsor-lenll-esoport, az X maradék jelentése nem fen;lesöpört. S, Egy 7. Igénypont szsrtntl vegyidéi áltól A jelentése fenüesopoit, ahol a fenil maradék adod esetben ! vagy 3 csoporttal helyettesíted; egymástól függetlenül F, Cl, §&amp; $$h,. {C}-Cla|-alliIÍ-,. €%, CF2HR GFIlj-, mgtoxi-, etoyl-, CICfr és CCrCrtmikil-S-esoport köréből választva^ X jelentése fcplesopert, ahnt fee fenti maradék adott esetben: 1 vagy 2 espporttal helyettesített egymástól függetlenül f, C'l, Br,; €bf, pj-C^-alkd·', CFy-vCfFÄ 0¾¾ «tel ÜOV* iCK-hHikil-S-, (Ch-Cb-alkihCR ('(O)·· és metil-SOs-esopert köréből választva,: R I jelentése R$~€t :::0>- vagy petil-50resoport;;; 312 jelentése H, C€rCV}-aikil-, ciktapropil-esopoti; IP jelentése H, metd-csoport; R4 jetenése 11, mstil-esopoït;.: vagy ahol R3 és R4 együtt egy etilé« hidat alkot; és aha! R5 jelentése egy hetetoadi- vagy he$eroariHCrCí.)-alk;l-cvopoí1.. ahol a hetemen! maradékok ptri* din-2-il-, plrkba-B··!!·, piridin-4-ίΙ-, Uoférs-2··’!-·. tioíén-3--11-.. U3.zo!~2-ib, dazoj~4-il~, tiarol-S-ik k-öteaalrS-IH rrotlaeolkdl-, IzotlazolkXb., piranl-S-lk pirazoî-4-il-, TOfenkhik, imidaœl-4“ il-, pirhnidin-2-il-, pktoicimd-ik, pltlnndjn^S-'ik pkidazIa-S-H-, ppidafen~4jk plraÄ-2-ll- és plraXs-kikesoport koréból választott, és ahol ezéfy* paradékok adott esetben i vagy 2 csoporttal helyettesítették egypásídl Slggetlenhi k, ö, Br, €f;r, ptóh «&amp;K ïnetoxi-·, etoxiy .€$$-, meltl-böj-esoporí köréből választva, vagy ahol R5 jelentése H vagy ahol 15 jelentése clkloprepih, diklídíhMh, eMopenfit-, dktetafk vap.|03^)rdkle»tól|ft^J-alkth csoport, vagy ahol 15 jelentése íCr<.V}~aIkil--0· vagy <€r€b)~a!k.U~S~csoport, vagy ahol 15 jelentése CCi-C^)-alkikOvroetíl-, HO-t.Cj-€;>>-alkíhcso|x>rí, vagy ahol RS jelentése leáll- vagy térdlmetfesopott, ahol a fenti maradékok adott esetben 3-3 csoptsf^l heiyeEesköÄ egymástól liggetlmü 1,321,13¾ Cl'r, (C ·-Cj)-a!kli-, (CrCIshaikll-ö-, €H-, metil~SOresoport, és éhol m alkikspprtpk egy vagy több h idmgénaáonga inorahPnnál helyeEeskgti lehéh vagy ahol RS jelentése R2i6X-ésopoÉ,: ahol Ró jelentése H, t'CrC4)-aíki!·, ciklopropik ahol a?; ahklcsopott egy hidrogénatomja htdroxk meíoxi- vagy etok-csoportta! helyettesített lehet, és R? jelentése 13, mets!-, etil-csoport; vagy ahoi S3:jeleőfesé égy aJifas IfeferoeiMns,. ahol Μ : alÄ betemclklas ösetámK t^ÉÉÉiÍ*x tetspidropíraitóh morfoüntk pifeddl^il-, ptmAidinil-csoport köréből választott, és; ahól az alifes ife^Brodfefossaáot esetben I vagy 2 csoporttal belybP^sltetí Ibhét egymástól í%gA~ r|íi f> Cfeh, |€ís:C}>aÍlílSi-í> ék íCj -C*|ral|íii;bcsopost. köréből és aboi m aík besöpörtök egy yap^Äfe Ityr0génaióí8ja: inoratogtpal helyettesített (ebet; ésévagy m (I) általános képiető vegyidet sApreohsomcr alakja» és/vagy e:pn alakok keverékei és/vagy gv ogyásaaííiag eibgadhaíő sóik, '&amp; Egy 7. ígéíypöst szerinti vegyidet, ahol A jelentése femtesopöri, ilila fon! maradék ÄiÄ í vagy 2 esopobfelhelysdeaííefí egymástőí ilggetlesül F, Cl Br, CN-, (CrCO-aíkíb. €Fr, CF2H-, CF.Hr, metexi-, etoxi-, OCFy és (C,^2>-alkil-S-c«>port kóréból választva; X jelentése fenücsopozt. ahöl à feni maradék adott esetben I va®? 2 ésoporttal helyettesített egprástól föggetlenil F, Cl, Bt, CM-, {Cí-ChValkll··. CFr, €FXk CFHr, metoxk etoxK OCP.r, CQ-CB-alkif-S-, (Cr-Cv)· alkthOC(Ö> és feolihSÜr, Rí jöíeoídsé i^§"C’i:“0>caopöít; R2 jelentése FF (CyCA-alkil··, c-klopropiI<:sop«rt; R3 jóteitése Fls meíd-esoport; &amp;4 jelentése FI, meíil-eseport; vagy aholíö és R4 egylife egy etilén hidat alfeett és ahol R5 jelentése (Ca-Gíj-alkd-espöÁ, vágyából R5 jelentése metilcsoport; azzal a feltétellel, bő®' ha R5 jelentése otetitesopori: is ÍO, R3 és R4 jelentése M és A Jelentése 4-feon-fetnltesőpoít az 'K maradék jelentése nem fenik, AJlnor-fenil'v 4~klófete»ife, 4^tnetli--fend-,- 4~ :spetoxl-fenil'y i-aceíoytfettll-,: lAlor-f eolI-, 3,4-diklörfenil-cseport; ésévagy az ti) általános képletl: vegyidet szteteoizem«nalakja,: étvágy ®fi alakok keverékei esz vagy gyógyászati iag e (fogadható sóik. (0. Egy I, igénypont szerinti vegyidet ahol A jelentése Y«P ep S vágj? '&amp; heteröáttt-esépöA, amely 1-3 hetereatobtot tartalmáé N, O és S köréből választva, ahol az éri·· és he teroari 1--£söpört adott esetben 1 -3 csoporttal helyetteshett egymástól függetlenül F, €|*®Μ*ΚΚ (Çj-CgJ-aMÎ-, (€r€s)-állöl'Ö··· és ahol # eiesoportoií égy vágy főbb httegémnomfa Rsoratommal helyettesített lehet; X |éleöSesé|iG^-Cjg}'ar}i·' vagy S· váptMagö heteroarif-esopÄ amely 1-3 heteRMernet tartalmai N, O és $ koréból váláséivá, ahol m -tói- és feteroari-csoport adott esetben 14 csoporttal helyéhsshett egymástól Elggetleoil: F, CL Bf\ Ohl-, |CsC*BalkÍ^ PîC^alàKR és íCrCsBalill-S-, (CrCR)-alki 1-0-0(0)- és (Or Cfó^&amp;ll-SÖ2“ésbport Mrébil választva, éiüi'áz alkílesopertók egy vagy több hMrógénaíotma EetÄOmtnaf helyeferteft lehet; 11 jelentése RS-CC^O)- yagy (CrCs)~alkll-S02“ésoporíí R2 jelentése 11, {CrC4*á$bh (Cs-Csl-clkfoálkll-esopöirt; lö jelentése 11, (Oi'-C^Balki'-esopoA; M jelentése IX CCrC^mfklM vagy aim! Ej és,R4 egyll« (0;rC3^alfcílén hidat alkot; és ahol RS jelentése egy heteroani- vagy héter0aril-(O|-Oö)-alk 11-, ahol a heterotól ntamdekok S vagy é-mga gy&amp;rá reedsKépk, amelyek 1-3 heteroatornot îaarlaipaæM* O és B választva, és ahol a beletöärti maradékok maradik adott esetben 1-4 csoporttal helyettéaltetíek egymástól függetlenül I, Cl, Br, CFr, (Cj-Osl-alki-ÿ 02,* választva, ahol az alkllesoportok ep vap több hldroglaaiomfa iluoraiernmal heiyeöeslelt lehet, azzal a feltétellel, hop ha az (!) képiét szerlni vepületekben A jelentése egy 3~eiaao(fen:ií mazadgk ás X jelentése ep 2,4-dtRumjánil maradék. Rá jeleatése mm pírimid!o-4~f~s plrldnnl-rl-, l-mettl-ptrazot-3-§- vap Í-metil-imtdaKol441resport, vap ahol ES jelentése metllcsoport, azzal a feltételiek hogy ha az (1) képiét szerinti vepiliétéhiéü Rí, R3 és R4 jelentése hidrogénatmh és X jelentése ep 2,d-dl0nofféni matadék., A jelentésé nem pirtdmOAl-·, 2-Buer-femi~, 3-öuem teniK 4-Bnorfèm!~, 3-élano-tebtK a-mefep-feml-·, S-ttilleormetoxi-íéell·, S-önof-é-metoki-tenll·· csoport, és azzal a feltétellel, Itop ha az (!) képlet: szeried vegyütétékben R2< R3 és R4 jelentése hidrogénatom és X jelentése egy 3-cÉnöfeöd maradék, A jelentése irenr 4«ÍtmtfesS rnáradék, és azzal á féltéteílel, hogy ha az (1) képlet szerinti vegy öletekben R3: jelentése metilcsoport; R2 és R4 jelentése hldrogén-atons és X jelentése 2,44i|nor-íend ütamdék, A jelentése nem 4-iiiór-femlcsopórt, és azaa! a feltételiéi, hogy ha m (1) képlet szerinti vegyületekben R2, R3 ës R4 jelentése bktrpgenatora |s X jelentése fenrlesoport., A jelentése «ens ÍMíH 441tj«pféní]-y 4-Étefeaîl-, 4-mëîÎi^fpnik,. 4-eölöxl--feniÍ~, 4-aoefexilÄk AfeethdiefeatK 2~tlo|éüiK és azzal a felfeieijek hogy ka ax (!) képlet szeiiöi var^liétekhett R2>: Ili és R4 jelentése hidrogénatom és A: jelentés« 4--inor~léniResöpohk X jelentése mm fèftîlk 2<-klóricnlk -U-dvkÍ^te^ 4-klór- fend-, 4iluor-iemf~, 4-metiMhníí··, 4-meíoxóíeosk d-etsfoxhfenii-osnport, és azzal a íéltétetfel, hogy ha. Rí jelentése metllesoport és 12 jelentése melltejfepörí, és Rifes R4 jelenté*: m M: és k jelentése 4~fíndGtai!-csópórh az X maradék jelentése nem feaílcsoport, |s vagy ahol RS jelentésed^ fCrCsjhdtó*, CFy, €F*B~< €i?llresopork ahol az aihf lesöpörtök egy vagy több hidrogénatomja fhiotaiomtnaf kelymtesiiett lehet; vagy ahol 15 jelest lése {;C5-Cs)--cl|:laa;lkil- vagy (Ch-C^};--6Íkloalfell-{C^C,;)~a|kih6sppöX,: azzal a: Ipltétallel, hogy ha az (I) képlet szerinti vegytlletekbeo A jelentése: l^lanpfeoll maradék és X jélesrtése 2,4-d í fluo r f® íi i I ppadek, RS jelesttás© mm. olllópropíXcsoport, vagy ahol Iá j eléntésé (Ch-C^^alklkÖ-· vagy |jG A(¾ j*alkiRSfesoport, ahol az alkilcsopoRpk égy vagy tdbb hidrogénatomja fluötratÄÄ^/iglf^^tfÄ'lehsu vagy ahol 15 jelentése (CjX^ij-alkjl-ÖAÜRGgAÄi“» MO-CCrGsI-alkil-ésopork vagy rmot 15 jelentése ieöh-, ahol a lem! maradékok adott esetben 1-3 csoporttal helyettesítettek egymástól függetlenül F, Cl. Br. C|>, (CrCA^k'tl-? #ϋΓ€^ΜΙ114Χ, Ql m ahol az dkítesssporiok egy vágy íobfe hidrogénatomja Ííaomíommél helyettesített lehet,; azzal a leltétel léi, hogy ha az (I) képiét szerinti vegyilsfekhen A jelentése 3-oianoíehtl mamáék és X jelentése SA-difínotiéíil maradék, 15 jelentésé nem vttgyj· 4-metllá2StÍÍMis|- fenihesopöäl;; vagy ahol R5 jelentése ITRéN-esoporf ahol M jelentésé: li, (Cv-C^l-alklk, dklopropIK ahol az alkilcsopott egy hidrogénatomja Old-* metoxl-· vagy etoahéisoporttal helyettesített lehet és : le jelentése Ily (C s XX)-alkil-esoport vagy· ahol Rá jelentése egy alias hefetoelkte, ahol az átiUs heteroeiklus oxetanil-, íetrabldtölpfanh--, teialrtdropiraníi'·, moflblintk píperídmik kV^fv^í/t! VfttaóVXÍftí'í ahol. az aiSs betetöeíkte ad«)» esetei 1 -vagy 2 csoporttal helyeriesítel tehet egymást# ílggeíknSt F.O!K(C:-C4> -aikíl-Ö- és <Cv~C4>#ki^s0p(>;rtMfebót választva, és g|ol m. alcsoportok egy vagy több lídrogenaíopiga iltmratoramttl helyettesített tehet, .mœâ.%. íéiíéíaftel, hagy ha az (!) léptet sstetdí vevőietekben A jelentése tesmsoMíi maradél és % jetentése 2,4#iÉimr#di tétetek, RS jetentése aem 3-metil-ö5te«~Mk tetmM#a#taö#-sK totrahídifopiráa-iéte vagy I -TOéPl^iperiPia-d^lkcs^ort. ! I. Így 10- igénypont szerinti vegyétek ahol A jelesléss íeníl-·, ptridm-S-ík gíridimNk piÄi-4-ik tlotettOFií- vagy tiote#4Fesoport alpi ezek a taamdékok áé#t esetben 1 vagy 2 asoporitai: helyettesítettek egymást# föggetieoul 1, Ci; Bt, Cbk <€rCí|«alkjH OV, Ciyk CFfír, tetek etek 0€Fr és lCjC#alkil~S~csopert köréből választva; í' jelentése téaicsepori, ahol. a teniteVóporí eddi esetben í vagy 2 csapolt# helyedesífett egymástól fôggeitenul F, Cí, Bp Cbk tC · CFr. CFjH·, CFlr, meitek étek ÖCFr, (Cs Ak)~a!klFS·, tC i “Cjj-alkll-Ö- C(ÖF és vn etü-SOr > vagy piridín-2-ik piridin-B-ik pirklin~4dk tte#m2-i§~, dolén-kík tiazol-2-il-, tiazol-4-sl-, tiazol-5-il-esoport köréből választva. ahol ezek a csoportok adott esetben I vagy 2 csoporttal helyettesítettek egymástól fedetlenül F, €1 Bt, CN-, (CrCO-aiktK CF3-, CFjH-, CFFfr, teoxk etek Mk, yCä-C2FalFd-S-, ICrCsF alkil ö-CtO}.· és meiihSOrcsoport köréből választva; Rt jeisitése 15-Ck®F vagy (0i-C2}mlkiFSÖä-esöpott· R2 jelentése 34, {Cs~C2)-atkik ciktepropil-csoport: 83 jetentese HvICrüsl-nlkil-esi^port; R4 jetentes© lót, CCvï~Ç>>)-alics í-csnpm'í; vagy aboi R3 és Ki együtt egy éti léd h idat alkot; és aboí 15 pteníése heteroaril- vagy heteroaJií.(Cv<'<;)-#kil-csoport ahol a heteroarií-csoporiok piridin-2-ík plldm#-iF, pirídta-l-ik tioíérkkik tioÄHrik tiazo!~2-ik ttezol-irik líazoHSOk izoíiaz##-ik köiaäöM-ii, izoMaÄ-kik pímz##·#·, pbatekrik tmMazoi-2~ik ímldazóNrik piHí#d®#.ih pMt#&amp;-4~lk plrimldia-SdF^flridazte-ií-, plridazin-4-îl-, pirazin~24F és(pirazip^-ilASöpöri kö-féből választott: és ahol ezek á maradékokadoít esetben I vagy 2 csoporttal belyéttesfeítek egymástól ilggéieöül F, Cl, Br, CFr, mets:!-, etil-, etetek etek Chk meílFSOj-Fkopori kórét# választva, azzal a feltételiéi hogy ha az (I) képlet szerinti vegyűletekben A jelentése 3 ~c ί anofeοίI maradék és X jelentése 2.4-diíl«orfe>ab maradék, RS jelentése oempírinbdin-A-ií-, piridhteIK l~meíít-pirazoi-3-ií-vagy l-meülémíbagöb2»{be^oii:, ahol K.5 jelentése raet|eso|iort, azzal a fehéteileb hogy ha m (I) képlei szerinti vegyűletekben ®, R3 és E4 jelentése hidrogénatom és X jelentése SX-dlSoorfeotl maradék, A jefettes nem píridm~3d!~, 2-E«0f*fep|1~, S-riuoivfemk 4-· Äorfeni!*, 3-eiaoo~fetrik b-metoshfentk lAtífíóörmeíoxiteúl·-, Xfttmr-S-metoal-femi-, és azzal a feltételiéi hogy ha az (t) képlet steinii vepülétekbén R2, R3 és; E4 jelentése bldtögénalPht és X jelentése ilfeíanofenll maradék,: A jelentése neat: 4-fÍnotféhll mamdék, és ássál a feltételiéi kap ha te (Íj képét SKeripii yeplletekbéh 1E3 je lettee: meri lesöpöri, Eli és fM jelentése hidrogénatom és X jbiéntésé 2,4-diÍbe?~feml maradék, Λ jelentése nem 4-0uoM%m!·-ösogorl É? azzal b feltétellel, bogy ha az (I) képlet szerinti vdgyriléfekben R2, E3 és R4 jelentése hidrogénatom és X jelentése fenricsoport, Á jelentése: nem fenti-,. S-itlrinonóetihfemk 4-riuomfetnb, 4-tóór-lémb, 4-metíl-fentE, 4~©tehfemi-, Srifofetrik 4~meíiiílöfehifesopori, és azzal a lélfetellek begy ha az © képiéi szerinti vegyltleteklíéb R2, R3 és E4 jelent#« Mdiógeoátom és A jefenfese 4-ílbor~ fenli-esopori, %. jelentése tient 2-klërifenlt-, 3,4-dikltefernk 4»klór~ferrik 4d1tK>r~íeoík 4-métil-ieni-j, 4-metosi-fenn-, 4-etosíí-feblh vágy 4~aeet0xlfeml-esopori;, es; vagy aboi R5 jelentése H, (C - C.t ) - a ! k H -, CF;,-csoport: vagy ahol ES jelentése elklopmpli-, -dklobatüs ciklopeprik eikfohexll- vagy (Cs-C^I-eikloalklNCj-Csl-atkil“ csoport, azzal a lattételiéi hogy ha m i) képlet stelbi vegyietekben A jelentése Si-elnnofetril maradék és X jelentése 2,4-dlÉtmrfedil maMt^ks R$ jelentése te» élkk>pröp|i-íesopori, vápából E5 jelentése (C:-€;0-aikil-O· vagy |Çi-ClE-nlkliSfesopotl, ahol az alkltesoperiok égy vagy több Iridrogénmomja ilnoratoramal helyettes ítélt; leheti vagy ahol R5 jelenése cC;-C0raikll-O-metsk MO~(Ci-Cibalkil-esopori, ahol az alki(csoportok egy vagy több ildrogbRatpnvta ritmratommál helyetekéit lehet; vagy ahol R5 jelentése t'enil. feni:KCtXSj}'alkU46i^pt|,. aboi rite fenü-esoporiek adott esetben IS éSoporital ho|ye#sltepk egymástól függetlenül F, Cl, Br, CP*-, |Cj-C2)~4&amp;ri··, CCiCyhalkltAK CM, mgril-SO^-osoport koréból választva, és ahol az alklteoporiok egy vágy több blÉóiéeáttsnja Buoratoramal helyetekéit lehet. s teltétellel, ifeogy ItaiM 0} képlet jppptóí vegyüfctekbén A jelenese J-eláaofenit toaradék 4s X ieientèse 2,4-difl«0ffmU maradók, RS jelentése «ern 3-metiíszulfonü-íenít vagy 4 -sVt&amp;ii Is sat 1 f öpil ^ íeíáWsopop; vagy altöl ES jelsntese R7R6hl~csoport, ahol Ré jeteése Ri fCj-C^IktK eikl©propll*?; shot az alkilcsoport agy hldt^génatanya Iddroxk. Äk vagy etox i-osopoxtta f helyette&amp;ítef leket és Ii7 jelentése J·!, metil-, etil^sdpot* vagy ahal ܧ jelentése alifás hetemelhles:, ahol m áiíls Wtóii öxétShi~, MralddroRnáhtk íetntddíóprami*, laovMMk ppéhdhuk plmsIldliall-vsofKîRJidtébol választott #·' ahol az alifás hetetólcte ade# esetben I vagy 2 haopöríiai: helytítíesílsR egymásiél Elggeilonilî 1% OB*, (Cí-CR-álkihO· éa it.'vCB-alkïl'-csoport köréből választva, és ahol az allsfesapoAok egy vagy több hltfegénslonp, iooratopgpa! Wphesfett lehet, mmI a: feltételiéi, hogy fes a« ifi) képlet szerinti vegyliekkbea A jeiehïese J-datkifeni! ntatadéh és X jelentése &amp;4*di£horíéüit hiamdék, IS jelentése hens 3~nteitl*ovetan~3*ik tPtfahifelhtáasSAl*, teRaItídtópitáit-4~y* vagy k^tííiiipehiW-ll^ssf^. ésÁagy'm (!) általános képlete yegyäjetsztemerzomci alakja, és/vagy ezen alakok keverékei és/vagy gyógy ászát! lag elfogadható sóik.
7. 12. Egy ](}. igénypont szerinti vegyülök ahol A jelentése fen (lesöpört, ahol a fomleseport adott esetbe« I, 2 vagy 3 csoporttal helyettesített egymástól függetlenülp, Cl, Bt, ÇN* i|€i-€4Hlk|l%|&amp;C4;ViSWI"Ö- és C©ÄHWM^iß|KSrt köréfeil választva, ahol az alkrlcsopörtokegy vagy iöbh hidrogtetajs Haozafosatnal helyeRfoftetí Rbet, és X jelentése fonlíésöpoft aha! aietthcsopori adoA pSötbeei !s 2 vagy 3 csoporttal heí^lt©sl^-!|gy#áátSí lögg^eoii. F» 'Q% -ßt* €N··, jCrCppalklA, :(Crehrslk:ihCh (Ck-Cdj-alkU-S·, (Cj-CíMkiJ-O-CíO}- és (är€B~aiMbSÖr esopon kötőből választva, ahol az 8l:kicsopötlok.egy vágy több hldregénatotsjá iooraíórmnal helyettesíted lehel, és RÍ jelentése R5-C(:::0}· vagy {€·. -CR-alkil-SOrcsoport; R2 jelentése H, f^*C$jha'Ík;iK (Cli-Ckk-eiklöalktkosopÄ R3 jelentése B* R4 jelentése H, (CrOj-alkit-csoport; vagy ahoi. R3 és R4 együtt egy CtVC^aMèa hidat alkot; és;s;W IS jelentése beíétoaA vagy ^ito^ll^Ct^^alikil^pQ^ - ahol » heteroail csoportok 3 vagy 6-tâgù gvümrestdszerek, amelyek !··3: teMü' igdälmasSsak Μ* Q # S kóréhéi választva, és khttl a belemart! csoportok adott esetbe» 13 csoporttal helyettesítettek egymást függetlenéi F, C| Br, £í?r> (CrC^aikM-·, (Cr€s>Ätth<H Gfh φοί az a!k (lesöpörtök egy vúg$ több bMmgérKttcasp Úworat03B^abbe|pdtesftett lehet, szxai a teltétellel, http ha az (!) képlet szerinti vegytttóekhea  jelenléte 3-eíanoíeni! maradék ésX jelentése 2,4Ä3ttörfenil maradék, ÉS Jetoíese sem pinmklm~4Ak piHdin-24k lmnettl~pira:Ä3~lk vagy í~aietsbkr»dai<ol^2"Sl~CvVoporL vagy étól 15 jelentése roetllesoport, azzal a ittttéíslielj: hop h» m ($) képlet szerb# vepölelekhétt E2:í 13 és Ed jblétttésie hidmgéííSítem: |s % JgieæÂe; 2,#-dîSaorfesîi: sttaradék,: A jelentése ;nem$É4Â#4k 3d8bör^fjh* 3#ttttr-í«pft-\ 4-ittotleml-, 3~eiáhtt*feelk 3~t»eto#~forák 34rifcormetodÄbk és «zzal a Mtéíéllél, hop lm az: ÇI) képlet saesasti vegyöetékbett E2, 13 és Mjeietttése: MÉSïgéhatons és .'K jelentése 3<ekoofem! maradék, á jelentése item d^ílpoiíiettikesopott, «sózzál a feltételiek http ha az (I) képlet szerinti vegyttletekben EB jelentése rnetMeáéport, 12 és R4 jelentése íhdrogenaton* és M jelentése 2,4#lf!óor#nll-vSöp0rk A jelentése nern d^Pottfenihesoport, és azzal a feltétellel, bogy ha ait: (I) képlet sxsdttti vephletekhsti 12,13 és 14 jelentése hidrogénatom és X jelentése fenilesoporh &amp; jelentése nem fenik JdrlflnormÄÄmk d^oor-fenlk Addor-feolk •4Ars<'tü' fenik, 4^!ÍttkídMfcy azzal a ..feltételiéi., bogy ha az (t) képiéi yegy8tó«Étó» 12,: 13 és R4 jelentése hidrogepatom és A jelentése d^npÄnil-esopörh M jelentése nem fenik 2#kk~fétttk 354~dlklortteoil-, 44(:100 fenik 4-Äomfenik ÄÄl-femk 4-m«tt>xi-femk 4Äkna4fenik Ameetoxlfemlgsopott, és azzal a feltételiét, hop ha R5 jélétttése hÄlesöpprt és 12 jeleatése metllcsoport, és 13 és 14 jslenté-se H és A jelentése 4:4kíor4éntt<soport, az X maradék jelentése nem feniksoport, és vagy ahol E.5 jelettíése H, (Cr^-alktH. ßlr» CF>H , CFfR-csopott, ahol ax slkilésopert egy vagy Äh hídropnafemja luoratoatmal hélyétlesltett lehet; vagy ahol R5 jelentése {GrC.spctkloalkíl-· vagy (C:rC,$K.lkk>alkU-{Cr€.sValkí!”Csoport, axzal a fehétéllek hogy ha az ti) képlet sxeehttr vegyttletekhen A jelentése Seianofeml maradék és X jelentése 2,4#lR»orfenil maradék, 15 jefenMs© nem eiklepn^kesöpot% vagy ahol IS jeléhtése IGpCílalklhO'· vagy .(€? -C^Äikl'esopork ahol m alki lesöpörtek egy vagy Äh hMro^aatomja ßnttratttmnpl helyettesített lebet; vagy aboi IS jelentése íCr^CiA^tklhÖ^(Gi-G:;4-alltl-\ !4Ö"{€|^ijmÍktl-esopott, vagy ahol Eg jelentése felibe i-Cíl-a&amp;il-ssopojt, ahola îentlcsoport adott esetben 1-3 csoporttá! helyettesített egymásul ïiggetlénüf F* €4 Br, ÇfV, (CrCá)“s!ki-, (Cî-C$>-ÂM-0~. CM·-, (GjrC^I'alkll-SQresopiirt köréből választva, és ahol aK sIkllcsöportők egy vagy tébb hldrö|éí5atofi^ Ittotatommal helyettesben lehel, azzal a feltétellel, hogy k&amp;m $} klpfei széríhti vegyüiefekben A jeletttése 3 -c ianhfénltïaÂa èi X jelentése 2,4-310oorfenil Avaraiéi, RS jelentése mm S-imeBlszuterlBfe'ű!-, i^neíiteztdfetti'fetoh csoport; vagy ahoi R5 jelentése R7R6.N-csoport, a.ho.1 M6 jelentése 13, iCrC^aíklK cllSopropsl-esopori, ától az alkiksoport; egy hiiitogénatoa-p ÛH-, metoxs- vagy etoxí-csoporttal bclyettesiíeö; lehet, éa 117 jelentése H, (CrCA-aikíl-csoport. vagy ahol US jelptiése egy: aljfes heiemcikltts, ahol az alifás heíetoeí&amp;los oxelahlík Îe4pib3î®îhiraaii-, tetralhdropiraoik, $pjprfoimvk piperidinll-, :pim)Ä«ö-cäS®|^ii': választott, és ahol az alifás heteröeékies adott eséfbea 1 vagy 2 esoposttai helpííesttetí lehetegymáslói ttigggíferíöl F, (M-.(C:-C,)-aiMi~Q~ és^r&amp;ê~^}^m)ff(^}0r^M véMs&amp;m, és a%á az alkiksopottok egy vagy többipdpßgÄÄfrnj^ 0ttô«8É0»ÂÂîÿet^lteitt::.jy|^ azzal: a fettétellel, hogy |g m. (ï) MpBf %&amp;£&amp;&amp; yfcgÿSletekiæàtà· jeleitése 3-dSîmfëjïiI maradék és X jelentése 2,4-difiáoFlcttíl maradik, R5 jelesébe nem d-metilAtxeiäo-a-lK iólrahtdíoferáií-áAf-, tetrahiâropirân-4-ii" vagy i-meti!-piperiÂ~441-esoporî, M jeletttéxe 14, (CrQ^aikä-, (€34isj^Äioalkihcsopott, ahol az alkitssopor i egy hidrogénatomja OB- vagy (C< QValkis-O-esoporítal helyettesített lehet, és aboi m alkilesoportoi. egy ItaratomMál helyettesített lehet; R? jelentése 11, (Q-C<,)-aikil-esoport; ahol az alkíicsopottok egy yagy íóbh hidropoatottp flnoratommal helyeth^iett lelet,
8. 13, Egy 12, igénypont szerinti vegvölet, ahol A jelentése feni lesöpört, ahol a feÄsoport 1 vagy 2 ssoporttal helyetteshetí egymástól üggcilennl F, Cl, Br, CM-, (€y»€hj-âlkik CF.·-, CF;,H-, CFB>-, metoxí-, etoxk OCFr és {CrCjFalkibS-csoport köréből választva; X jelentése fenifaoport. shpl a fénilcaoport 1 vagy 2 csoporttal belyefeltefí Egymástól fhggetfc»ftf F« Cl, Br, 04-* {Ci-&amp;t)~ aîkik CFr, €F;1Í~,. Ä roetoxk «foxi-, OCF<-, (C r€.;>.a?kihS% (Cä-C;)-alkn-0-C(0> és me-ílf-S-Oj-csopoa köréből választva, Itjsbniésé ÍS€l(*€l-- vagy mmibSO^esopori:, 12 jeleMésé Η* pvCB^lkU··,: c ikloprogrl-esopori; fô-Jek»ë$e H, metd-esdpeit; 14 jelentése H, oteti besöpöri; vagy áW 13 és 14 egyöh egjt etilén hidat síkét; és ahoi RS: jéleskésé égy hetefölrU- vagy beferoafil-ÇCrCftFaikibcsopori;, ahol « heferoarll maradék. pkídttt»^ m. piridie-Sdl··, piHdin-4-ll-, tíöfé«-2-il-* tioléíe3öÍ'> hazol-S-il, tiáxeM-lK fiazel-S-íj'·, izoltszol-á-i:b, ix0ilsyoi-4db, szotlazel-S-ii-, pirazol-BXk, ís»idagol-4«-iFv: pinnrídin-
9. 24.K plnmidin-d-ik pirimidk-S-il-, piridazm^yh* praxmXblh és pirazin-3~M~ csopörgés áhol ezek a maradékok: adod esæi|» .1. vagy 2 esoporttal helyedesltcííek egytnástőí ISggetfeaüí F, Cl, Bi PF-, metlK Mil·, metoxl-, etex!-, GM~, meflhiC^esoport köréből választva*. azzal a jéitételleL hogy ha ax (iyk«f lot széöfífi vogyuleíbeo A jelentése 3-ciano|bmFísarad«kés X fe- lentése: 2sMi$uoffemf maradék, -M- jeietdéss: nem; pirifmdim44F,: ghidkvőMil, Í~n»kpiíazol-3- íF vagy !-ö^isbiniidax0h2#il-csopof1, vagy ahol R5 jelentése metdesoport, azzal a: J é hetedei, hogy ha áz (í) képlet szetélíí vegyülelskbén 12, 13 és R4 jelentése feidrogÉmfopj és X jélentéSé 2,4-dIÍoorfeídÍ maradék, A jelentése aera pirÄ-3'fl-, 2-fíuór-feilX: 3~llaordémh, 4-flöOrSlb, f-eisPö'lsbíF, d-metoxirip&amp;tbN o-ínlsxametoxi-iahik 2-fíoof-5-íhe3oxf-fesi4ssöporf, és azzal a feltétellel, hogy ha az (I) képiét; szerinti vegyületeklnm R2, R3 és R4 jiiie és X jeiethése maradék, A jelentése nem 4~8«ort®ml maradék, és azzal a feiételíeh hogy ha az (I) képlet szerinti vegyiletakfeen 13 jelentése nmtilasopott, 12 és R4 jelentése Indrogénatont Is X jelentése maradék, A jelentése nem 4-Baer--Íénil-esíípofts és azzal a feltétellel, högy: ha az (1) képiek szerinti yegyölefekben 12,13 és 14 jélsatése hidrogénatom és Ä jelentése é-lnpr-fénibeaígíört, X jelentése nem 2-klof-témÍ~, 3i4-díklér-hmíP> 4-klór-ienih, driánor-fenih-v 4-metlÍ4fen'H-, 4-metexi-lénil·-, 4«etóxkfé^|h vagy 4~aeetoxífeni3-csopört, és vagy ahol 15 jelentése 11, (Cj-Chj-alkik CFrc»oport; vagy ahol R| jelentése cikiopropil-, eiklobmih, elktopentll-, eiklohexih vagy |CrC6j-etkloalkll-(C;-C>)-alkií'· csoport, ami a feltétellel,. bogy ba .az (!) 'képlet szerinti végletekben A jelentése· 3-danofasÍ maradék és X jelentése 2,4K!lfíaorfeml maradék, R5 jelentése nem elfelopropll-esopert;» vagy ahol R5 jelentése (CrC;.)-a!kl~0- vagy (CivCjjhalkil-S-esopott,. almi az alkiksnportok egy vagy több ydmgénsíomja 'flnoeatopmal fceïyettes&amp;est lehet vagy ahol RS Jelentése (C»«C*)«alk ü-CMneíik HCKCpQ t-alkíl-csopott, ahol az alki lesöpörtek egy vagy több hidrogénatomja Eueraiomnm! helyettesített lebeg vagy ahol R5 jelentése feni-, íeniKCV-CEKílkli-esoport ahol a feoílesoportok adott esetben 1-3 csoporttal helyettesítettek egymástól független«! P, Cl, Br, CFys (Cv-Cjl-alkll-, {C.rCv)-alkil-Ö-5 CN~, metikSOrcsopo?t köréből választva, és ahol m alk besöpörtök egy vagy több fridrogénatömja ßnoralomma] Imlyettesltett lebet, azzal a feltétellel, bogy ba az (!) képlet szerinti vegyöletekben A jelentése 3-danofensÍ maradék és X jelentése Sy't-dMttorfeal maradék. R5 jelentése, nem 3-míeífiszefltmibfemk 4-metifenîfbnil-feA. csoport; vagy ahol R5 jelentése R7R0M~csoport, ahol Ró jelentése íl, (CrC,í)~alkik mklopropll-esopoft, ahol az alkifcsoport egy hidrogénatomja Iriötoxk metoxk vagy etoxlcsopofttal helyetiesitett lebet és ,R? jelentése ti maiik, etifcsoport vagy ahol RS jelentése egy aillas heterodklus, ahol az allias beteroeiklos oxotanib, tetralridrofeamk tettabklropiratbk morfoHník piperidlmk plmdidmO-esoport köréből választott, és ahol az alifás heteroeiklns adott esetben \ vagy 2 csoporttá] helyettesített lehet egymástól fíiggeilenöi F, ÖH~. {CrC'jlhaiyi-O- és (CrChRalklkcsopod. koréból választva, és ahol az alkdosoportok egy vagy több hidrogénatomja ffeoratommal helyettesített lehet, azzal a feltételiek hogy ba az (!) képlet szerinti vegyietekben A jelentése 3~eianofenif maradék és X jelentése 2,4-dÄorferil maradék, RS jelentése nem S-meti-oxeián-j-tk tetralMdrofeánmrik tetrahidtop iráo-4rib vagy I mmíikpiperidimáribesopoft, és/vagy az (I) általános képiéin vegyhlet sztereolzomer alakja, és/vagy ezets alakok keverékei és/vagy gyógyászatüag elogadbafó sóik, |4, Egy KI. igénypont szemű vegyidet, ahol A jelenese fen! lesöpört, ahö! 8 íémlesojpert 1 vagy 2. csoporttal helyettesített egymástól fÖggetleBöt Fr C|, Br,CH-, (€3~€b)-alkik €P;r> €2211-. €FHr, motosi-, eso>o~, OCFr ès (CpCrHRkd-S-osopcst koréból válásaivá: X je iemése: fèa-Éesopoit» aboi a femlesopori 1 vagy :2 csoporttal helye tics ítélt egytoástól itgpgfeoüf F; CI, Br, CH-, (CrCp-alkil-, CF^, CFjH-. €PH>-, metoxk eîoxk OCI'V· (CrC^-alMRS-,, {€ä-(72)-0Skll-Ö-C(ö)·· es me·· til-SCk-csoport köréből választott, RI jelentése R$-0(K)}-csoport; R2 jelentése H, (Cj C-)-‘dkik c iklopropll-esoporÇ R3 jelentése H, metis-csoport; R4jelentése H, «tetil-esoport; vagy ahol R3 és R4 együtt egy etilé« hidat alkot; és ahol R5 jelentése (CrCO-HkO-csopotr; és/vagv -m {!} általános képiéin vegyilét sÄceöiiomet: atóp, és/vagy ea alakok keverékei és/yagy gydgyászafilag elfogadható sóik.
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