Substituted diazaheterobic compounds and their use

Description

[0001] The present application relates to (imidazo[1,2-a]pyridin-3-yl)methyl-substituted diazaheterobicyclic compounds, processes for their preparation, their use alone or in combinations for the treatment and / or prevention of diseases, and their use for the production of medicaments for the treatment and / or prevention of diseases, in particular for the treatment and / or prevention of respiratory disorders, including sleep-related respiratory disorders such as obstructive and central sleep apnea and snoring. Furthermore, the present application relates to a method for identifying a compound with TASK-1 and / or TASK-3 blocking properties.

[0002] Potassium channels are virtually ubiquitous membrane proteins that are involved in a wide variety of physiological processes. This includes the regulation of membrane potential and the electrical excitability of neurons and muscle cells. Potassium channels are divided into three major groups, which differ in the number of transmembrane domains (2, 4, or 6). The group of potassium channels in which two pore-forming domains are flanked by four transmembrane domains is called K2P channels. Functionally, K2P channels mediate background K+ / < currents in a largely time- and voltage-independent manner and play a crucial role in maintaining the resting membrane potential. The K2P channel family comprises 15 members, divided into six subfamilies based on similarities in sequence, structure, and function: TWIK, TREK, TASK, TALK, THIK, and TRESK.

[0003] Of particular interest are TASK-1 (KCNK3 or K2P3.1) and TASK-3 (KCNK9 or K2P9.1) of the TASK (TWIK-related acid-sensitive K +< channel) subfamily. These channels are functionally characterized by the fact that so-called "leakage" or "background" currents flow through them while maintaining voltage-independent kinetics, responding to a variety of physiological and pathological influences with an increase or decrease in activity. A characteristic of TASK channels is their sensitive response to changes in extracellular pH: the channels are inhibited at acidic pH and activated at alkaline pH.

[0004] TASK-1 is predominantly expressed in the central nervous system and the cardiovascular system. Relevant expression of TASK-1 has been observed in the brain, spinal ganglia, motor neurons of the Hypoglossal nerve and Trigeminal nerve, in heart, Carotid body,Pulmonary artery, aorta, lung, pancreas, placenta, uterus, kidney, adrenal gland, small intestine, and stomach, as well as on T lymphocytes. TASK-3 is mainly expressed in the central nervous system. Relevant expression of TASK-3 has been observed in the brain, motor neurons of the Hypoglossal nerve and Trigeminal nerve and in neuroepithelial cells of the Carotid body and lungs, as well as on T lymphocytes. Lower expression is found in the heart, stomach, testicular tissue, and adrenal gland.

[0005] TASK-1 and TASK-3 channels play a role in the regulation of respiration. Both channels are expressed in the respiratory neurons of the respiratory center in the brainstem, including neurons that generate the respiratory rhythm (ventral respiratory group with the pre-Bötzinger complex), and in the noradrenergic Locus caeruleusas well as in serotonergic neurons of the raphe nuclei. Due to their pH dependence, the TASK channels act as a sensor that translates extracellular pH changes into corresponding cellular signals [Bayliss et al., Pflügers Arch. 467, 917-929 (2015)]. Carotid body, TASK-1 and TASK-3 are expressed in a peripheral chemoreceptor that measures pH, O 2 , and CO 2 levels in the blood and transmits signals to the respiratory center in the brainstem to regulate respiration. TASK-1 knockout mice have been shown to exhibit a reduced ventilatory response (increase in respiratory rate and tidal volume) to hypoxia and normoxic hypercapnia [Trapp et al., J. Neurosci. 28, 8844-8850 (2008)]. Furthermore, TASK-1 and TASK-3 channels have been identified in motor neurons of the Hypoglossal nerve, the XII cranial nerve, which has an important function in maintaining the patency of the upper airways [Berg et al., J. Neurosci. 24, 6693-6702 (2004)].

[0006] In a sleep apnea model in an anesthetized pig, intranasal administration of a potassium channel blocker that blocks the TASK-1 channel in the nanomolar range inhibited the collapsibility of the pharyngeal airway muscles and sensitized the negative pressure reflex of the upper airway. It is hypothesized that intranasal administration of the potassium channel blocker depolarizes mechanoreceptors in the upper airway and, via activation of the negative pressure reflex, leads to increased activity of the upper airway muscles, thereby stabilizing the upper airway and preventing collapse. Through such stabilization of the upper airway, TASK channel blockade may be of great importance for obstructive sleep apnea and snoring [Wirth et al., Sleep 36, 699-708 (2013); Kiper et al., Pflügers Arch. 467, 1081-1090 (2015)].

[0007] Obstructive sleep apnea (OSA) is a sleep-related breathing disorder characterized by repeated episodes of upper airway obstruction. During inspiration, the patency of the upper airway is maintained by the interplay of two opposing forces. The dilating effects of the upper airway muscles counteract the negative intraluminal pressure that constricts the lumen. The active contraction of the diaphragm and other accessory respiratory muscles creates negative airway pressure, thus providing the driving force for breathing. The stability of the upper airway is largely determined by the coordination and contractile properties of the dilating muscles of the upper airway.

[0008] The Genioglossus muscle plays a crucial role in the pathogenesis of obstructive sleep apnea. The activity of the Genioglossus muscleincreases with decreasing pressure in the pharynx in the sense of a dilating compensatory mechanism. Innervated by the Hypoglossal nerve It pulls the tongue forward and downward, thus expanding the pharyngeal airway [Verse et al., Somnologie 3, 14-20 (1999)]. The tension of the dilating muscles of the upper airway is modulated, among other things, by mechanoreceptors / stretch receptors in the nasopharynx [Bouillette et al., J. Appl. Physiol. Respir. Environ. Exerc. Physiol. 46, 772-779 (1979)]. Local anesthesia of the upper airway can result in an additional reduction in the activity of the Genioglossus muscle [Berry et al., Am. J. Respir. Crit. Care Med. 156, 127-132 (1997)]. Patients with obstructive sleep apnea have a high mortality and morbidity due to cardiovascular diseases such as hypertension, myocardial infarction, and stroke [Vrints et al., Acta Clin. Belg. 68, 169-178 (2013)].

[0009] In central sleep apnea, episodic inhibition of the respiratory drive occurs as a result of impaired brain function or impaired respiratory regulation. Centrally caused respiratory disorders lead to mechanical apnea, meaning that during these episodes, no breathing activity occurs; all respiratory muscles, including the diaphragm, temporarily stop working. In central sleep apnea, there is no obstruction of the upper airway.

[0010] Primary snoring also doesn't involve an obstruction of the upper airway. However, the narrowing of the upper airway increases the velocity of inhaled and exhaled air. This, combined with the relaxed muscles, causes the soft tissues of the mouth and throat to flutter in the airstream. This slight vibration then produces the typical snoring noise.

[0011] Obstructive snoring ( upper airway resistance syndrome, heavy snoring,Hypopnea syndrome (also known as hypopnea syndrome) is caused by recurrent partial obstruction of the upper airways during sleep. This leads to an increase in airway resistance and thus to an increase in the work of breathing with significant intrathoracic pressure fluctuations. The negative intrathoracic pressure development during inspiration can reach levels similar to those resulting from complete airway obstruction in obstructive sleep apnea. The pathophysiological effects on the heart, circulation, and sleep quality are similar to those in obstructive sleep apnea. As with obstructive sleep apnea, the pathogenesis is assumed to be a disturbed reflex mechanism of the pharyngeal dilating muscles during inspiration. Obstructive snoring is often a precursor to obstructive sleep apnea [Hollandt et al., HNO 48, 628-634 (2000)].

[0012] TASK channels also appear to play a role in neuronal cell death. In the animal model of myelin oligodendrocyte glycoprotein (MOG)-induced autoimmune encephalomyelitis, an animal model for multiple sclerosis, TASK-1 knockout mice showed reduced neuronal degeneration. Inhibition of TASK channels appears to exert a neuroprotective effect by preventing neuronal apoptosis and may therefore be of interest for the treatment of neurodegenerative diseases [Bittner et al., Brain 132, 2501-2516 (2009)].

[0013] Furthermore, it has been described that T lymphocytes express TASK-1 and TASK-3 channels, and that inhibition of these channels leads to reduced cytokine production and proliferation after stimulation of T lymphocytes. Selective inhibition of TASK channels on T lymphocytes improved disease progression in an animal model of multiple sclerosis. Blockade of TASK channels may therefore also be important for the treatment of autoimmune diseases [Meuth et al., J. Biol. Chem. 283, 14559-14579 (2008)].

[0014] TASK-1 and TASK-3 are also expressed in the heart [Rinné et al., J. Mol. Cell. Cardiol. 81, 71-80 (2015)]. Since TASK-1 is particularly highly expressed in the conduction system and in the atrium, this channel may play a role in the initiation of conduction disturbances or supraventricular arrhythmias. In the heart, TASK-1 appears to contribute to a background current, which in turn contributes to the maintenance of the resting potential, action potential duration, and repolarization [Kim et al., Am. J. Physiol. 277, H1669-1678 (1999)]. It has been shown in human cardiac myocytes that blockade of the TASK-1 ion current leads to a prolongation of the action potential [Limberg et al., Cell. Physiol. Biochem. 28, 613-624 (2011)]. Furthermore, a prolonged QT interval was demonstrated in TASK-1 knock-out mice [Decher et al., Cell. Physiol. Biochem. 28 77-86 (2011)].The inhibition of TASK channels could therefore be important for the treatment of cardiac arrhythmias, especially atrial fibrillation.

[0015] TASK channels also appear to play a role in the regulation of vascular tone in certain vessels. Significant expression of TASK-1 has been observed in the smooth muscle of pulmonary and mesenteric arteries. Studies on smooth muscle cells from human pulmonary arteries have shown that TASK-1 plays a role in the regulation of pulmonary vascular tone. TASK-1 may be involved in hypoxic and acidosis-induced pulmonary vasoconstriction [Tang et al., Am. J. Respir. Cell. Mol. Biol. 41, 476-483 (2009)].

[0016] In glomerulosa cells of the adrenal cortex, TASK-1 plays a role in potassium conductance [Czirjak et al., Mol. Endocrinol. 14, 863-874 (2000)].

[0017] TASK channels may also play an important role in apoptosis and tumorigenesis. TASK-3 has been found to be highly overexpressed in breast cancer, colon cancer, and lung cancer biopsies, as well as in metastatic prostate cancer and melanoma cells [Mu et al., Cancer Cell 3, 297-302 (2003); Kim et al., APMIS 112, 588-594 (2004); Pocsai et al., Cell. Mol. Life Sci. 63, 2364-2376 (2006)]. A point mutation in the TASK-3 channel, which inactivates channel function, simultaneously abolishes its tumorigenic effect (proliferation, tumor growth, apoptosis resistance) [Mu et al., Cancer Cell 3, 297-302 (2003)]. Overexpression of TASK-3 and TASK-1 in a murine fibroblast cell line (C8 cells) inhibits intracellular apoptosis pathways [Liu et al., Brain Res. 1031, 164-173 (2005)]. Blockade of TASK channels may therefore also be important for the treatment of various cancers.

[0018] The object of the present invention is therefore to provide new substances that act as potent and selective blockers of TASK-1 and TASK-3 channels and as such are particularly suitable for the treatment and / or prevention of breathing disorders, including sleep-related breathing disorders such as obstructive and central sleep apnea and snoring, as well as other diseases.

[0019] US 2002 / 0022624-A1 describes various azaindole derivatives, including imidazo[1,2-a]pyridines, as substance P antagonists for the treatment of CNS diseases. WO 02 / 066478-A1 discloses substituted imidazo[1,2-a]pyridines as GnRH antagonists for the treatment of sex hormone-dependent diseases. WO 2004 / 035578-A1 discloses 3-(aminomethyl)imidazo[1,2-a]pyridine derivatives as NO synthase inhibitors, which can be used to treat various diseases. WO 02 / 02557-A2 and WO 2009 / 143156-A2 claim 2-phenylimidazo[1,2-a]pyridine derivatives suitable as modulators of GABA A receptors for the treatment of CNS diseases. WO 2011 / 113606-A1 and WO 2012 / 143796-A2 disclose bicyclic imidazole derivatives suitable for the treatment of bacterial infections and inflammatory diseases, respectively.EP 2 671 582-A1 describes bicyclic imidazole derivatives and their therapeutic applications as inhibitors of T-type calcium channels. WO 2012 / 130322-A1 describes 2,6-diaryl-3-(piperazinomethyl)imidazo[1,2-a]pyridine derivatives, which, due to their HIF-1 inhibiting activity, are particularly suitable for the treatment of inflammatory and hyperproliferative diseases. WO 2014 / 187922-A1 discloses various 2-phenyl-3-(piperazinomethyl)imidazo[1,2-a]pyridine derivatives as inhibitors of glucose transporters (GLUT), which can be used for the treatment of inflammatory, proliferative, metabolic, neurological, and / or autoimmune diseases. WO 2015 / 144605-A1 describes acylated bicyclic amine compounds that are suitable as inhibitors of autotaxin and lysophosphatidic acid production for the treatment of various diseases.WO 2016 / 084866-A1 and WO 2016 / 088813-A1 disclose acylated diazabicyclic compounds which, due to their antagonistic effect on orexin receptors, can be used for the treatment of neurodegenerative diseases, mental disorders and eating and sleeping disorders, in particular insomnia.

[0020] The present invention relates to compounds of the general formula (I) in which the ring Q represents a diaza-heterobicycle of the formula or wherein * denotes the link to the adjacent methylene group and ** denotes the link to the carbonyl group, A and D each represent CH or one of these ring members represents CH and the other represents N, R 1< represents halogen, cyano, (C 1 -C 4 )-alkyl, cyclopropyl or cyclobutyl, where (C 1 -C 4 )-alkyl may be substituted up to three times by fluorine and cyclopropyl and cyclobutyl may be substituted up to two times by fluorine, and R 2< represents (C 4 -C 6 )-cycloalkyl, where one ring CH 2 group may be replaced by -O-, or R 2< represents a phenyl group of the formula (a), a pyridyl group of the formula (b) or (c) or an azole group of the formula (d) where *** marks the link to the adjacent carbonyl group and R 3< denotes hydrogen, fluorine, chlorine, bromine or methyl, R 4< denotes hydrogen, fluorine, chlorine, bromine, cyano, (C 1 -C 3 )-alkyl or (C 1 -C 3 )-alkoxy, where (C 1 -C 3 )-alkyl and (C 1 -C 3 )-alkoxy may be substituted up to three times by fluorine, R 5< denotes hydrogen, fluorine, chlorine, bromine or methyl, R 6< denotes hydrogen, (C 1 -C 3 )-alkoxy, cyclobutyloxy, oxetan-3-yloxy, tetrahydrofuran-3-yloxy or tetrahydro-2 H-pyran-4-yloxy, where (C 1 -C 3 )-alkoxy may be substituted up to three times by fluorine, R 7< denotes hydrogen, fluorine, chlorine, bromine, (C 1 -C 3 )-alkyl or (C 1 -C 3 )-alkoxy, R 8A< and R 8B< are identical or different and independently of one another denote hydrogen or (C 1 -C 3 )-alkyl and Y denotes(R 9<), O or S, where R 9< denotes hydrogen or (C 1 -C 3 )-alkyl, or R 2< denotes a group -OR 10< or -NR 11< R 12<, where R 10< denotes (C 1 -C 4 )-alkyl or (C 4 -C 6 )-cycloalkyl, R 11< denotes hydrogen or (C 1 -C 3 )-alkyl and R 12< (C 1 -C 6 )-alkyl, (C 3 -C 6 )-cycloalkyl, phenyl or benzyl, where (C 1 -C 6 )-alkyl may be substituted up to three times by fluorine and where phenyl and the phenyl group in benzyl may be substituted up to two times, identically or differently, by a radical selected from the series fluorine, chlorine, methyl, ethyl and trifluoromethyl,or R 11< and R 12< are linked together and together with the nitrogen atom to which they are attached form a pyrrolidine, piperidine, morpholine or thiomorpholine ring, as well as their salts, solvates and solvates of the salts. ,

[0021] Compounds according to the invention are the compounds of formula (I) and their salts, solvates and solvates of the salts, the compounds of the formulas (IA), (IB) and (IC) included in formula (I) and their salts, solvates and solvates of the salts, as well as the compounds included in formula (I) and mentioned below as working examples and their salts, solvates and solvates of the salts, insofar as the compounds included in formula (I) and mentioned below are not already salts, solvates and solvates of the salts.

[0022] As SaltsFor the purposes of the present invention, physiologically acceptable salts of the compounds according to the invention are preferred. Also included are salts that are not suitable for pharmaceutical applications themselves, but can be used, for example, for the isolation, purification, or storage of the compounds according to the invention.

[0023] Physiologically acceptable salts of the compounds according to the invention include acid addition salts of mineral acids, carboxylic acids and sulfonic acids, e.g. salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, naphthalenedisulfonic acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, succinic acid, fumaric acid, maleic acid, lactic acid, tartaric acid, malic acid, citric acid, gluconic acid, benzoic acid and embonic acid.

[0024] As SolvatesFor the purposes of the invention, "hydrates" refer to those forms of the compounds according to the invention which, in the solid or liquid state, form a complex by coordination with solvent molecules. Hydrates are a special form of solvates in which coordination occurs with water. Hydrates are preferred as solvates for the purposes of the present invention.

[0025] Depending on their structure, the compounds according to the invention can exist in different stereoisomeric forms, i.e., in the form of configurational isomers or, optionally, also as conformational isomers (enantiomers and / or diastereomers, including those in the case of atropisomers). The present invention therefore encompasses the enantiomers and diastereomers and their respective mixtures. From such mixtures of enantiomers and / or diastereomers, the stereoisomerically uniform components can be isolated in a known manner; chromatographic methods are preferably used for this purpose, in particular HPLC chromatography on chiral or achiral separating phases. In the case of chiral amines as intermediates or end products, separation via diastereomeric salts using enantiomerically pure carboxylic acids can alternatively be carried out.

[0026] If the compounds according to the invention can occur in tautomeric forms, the present invention encompasses all tautomeric forms.

[0027] The present invention also encompasses all suitable isotopic variants of the compounds according to the invention. An isotopic variant of a compound according to the invention is understood to mean a compound in which at least one atom within the compound according to the invention is exchanged for another atom of the same atomic number but with a different atomic mass than the atomic mass usually or predominantly occurring in nature. Examples of isotopes that can be incorporated into a compound according to the invention are those of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine and iodine, such as 2<H (deuterium), 3<H (tritium), 13<C, 14<C, 15<N, 17<O, 18<O, 32<P, 33<P, 33<S, 34<S, 35<S, 36<S, 18<F, 36<Cl, 82<Br, 123<I, 124<I, 129<I and 131<I.Certain isotopic variants of a compound according to the invention, particularly those incorporating one or more radioactive isotopes, can be useful, for example, for investigating the mechanism of action or the distribution of the active ingredient in the body. Due to their comparative ease of preparation and detection, compounds labeled with 3< H or 14< C isotopes are particularly suitable for this purpose. Furthermore, the incorporation of isotopes, such as deuterium, can lead to certain therapeutic advantages as a result of greater metabolic stability of the compound, such as an extension of the half-life in the body or a reduction in the required effective dose. Such modifications of the compounds according to the invention can therefore also represent a preferred embodiment of the present invention.Isotopic variants of the compounds according to the invention can be prepared by generally customary methods known to the person skilled in the art, such as:

[0028] for example, according to the methods described below and the instructions given in the working examples, by using appropriate isotopic modifications of the respective reagents and / or starting compounds.

[0029] In the context of the present invention, the substituents and radicals, unless otherwise specified, have the following meaning: (C 1 -C 6 )-alkyl In the context of the invention, represents a straight-chain or branched alkyl radical having 1 to 6 carbon atoms. Examples include: methyl, ethyl, n -Propyl, Isopropyl, n -Butyl, Isobutyl, sec .-Butyl, tert .-Butyl, n -Pentyl, 2-Pentyl, 3-Pentyl, Neopentyl, n-Hexyl, 2-hexyl and 3-hexyl. (C 1 -C 4 )-alkyl In the context of the invention, R represents a straight-chain or branched alkyl radical having 1 to 4 carbon atoms. Examples include: methyl, ethyl, n -Propyl, Isopropyl, n -Butyl, Isobutyl, sec .-Butyl and tert. -Butyl . (C 1 -C 3 )-alkyl In the context of the invention, R represents a straight-chain or branched alkyl radical having 1 to 3 carbon atoms. Examples include: methyl, ethyl, n -Propyl and isopropyl. (C 1 -C 3 )-alkoxy In the context of the invention, R represents a straight-chain or branched alkoxy radical having 1 to 3 carbon atoms. Examples include: methoxy, ethoxy, n -Propoxy and isopropoxy. (C 3 -C 6 )-CycloalkylIn the context of the invention, R represents a monocyclic, saturated cycloalkyl group having 3 to 6 ring carbon atoms. Examples include: cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. (C 4 -C 6 )-Cycloalkyl In the context of the invention, represents a monocyclic, saturated cycloalkyl group having 4 to 6 carbon atoms. Examples include: cyclobutyl, cyclopentyl, and cyclohexyl. halogen Within the scope of the invention, includes fluorine, chlorine, bromine, and iodine. Fluorine, chlorine, or bromine are preferred.

[0030] Within the scope of the present invention, the meaning of all radicals that occur multiple times is independent of one another. If radicals in the compounds according to the invention are substituted, the radicals may be mono- or polysubstituted, unless otherwise specified. Substitution with one or two identical or different substituents is preferred. Substitution with one substituent is particularly preferred.

[0031] Preferred in the context of the present invention are compounds of formula (I) in which the ring Q represents a diaza-heterobicycle of the formula where * denotes the link to the adjacent methylene group and ** denotes the link to the carbonyl group, A and D each denote CH or one of these ring members denotes CH and the other denotes N, R 1< represents fluorine, chlorine, bromine, methyl, isopropyl, tert-butyl,Cyclopropyl or cyclobutyl, and R 2< is cyclobutyl, cyclopentyl or cyclohexyl or R 2< is a phenyl group of formula (a), a pyridyl group of formula (b) or an azole group of formula (d) where *** marks the link to the adjacent carbonyl group and R 3< denotes hydrogen, fluorine or chlorine, R 4< denotes fluorine, chlorine, cyano, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy or trifluoromethoxy, R 5< denotes hydrogen, fluorine, chlorine, bromine or methyl, R 6< denotes (C 1 -C 3 )-alkoxy, which may be substituted up to three times by fluorine, or cyclobutyloxy, R 8A< and R 8B< independently denote hydrogen or methyl and Y denotes(CH 3 ), O or S, or R 2< represents a group -NR 11< R 12<, in which R 11< is hydrogen or (C 1 -C 3 )-alkyl and R 12< is (C 1 -C 6 )-alkyl or phenyl, where phenyl may be substituted up to two times, identically or differently, by a radical selected from the group consisting of fluorine, chlorine, methyl, ethyl and trifluoromethyl, or R 11< and R 12< are linked to one another and together with the nitrogen atom to which they are attached form a pyrrolidine, piperidine or thiomorpholine ring, as well as their salts, solvates and solvates of salts.

[0032] A further preferred embodiment of the present invention comprises compounds of formula (I) in which the ring Q represents a diaza-heterobicycle of the formula where * denotes the link to the adjacent methylene group and ** denotes the link to the carbonyl group, A stands for CH or N, D stands for CH, R 1< stands for fluorine, chlorine, bromine, methyl, isopropyl, tert-butyl,Cyclopropyl or cyclobutyl, and R 2< is cyclobutyl, cyclopentyl or cyclohexyl or R 2< is a phenyl group of formula (a), a pyridyl group of formula (b) or an azole group of formula (d) where *** marks the link to the adjacent carbonyl group and R 3< denotes hydrogen, fluorine or chlorine, R 4< denotes fluorine, chlorine, cyano, (C 1 -C 3 )-alkyl, (C 1 -C 3 )-alkoxy or trifluoromethoxy, R 5< denotes hydrogen, fluorine, chlorine, bromine or methyl, R 6< denotes (C 1 -C 3 )-alkoxy, which may be substituted up to three times by fluorine, or cyclobutyloxy, R 8A< and R 8B< independently denote hydrogen or methyl and Y denotes(CH 3 ), O or S, or R 2< represents a group -NR 11< R 12<, in which R 11< is hydrogen or (C 1 -C 3 )-alkyl and R 12< is (C 1 -C 6 )-alkyl or phenyl, where phenyl may be substituted up to two times, identically or differently, by a radical selected from the group consisting of fluorine, chlorine, methyl, ethyl and trifluoromethyl, or R 11< and R 12< are linked to one another and together with the nitrogen atom to which they are attached form a pyrrolidine, piperidine or thiomorpholine ring, as well as their salts, solvates and solvates of salts.

[0033] A particular embodiment of the present invention relates to compounds of formula (I) in which the ring Q represents a diaza-heterobicycle of the formula where * denotes the linkage to the adjacent methylene group and ** denotes the linkage to the carbonyl group, as well as their salts, solvates and solvates of the salts.

[0034] A further particular embodiment of the present invention relates to compounds of formula (I) in which the ring Q represents a diaza-heterobicycle of the formula where * denotes the linkage to the adjacent methylene group and ** denotes the linkage to the carbonyl group, as well as their salts, solvates and solvates of the salts.

[0035] A further particular embodiment of the present invention relates to compounds of formula (I) in which the ring Q represents a diaza-heterobicycle of the formula where * denotes the linkage to the adjacent methylene group and ** denotes the linkage to the carbonyl group, as well as their salts, solvates and solvates of the salts.

[0036] A further particular embodiment of the present invention relates to compounds of formula (I) in which A and D each represent CH, as well as their salts, solvates and solvates of the salts.

[0037] A further particular embodiment of the present invention relates to compounds of formula (I) in which A stands for N and D for CH, as well as their salts, solvates and solvates of the salts.

[0038] A further particular embodiment of the present invention relates to compounds of formula (I) in which R 1< represents chlorine, bromine or isopropyl, as well as their salts, solvates and solvates of salts.

[0039] A further particular embodiment of the present invention relates to compounds of formula (I) in which R 2< represents cyclobutyl, cyclopentyl or cyclohexyl, as well as their salts, solvates and solvates of salts.

[0040] A further particular embodiment of the present invention relates to compounds of formula (I) in which R 2< represents a phenyl group of formula (a) where *** marks the link to the adjacent carbonyl group, R 3< represents hydrogen, fluorine or chlorine and R 4< represents fluorine, chlorine, (C 1 -C 3 )-alkyl or (C 1 -C 3 )-alkoxy, as well as their salts, solvates and solvates of salts.

[0041] A further particular embodiment of the present invention relates to compounds of formula (I) in which R 2< represents a pyridyl group of formula (b) where *** marks the link to the adjacent carbonyl group, R 5< is hydrogen, fluorine, chlorine, bromine or methyl and R 6< is (C 1 -C 3 )-alkoxy, which may be substituted up to three times by fluorine, or cyclobutyloxy, as well as their salts, solvates and solvates of salts.

[0042] Particularly preferred in the context of the present invention are compounds of formula (I) in which the ring Q represents a diaza-heterobicycle of the formula where * denotes the link to the adjacent methylene group and ** denotes the link to the carbonyl group, A and D each represent CH or one of these ring members represents CH and the other represents N, R 1< represents chlorine, bromine, isopropyl or cyclopropyl, and R 2< represents cyclobutyl, cyclopentyl or cyclohexyl or R 2< represents a phenyl group of the formula (a), a pyridyl group of the formula (b) or an azole group of the formula (d) wherein *** marks the linkage to the adjacent carbonyl group and R 3< is hydrogen, fluorine or chlorine, R 4< is fluorine, chlorine, methyl, isopropyl, methoxy or ethoxy, R 5< is hydrogen, fluorine, chlorine, bromine or methyl, R 6< is methoxy, difluoromethoxy, trifluoromethoxy, isopropoxy or cyclobutyloxy, R 8A< and R 8B< are each hydrogen and Y N(CH 3 ), as well as their salts, solvates and solvates of the salts.

[0043] A further particularly preferred embodiment of the present invention comprises compounds of formula (I) in which the ring Q represents a diaza-heterobicycle of the formula where * denotes the link to the adjacent methylene group and ** denotes the link to the carbonyl group, A denotes CH or N, D denotes CH, R 1< denotes chlorine, bromine, isopropyl or cyclopropyl, and R 2< denotes cyclobutyl, cyclopentyl or cyclohexyl or R 2< denotes a phenyl group of formula (a), a pyridyl group of formula (b) or an azole group of formula (d) wherein *** marks the linkage to the adjacent carbonyl group and R 3< is hydrogen, fluorine or chlorine, R 4< is fluorine, chlorine, methyl, isopropyl, methoxy or ethoxy, R 5< is hydrogen, fluorine, chlorine, bromine or methyl, R 6< is methoxy, difluoromethoxy, trifluoromethoxy, isopropoxy or cyclobutyloxy, R 8A< and R 8B< are each hydrogen and Y N(CH 3 ), as well as their salts, solvates and solvates of the salts.

[0044] The individual radical definitions specified in the respective combinations or preferred combinations of radicals can be replaced at will by radical definitions of other combinations, regardless of the respective specified combinations of radicals. Combinations of two or more of the above-mentioned preferred ranges are particularly preferred.

[0045] The invention further relates to a process for the preparation of the compounds of the formula (I) according to the invention, characterized in that a compound of the formula (II) in which A, D and R 1< have the meanings given above, in the presence of a suitable reducing agent, either [A] with a compound of formula (III) in which R 2< and the ring Q have the meanings given above, to a compound of formula (I) or [B] with a protected diaza-heterobicycle of formula (IV) in which the ring Q has the meaning given above and PG represents a suitable amino protecting group such as tert-butoxycarbonyl, benzyloxycarbonyl or (9H-fluoren-9-ylmethoxy)carbonyl, initially to a compound of formula (V) in which A, D, PG, R 1< and the ring Q have the meanings given above, then the protecting group PG is split off and the resulting compound of formula (VI) in which A, D, R 1< and the ring Q have the meanings given above, then depending on the specific meaning of the radical R 2< [B-1] with a carboxylic acid of the formula (VII) in which R 2A< represents (C 4 -C 6 )-cycloalkyl, in which a ring CH 2 group may be replaced by -O-, or represents a phenyl group of formula (a), a pyridyl group of formula (b) or (c) or an azole group of formula (d), as described above, with activation of the carboxylic acid function in (VII) or with the corresponding acid chloride of formula (VIII) in which R 2A< has the meaning given above, to a compound of formula (IA) in which A, D, R 1< , R 2A< and the ring Q have the meanings given above, or [B-2] with a chloroformate or carbamoyl chloride of the formula (IX) in which R 2B< represents the group -OR 10< or -NR 11A< R 12<, in which R 10< and R 12< have the meanings given above and R 11A< has the meaning given above of R 11<, but is not hydrogen, to a compound of the formula (IB) in which A, D, R 1< , R 2B< and the ring Q have the meanings given above, or [B-3] with an isocyanate of the formula (X) R 12< -N=C=O (X), in which R 12< has the meaning given above, to give a compound of the formula (IC) in which A, D, R 1< , R 12< and the ring Q have the meanings given above, and the compounds of formulas (I), (IA), (IB) or (IC) thus obtained are optionally separated into their enantiomers and / or diastereomers and / or optionally treated with the corresponding ( i ) solvents and / or ( ii ) Acids are converted into their solvates, salts and / or solvates of the salts.

[0046] Suitable reducing agents for process steps [A] (II) + (III) -> (I) and [B] (II) + (IV) -> (V) [reductive aminations] are conventional alkali metal borohydrides such as sodium borohydride, sodium cyanoborohydride, or sodium triacetoxyborohydride; sodium triacetoxyborohydride is preferably used. The addition of an acid, such as acetic acid, and / or a dehydrating agent, such as molecular sieve or trimethyl or triethyl orthoformate, can be advantageous in these reactions.

[0047] Solvents used for these reactions are particularly alcohols such as methanol, ethanol, n -Propanol or isopropanol, ethers such as diisopropyl ether, methyl- tert .-butyl ether, tetrahydrofuran, 1,4-dioxane or 1,2-dimethoxyethane, polar aprotic solvents such as acetonitrile or N , N Dimethylformamide (DMF) or mixtures of such solvents are suitable; tetrahydrofuran is preferred. The reactions generally take place in a temperature range from 0°C to +50°C.

[0048] As a protecting group PG in compound (IV) a common amino protecting group such as tert .-Butoxycarbonyl (Boc), benzyloxycarbonyl (Z) or (9 H -Fluoren-9-ylmethoxy)carbonyl (Fmoc) can be used; preference is given to tert .-Butoxycarbonyl (Boc) is used. The cleavage of the protecting group in process step [B] (V) → (VI) is carried out according to known methods. tertThe .-butoxycarbonyl group is usually removed by treatment with a strong acid, such as hydrogen chloride, hydrogen bromide, or trifluoroacetic acid, in an inert solvent such as diethyl ether, 1,4-dioxane, dichloromethane, or acetic acid. In the case of benzyloxycarbonyl as the protecting group, this is preferably removed by hydrogenolysis in the presence of a suitable palladium catalyst, such as palladium on activated carbon. The (9 H -Fluoren-9-ylmethoxy)carbonyl group is generally cleaved using a secondary amine base such as diethylamine or piperidine [see, for example, TW Greene and PGM Wuts, Protective Groups in Organic Synthesis, Wiley, New York, 1999; PJ Kocienski, Protecting Groups, 3rd edition, Thieme, 2005].

[0049] Certain compounds of formula (V), in particular those in which PG represents tert.-Butoxycarbonyl, also exhibit significant inhibitory activity against TASK-1 and / or TASK-3 and are therefore also encompassed by the scope of the present invention, ie the compounds of formula (I).

[0050] Process step [B-1] (VI) + (VII) → (IA) [amide formation] is carried out according to known methods using a condensing or activating agent. Suitable agents include, for example, carbodiimides such as N,N' -Diethyl-, N,N' -Dipropyl-, N,N' -Diisopropyl-, N , N'- Dicyclohexylcarbodiimide (DCC) or N -(3-Dimethylaminopropyl)- N '-ethylcarbodiimide hydrochloride (EDC), phosgene derivatives such as N , N '-Carbonyldiimidazole (CDI) or isobutyl chloroformate, 1,2-oxazolium compounds such as 2-ethyl-5-phenyl-1,2-oxazolium-3-sulfate or 2- tert.-Butyl-5-methylisoxazolium perchlorate, acylamino compounds such as 2-ethoxy-1-ethoxycarbonyl-1,2-dihydroquinoline, α-chlorenamines such as 1-chloro- N , N ,2-trimethylprop-1-en-1-amine, 1,3,5-triazine derivatives such as 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, phosphorus compounds such as n -Propanephosphonic anhydride (PPA), cyanophosphonic acid diethyl ester, diphenylphosphoryl azide (DPPA), bis-(2-oxo-3-oxazolidinyl)-phosphoryl chloride, benzotriazol-1-yloxy-tris-(dimethylamino)phosphonium hexafluorophosphate or benzotriazol-1-yloxy-tris(pyrrolidino)-phosphonium hexafluorophosphate (PyBOP), or uronium compounds such as O -(Benzotriazol-1-yl)- N , N , N' , N' -tetramethyluronium tetrafluoroborate (TBTU), O -(1 H -6-Chlorobenzotriazol-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TCTU), O -(Benzotriazol-1-yl)- N , N , N' , N'-tetramethyl uronium hexafluorophosphate (HBTU), O -(7-Azabenzotriazol-1-yl)- N , N , N' , N' -tetramethyluronium hexafluorophosphate (HATU) or 2-(2-oxo-1-(2 H )-pyridyl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TPTU), optionally in combination with other excipients such as 1-hydroxybenzotriazole (HOBt) or N -Hydroxysuccinimide (HOSu), and as base an alkali carbonate, e.g. sodium or potassium carbonate, or a tertiary amine base, such as triethylamine, N , N -Diisopropylethylamine, N -Methylmorpholine (NMM), N -Methylpiperidine (NMP), pyridine or 4-N,N- Dimethylaminopyridine (DMAP). The preferred condensation or activating agent is O -(7-Azabenzotriazol-1-yl)- N , N , N' , N' -tetramethyluronium hexafluorophosphate (HATU) in combination with N , N-Diisopropylethylamine as base.

[0051] The alternative process via the carboxylic acid chloride (VIII) [(VI) + (VIII) -> (IA)] is generally carried out in the presence of a base such as sodium carbonate, potassium carbonate, triethylamine, N , N -Diisopropylethylamine, N -Methylmorpholine (NMM), N -Methylpiperidine (NMP), pyridine, 2,6-dimethylpyridine, 4- N , N -Dimethylaminopyridine (DMAP), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU); preferably triethylamine or N , N -Diisopropylethylamine is used.

[0052] Suitable inert solvents for these amide formation reactions are, for example, ethers such as diethyl ether, diisopropyl ether, methyl tert.-butyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane or bis(2-methoxyethyl) ether, hydrocarbons such as benzene, toluene, xylene, pentane, hexane or cyclohexane, halogenated hydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane, 1,2-dichloroethane, trichloroethylene or chlorobenzene, or polar aprotic solvents such as acetone, methyl ethyl ketone, ethyl acetate, acetonitrile, butyronitrile, pyridine, dimethyl sulfoxide (DMSO), N , N -Dimethylformamide (DMF), N , N' -Dimethylpropyleneurea (DMPU) or N -Methylpyrrolidinone (NMP); mixtures of such solvents can also be used. Preferred solvents are dichloromethane, 1,2-dichloroethane, tetrahydrofuran, N,N Dimethylformamide or mixtures thereof are used. The reactions are generally carried out in a temperature range from -20°C to +60°C, preferably from 0°C to +40°C.

[0053] The process [B-2] (VI) + (IX) -> (IB) [formation of urethanes or substituted ureas] is carried out under similar reaction conditions regarding solvent, base addition and temperature as previously described for the amide formation [B-1] (VI) + (VIII) -> (IA).

[0054] The reaction [B-3] (VI) + (X) → (IC) is also carried out in one of the previously listed inert solvents or solvent mixtures at a temperature in the range of 0°C to +60°C; the addition of a base can be omitted in this reaction if necessary.

[0055] The amine compound (VI) can also be used in the form of a salt, for example as hydrochloride or trifluoroacetate, in process steps [B-1] (VI) + (VII) or (VIII) → (IA), [B-2] (VI) + (IX) → (IB), and [B-3] (VI) + (X) → (IC). In such a case, the reaction takes place in the presence of a correspondingly increased amount of the auxiliary base used.

[0056] The processes described above can be carried out at normal, elevated, or reduced pressure (e.g., in the range of 0.5 to 5 bar); in general, the pressure is normal.

[0057] Separation of the compounds according to the invention into the corresponding enantiomers and / or diastereomers can optionally, if appropriate, also be carried out at the stage of the compounds (III), (IV), (V) or (VI), which are then further reacted in separated form according to the process steps described above. Such separation of the stereoisomers can be carried out by customary methods known to the person skilled in the art. Within the scope of the present invention, chromatographic processes on chiral or achiral separation phases are preferably used; in the case of chiral amines as intermediates or end products, separation via diastereomeric salts using enantiomerically pure carboxylic acids can alternatively be carried out.

[0058] The compounds of formula (II) can be prepared by a process known from the literature by reacting 2-aminopyridine (XI) under the influence of a base with a compound of formula (XII) in which A, D and R 1< have the meanings given above and X represents a suitable leaving group such as chlorine, bromine or iodine, to an imidazo[1,2-a]pyridine derivative of the formula (XIII) in which A, D and R 1< have the meanings given above, and then condensed with a mixture of N , N -Dimethylformamide and phosphorus oxychloride to (II).

[0059] The condensation reaction (XI) + (XII) → (XIII) is usually carried out in an alcoholic solvent such as methanol, ethanol, n -Propanol, isopropanol or n-butanol, in an ether such as diethyl ether, diisopropyl ether, methyl- tert .-butyl ether, tetrahydrofuran, 1,4-dioxane, 1,2-dimethoxyethane or bis(2-methoxyethyl)ether, in a dipolar aprotic solvent such as N , N -Dimethylformamide (DMF), N , N'-Dimethylpropyleneurea (DMPU) or N -Methylpyrrolidinone (NMP), or in water at a temperature in the range of +50°C to +150°C; ethanol or water is preferably used as solvent.

[0060] Suitable bases for this reaction include, in particular, alkali metal bicarbonates or carbonates such as sodium or potassium bicarbonate or lithium, sodium, potassium, or cesium carbonate; alkali metal hydroxides such as sodium or potassium hydroxide; or even aluminum oxide; sodium bicarbonate or sodium hydroxide is preferred. If necessary, the reaction can also be carried out without the addition of a base—with a corresponding increase in the reaction temperature.

[0061] The regioselective formylation (XIII) → (II) is carried out under the usual conditions of a Vilsmaier-Haack reaction by treating (XIII) with a preformed mixture of N,N-Dimethylformamide and phosphorus oxychloride, which is used in large excess and also serves as a solvent. The reaction is generally carried out at a temperature range of 0°C to +100°C.

[0062] The compounds of formulas (III), (IV), (VII), (VIII), (IX), (X), (XI), and (XII) are either commercially available or described as such in the literature, or they can be readily prepared starting from other commercially available compounds using methods known from the literature and familiar to those skilled in the art. Numerous detailed procedures and further references can also be found in the Experimental Section in the section on the preparation of starting compounds and intermediates.

[0063] The preparation of the compounds according to the invention can be illustrated by the following reaction schemes:

[0064] The compounds of the invention have valuable pharmacological properties and can be used for the prevention and treatment of diseases in humans and animals.

[0065] The compounds according to the invention are potent and selective blockers of TASK-1 and TASK-3 channels and are therefore suitable for the treatment and / or prevention of diseases and pathological processes, in particular those caused by activation of TASK-1 and / or TASK-3 or by activated TASK-1 and / or TASK-3, as well as diseases induced secondarily by TASK-1 and / or TASK-3-related damage.

[0066] In the context of the present invention, these include in particular diseases from the group of breathing disorders and sleep-related breathing disorders, such as obstructive sleep apnea (in adults and children), primary snoring, obstructive snoring ( upper airway resistance syndrome, heavy snoring,Hypopnea syndrome), central sleep apnea, mixed sleep apneas, Cheyne-Stokes respiration, primary sleep apnea in childhood, apnea of ​​prematurity, central sleep apnea due to medication or substance use, obesity hypoventilation syndrome, impaired central respiratory drive, sudden infant death syndrome, primary alveolar hypoventilation syndrome, postoperative hypoxia and apnea, muscular-related breathing disorders, breathing disorders after long-term ventilation, breathing disorders during adaptation in high mountains, acute and chronic lung diseases with hypoxia and hypercapnia, sleep-related non-obstructive alveolar hypoventilation and congenital central alveolar hypoventilation syndrome.

[0067] The compounds according to the invention can further be used for the treatment and / or prevention of neurodegenerative diseases, such as dementia, dementia with Lewy bodies, Alzheimer's disease, Parkinson's disease, Huntington's disease, Pick's disease, Wilson's disease, progressive supranuclear palsy, corticobasal degeneration, Silberkorn disease, frontotemporal dementia and parkinsonism of chromosome 17, multiple system atrophy, spinocerebellar ataxias, spinobulbar muscular atrophy of Kennedy type, Friedreich's ataxia, dentatorubropallidoluysian atrophy, amyotrophic lateral sclerosis, primary lateral sclerosis, spinal muscular atrophy, Creutzfeldt-Jakob disease and variants of Creutzfeldt-Jakob disease, infantile neuroaxonal dystrophy, neurodegeneration with iron deposition in the brain, frontotemporal lobe degeneration with ubiquitin-proteasome system and familial encephalopathy with Neuroserpin inclusions.

[0068] The compounds according to the invention can furthermore be used for the treatment and / or prevention of neuroinflammatory and neuroimmunological diseases of the central nervous system (CNS), such as multiple sclerosis (disseminated encephalomyelitis), transverse myelitis, neuromyelitis optica, acute disseminated encephalomyelitis, optic neuritis, meningitis, encephalitis, demyelinating diseases and inflammatory vascular changes of the central nervous system.

[0069] The compounds according to the invention are also suitable for the treatment and / or prevention of cancers, such as skin cancer, breast cancer, lung cancer, colon cancer and prostate cancer.

[0070] The compounds according to the invention are also suitable for the treatment and / or prevention of cardiac arrhythmias and arrhythmias, such as, for example, atrial and ventricular rhythm disturbances, conduction disturbances such as grade I-III atrioventricular blocks, supraventricular tachyarrhythmia, atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular flutter, ventricular tachyarrhythmia, torsade de pointes tachycardia, atrial and ventricular extrasystoles, AV junctional extrasystoles, sick sinus syndrome, syncope and AV nodal reentrant tachycardia.

[0071] Other cardiovascular diseases for the treatment and / or prevention of which the compounds according to the invention can be used include, for example, heart failure, coronary heart disease, stable and unstable angina pectoris, high blood pressure (hypertension), pulmonary arterial hypertension (PAH) and other forms of pulmonary hypertension (PH), renal hypertension, peripheral and cardiac vascular diseases, Wolff-Parkinson-White syndrome, acute coronary syndrome (ACS), autoimmune heart diseases (pericarditis, endocarditis, valvolitis, aortitis, cardiomyopathies), boxer cardiomyopathy, aneurysms, shock such as cardiogenic shock, septic shock and anaphylactic shock, as well as thromboembolic diseases and ischemias such as myocardial ischemia, myocardial infarction, stroke, cardiac hypertrophy, transient and ischemic attacks, Preeclampsia, inflammatory cardiovascular diseases, spasms of coronary arteries and peripheral arteries,Edema formation such as pulmonary edema, cerebral edema, renal edema or heart failure-related edema, peripheral circulatory disorders, reperfusion injuries, arterial and venous thrombosis, microalbuminuria, heart muscle weakness, endothelial dysfunction, micro- and macrovascular damage (vasculitis), as well as for the prevention of restenosis, for example, after thrombolysis therapies, percutaneous transluminal angioplasties (PTA), percutaneous transluminal coronary angioplasties (PTCA), heart transplants and bypass operations.

[0072] For the purposes of the present invention, the term heart failure includes both acute and chronic manifestations of heart failure as well as specific or related disease forms thereof, such as acute decompensated heart failure, right heart failure, left heart failure, global insufficiency, ischemic cardiomyopathy, dilated cardiomyopathy, hypertrophic cardiomyopathy, idiopathic cardiomyopathy, congenital heart defects, heart valve defects, heart failure in heart valve defects, mitral valve stenosis, mitral valve insufficiency, aortic valve stenosis, aortic valve insufficiency, tricuspid stenosis, tricuspid insufficiency, pulmonary valve stenosis, pulmonary valve insufficiency, combined heart valve defects, inflammation of the heart muscle (myocarditis), chronic myocarditis, acute myocarditis, viral myocarditis, diabetic heart failure, alcoholic toxic Cardiomyopathy, cardiac storage diseases, and diastolic and systolic heart failure.

[0073] The compounds according to the invention can further be used for the treatment and / or prevention of asthmatic diseases of varying severity with an intermittent or persistent course (refractory asthma, bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma, drug-induced or dust-induced asthma), various forms of bronchitis (chronic bronchitis, infectious bronchitis, eosinophilic bronchitis), bronchiectasis, pneumonia, farmer's lung and related diseases, coughs and colds (chronic inflammatory cough, iatrogenic cough), inflammations of the nasal mucosa (including drug-induced rhinitis, vasomotor rhinitis and seasonal allergic rhinitis, e.g. hay fever) and polyps.

[0074] In addition, the compounds according to the invention are suitable for the treatment and / or prevention of kidney diseases, in particular renal insufficiency and renal failure. For the purposes of the present invention, the terms renal insufficiency and renal failure encompass both acute and chronic manifestations thereof, as well as underlying or related kidney diseases, such as renal hypoperfusion, intradialytic hypotension, obstructive uropathy, glomerulopathies, glomerulonephritis, acute glomerulonephritis, glomerulosclerosis, tubulointerstitial diseases, nephropathic diseases such as primary and congenital kidney disease, nephritis, immunological kidney diseases such as kidney transplant rejection and immune complex-induced kidney diseases, toxic substance-induced nephropathy, contrast medium-induced nephropathy, diabetic and non-diabetic nephropathy, pyelonephritis, kidney cysts, nephrosclerosis,Hypertensive nephrosclerosis and nephrotic syndrome, which can be characterized diagnostically, for example, by abnormally reduced creatinine and / or water excretion, abnormally elevated blood concentrations of urea, nitrogen, potassium, and / or creatinine, altered activity of renal enzymes such as glutamyl synthetase, altered urine osmolarity or urine volume, increased microalbuminuria, macroalbuminuria, lesions of glomeruli and arterioles, tubular dilation, hyperphosphatemia, and / or the need for dialysis. The present invention also encompasses the use of the compounds according to the invention for the treatment and / or prevention of sequelae of renal insufficiency, such as hypertension, pulmonary edema, heart failure, uremia, anemia, electrolyte disturbances (e.g., hyperkalemia, hyponatremia), and disorders of bone and carbohydrate metabolism.

[0075] Furthermore, the compounds according to the invention are suitable for the treatment and / or prevention of diseases of the urogenital system, such as benign prostatic syndrome (BPS), benign prostatic hyperplasia (BPH), benign prostatic enlargement (BPE), bladder emptying disorders (BOO), lower urinary tract syndromes (LUTS), neurogenic overactive bladder (OAB), incontinence such as mixed, urge, stress or overflow incontinence (MUI, UUI, SUI, OUI), pelvic pain as well as erectile dysfunction and female sexual dysfunction.

[0076] The compounds according to the invention are also suitable for the treatment and / or prevention of inflammatory diseases and autoimmune diseases, such as rheumatoid diseases, inflammatory eye diseases, chronic obstructive pulmonary disease (COPD), acute respiratory syndrome (ARDS), acute lung injury (ALI), alpha-1-antitrypsin deficiency (AATD), pulmonary emphysema (e.g.Suitable for the treatment of diseases such as cigarette smoke-induced pulmonary emphysema, cystic fibrosis (CF), sepsis (SIRS), multiple organ failure (MODS, MOF), inflammatory diseases of the kidney, chronic intestinal inflammation (IBD, Crohn's disease, ulcerative colitis), pancreatitis, peritonitis, cystitis, urethritis, prostatitis, epiduralism, oophoritis, salpingitis and vulvovaginitis, as well as for the treatment and / or prevention of fibrotic diseases of the internal organs, such as the lungs, heart, kidneys, bone marrow and especially the liver, dermatological fibroses and fibrotic diseases of the eye.For the purposes of the present invention, the term "fibrotic diseases" encompasses, in particular, diseases such as liver fibrosis, liver cirrhosis, pulmonary fibrosis, endomyocardial fibrosis, nephropathy, glomerulonephritis, interstitial renal fibrosis, fibrotic damage resulting from diabetes, bone marrow fibrosis, peritoneal fibrosis, and similar fibrotic diseases, scleroderma, morphea, keloids, hypertrophic scarring, nevi, diabetic retinopathy, proliferative vitroretinopathy, and connective tissue diseases (e.g., sarcoidosis). The compounds according to the invention can also be used to promote wound healing, to combat postoperative scarring, e.g., after glaucoma surgery, and for cosmetic purposes in aging or keratinizing skin.

[0077] In addition, the compounds according to the invention can be used for the treatment and / or prevention of arteriosclerosis, lipid metabolism disorders and dyslipidemias (hypolipoproteinemia, hypertriglyceridemia, hyperlipidemia, combined hyperlipidemias, hypercholesterolemia, abetalipoproteinemia, sitosterolemia), xanthomatosis, Tangier disease, obesity, metabolic diseases (metabolic syndrome, hyperglycemia, insulin-dependent diabetes, non-insulin-dependent diabetes, gestational diabetes, hyperinsulinemia, insulin resistance, glucose intolerance and late diabetic complications such as retinopathy, nephropathy and neuropathy), anemias such as hemolytic anemias, in particular hemoglobinopathies such as sickle cell anemia and thalassemia, megaloblastic anemias, iron deficiency anemias, anemias due to acute blood loss, displacement anemias and aplastic anemias, diseases of the gastrointestinal tract and abdomen (glossitis,Gingivitis, periodontitis, esophagitis, eosinophilic gastroenteritis, mastocytosis, Crohn's disease, colitis, proctitis, pruritis ani, diarrhea, celiac disease, hepatitis, liver fibrosis, liver cirrhosis, pancreatitis and cholecystitis), diseases of the central nervous system (stroke, epilepsy, depression), immune diseases, thyroid diseases (hyperthyroidism), skin diseases (psoriasis, acne, eczema, neurodermatitis, various forms of dermatitis, keratitis, bullosis, vasculitis, cellulitis, panniculitis, lupus erythematosus, erythema, lymphomas, skin cancer, Sweet's syndrome, Weber-Christian syndrome, scarring, warts, chilblains), inflammatory eye diseases (saccoidosis, blepharitis, conjunctivitis, iritis, uveitis, choroiditis, Ophthalmitis), viral diseases (caused by influenza, adenoviruses and coronaviruses, such as HPV, HCMV, HIV, SARS), diseases of the skeletal bones, joints and skeletal muscles,Inflammatory arterial changes (various forms of arteritis such as endarteritis, mesarteritis, periarteritis, polyarteritis, rheumatic arteritis, deforming arteritis, temporal arteritis, cranial arteritis, gigantocellular arteritis, and granulomatous arteritis, as well as Horton syndrome, Churg-Strauss syndrome, and Takayasu arteritis), Muckle-Well syndrome, Kikuchi disease, polychondritis, scleroderma, and other diseases with an inflammatory or immunological component, such as cataracts, cachexia, osteoporosis, gout, incontinence, leprosy, Sezary syndrome, and paraneoplastic syndrome, in rejection reactions after organ transplantation, and for wound healing and angiogenesis, particularly in chronic wounds.

[0078] Due to their property profile, the compounds according to the invention are preferably suitable for the treatment and / or prevention of respiratory disorders, in particular sleep-related respiratory disorders such as obstructive and central sleep apnea and primary and obstructive snoring, for the treatment and / or prevention of cardiac arrhythmias and arrhythmias, and for the treatment and / or prevention of neurodegenerative, neuroinflammatory and neuroimmunological diseases.

[0079] The aforementioned well-characterized human diseases can also occur in other mammals with comparable etiology and can also be treated there with the compounds of the present invention.

[0080] For the purposes of the present invention, the term "treatment" or "treat" encompasses inhibiting, delaying, stopping, alleviating, attenuating, limiting, reducing, suppressing, repressing, or curing a disease, ailment, illness, injury, or health disorder, the development, course, or progression of such conditions, and / or the symptoms of such conditions. The term "therapy" is understood here as synonymous with the term "treatment."

[0081] The terms "prevention", "prophylaxis" or "prevention" are used synonymously in the context of the present invention and refer to the avoidance or reduction of the risk of getting, experiencing, suffering or having a disease, ailment, illness, injury or health disorder, the development or progression of such conditions and / or the symptoms of such conditions.

[0082] The treatment or prevention of a disease, condition, illness, injury or health disorder may be partial or complete.

[0083] The present invention thus further relates to the use of the compounds according to the invention for the treatment and / or prevention of diseases, in particular the diseases mentioned above.

[0084] The present invention further relates to the use of the compounds according to the invention for producing a medicament for the treatment and / or prevention of diseases, in particular the diseases mentioned above.

[0085] The present invention further relates to a medicament containing at least one of the compounds according to the invention for the treatment and / or prevention of diseases, in particular the diseases mentioned above.

[0086] The present invention further relates to the use of the compounds according to the invention in a method for the treatment and / or prevention of diseases, in particular the diseases mentioned above.

[0087] The present invention further relates to a method for the treatment and / or prevention of diseases, in particular the aforementioned diseases, using an effective amount of at least one of the compounds according to the invention.

[0088] The compounds according to the invention can be used alone or, if necessary, in combination with one or more other pharmacologically active substances, as long as this combination does not lead to undesirable and unacceptable side effects. The present invention therefore further relates to medicaments containing at least one of the compounds according to the invention and one or more other active ingredients, in particular for the treatment and / or prevention of the aforementioned diseases. Examples of suitable combination active ingredients include, but are not limited to: Respiratory stimulants, such as, for example and preferably, theophylline, doxapram, nicethamide or caffeine; psychostimulant compounds, such as, for example and preferably, modafinil or armodafinil; amphetamines and amphetamine derivatives, such as, for example and preferably, amphetamine, methamphetamine or methylphenidate; serotonin reuptake inhibitors, such as, for example and preferably, fluoxetine, paroxetine, citalopram, escitalopram, sertraline, fluvoxamine or trazodone; serotonin precursors, such as, for example and preferably, L-tryptophan; selective serotonin-noradrenaline reuptake inhibitors, such as, for example and preferably, venlafaxine or duloxetine; noradrenergic and specifically serotonergic antidepressants, such as, for example and preferably, mirtazapine; selective noradrenaline reuptake inhibitors, such as, for example and preferably, reboxetine; tricyclic antidepressants, such as, by way of example and preference, amitriptyline, protriptyline, doxepin, trimipramine, imipramine, clomipramine or desipramine;Alpha2-adrenergic agonists, such as, for example and preferably, clonidine; GABA agonists, such as, for example and preferably, baclofen; alpha-sympathomimetics, such as, for example and preferably, xylometazoline, oxymetazoline, phenylephrine, naphazoline, tetryzoline or tramazoline; glucocorticoids, such as, for example and preferably, fluticasone, budesonide, beclomethasone, mometasone, tixocortol or triamcinolone; cannabinoid receptor agonists; carbonic anhydrase inhibitors, such as, for example and preferably, acetazolamide, methazolamide or diclofenamide; opioid and benzodiazepine receptor antagonists, such as, for example and preferably, flumazenil, naloxone or naltrexone; Cholinesterase inhibitors, such as, by way of example and preferably, neostigmine, pyridostigmine, physostigmine, donepezil, galantamine or rivastigmine; ; N-Methyl-D-aspartate and glutamate antagonists, such as, for example and preferably, amantadine, memantine or sabeluzole; nicotine receptor agonists; leukotriene receptor antagonists, such as, for example and preferably, montelukast or tripelukast; dopamine receptor antagonists, such as, for example and preferably, dromperidone, metoclopramide or benzamide, butyrophenone or phenothiazine derivatives; appetite suppressants, such as, for example and preferably, sibutramine, topiramate, phentermine, lipase inhibitors or cannabinoid receptor antagonists; proton pump inhibitors, such as, for example and preferably, pantoprazole, omeprazole, esomeprazole, lansoprazole or rabeprazole; organic nitrates and NO donors, such as sodium nitroprusside, nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, molsidomine or SIN-1, as well as inhaled NO;Compounds that inhibit the degradation of cyclic guanosine monophosphate (cGMP) and / or cyclic adenosine monophosphate (cAMP), such as, for example, inhibitors of phosphodiesterases (PDE) 1, 2, 3, 4 and / or 5, in particular PDE 5 inhibitors such as sildenafil, vardenafil, tadalafil, udenafil, dasantafil, avanafil, mirodenafil or lodenafil; NO- and heme-independent activators of soluble guanylate cyclase (sGC), such as in particular the compounds described in WO 01 / 19355, WO 01 / 19776, WO 01 / 19778, WO 01 / 19780, WO 02 / 070462 and WO 02 / 070510; NO-independent, but heme-dependent stimulators of soluble guanylate cyclase (sGC), such as in particular riociguat, vericiguat, and the compounds described in WO 00 / 06568, WO 00 / 06569, WO 02 / 42301, WO 03 / 095451, WO 2011 / 147809, WO 2012 / 004258, WO 2012 / 028647, and WO 2012 / 059549; prostacyclin analogues and IP receptor agonists, such as, by way of example and by way of preference, iloprost, beraprost, treprostinil, epoprostenol, or selexipag;Endothelin receptor antagonists, such as, for example and preferably, bosentan, darusentan, ambrisentan, or sitaxsentan; compounds that inhibit human neutrophil elastase (HNE), such as, for example and preferably, sivelestat or DX-890 (Reltran); compounds that inhibit the degradation and remodeling of the extracellular matrix, for example and preferably, inhibitors of matrix metalloproteases (MMPs), in particular inhibitors of stromelysin, collagenases, gelatinases, and aggrecanases (especially MMP-1, MMP-3, MMP-8, MMP-9, MMP-10, MMP-11, and MMP-13) as well as metalloelastase (MMP-12); Compounds that block the binding of serotonin to its receptor, by way of example and preferably antagonists of the 5-HT 2B receptor such as PRX-08066; antagonists of growth factors, cytokines and chemokines, by way of example and preferably antagonists of TGF-β, CTGF, IL-1, IL-4, IL-5, IL-6, IL-8, IL-13 and integrins;Rho kinase-inhibiting compounds, such as, by way of example and preferably, fasudil, Y-27632, SLx-2119, BF-66851, BF-66852, BF-66853, KI-23095, or BA-1049; compounds influencing cardiac energy metabolism, such as, by way of example and preferably, etomoxir, dichloroacetate, ranolazine, or trimetazidine; compounds which inhibit the signal transduction cascade, by way of example and with preference from the group of kinase inhibitors, in particular from the group of tyrosine kinase and / or serine / threonine kinase inhibitors, such as by way of example and with preference nintedanib, dasatinib, nilotinib, bosutinib, regorafenib, sorafenib, sunitinib, cediranib, axitinib, telatinib, imatinib, brivanib, pazopanib, vatalanib, gefitinib, erlotinib, lapatinib, canertinib, lestaurtinib, pelitinib, semaxanib or tandutinib;anti-obstructive agents, such as those used for the treatment of chronic obstructive pulmonary disease (COPD) or bronchial asthma, for example and preferably from the group of inhaled or systemically administered beta-adrenergic receptor agonists (beta-mimetics) and inhaled anti-muscarinic substances; anti-inflammatory, immunomodulating, immunosuppressive and / or cytotoxic agents, for example and preferably from the group of systemically or inhaled corticosteroids as well as dimethyl fumarate, fingolimod, glatiramer acetate, β-interferons, natalizumab, teriflunomide, mitoxantrone, immunoglobulins, acetylcysteine, montelukast, tripelukast, azathioprine, cyclophosphamide, hydroxycarbamide, azithromycin, interferon-γ, pirfenidone or etanercept;Antifibrotic agents, such as, for example and preferably, lysophosphatidic acid receptor 1 (LPA-1) antagonists, CTGF inhibitors, IL-4 antagonists, IL-13 antagonists, TGF-β antagonists, or pirfenidone; antithrombotic agents, for example and preferably from the group of platelet aggregation inhibitors, anticoagulants, and profibrinolytic substances; blood pressure-lowering agents, for example and preferably from the group of calcium antagonists, angiotensin AII antagonists, ACE inhibitors, vasopeptidase inhibitors, endothelin antagonists, renin inhibitors, alpha-receptor blockers, beta-receptor blockers, mineralocorticoid receptor antagonists, and diuretics;and / or active substances that modify lipid metabolism, for example and preferably from the group of thyroid receptor agonists, cholesterol synthesis inhibitors such as for example and preferably HMG-CoA reductase or squalene synthesis inhibitors, ACAT inhibitors, CETP inhibitors, MTP inhibitors, PPAR-alpha, PPAR-gamma and / or PPAR-delta agonists, cholesterol absorption inhibitors, lipase inhibitors, polymeric bile acid adsorbers, bile acid reabsorption inhibitors and lipoprotein(a) antagonists. ;

[0089] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a beta-adrenergic receptor agonist, such as, by way of example and by way of preference, albuterol, isoproterenol, metaproterenol, terbutaline, fenoterol, formoterol, reproterol, salbutamol or salmeterol.

[0090] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with an anti-muscarinic substance, such as, by way of example and by way of preference, ipratropium bromide, tiotropium bromide or oxitropium bromide.

[0091] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a corticosteroid, such as, by way of example and by way of preference, prednisone, prednisolone, methylprednisolone, triamcinolone, dexamethasone, betamethasone, beclomethasone, flunisolide, budesonide or fluticasone.

[0092] Antithrombotic agents are preferably understood to mean compounds from the group of platelet aggregation inhibitors, anticoagulants and profibrinolytic substances.

[0093] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a platelet aggregation inhibitor, such as, by way of example and preferably, aspirin, clopidogrel, ticlopidine or dipyridamole.

[0094] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a thrombin inhibitor, such as, by way of example and by way of preference, ximelagatran, melagatran, dabigatran, bivalirudin or clexane.

[0095] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a GPIIb / IIIa antagonist, such as, by way of example and preferably, tirofiban or abciximab.

[0096] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a factor Xa inhibitor, such as, by way of example and with preference, rivaroxaban, apixaban, fidexaban, razaxaban, fondaparinux, idraparinux, DU-176b, PMD-3112, YM-150, KFA-1982, EMD-503982, MCM-17, MLN-1021, DX 9065a, DPC 906, JTV 803, SSR-126512 or SSR-128428.

[0097] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with heparin or a low molecular weight (LMW) heparin derivative.

[0098] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a vitamin K antagonist, such as, by way of example and preferably, coumarin.

[0099] Antihypertensive agents preferably include compounds from the group of calcium antagonists, angiotensin AII antagonists, ACE inhibitors, endothelin antagonists, renin inhibitors, alpha-receptor blockers, beta-receptor blockers, mineralocorticoid receptor antagonists and diuretics.

[0100] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a calcium antagonist, such as, by way of example and preferably, nifedipine, amlodipine, verapamil or diltiazem.

[0101] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with an alpha-1 receptor blocker, such as, by way of example and preferably, prazosin.

[0102] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a beta-receptor blocker, such as, by way of example and with preference, propranolol, atenolol, timolol, pindolol, alprenolol, oxprenolol, penbutolol, bupranolol, metipranolol, nadolol, mepindolol, carazalol, sotalol, metoprolol, betaxolol, celiprolol, bisoprolol, carteolol, esmolol, labetalol, carvedilol, adaprolol, landiolol, nebivolol, epanolol or bucindolol.

[0103] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with an angiotensin AII antagonist, such as, by way of example and by way of preference, losartan, candesartan, valsartan, telmisartan or embusartan.

[0104] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with an ACE inhibitor, such as, by way of example and with preference, enalapril, captopril, lisinopril, ramipril, delapril, fosinopril, quinopril, perindopril or trandopril.

[0105] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with an endothelin antagonist, such as, by way of example and preferably, bosentan, darusentan, ambrisentan or sitaxsentan.

[0106] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a renin inhibitor, such as, by way of example and by way of preference, aliskiren, SPP-600 or SPP-800.

[0107] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a mineralocorticoid receptor antagonist, such as, by way of example and by way of preference, spironolactone, eplerenone or finerenone.

[0108] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a diuretic, such as, by way of example and with preference, furosemide, bumetanide, torsemide, bendroflumethiazide, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methyclothiazide, polythiazide, trichlormethiazide, chlorthalidone, indapamide, metolazone, quinethazone, acetazolamide, dichlorphenamide, methazolamide, glycerol, isosorbide, mannitol, amiloride or triamterene.

[0109] Lipid metabolism-altering agents are preferably understood to mean compounds from the group of CETP inhibitors, thyroid receptor agonists, cholesterol synthesis inhibitors such as HMG-CoA reductase or squalene synthesis inhibitors, ACAT inhibitors, MTP inhibitors, PPAR-alpha, PPAR-gamma and / or PPAR-delta agonists, cholesterol absorption inhibitors, polymeric bile acid adsorbers, bile acid reabsorption inhibitors, lipase inhibitors and lipoprotein(a) antagonists.

[0110] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a CETP inhibitor, such as, by way of example and preferably, torcetrapib (CP-529 414), JJT-705 or CETP vaccine (Avant).

[0111] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a thyroid receptor agonist, such as, by way of example and by way of preference, D-thyroxine, 3,5,3'-triiodothyronine (T3), CGS 23425 or axitirome (CGS 26214).

[0112] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with an HMG-CoA reductase inhibitor from the class of statins, such as, by way of example and with preference, lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin or pitavastatin.

[0113] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a squalene synthesis inhibitor, such as, by way of example and preferably, BMS-188494 or TAK-475.

[0114] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with an ACAT inhibitor, such as, by way of example and by way of preference, avasimibe, melinamide, pactimibe, eflucimibe or SMP-797.

[0115] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with an MTP inhibitor, such as, by way of example and preferably, implitapide, BMS-201038, R-103757 or JTT-130.

[0116] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a PPAR-gamma agonist, such as, by way of example and by way of preference, pioglitazone or rosiglitazone.

[0117] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a PPAR-delta agonist, such as, by way of example and preferably, GW 501516 or BAY 68-5042.

[0118] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a cholesterol absorption inhibitor, such as, by way of example and preferably, ezetimibe, tiqueside or pamaqueside.

[0119] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a lipase inhibitor, such as, by way of example and preferably, orlistat.

[0120] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a polymeric bile acid adsorber, such as, by way of example and by way of preference, cholestyramine, colestipol, colesolvam, CholestaGel or colestimide.

[0121] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a bile acid reabsorption inhibitor, such as, by way of example and preferably, ASBT (= IBAT) inhibitors such as, for example, AZD-7806, S-8921, AK-105, BARI-1741, SC-435 or SC-635.

[0122] In a preferred embodiment of the invention, the compounds according to the invention are administered in combination with a lipoprotein(a) antagonist, such as, by way of example and preferably, Gemcabene calcium (CI-1027) or nicotinic acid.

[0123] Particularly preferred are combinations of the compounds according to the invention with one or more further active ingredients selected from the group consisting of respiratory stimulants, psychostimulant compounds, serotonin reuptake inhibitors, noradrenergic, serotonergic and tricyclic antidepressants, sGC stimulators, mineralocorticoid receptor antagonists, anti-inflammatory agents, immunomodulatory agents, immunosuppressive agents and cytotoxic agents.

[0124] If necessary, the substances according to the invention can also be used in conjunction with one or more medical devices or aids, as long as this does not lead to undesirable and unacceptable side effects. Medical devices and aids considered for such a combined application are, by way of example and preference: Devices for positive airway pressure ventilation, such as, for example and preferably, CPAP ( continuous positive airway pressure ) -Devices, BiPAP ( bilevel positive airway pressure ) -Devices and IPPV ( intermittent positive pressure ventilation ) -Devices; Neurostimulators of the hypoglossal nerve; Intraoral devices, such as, for example and preferably, protrusion braces; nasal one-way valves; nasal stents.

[0125] The present invention further relates to medicaments which contain at least one compound according to the invention, usually together with one or more inert, non-toxic, pharmaceutically suitable excipients, and to their use for the aforementioned purposes.

[0126] The compounds of the invention can act systemically and / or locally. For this purpose, they can be administered in a suitable manner, such as orally, parenterally, pulmonarily, intrapulmonarily (by inhalation), nasally, intranasally, pharyngeally, lingually, sublingually, buccally, rectally, dermally, transdermally, conjunctivally, otically, or as an implant or stent.

[0127] For these routes of administration, the compounds according to the invention can be administered in suitable administration forms.

[0128] For oral administration, suitable dosage forms which function according to the state of the art and release the compounds according to the invention rapidly and / or in a modified form and which contain the compounds according to the invention in crystalline and / or amorphized and / or dissolved form are used, such as tablets (uncoated or coated tablets, for example with gastro-resistant or delayed-dissolving or insoluble coatings which control the release of the compound according to the invention), tablets or films / wafers which disintegrate rapidly in the oral cavity, films / lyophilisates, capsules (for example hard or soft gelatin capsules), coated tablets, granules, pellets, powders, emulsions, suspensions, aerosols or solutions.

[0129] Parenteral administration can be performed without an absorption step (e.g., intravenous, intraarterial, intracardiac, intraspinal, or intralumbar) or with absorption (e.g., inhalation, intramuscular, subcutaneous, intracutaneous, percutaneous, or intraperitoneal). Suitable administration forms for parenteral administration include injection and infusion preparations in the form of solutions, suspensions, emulsions, lyophilisates, or sterile powders.

[0130] Other routes of application include, for example, inhalation dosage forms (including powder inhalers, nebulizers, metered dose aerosols), nasal drops, solutions or sprays, throat sprays, lingual, sublingual or buccally administered tablets, films / wafers or capsules, suppositories, ear or eye preparations, vaginal capsules, aqueous suspensions (lotions, shake mixtures), lipophilic suspensions, ointments, creams, transdermal therapeutic systems (e.g. plasters), milk, pastes, foams, powders, implants or stents.

[0131] Oral, intravenous, intranasal and pharyngeal administration are preferred.

[0132] According to one embodiment, the application is intranasal. According to one embodiment, the intranasal application is carried out using nasal drops or a nasal spray. According to one embodiment, the intranasal application is carried out using a nasal spray.

[0133] The compounds according to the invention can be converted into the stated application forms. This can be done in a conventional manner by mixing with inert, non-toxic, pharmaceutically suitable excipients. These excipients include, among others, carriers (e.g., microcrystalline cellulose, lactose, mannitol), solvents (e.g., liquid polyethylene glycols), emulsifiers and dispersing or wetting agents (e.g., sodium dodecyl sulfate, polyoxysorbitan oleate), binders (e.g., polyvinylpyrrolidone), synthetic and natural polymers (e.g., albumin), stabilizers (e.g., antioxidants such as ascorbic acid), dyes (e.g., inorganic pigments such as iron oxides), and flavor and / or odor correctors.

[0134] In general, it has proven advantageous to administer amounts of approximately 0.001 to 1 mg / kg, preferably approximately 0.01 to 0.5 mg / kg body weight, for parenteral administration to achieve effective results. For oral administration, the dosage is approximately 0.01 to 100 mg / kg, preferably approximately 0.01 to 20 mg / kg, and most preferably 0.1 to 10 mg / kg body weight.

[0135] According to one embodiment, the dosage for intranasal administration is approximately 0.1 µg to 500 µg per day. According to another embodiment, the dosage for intranasal administration is approximately 1 µg to 250 µg per day. According to another embodiment, the dosage for intranasal administration is approximately 1 µg to 120 µg per day. According to another embodiment, the dose of approximately 0.1 µg to 500 µg per day, or approximately 1 µg to 250 µg per day, or approximately 1 µg to 120 µg per day, is administered intranasally once daily before bedtime. According to one embodiment, the dose of about 0.1 µg to 500 µg per day, or about 1 µg to 250 µg per day, or about 1 µg to 120 µg per day is administered once daily before bedtime, half into each nostril.

[0136] Nevertheless, it may be necessary to deviate from the stated amounts, depending on body weight, route of administration, individual response to the active ingredient, type of preparation, and time or interval at which administration takes place. In some cases, it may be sufficient to administer less than the aforementioned minimum amount, while in other cases the stated upper limit must be exceeded. When administering larger amounts, it may be advisable to distribute them into several individual doses throughout the day.

[0137] Methods for two-electrode voltage clamp (TEVC) measurements in Xenopus laevis oocytes are described in Experiment B-4. Methods from Decher et al., FEBS Lett. 492, 84-89 (2001) and Stühmer, Methods Enzymol. 207, 319-339 (1992) are used.

[0138] According to the invention, cLogP and cLogD are determined using a standard method, such as that described in Corner and Tam, "Lipophilicity Profiles: Theory and Measurement," in: Testa, van de Waterbed, Folkers & Guy, Pharmacokinetic Optimization in Drug Research: Biological, Physicochemical and Computational Strategies, Weinheim, Wiley-VCH, pp. 275-304. The method used to calculate the tPSA value is described in detail in Ertl et al., J. Med. Chem. 43, 3714-3717 (2000). The method is based on summing the tabulated literature values ​​of the surface contributions of the polar portions of the molecule.

[0139] The determination of apparent permeability (PAPP), for example, is carried out according to Artursson and Karlsson, Biochem. Biophys. Res. Commun. 175 (3), 880-885 (1991). To eliminate the influence of transporters, the apparent permeabilities are determined both from the apical to the basolateral side and from the basolateral to the apical side. The values ​​are added and divided by two.

[0140] The quantities used to calculate oral bioavailability, AUC norm (oral administration) and AUC norm (intravenous administration), are determined using standard methods. According to the invention, the determination of blood clearance (CL blood ) in % of the species-specific liver blood flow is carried out using generally accepted methods. in vivo experiments using intravenous drug administration, such as the standard PK methods described in Rowland & Tozer, Clinical Pharmacokinetics and Pharmacodynamics, 4th edition.

[0141] In a further embodiment, the compound is suitable for the prevention or treatment of obstructive sleep apnea (OSA) or one or more symptoms associated therewith.

[0142] In a further embodiment, the compound is suitable for nasal administration.

[0143] In a further embodiment, the compound inhibits upper airway collapsibility in a porcine model of OSA.

[0144] In a further embodiment, the duration of inhibition of upper airway collapsibility in the OSA pig model after intranasal administration of between 0.3 µg and 300 µg of the compound is more than 240 min, measured at a negative pressure of 100 cm water column.

[0145] The invention further provides a compound having TASK-1 and / or TASK-3 blocking properties, which is obtainable by the screening method described above.

[0146] In one embodiment, the compound has at least one functional feature selected from the following group: a) the inhibitory concentration (IC 50 value) concerning the K +< conductance of the TASK-1 or TASK-3 channel is ≤ 200 nM; b) the washout rate is ≤ 50% h -1< ; c) the maximum possible bioavailability ("F max well-stirred") is ≤ 40%.

[0147] In a further embodiment, it is provided that the connection has at least one of the further features mentioned above, in particular selected from the features d) - k) has.

[0148] In a further embodiment, the compound is an (imidazo[1,2-a]pyridin-3-yl)methyl-substituted diazaheterobicyclic compound.

[0149] In one embodiment, the compounds disclosed in EP patent application 15199270.8 and EP patent application 15199268.2 are not included.

[0150] In one embodiment of the process or the compound, the washout rate of the compound is preferably ≤ 40% h -1< , more preferably ≤ 30% h -1< and most preferably < 20% h -1< .

[0151] Furthermore, the invention provides a compound that competes with a compound according to the above description for interaction with TASK-1 and / or TASK-3. The term "interaction" refers to at least one feature from the group consisting of: Reduction of the K +< conductance of the TASK-1 or TASK-3 channel, binding to one or more epitopes and / or domains of TASK-1 and / or TASK-3.

[0152] The following embodiments explain the invention. A. Examples Abbreviations and acronyms:

[0153] abs.absolute AcAcetyl aq.aqueous, aqueous solution Boc tert .-Butoxycarbonyl br.broad (at NMR signal) Example BuButyl cConcentration approx. approximately, approximately cat.catalytic CIchemical ionization (in MS) dDoublet (in NMR) dDay(s) DCIdirect chemical ionization (in MS) ddDoublet of Doublet (in NMR) DMF N , N -Dimethylformamide DMSODimethyl sulfoxide dqDoublet of quartet (in NMR) dtDoublet of triplet (in NMR) d. Th.of theory (at chemical yield) EIElectron impact ionization (in MS) eq.Equivalent(s) ESIElectrospray ionization (in MS) EtEthyl hhour(s) HATU O -(7-Azabenzotriazol-1-yl)- N , N ,N' , N' -tetramethyluronium hexafluorophosphate HOBt1 -Hydroxy-1H-benzotriazole hydrate HPLCHigh pressure, high performance liquid chromatography iPrIsopropyl conc. concentrated (in solution) LCLiquid chromatography LC-MSLiquid chromatography coupled to mass spectrometry Lit.Literature (reference) mMultiplet (in NMR) MeMethyl minMinute(s) MSMass spectrometry NMRNuclear magnetic resonance spectrometry PhPhenyl PrPropyl qQuartet (in NMR) quant.quantitative (in chemical yield) RPreverse phase (reverse phase, in HPLC) RTRoom temperature R tRetention time (in HPLC, LC-MS) sSinglet (in NMR) tTriplet (in NMR) tBu tert-butyl TFATrifluoroacetic acid THFTetrahydrofuran UVUltraviolet spectrometry v / vVolume to volume ratio (of a solution) together LC-MS and HPLC methods: Method 1 (LC-MS):

[0154] Instrument: Waters Acquity SQD UPLC System; Column: Waters Acquity UPLC HSS T3 1.8 µm, 50 mm × 1 mm; Eluent A: 1 L water + 0.25 ml 99% formic acid, Eluent B: 1 L acetonitrile + 0.25 ml 99% formic acid; Gradient: 0.0 min 90% A → 1.2 min 5% A → 2.0 min 5% A; Temperature: 50°C; Flow: 0.40 ml / min; UV detection: 208-400 nm. Method 2 (LC-MS):

[0155] MS instrument: Thermo Scientific FT-MS; UHPLC device: Thermo Scientific UltiMate 3000; Column: Waters HSS T3 C18 1.8 µm, 75 mm × 2.1 mm; Eluent A: 1 L water + 0.01% formic acid, Eluent B: 1 L acetonitrile + 0.01% formic acid; Gradient: 0.0 min 10% B → 2.5 min 95% B → 3.5 min 95% B; Temperature: 50°C; Flow: 0.90 ml / min; UV detection: 210 nm / optimum integration path 210-300 nm. Method 3 (LC-MS):

[0156] Instrument MS: Waters Micromass QM; Instrument HPLC: Agilent 1100 Serie; Säule: Agilent ZORBAX Extend-C18 3.5 µm, 50 mm × 3.0 mm; Eluent A: 1 l Wasser + 0.01 mol Ammoniumcarbonat, Eluent B: 1 l Acetonitril; Gradient: 0.0 min 98% A → 0.2 min 98% A → 3.0 min 5% A → 4.5 min 5% A; Temperatur: 40°C; Fluss: 1.75 ml / min; UV-Detektion: 210 nm. Method 4 (LC-MS):

[0157] Instrument MS: Waters Micromass Quattro Micro; Instrument HPLC: Waters UPLC Acquity; Säule: Waters BEH C18 1.7 µm, 50 mm × 2.1 mm; Eluent A: 1 l Wasser + 0.01 mol Ammoniumformiat, Eluent B: 1 l Acetonitril; Gradient: 0.0 min 95% A → 0.1 min 95% A → 2.0 min 15% A → 2.5 min 15% A → 2.51 min 10% A → 3.0 min 10% A; Temperatur: 40°C; Fluss: 0.5 ml / min; UV-Detektion: 210 nm. Method 5 (LC-MS):

[0158] Instrument: Agilent MS Quad 6150 with HPLC Agilent 1290; Column: Waters Acquity UPLC HSS T3 1.8 µm, 50 mm × 2.1 mm; Eluent A: 1 l water + 0.25 ml 99% formic acid, Eluent B: 1 l acetonitrile + 0.25 ml 99% formic acid; Gradient: 0.0 min 90% A → 0.3 min 90% A → 1.7 min 5% A → 3.0 min 5% A; Flow: 1.20 ml / min; Temperature: 50°C; UV detection: 205-305 nm. Method 6 (preparative HPLC):

[0159] Instrument: Abimed Gilson 305; Column: Reprosil C18 10 µm, 250 mm × 30 mm; Eluent A: water, Eluent B: acetonitrile; Gradient: 0-3 min 10% B, 3-27 min 10% B → 95% B, 27-34.5 min 95% B, 34.5-35.5 min 95% B → 10% B, 35.5-36.5 min 10% B; Flow: 50 ml / min; Room temperature; UV detection: 210 nm. Method 7 (LC-MS):

[0160] MS instrument: Waters SQD; HPLC instrument: Waters UPLC; Column: Zorbax SB-Aq (Agilent), 50 mm × 2.1 mm, 1.8 µm; Eluent A: water + 0.025% formic acid, Eluent B: acetonitrile + 0.025% formic acid; Gradient: 0.0 min 98% A → 0.9 min 25% A → 1.0 min 5% A → 1.4 min 5% A → 1.41 min 98% A → 1.5 min 98% A; Oven: 40°C; Flow: 0.60 ml / min; UV detection: DAD, 210 nm. More information:

[0161] The following descriptions of the coupling patterns of 1< H NMR signals are based on the optical appearance of the signals in question and do not necessarily correspond to a strictly physically correct interpretation. The chemical shift is usually given relative to the center of the respective signal; for broad multiplets, an interval is usually given.

[0162] Melting points and melting ranges, where indicated, are uncorrected.

[0163] In cases where reaction products were obtained by stirring, agitating, or recrystallization, it was often possible to isolate additional amounts of product from the respective mother liquor by chromatography. However, a description of this chromatography will be omitted below unless a large portion of the total yield could only be isolated in this step.

[0164] For all reactants or reagents whose preparation is not explicitly described below, it is assumed that they were obtained commercially from publicly accessible sources. For all other reactants or reagents whose preparation is also not described below and which were not commercially available or were obtained from sources that are not publicly accessible, a reference to the published literature describing their preparation is provided. Starting compounds and intermediates: Example 1A 2-(4-Chlorophenyl)imidazo[1,2-a]pyridine

[0165]

[0166] A solution of 20 g (85.65 mmol) of 2-bromo-1-(4-chlorophenyl)ethanone and 8.87 g (94.22 mmol) of pyridin-2-amine in 200 mL of ethanol was treated with 10.95 g (130 mmol) of sodium bicarbonate and stirred at 80°C for 5 hours. The mixture was then cooled first to room temperature and then to 0°C (ice bath). The resulting precipitate was filtered off and washed several times with an ethanol / water mixture (2:1). The solid was then dried under vacuum overnight at 40°C. 19.8 g of the target product were obtained, which was used in subsequent reactions without further purification.

[0167] 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 6.87-6.94 (m, 1H), 7.23-7.29 (m, 1H), 7.50 (d, 2H), 7.58 (d, 1H), 7.99 (d, 2H), 8.43 (s, 1H), 8.53 (d, 1H).

[0168] LC-MS (Method 1): R t = 0.58 min; m / z = 229 / 231 (M+H) +< . Example 2A 2-(5-Chloropyridin-2-yl)imidazo[1,2-a]pyridine

[0169]

[0170] 5 g (32.14 mmol) of 1-(5-chloropyridin-2-yl)ethanone, 6.96 g (73.92 mmol) of pyridin-2-amine, and 9.79 g (38.56 mmol) of iodine were stirred at 120°C for 2 h. After cooling to room temperature, 15 ml of water and 1.93 g (48 mmol) of sodium hydroxide were added, and the reaction mixture was stirred at 100°C for another 1 h. The reaction mixture was then cooled to room temperature, and the resulting precipitate was filtered off and washed several times with water. The solid was dissolved in cyclohexane / ethyl acetate (1:1), silica gel was added, the mixture was evaporated to dryness, and the residue was purified by column chromatography on silica gel (eluent: cyclohexane / ethyl acetate 1:1). 4.32 g (18.81 mmol, 59% of theory) of the target compound were obtained.

[0171] 1< H-NMR (400 MHz, DMSO- d6 , δ / ppm): 6.95 (t, 1H), 7.30 (t, 1H), 7.61 (d, 1H), 8.00 (dd, 1H), 8.12 (d, 1H), 8.50 (s, 1H), 8.59 (d, 1H), 8.65 (d, 1H).

[0172] LC-MS (Methode 1): R t = 0.50 min; m / z = 230 / 232 (M+H) +< . Example 3A 2-(6-Isopropylpyridin-3-yl)imidazo[1,2-a]pyridin

[0173]

[0174] 5 g (30.63 mmol) of 1-(6-isopropylpyridin-3-yl)ethanone [CAS Registry Number 80394-97-4], 6.63 g (70.46 mmol) of pyridin-2-amine, and 9.33 g (36.76 mmol) of iodine were stirred at 120°C for 2 h. After cooling to room temperature, 50 ml of water and 46 ml (46 mmol) of 1 M sodium hydroxide solution were added, and the reaction mixture was stirred for another 1 h at 100°C. The reaction mixture was then cooled to room temperature, whereupon an oily liquid separated. The reaction mixture was partitioned between water and ethyl acetate, and the organic phase was separated. The organic phase was washed twice with water, dried over magnesium sulfate, and then concentrated. The resulting oil was pre-purified by chromatography over neutral aluminum oxide (eluent: cyclohexane / ethyl acetate 1:1). The resulting material was further purified by two column chromatographies on silica gel (Biotage SNAP Cartridge KP-NH column; eluent: cyclohexane / ethyl acetate 1:2). 1.62 g (6.5 µl) were obtained.83 mmol, 22% of theory) of the target compound.

[0175] 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.27 (d, 6H), 2.98-3.12 (m, 1H), 6.91 (t, 1H), 7.27 (t, 1H), 7.35 (d, 1H), 7.60 (d, 1H), 8.22 (dd, 1H), 8.45 (s, 1H), 8.54 (dd, 1H), 9.06 (d, 1H).

[0176] LC-MS (Method 2): R t = 0.86 min; m / z = 238 (M+H) +< .

[0177] Analogously to Example 1A, the following compounds were prepared from the indicated starting materials: Example Name / Structure / Educts Analytical data 4A 2-(4-Bromophenyl)imidazo[1,2-a]pyridine 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 6.88-6.94 (m, 1H), 7.23-7.29 (m, 1H), 7.58 (d, 1H), 7.63 (d, 2H), 7.92 (d, 2H), 8.44 (s, 1H), 8.53 (d, 1H). from 2-bromo-1-(4-bromophenyl)ethanone and pyridin-2-amine LC-MS (Method 1): R t = 0.63 min; m / z = 273 / 275 (M+H) +< . 5A 2-(4-Isopropylphenyl)imidazo[1,2-a]pyridine 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.23 (d, 6H), 2.85-2.96 (m, 1H), 6.88 (t, 1H), 7.19-7.26 (m, 1H), 7.31 (d, 2H), 7.56 (d, 1H), 7.88 (d, 2H), 8.34 (s, 1H), 8.51 (d, 1H). from 2-bromo-1-(4-isopropylphenyl)ethanone and pyridin-2-amine LC-MS (Method 1): R t = 0.68 min; m / z = 237 (M+H) +< . Example 6A 2-(4-Chlorophenyl)imidazo[1,2-a]pyridine-3-carbaldehyde

[0178]

[0179] 300 ml of DMF were cooled to 0°C. Then, 44 ml (470.08 mmol) of phosphorus oxychloride were slowly added dropwise. The reaction solution was then slowly warmed to room temperature and stirred at this temperature for one hour. 43 g (188.03 mmol) of 2-(4-chlorophenyl)imidazo[1,2-a]pyridine were then added portionwise. The reaction solution warmed to 35°C. After the addition was complete, the reaction mixture was heated to 80°C and stirred at this temperature for 2 hours. After cooling to room temperature, the solution was slowly added to 3 liters of ice water. The resulting solid was filtered off with suction, washed several times with water, and dried overnight in a high-vacuum drying oven at 40°C. This yielded 39.6 g (154.27 mmol, 82% of theory) of the target product.

[0180] 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 7.37 (t, 1H), 7.63 (d, 2H), 7.78 (t, 1H), 7.90-7.99 (m, 3H), 9.58 (d, 1H), 10.02 (s, 1H).

[0181] LC-MS (Methode 1): R t = 0.97 min; m / z = 257 / 259 (M+H) +< . Example 7A 2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-carbaldehyd

[0182]

[0183] 80 ml of DMF was cooled to 0°C. Then, 4.4 ml (47.02 mmol) of phosphorus oxychloride was slowly added dropwise. The reaction solution was then slowly warmed to room temperature and stirred at this temperature for one hour. Then, 4.32 g (18.81 mmol) of 2-(5-chloropyridin-2-yl)imidazo[1,2-a]pyridine were added portionwise. After the addition was complete, the reaction mixture was heated to 80°C and stirred at this temperature for 1 h. After cooling to room temperature, the solution was slowly poured into ice-water. Ethyl acetate was added, and after careful shaking, the organic phase was separated. The organic phase was washed with saturated sodium chloride solution, dried over magnesium sulfate, and evaporated to dryness. The residue was purified by column chromatography on silica gel (eluent: cyclohexane / ethyl acetate 2:1). 4.46 g (17.31 mmol, 92% of theory) of the target compound were obtained.

[0184] 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 7.36 (td, 1H), 7.76 (ddd, 1H), 7.94 (d, 1H), 8.15 (dd, 1H), 8.35 (d, 1H), 8.81 (d, 1H), 9.60 (d, 1H), 10.87 (s, 1H).

[0185] LC-MS (Methode 1): R t = 0.92 min; m / z = 258 / 260 (M+H) +< . Example 8A 2-(6-Isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-carbaldehyd

[0186]

[0187] 20 ml of DMF were cooled to 0°C. Then, 1.6 ml (17.07 mmol) of phosphorus oxychloride were slowly added dropwise. The reaction solution was then slowly warmed to room temperature and stirred at this temperature for one hour. Then, 1.62 g (6.83 mmol) of 2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridine were added. After the addition was complete, the reaction mixture was heated to 80°C and stirred at this temperature for 1 h. After cooling to room temperature, the solution was slowly poured into ice-water. The pH of the solution was slowly adjusted from pH 1 to pH 4 with stirring by adding 1 M sodium hydroxide solution. The solution was then extracted several times with ethyl acetate, and the combined organic phases were dried over magnesium sulfate and evaporated to dryness. The residue obtained was purified by column chromatography on silica gel (Biotage SNAP-Cartridge KP-NH column; eluent: cyclohexane / ethyl acetate 1:1).Two fractions of the target compound were isolated: Fraction 1: 850 mg (pure), Fraction 2: 640 mg (still contaminated). The latter fraction was purified again under the same chromatographic conditions, yielding an additional 350 mg of the pure target compound. A total of 1.20 g (4.52 mmol, 66% of theory) of the target compound was obtained.

[0188] LC-MS (Method 2): R t = 1.37 min; m / z = 266 (M+H) +< .

[0189] Analogously to Example 6A, the following compounds were prepared from the indicated starting materials: Example Name / Structure / Educt Analytical data 9A 2-(4-Bromophenyl)imidazo[1,2-a]pyridine-3-carbaldehyde 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 7.35 (t, 1H), 7.72-7.80 (m, 3H), 7.85-7.95 (m, 3H), 9.58 (d, 1H), 10.02 (s, 1H). LC-MS (Method 2): R t = 1.76 min; m / z = 301 / 303 (M+H) +< . from 2-(4-bromophenyl)imidazo[1,2-a]pyridine 10A 2-(4-Isopropylphenyl)imidazo[1,2-a]pyridine-3-carbaldehyde 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.27 (d, 6H), 2.93-3.05 (m, 1H), 7.33 (t, 1H), 7.44 (d, 2H), 7.74 (t, 1H), 7.85 (d, 2H), 7.91 (d, 1H), 9.58 (d, 1H), 10.03 (s, 1H). LC-MS (Method 1): R t = 1.03 min; m / z = 265 (M+H) +< . from 2-(4-isopropylphenyl)imidazo[1,2-a]pyridine Example 11A 2-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride ( Enantiomer 1 )

[0190]

[0191] 2.64 g (5.83 mmol) tert.-Butyl 5-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-di-azabicyclo[2.2.2]octane-2-carboxylate (enantiomer 1) was treated with 14.6 ml of a 4 M solution of hydrogen chloride in dioxane while stirring. The mixture was stirred overnight at room temperature. The resulting solid was then filtered off with suction, washed several times with diethyl ether, and dried under high vacuum at 40°C. 3.55 g of a solid were obtained, which was used in subsequent reactions without further purification.

[0192] LC-MS (Method 5): R t = 0.44 min; m / z = 353 / 355 (M+H) +< . Example 12A 2-{[2-(5-Chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride ( Enantiomer 1 )

[0193]

[0194] 450 mg (0.99 mmol) tert.-Butyl 5-{[2-(5-chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane-2-carboxylate (enantiomer 1) was treated with 1.49 ml of a 4 M solution of hydrogen chloride in dioxane and a further 5 ml of dioxane while stirring. The mixture was stirred overnight at room temperature. The resulting solid was then filtered off with suction, washed several times with diethyl ether, and dried under high vacuum at 40°C. 464 mg of a solid were obtained, which was used in subsequent reactions without further purification.

[0195] LC-MS (Method 2): R t = 0.70 min; m / z = 354 (M+H) +< . Example 13A 2-{[2-(6-Isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride ( Racemate )

[0196]

[0197] 820 mg (1.78 mmol) tert.-Butyl 5-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]-methyl}-2,5-diazabicyclo[2.2.2]octane-2-carboxylate (racemate) was treated with 4.44 ml of a 4 M solution of hydrogen chloride in dioxane and a further 10 ml of dioxane while stirring. The mixture was stirred overnight at room temperature. The resulting solid was then filtered off with suction, washed several times with diethyl ether, and dried under high vacuum at 40°C. 883 mg of a solid were obtained, which was used in subsequent reactions without further purification.

[0198] LC-MS (Method 1): R t = 0.40 min; m / z = 362 (M+H) +< . Example 14A 7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonane dihydrochloride

[0199]

[0200] 1.87 g (3.99 mmol) tert.-Butyl 7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonane-9-carboxylate was treated with 10 ml of a 4 M solution of hydrogen chloride in dioxane while stirring. The mixture was stirred overnight at room temperature. The resulting solid was then filtered off with suction, washed several times with diethyl ether, and dried under high vacuum at 40°C. This yielded 1.99 g of a solid, which was used in subsequent reactions without further purification.

[0201] LC-MS (Method 4): R t = 1.30 min; m / z = 369 / 371 (M+H) +< .

[0202] Analogously to Examples 11A-14A, the following compounds were prepared from the indicated starting materials: Example Name / Structure / Educt Analytical data 15A 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 2 ) LC-MS (Method 5): R t = 0.40 min; m / z = 353 / 355 (M+H) +< . aus tert.-Butyl-5-{[2-(4-chlorphenyl)imidazo[1,2-a]-pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-2-carboxylat ( Enantiomer 2 ) 16A 2-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 1 ) LC-MS (Method 1): R t = 0.48 min; m / z = 361 (M+H) +< . aus tert .-Butyl-5-{[2-(4-isopropylphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octan-2-carboxylat ( Enantiomer 1 ) 17A 2-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 2 ) LC-MS (Method 1): R t = 0.49 min; m / z = 361 (M+H) +< . aus tert .-Butyl-5-{[2-(4-isopropylphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octan-2-carboxylat ( Enantiomer 2 ) 18A 8-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid LC-MS (Methode 1): R t = 0.48 min; m / z = 397 / 399 (M+H) +< . aus tert .-Butyl-8-{[2-(4-bromphenyl)imidazo[1,2-a]-pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-3-carboxylat 19A 8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid LC-MS (Methode 4): R t = 1.24 min; m / z = 353 / 355 (M+H) +< . aus tert .-Butyl-8-{[2-(4-chlorphenyl)imidazo[1,2-a]-pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-3-carboxylat 20A 8-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid LC-MS (Methode 4): R t = 1.41 min; m / z = 361 (M+H) +< . aus tert .-Butyl-8-{[2-(4-isopropylphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]-octan-3-carboxylat 21A 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid LC-MS (Methode 4): R t = 1.22 min; m / z = 339 / 341 (M+H) +< . aus tert .-Butyl-3- {[2-(4-chlorphenyl)imidazo[1,2-a]-pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-6-carboxylat 22A 3-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid LC-MS (Methode 4): R t = 1.33 min; m / z = 347 (M+H) +< . aus tert .-Butyl-3-{[2-(4-isopropylphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]-heptan-6-carboxylat 23A 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid LC-MS (Methode 4): R t = 1.23 min; m / z = 353 / 355 (M+H) +< . aus tert .-Butyl-3-{[2-(4-chlorphenyl)imidazo[1,2-a]-pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat 24A 3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid LC-MS (Methode 1): R t = 0.46 min; m / z = 397 / 399 (M+H) +< . aus tert .-Butyl-3- {[2-(4-Bromphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]-octan- 8-carboxylat 25A 3-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid LC-MS (Methode 4): R t = 1.38 min; m / z = 361 (M+H) +< . aus tert .-Butyl-3-{[2-(4-isopropylphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]-octan- 8-carboxylat 26A 3-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid LC-MS (Methode 2): R t = 0.74 min; m / z = 354 (M+H) +< . aus tert .-Butyl-3-{[2-(5-chlorpyridin-2-yl)imidazo-[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]-octan-8-carboxylat 27A 2- {[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Racemat ) LC-MS (Methode 4): R t = 1.27 min; m / z = 354 / 356 (M+H) +< . aus tert .-Butyl-5-{[2-(5-chlorpyridin-2-yl)imidazo-[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]-octan-2-carboxylat ( Racemat ) 28A 2- {[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 2 ) LC-MS (Methode 2): R t = 0.70 min; m / z = 354 (M+H) +< . aus tert .-Butyl-5-{[2-(5-chlorpyridin-2-yl)imidazo-[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]-octan-2-carboxylat ( Enantiomer 2 ) 29A 7-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[33.1]nonan- LC-MS (Methode 2): R t = 0.71 min; MS (ESIpos): m / z = 370 [M+H] +< . aus tert .-Butyl-7-{[2-(5-chlorpyridin-2-yl)imidazo-[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo-[3.3.1]nonan-9-carboxylat 30A 3-(3,8-Diazabicyclo[3.2.1]oct-3-ylmethyl)-2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-Dihydrochlorid LC-MS (Methode 2): R t = 0.64 min; MS (ESIpos): m / z = 362 [M+H] +< . aus tert .-Butyl-3-{[2-(6-isopropylpyridin-3-yl)-imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat 31A 2-(4-Bromphenyl)-3-(2,5-diazabicyclo[2.2.2]oct-2-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid ( Racemate ) LC-MS (Method 5): R t = 0.61 min; MS (ESIpos): m / z = 397 [M+H] +< . aus tert .-Butyl-5-{[2-(4-bromphenyl)imidazo[1,2-a]-pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-2-carboxylat ( Racemate ) Example 32A 2-{[2-(6-Isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 1 )

[0203]

[0204] 1090 mg (2.36 mmol) tert.-Butyl 5-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]-methyl}-2,5-diazabicyclo[2.2.2]octane-2-carboxylate (enantiomer 1) was treated with 8.86 ml of a 4 M solution of hydrogen chloride in dioxane and a further 10 ml of dioxane while stirring. The mixture was stirred overnight at room temperature. The resulting solid was then filtered off with suction, washed several times with diethyl ether, and dried under high vacuum at 40°C. 1195 mg of a solid were obtained, which was used in subsequent reactions without further purification.

[0205] LC-MS (Method 2): R t = 0.61 min; m / z = 362 (M+H) +< . Example 33A 2-{[2-(6-Isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride ( Enantiomer 2 )

[0206]

[0207] 1010 mg (2.19 mmol) tert.-Butyl 5-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]-methyl}-2,5-diazabicyclo[2.2.2]octane-2-carboxylate (enantiomer 2) was treated with 8.86 ml of a 4 M solution of hydrogen chloride in dioxane while stirring. The mixture was stirred overnight at room temperature. The resulting solid was then filtered off with suction, washed several times with diethyl ether, and dried under high vacuum at 40°C. 1050 mg of a solid were obtained, which was used in subsequent reactions without further purification.

[0208] LC-MS (Method 2): R t = 0.63 min; m / z = 362 (M+H) +< . Examples of implementation: Example 1 tert .-Butyl-5-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane-2-carboxylate ( Racemate )

[0209]

[0210] Under argon at room temperature, 5 g (19.48 mmol) of 2-(4-chlorophenyl)imidazo[1,2-a]pyridine-3-carbaldehyde were dissolved in 100 ml of THF and treated with 8.27 g (38.96 mmol) tert.-Butyl 2,5-diazabicyclo-[2.2.2]octane-2-carboxylate (racemate) and 2.23 ml (38.96 mmol) of acetic acid were added. Subsequently, 6.19 g (29.22 mmol) of sodium triacetoxyborohydride were added portionwise, and the reaction solution was stirred overnight at room temperature. Water was then slowly and carefully added dropwise (caution: gas evolution) and subsequently ethyl acetate was added. The resulting organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to dryness in a rotary evaporator under reduced pressure. The residue obtained was applied to silica gel and purified by column chromatography on silica gel (eluent: cyclohexane / ethyl acetate 1:1). 6.58 g (13.70 mmol, 70% of theory) of the target compound were obtained.

[0211] 1< H-NMR (400 MHz, DMSO- d6 , δ / ppm): 1.36 (2 s, 9H), 1.43-1.54 (m, 1H), 1.57-1.73 (m, 2H), 1.79-1.89 (m, 1H), 2.61-2.78 (m, 3H), 3.13 (br. t, 1H), 3.50 (br. t, 1H), 3.81 (br. d, 1H), 4.16-4.27 (m, 2H), 6.97 (t, 1H), 7.31 (t, 1H), 7.52 (d, 2H), 7.59 (d, 1H), 7.82-7.90 (m, 2H), 8.57 (d, 1H).

[0212] LC-MS (Methode 2): R t = 1.50 min; m / z = 453 / 455 (M+H) +< . Example 2 tert .-Butyl-5-{[2-(5-chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]-octan-2-carboxylat ( Racemate )

[0213]

[0214] Unter Argon wurden bei Raumtemperatur 1.1 g (4.27 mmol) 2-(5-Chlorpyridin-2-yl)imidazo-[1,2-a]pyridin-3-carbaldehyd in 35 ml THF gelöst und mit 1.36 g (6.40 mmol) tert.-Butyl 2,5-diazabicyclo[2.2.2]octane-2-carboxylate (racemate) and 0.49 ml (8.54 mmol) of acetic acid were added. Subsequently, 1.36 g (6.40 mmol) of sodium triacetoxyborohydride were added portionwise, and the reaction solution was stirred overnight at room temperature. Water was then slowly and carefully added dropwise (caution: gas evolution) and then ethyl acetate was added. The resulting organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered, and concentrated to dryness in a rotary evaporator under reduced pressure. The resulting residue was purified by column chromatography on silica gel (Biotage SNAP Cartridge KP-NH column; mobile phase: cyclohexane / ethyl acetate 1:1). 1.57 g (3.46 mmol, 81% of theory) of the target compound were obtained.

[0215] 1< H-NMR (400 MHz, DMSO-d 6 , δ / ppm): 1.39 (2 s, 9H), 1.44-1.58 (m, 1H), 1.70 (br. t, 2H), 1.85-2.01 (m, 1H), 2.70 (br. s, 0.5H), 2.78 (br. s, 0.5H), 2.82-2.96 (m, 2H), 3.14 (br. d, 1H), 3.63 (br. dd, 1H), 3.81 (br. s, 0.5H), 3.87 (br. s, 0.5H), 4.55-4.71 (m, 2H), 6.99 (t, 1H), 7.35 (t, 1H), 7.62 (d, 1H), 8.01 (br. d, 1H), 8.21 (d, 1H), 8.48 (d, 1H), 8.63 (dd, 1H).

[0216] LC-MS (Methode 2): R t = 1.27 min; m / z = 454 / 456 (M+H) +< . Example 3 tert .-Butyl-5-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octan-2-carboxylat ( Racemate )

[0217]

[0218] Unter Argon wurden bei Raumtemperatur 670 mg (2.53 mmol) 2-(6-Isopropylpyridin-3-yl)-imidazo[1,2-a]pyridin-3-carbaldehyd in 15 ml THF gelöst und mit 643 mg (3.03 mmol) tert.-Butyl 2,5-diazabicyclo[2.2.2]octane-2-carboxylate (racemate) and 0.29 ml (5.05 mmol) of acetic acid were added. Then, 803 mg (3.79 mmol) of sodium triacetoxyborohydride were added portionwise, and the reaction solution was stirred overnight at room temperature. Water was then slowly and carefully added dropwise (caution: gas evolution) and then ethyl acetate was added. The resulting organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to dryness in a rotary evaporator under reduced pressure. The residue was taken up in dichloromethane and filtered. The resulting filtrate was again concentrated to dryness. The resulting residue was purified by column chromatography on silica gel (Biotage SNAP Cartridge KP-NH column; mobile phase: cyclohexane / ethyl acetate 1:1). 720 mg (1.56 mmol, 62% of d.Th.) of the target compound.

[0219] 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.28 (d, 6H), 1.36 (2 s, 9H), 1.43-1.55 (m, 1H), 1.57-1.75 (m, 2H), 1.78-1.91 (m, 1H), 2.65-2.82 (m, 3H), 3.01-3.19 (m, 2H), 3.53 (dd, 1H), 3.81 (br. d, 1H), 4.17-4.28 (m, 2H), 6.98 (t, 1H), 7.31 (t, 1H), 7.38 (d, 1H), 7.61 (d, 1H), 8.13 (dt, 1H), 8.58 (d, 1H), 8.92 (dd, 1H).

[0220] LC-MS (Method 2): R t = 1.41 min; m / z = 462 (M+H) +< . Example 4 tert .-Butyl-7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo-[3.3.1]nonane-9-carboxylate

[0221]

[0222] Under argon at room temperature, 1.406 g (5.48 mmol) of 2-(4-chlorophenyl)imidazo[1,2-a]-pyridine-3-carbaldehyde were dissolved in 25 ml of THF and treated with 1.5 g (6.57 mmol) tert.-Butyl-3-oxa-7,9-diazabicyclo[3.3.1]nonane-9-carboxylate and 0.63 ml (10.95 mmol) of acetic acid were added. Subsequently, 1.74 g (8.21 mmol) of sodium triacetoxyborohydride were added portionwise, and the reaction solution was stirred overnight at room temperature. Water was then slowly and carefully added dropwise (caution: gas evolution) and subsequently ethyl acetate was added. The resulting organic phase was separated, and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to dryness in a rotary evaporator under reduced pressure. The residue was purified by column chromatography on silica gel (Biotage SNAP Cartridge KP-NH column; mobile phase: cyclohexane / ethyl acetate 1:1). 1.87 g (3.99 mmol, 73% of theory) of the target compound was obtained.

[0223] 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.35-1.46 (m, 9H), 2.43 (br. d, 2H), 2.85 (br. d, 2H), 3.57 (br. d, 2H), 3.71 (d, 2H), 3.81-3.92 (m, 4H), 6.93 (td, 1H), 7.30 (ddd, 1H), 7.51 (d, 2H), 7.60 (d, 1H), 7.97 (d, 2H), 8.81 (d, 1H).

[0224] LC-MS (Method 2): R t = 1.52 min; m / z = 469 / 471 (M+H) +< .

[0225] Analogously to Examples 1-4, the following compounds were prepared from the indicated starting materials: Example Name / Structure / Educts Analytical data 5 tert .-Butyl-8-{[2-(4-bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-3-carboxylat 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.36 (s, 9H), 1.42-1.50 (m, 2H), 1.78-1.91 (m, 2H), 2.63-2.75 (m, 1H), 2.76-2.88 (m, 1H), 3.00-3.14 (m, 2H), 3.44-3.61 (m, 2H), 3.98 (s, 2H), 6.98 (td, 1H), 7.32 (ddd, 1H), 7.60 (d, 1H), 7.67 (d, 2H), 7.81 (d, 2H), 8.64 (d, 1H). LC-MS (Methode 2): R t = 1.64 min; m / z = 497 / 499 (M+H) +< . aus 2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3,8-diazabicyclo[3.2.1]octan-3-carboxylat 6 tert .-Butyl-8-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-3-carboxylat 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.35 (s, 9H), 1.46 (q, 2H), 1.79-1.89 (m, 2H), 2.63-2.76 (m, 1H), 2.77-2.88 (m, 1H), 3.00-3.14 (m, 2H), 3.42-3.61 (m, 2H), 3.98 (s, 2H), 6.98 (td, 1H), 7.32 (ddd, 1H), 7.53 (d, 2H), 7.60 (d, 1H), 7.87 (d, 2H), 8.64 (d, 1H). LC-MS (Methode 1): R t = 0.84 min; m / z = 453 / 455 (M+H) +< . aus 2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3,8-diazabicyclo[3.2.1]octan-3-carboxylat 7 tert .-Butyl-8-{[2-(4-isopropylphenyl)imidazo[1,2-a]-pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-3-carboxylat 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.24 (d, 6H), 1.35 (s, 9H), 1.46 (q, 2H), 1.78-1.89 (m, 2H), 2.65-2.75 (m, 1H), 2.77-2.87 (m, 1H), 2.87-3.01 (m, 1H), 3.04-3.17 (m, 2H), 3.43-3.62 (m, 2H), 3.98 (s, 2H), 6.96 (t, 1H), 7.29 (t, 1H), 7.34 (d, 2H), 7.58 (d, 1H), 7.74 (d, 2H), 8.64 (d, 1H). LC-MS (Methode 2): R t = 1.63 min; m / z = 461 (M+H) +< . aus 2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3,8-diazabicyclo[3.2.1]octan-3-carboxylat 8 tert. -Butyl-3-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-6-carboxylat 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.27 (s, 9H), 1.62 (d, 1H), 2.20 (q, 1H), 2.57-3.04 (m, 4H), 3.83-3.98 (m, 2H), 4.09-4.26 (m, 2H), 6.98 (t, 1H), 7.31 (t, 1H), 7.51 (d, 2H), 7.61 (d, 1H), 7.82 (d, 2H), 8.47 (d, 1H). LC-MS (Methode 1): R t = 0.87 min; m / z = 439 / 441 (M+H) +< . aus 2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3,6-diazabicyclo[3.1.1]heptan-6-carboxylat 9 tert .-Butyl-3-{[2-(4-isopropylphenyl)imidazo[1,2-a]-pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-6-carboxylat 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.25 (d, 6H), 1.28 (s, 9H), 1.65 (d, 1H), 2.20 (q, 1H), 2.56-3.02 (m, 5H), 3.81-4.03 (m, 2H), 4.05-4.24 (m, 2H), 6.94 (t, 1H), 7.24-7.35 (m, 3H), 7.59 (d, 1H), 7.71 (d, 2H), 8.44 (d, 1H). LC-MS (Methode 1): R t = 0.88 min; m / z = 447 (M+H) +< . aus 2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3,6-diazabicyclo[3.1.1]heptan-6-carboxylat 10 tert. -Butyl-3-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.39 (s, 9H), 1.64 (br. s, 4H), 2.27 (br. d, 2H), 2.48-2.58 (m, 2H, teilweise verdeckt durch DMSO-Signal), 3.97 (br. s, 2H), 4.03 (br. s, 2H), 6.99 (t, 1H), 7.31 (t, 1H), 7.53 (d, 2H), 7.60 (d, 1H), 7.92 (d, 2H), 8.58 (d, 1H). LC-MS (Methode 2): R t = 1.81 min; m / z = 453 / 455 (M+H) +< . aus 2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3,8-diazabicyclo[3.2.1]octan-8-carboxylat 11 tert .-Butyl-3-{[2-(4-bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.39 (s, 9H), 1.64 (br. s, 4H), 2.27 (br. d, 2H), 2.46-2.58 (m, 2H, verdeckt durch DMSO-Signal), 3.97 (s, 2H), 4.03 (br. s, 2H), 6.99 (td, 1H), 7.31 (ddd, 1H), 7.60 (d, 1H), 7.67 (d, 2H), 7.85 (d, 2H), 8.58 (d, 1H). LC-MS (Methode 2): R t = 1.86 min; m / z = 497 / 499 (M+H) +< . aus 2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3,8-diazabicyclo[3.2.1]octan-8-carboxylat 12 tert .-Butyl-3-{[2-(4-isopropylphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.25 (d, 6H), 1.39 (s, 9H), 1.65 (br. s, 4H), 2.26 (br. d, 2H), 2.46-2.59 (m, 2H, teilweise verdeckt durch DMSO-Signal), 2.88-3.01 (m, 1H), 3.97 (s, 2H), 4.03 (br. s, 2H), 6.96 (t, 1H), 7.28 (t, 1H), 7.34 (d, 2H), 7.58 (d, 1H), 7.79 (d, 2H), 8.55 (d, 1H). LC-MS (Methode 2): R t = 1.74 min; m / z = 461 (M+H) +< . aus 2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3,8-diazabicyclo[3.2.1]octan-8-carboxylat 13 tert .-Butyl-5-{[2-(4-isopropylphenyl)imidazo[1,2-a]-pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-2-carboxylat ( Racemate ) 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.25 (d, 6H), 1.36 (2 s, 9H), 1.43-1.56 (m, 1H), 1.58-1.76 (m, 2H), 1.77-1.93 (m, 1H), 2.64-2.82 (m, 3H), 2.87-3.01 (m, 1H), 3.13 (br. t, 1H), 3.52 (br. d, 1H), 3.82 (br. d, 1H), 4.21 (s, 2H), 6.95 (t, 1H), 7.28 (t, 1H), 7.34 (d, 2H), 7.58 (d, 1H), 7.70-7.79 (m, 2H), 8.55 (d, 1H). LC-MS (Methode 2): R t = 1.60 min; m / z = 461 (M+H) +< . aus 2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-2,5-diazabicyclo[2.2.2]octan-2-carboxylat ( Racemate ) 14 tert .-Butyl-3-{[2-(5-chlorpyridin-2-yl)imidazo-[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.38 (s, 9H), 1.62 (br. s, 4H), 2.25 (br. d, 2H), 2.45-2.59 (m, 2H, teilweise verdeckt durch DMSO-Signal), 3.98 (br. s, 2H), 4.45 (s, 2H), 7.01 (td, 1H), 7.34 (t, 1H), 7.62 (d, 1H), 8.00 (dd, 1H), 8.20 (d, 1H), 8.54 (d, 1H), 8.65 (d, 1H). LC-MS (Methode 2): R t = 1.50 min; m / z = 454 / 456 (M+H) +< . aus 2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3,8-diazabicyclo[3.2.1]octan-8-carboxylat Example 15 and Example 16 tert.-Butyl-5-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane-2-carboxylate ( Enantiomers 1 and 2 )

[0226]

[0227] 5.86 g (12.94 mmol) of the racemic tert .-Butyl-5-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane-2-carboxylate (Example 1) was separated into the enantiomers by preparative HPLC on a chiral phase [column: Daicel Chiralpak IC, 5 µm, 250 mm x 20 mm; eluent: isohexane / ethanol 80:20; flow rate: 15 ml / min; UV detection: 220 nm; temperature: 30°C]: Example 15 ( Enantiomer 1 ):

[0228] Yield: 2640 mg R t = 9.85 min; chemical purity >99%; >99% ee [Column: Daicel Chiralpak IC, 5 µm, 250 mm x 4.6 mm; eluent: isohexane / ethanol 80:20; flow: 1 ml / min; temperature: 30°C; UV detection: 220 mN]. LC-MS (Method 2): R t = 1.52 min; m / z = 453 / 455 (M+H) +< . 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.36 (2 s, 9H), 1.43-1.54 (m, 1H), 1.57-1.72 (m, 2H), 1.78-1.91 (m, 1H), 2.61-2.79 (m, 3H), 3.13 (br. t, 1H), 3.50 (br. t, 1H), 3.80 (br. d, 1H), 4.16-4.27 (m, 2H), 6.97 (t, 1H), 7.31 (t, 1H), 7.52 (d, 2H), 7.59 (d, 1H), 7.82-7.90 (m, 2H), 8.57 (d, 1H). Example 16 ( Enantiomer 2 ):

[0229] Ausbeute: 2430 mg R t = 10.62 min; chemische Reinheit >99%; >99% ee [Säule: Daicel Chiralpak IC, 5 µm, 250 mm x 4.6 mm; Elutionsmittel: Isohexan / Ethanol 80:20; Fluss: 1 ml / min; Temperatur: 30°C; UV-Detektion: 220 nm]. LC-MS (Methode 1): R t = 0.81 min; m / z = 453 / 455 (M+H) +< . 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.36 (2 s, 9H), 1.42-1.55 (m, 1H), 1.59-1.72 (m, 2H), 1.78-1.90 (m, 1H), 2.61-2.79 (m, 3H), 3.13 (br. t, 1H), 3.50 (br. t, 1H), 3.81 (br. d, 1H), 4.16-4.26 (m, 2H), 6.97 (t, 1H), 7.31 (t, 1H), 7.52 (d, 2H), 7.59 (d, 1H), 7.82-7.91 (m, 2H), 8.57 (d, 1H). Example 17 and Example 18 tert.-Butyl-5-{[2-(4-isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]-octane-2-carboxylate ( Enantiomers 1 and 2 )

[0230]

[0231] 3.91 g (14.79 mmol) of the racemic tert .-Butyl 5-{[2-(4-isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane-2-carboxylate (Example 13) was separated into the enantiomers by preparative supercritical liquid chromatography (SFC) on a chiral phase [column: Daicel Chiralpak ID-H, 5 µm, 250 mm x 20 mm; eluent: carbon dioxide / ethanol 67:33 (v / v); flow: 175 ml / min; pressure: 135 bar; UV detection: 210 nm; temperature: 38°C]: Example 17 (Enantiomer 1 ):

[0232] Ausbeute: 1889 mg R t = 3.39 min; chemische Reinheit >99%; >99% ee [Säule: Daicel Chiralpak AD-H, 3 µm, 50 mm x 4.6 mm; Elutionsmittel: Kohlendioxid / Methanol 5:95 → 50:50 (v / v); Fluss: 3 ml / min; Druck: 130 bar; Temperatur: 40°C; UV-Detektion: 220 nm]. LC-MS (Methode 1): R t = 0.88 min; m / z = 461 (M+H) +< . 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.25 (d, 6H), 1.36 (2 s, 9H), 1.43-1.56 (m, 1H), 1.58-1.76 (m, 2H), 1.77-1.93 (m, 1H), 2.64-2.82 (m, 3H), 2.87-3.01 (m, 1H), 3.13 (br. t, 1H), 3.52 (br. d, 1H), 3.82 (br. d, 1H), 4.21 (s, 2H), 6.95 (t, 1H), 7.28 (t, 1H), 7.34 (d, 2H), 7.58 (d, 1H), 7.70-7.79 (m, 2H), 8.55 (d, 1H). Example 18 (Enantiomer 2 ):

[0233] Ausbeute: 1860 mg R t = 3.72 min; chemische Reinheit >99%; >99% ee [Säule: Daicel Chiralpak AD-H, 3 µm, 50 mm x 4.6 mm; Elutionsmittel: Kohlendioxid / Methanol 5:95 ----> 50:50 (v / v); Fluss: 3 ml / min; Druck: 130 bar; Temperatur: 40°C; UV-Detektion: 220 nm]. LC-MS (Methode 1): R t = 0.87 min; m / z = 461 (M+H) +< . 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.25 (d, 6H), 1.36 (2 s, 9H), 1.44-1.56 (m, 1H), 1.58-1.75 (m, 2H), 1.79-1.92 (m, 1H), 2.64-2.83 (m, 3H), 2.87-3.00 (m, 1H), 3.13 (br. t, 1H), 3.52 (br. d, 1H), 3.82 (br. d, 1H), 4.21 (s, 2H), 6.95 (t, 1H), 7.28 (t, 1H), 7.34 (d, 2H), 7.58 (d, 1H), 7.71-7.78 (m, 2H), 8.55 (d, 1H). Example 19 and Example 20 tert .-Butyl-5-{[2-(5-chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]-octan-2-carboxylat ( Enantiomers 1 and 2 )

[0234]

[0235] 950 mg (2.09 mmol) des racemischen tert.-Butyl-5-{[2-(5-chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane-2-carboxylate (Example 2) was separated into the enantiomers by preparative HPLC on a chiral phase [column: YMC Cellulose SC, 5 µm, 250 mm x 20 mm; eluent: isohexane / isopropanol 50:50 + 0.2% diethylamine; flow rate: 15 ml / min; UV detection: 220 nm; temperature: 40°C]: Example 19 ( Enantiomer 1 ):

[0236] Yield: 450 mg R t = 6.48 min; chemical purity >99%; >99% ee [column: YMC Cellulose SC, 5 µm, 250 mm x 4.6 mm; eluent: n-heptane / isopropanol 70:30 + 0.2% diethylamine; flow: 1 ml / min; temperature: 40°C; UV detection: 235 nm]. 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.39 (2 s, 9H), 1.44-1.58 (m, 1H), 1.70 (br. t, 2H), 1.86-2.00 (m, 1H), 2.70 (br. s, 0.5H), 2.78 (br. s, 0.5H), 2.82-2.95 (m, 2H), 3.14 (br. d, 1H), 3.63 (br. dd, 1H), 3.81 (br. s, 0.5H), 3.87 (br. s, 0.5H), 4.55-4.72 (m, 2H), 6.99 (t, 1H), 7.35 (t, 1H), 7.62 (d, 1H), 8.01 (dt, 1H), 8.22 (d, 1H), 8.48 (d, 1H), 8.63 (dd, 1H). LC-MS (Methode 1): R t = 0.71 min; m / z = 454 / 456 (M+H) +< . Example 20 ( Enantiomer 2 ):

[0237] Ausbeute: 448 mg R t = 7.70 min; chemische Reinheit >99%; >99% ee [Säule: YMC Cellulose SC, 5 µm, 250 mm x 4.6 mm; Elutionsmittel: n-Heptan / Isopropanol 70:30 + 0.2% Diethylamin; Fluss: 1 ml / min; Temperatur: 40°C; UV-Detektion: 235 nm]. 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.39 (2 s, 9H), 1.44-1.58 (m, 1H), 1.70 (br. t, 2H), 1.85-2.01 (m, 1H), 2.70 (br. s, 0.5H), 2.78 (br. s, 0.5H), 2.82-2.96 (m, 2H), 3.14 (br. d, 1H), 3.63 (br. dd, 1H), 3.81 (br. s, 0.5H), 3.87 (br. s, 0.5H), 4.55-4.71 (m, 2H), 6.99 (t, 1H), 7.35 (t, 1H), 7.62 (d, 1H), 8.01 (dd, 1H), 8.21 (d, 1H), 8.48 (d, 1H), 8.63 (dd, 1H). LC-MS (Methode 1): R t = 0.71 min; m / z = 454 / 456 (M+H) +< . Example 21 (-)-[(1 S ,4 S )-5-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl](6-methoxypyridin-2-yl)methanon ( Enantiomer 1 )

[0238]

[0239] 59 mg (0.39 mmol) 6-Methoxypyridin-2-carbonsäure wurden in 2 ml DMF gelöst, mit 201 mg (0.53 mmol) 2-(7-Aza-1 H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 150 mg (0.35 mmol) of 2-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride (enantiomer 1) and 307 µl (1.76 mmol) of N,N- Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC (Method 6). 100 mg (0.2 mmol, 58% of theory) of the title compound was obtained.

[0240] LC-MS (Method 1): R t = 0.73 min; m / z = 488 / 490 (M+H) +< .

[0241] [α] D 20< = -40.83° (c = 0.320, methanol).

[0242] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.47-1.99 (m, 4H), 2.64 (br. s, 0.25H), 2.71 (dd, 0.75H), 2.82-2.92 (m, 2H), 3.38 (dd, 0.75H), 3.47 (dd, 0.25H), 3.70-3.78 (m, 3H), 3.80 (s, 0.75H), 3.92 (br. d, 0.25H), 3.98 (br. s, 0.75H), 4.21-4.33 (m, 2H), 4.38 (br. s, 0.25H), 6.84-7.02 (m, 2H), 7.17 (d, 0.75H), 7.25-7.36 (m, 1.25H), 7.44-7.55 (m, 2H), 7.60 (d, 1H), 7.75-7.91 (m, 3H), 8.54-8.64 (m, 1H).

[0243] Die Absolutkonfiguration der Verbindung wurde mittels VCD-Spektroskopie bestimmt [vgl. Kuppens, T., Bultinck, P., Langenaeker, W., "Determination of absolute configuration via vibrational circular dichroism", Drug Discovery Today: Technologies 1 (3), 269-275 (2004); Stephens, P. J., "Vibrational circular dichroism spectroscopy: A new tool for the stereochemical characterization of chiral molecules", Computational Medicinal Chemistry for Drug Discovery, 699-725 (2004)]. Example 22 (-)-(3-Chlor-6-methoxypyridin-2-yl)[(1 S ,4 S)-5-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl]methanone ( Enantiomer 1 )

[0244]

[0245] 363 mg (1.94 mmol) of 3-chloro-6-methoxypyridine-2-carboxylic acid were dissolved in 10 ml of DMF, with 1005 mg (2.64 mmol) of 2-(7-aza-1 H -benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 750 mg (1.76 mmol) of 2-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride (enantiomer 1) and 1.53 ml (8.8 mmol) of N,N-Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction solution was then slowly poured into ice-water, and the precipitated solid was filtered off with suction, washed several times with water, and finally dried at 40°C under high vacuum. The aqueous phase was extracted several times with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered, and evaporated to dryness. The residue was combined with the previously obtained solid and purified by column chromatography on silica gel (Biotage SNAP Cartridge KP-NH column; eluent: cyclohexane / ethyl acetate 1:1). This yielded 685 mg (1.24 mmol, 70% of theory) of the title compound. A portion of this (100 mg) was purified again by preparative HPLC (Method 6), and the specific optical rotation of this sample was determined (see below).

[0246] LC-MS (Methode 2): R t = 1.38 min; m / z = 522 / 523 / 524 (M+H) +< .

[0247] [α] D 20< = -62.64° (c = 0.455, Methanol).

[0248] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.51-1.99 (m, 4H), 2.61 (br. d, 0.7H), 2.65-2.77 (m, 1H), 2.81 (br. s, 0.6H), 2.93-3.00 (m, 1H), 3.20 (br. s, 0.7H), 3.37 (br. d, 0.3H), 3.42 (br. d, 0.7H), 3.71-3.85 (m, 3.7H), 4.16-4.42 (m, 2.3H), 6.85-7.02 (m, 2H), 7.31 (br. t, 1H), 7.46-7.64 (m, 3H), 7.77-7.99 (m, 3H), 8.53-8.65 (m, 1H). Example 23 (-)-[(1 S ,4 S )-5-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl](3-fluor-6-methoxypyridin-2-yl)methanon ( Enantiomer 1 )

[0249]

[0250] 332 mg (1.94 mmol) 3-Fluor-6-methoxypyridin-2-carbonsäure wurden in 10 ml DMF gelöst, mit 1005 mg (2.64 mmol) 2-(7-Aza-1 H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 750 mg (1.76 mmol) of 2-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride (enantiomer 1) and 1.53 ml (8.8 mmol) of N,N-Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction solution was then slowly poured into ice-water, and the precipitated solid was filtered off with suction, washed several times with water, and finally dried at 40°C under high vacuum. The aqueous phase was extracted several times with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered, and evaporated to dryness. The residue was combined with the previously obtained solid and purified by column chromatography on silica gel (Biotage SNAP Cartridge KP-NH column; eluent: cyclohexane / ethyl acetate 1:1). This yielded 581 mg (1.15 mmol, 65% of theory) of the title compound. A portion of this (100 mg) was purified again by preparative HPLC (Method 6), and the specific optical rotation of this sample was determined (see below).

[0251] LC-MS (Method 1): R t = 0.74 min; m / z = 505 / 506 (M+H) +< .

[0252] [α] D 20< = -47.17° (c = 0.460, Methanol).

[0253] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.51-2.10 (m, 4H), 2.63-2.72 (m, 2H), 2.77-2.86 (m, 1H), 2.87-2.92 (m, 1H), 3.42 (br. d, 1H), 3.48 (br. s, 1H), 3.73 (s, 3H), 4.22-4.41 (m, 2H), 6.89-7.04 (m, 2H), 7.26-7.35 (m, 1H), 7.47-7.56 (m, 2H), 7.60 (d, 1H), 7.74 (t, 1H), 7.82-7.91 (m, 2H), 8.54-8.63 (m, 1H). Example 24 (5-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(3-fluor-6-methoxypyridin-2-yl)methanon ( Enantiomer 1 )

[0254]

[0255] 41 mg (0.24 mmol) 3-Fluor-6-methoxypyridin-2-carbonsäure wurden in 1.5 ml DMF gelöst, mit 123 mg (0.32 mmol) 2-(7-Aza-1 H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 100 mg (0.22 mmol) of 2-{[2-(5-chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octane dihydrochloride (enantiomer 1) and 188 µl (1.08 mmol) of N,N- Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC (Method 6). 79 mg (0.16 mmol, 72% of theory) of the title compound was obtained.

[0256] LC-MS (Method 2): R t = 1.13 min; m / z = 507 / 509 (M+H) +< .

[0257] [α] D 20< = -77.15° (c = 0.270, methanol).

[0258] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.52-2.09 (m, 4H), 2.76 (br. s, 0.3H), 2.83-3.08 (m, 2.7H), 3.15 (br. d, 0.3H), 3.42 (br. d, 0.7H), 3.50 (br. s, 0.7H), 3.73-3.89 (m, 4H), 4.42 (br. s, 0.3H), 4.58-4.75 (m, 2H), 6.93 (dd, 0.7H), 6.96-7.05 (m, 1.3H), 7.30-7.39 (m, 1H), 7.58-7.66 (m, 1H), 7.76 (t, 0.7H), 7.84 (t, 0.3H), 7.96-8.04 (m, 1H), 8.17-8.26 (m, 1H), 8.44-8.53 (m, 1.3H), 8.66 (d, 0.7H). Example 25 (3-Chlor-6-methoxypyridin-2-yl)(5-{[2-(5-chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanon ( Enantiomer 1 )

[0259]

[0260] 45 mg (0.24 mmol) 3-Chlor-6-methoxypyridin-2-carbonsäure wurden in 1.5 ml DMF gelöst, mit 123 mg (0.32 mmol) 2-(7-Aza-1 H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 100 mg (0.22 mmol) of 2-{[2-(5-chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octane dihydrochloride (enantiomer 1) and 188 µl (1.08 mmol) of N,N- Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC (Method 6). 84 mg (0.16 mmol, 74% of theory) of the title compound were obtained.

[0261] LC-MS (Method 2): R t = 1.21 min; m / z = 523 / 524 / 525 (M+H) +< .

[0262] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.51-2.08 (m, 4H), 2.74 (br. s, 0.3H), 2.83 (br. d, 0.7H), 2.90-3.08 (m, 2.3H), 3.24 (br. s, 0.7H), 3.44 (br. d, 0.7H) 3.66 (br. d, 0.3H), 3.76 (s, 2.3H), 3.82-3.90 (m, 1.4H), 4.43 (br. s, 0.3H), 4.62-4.74 (m, 2H), 6.90 (d, 0.7H), 6.94-7.06 (m, 1.3H), 7.30-7.39 (m, 1H), 7.58-7.67 (m, 1H), 7.85 (d, 0.7H), 7.95 (d, 0.3H), 7.97-8.05 (m, 1H), 8.16-8.27 (m, 1H), 8.44 (d, 0.3H), 8.46-8.53 (m, 1H), 8.65 (d, 0.7H). Example 26 (-)-(5-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(6-methoxypyridin-2-yl)methanon ( Enantiomer 1 )

[0263]

[0264] Approach 1: 40 mg (0.26 mmol) 6-Methoxypyridin-2-carbonsäure wurden in 1.7 ml DMF gelöst, mit 137 mg (0.36 mmol) 2-(7-Aza-1 H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 111 mg (0.24 mmol) of 2-{[2-(5-chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octane dihydrochloride (enantiomer 1) and 210 µl (1.20 mmol) of N,N- Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then directly separated into its components by preparative HPLC (Method 6). Due to column damage during purification, only 16 mg (0.03 mmol, 14% of theory) of the title compound were obtained.

[0265] LC-MS (Method 2): R t = 1.12 min; m / z = 489 / 491 (M+H) +< .

[0266] [α] D 20< = -74.46° (c = 0.295, methanol).

[0267] Approach 2: 36 mg (0.24 mmol) of 6-methoxypyridine-2-carboxylic acid were dissolved in 1.5 ml of DMF, with 123 mg (0.32 mmol) of 2-(7-aza-1 H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 100 mg (0.22 mmol) of 2-{[2-(5-chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octane dihydrochloride (enantiomer 1) and 188 µl (1.08 mmol) of N,N- Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC (Method 6). 87 mg (0.18 mmol, 82% of theory) of the title compound were obtained.

[0268] LC-MS (Method 2): R t = 1.14 min; m / z = 489 / 491 (M+H) +< .

[0269] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.50-2.07 (m, 4H), 2.68-2.73 (m, 0.3H), 2.85-2.94 (m, 1.4H), 2.99-3.09 (m, 1.3H), 3.37 (dd, 0.7H), 3.49 (dd, 0.3H), 3.77 (s, 2.3H), 3.81-3.89 (m, 1.4H), 4.01 (br. s, 0.7H), 4.08 (br. d, 0.3H), 4.42 (br. s, 0.3H), 4.57-4.76 (m, 2H), 6.89 (d, 0.7H), 6.94 (d, 0.3H), 6.96-7.04 (m, 1H), 7.21 (d, 0.7H), 7.30-7.39 (m, 1.3H), 7.58-7.65 (m, 1H), 7.77-7.89 (m, 1H), 7.97-8.04 (m, 1H), 8.17-8.25 (m, 1H), 8.43 (d, 0.3H), 8.47-8.53 (m, 1H), 8.63 (d, 0.7H). Example 27 (5-{[2-(6-Isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(6-methoxypyridin-2-yl)methanon (Racemate)

[0270]

[0271] 79 mg (0.51 mmol) 6-Methoxypyridin-2-carbonsäure wurden in 2.5 ml DMF gelöst, mit 266 mg (0.70 mmol) 2-(7-Aza-1 H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 220 mg (0.47 mmol) of 2-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride (racemate) and 410 µl (2.34 mmol) of N,N- Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC (Method 6). 150 mg (0.30 mmol, 65% of theory) of the title compound was obtained.

[0272] LC-MS (Method 2): R t = 1.18 min; m / z = 497 (M+H) +< . Example 28 (3-Fluoro-6-methoxypyridin-2-yl)(5-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]-methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanone (Racemate)

[0273]

[0274] 88 mg (0.51 mmol) of 3-fluoro-6-methoxypyridine-2-carboxylic acid was dissolved in 2.5 ml of DMF, treated with 266 mg (0.70 mmol) of 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU), and stirred at room temperature for 30 min. Subsequently, 220 mg (0.47 mmol) of 2-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octane dihydrochloride (racemate) and 410 µl (2.34 mmol) of N,N- Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC (Method 6). 147 mg (0.29 mmol, 61% of theory) of the title compound was obtained.

[0275] LC-MS (Method 2): R t = 1.19 min; m / z = 515 (M+H) +< . Example 29 (7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(6-methoxypyridin-2-yl)methanone

[0276]

[0277] 35 mg (0.23 mmol) of 6-methoxypyridine-2-carboxylic acid were dissolved in 1.5 ml of DMF, with 119 mg (0.31 mmol) of 2-(7-aza-1 H -benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 100 mg (0.21 mmol) of 7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonane dihydrochloride and 150 µl (0.84 mmol) of N,N- Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC (Method 6). 71 mg (0.14 mmol, 67% of theory) of the title compound was obtained.

[0278] LC-MS (Method 1): R t = 0.72 min; m / z = 504 / 506 (M+H) +< .

[0279] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 2.56-2.69 (m, 2H), 2.90 (br. d, 1H), 3.04 (br. d, 1H), 3.66-3.78 (m, 3H), 3.80 (s, 3H), 3.89 (d, 1H), 3.94 (s, 2H), 4.21 (br. s, 1H), 4.46 (br. s, 1H), 6.89-6.97 (m, 2H), 7.26-7.33 (m, 2H), 7.51 (d, 2H), 7.60 (d, 1H), 7.83 (dd, 1H), 7.98 (d, 2H), 8.83 (d, 1H). Example 30 (7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(3-fluoro-6-methoxypyridin-2-yl)methanone

[0280]

[0281] 39 mg (0.23 mmol) of 3-fluoro-6-methoxypyridine-2-carboxylic acid were dissolved in 1.5 ml of DMF, with 119 mg (0.31 mmol) of 2-(7-aza-1 H -benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 100 mg (0.21 mmol) of 7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo-[3.3.1]nonane dihydrochloride and 146 µl (0.84 mmol) of N,N-Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then directly separated into its components by preparative HPLC [instrument: Waters Prep LC / MS system; column: XBridge C18 5 µm, 100 mm x 30 mm; eluent A: water, eluent B: acetonitrile; gradient profile: 0-2 min 10% B, 2-2.2 min to 30% B, 2.2-7 min to 70% B, 7-7.5 min to 92% B, 7.5-9 min to 92% B; flow rate: 65 mL / min; also constant 5 mL / min 2% ammonia in water; room temperature; UV detection: 200-400 nm]. This yielded 77 mg (0.15 mmol, 71% of theory) of the title compound.

[0282] LC-MS (Method 2): R t = 1.33 min; m / z = 522 / 524 (M+H) +< .

[0283] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 2.47-2.62 (m, 2H, partially obscured by DMSO signal), 2.88 (br. d, 1H), 3.04 (br. d, 1H), 3.59-3.76 (m, 4H), 3.80 (s, 3H), 3.88 (d, 1H), 3.94 (s, 2H), 4.47 (br. s, 1H), 6.90-7.01 (m, 2H), 7.30 (ddd, 1H), 7.52 (d, 2H), 7.60 (d, 1H), 7.80 (t, 1H), 7.97 (d, 2H), 8.82 (d, 1H). Example 31 (7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)[6-(cyclobutyloxy)pyridin-2-yl]methanone

[0284]

[0285] 44 mg (0.23 mmol) of 6-(cyclobutyloxy)pyridine-2-carboxylic acid were dissolved in 1.5 ml of DMF, with 119 mg (0.31 mmol) of 2-(7-aza-1 H -benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 100 mg (0.21 mmol) of 7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo-[3.3.1]nonane dihydrochloride and 146 µl (0.84 mmol) of N,N-Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC [instrument: Waters Prep LC / MS system; column: XBridge C18 5 µm, 100 mm x 30 mm; eluent A: water, eluent B: acetonitrile; gradient profile: 0-2 min 10% B, 2-2.2 min 30% B, 2.2-7 min 70% B, 7-7.5 min 92% B, 7.5-9 min 92% B; flow rate: 65 mL / min; also constant 5 mL / min 2% ammonia in water; room temperature; UV detection: 200-400 nm]. This yielded 79 mg (0.14 mmol, 69% of theory) of the title compound.

[0286] LC-MS (Method 2): R t = 1.60 min; m / z = 544 / 546 (M+H) +< .

[0287] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.45-1.61 (m, 1H), 1.68-1.80 (m, 1H), 1.93-2.10 (m, 2H), 2.23-2.38 (m, 2H), 2.57-2.65 (m, 2H), 2.87 (br. d, 1H), 3.07 (br. d, 1H), 3.63-3.77 (m, 3H), 3.87-4.01 (m, 3H), 4.14 (br. s, 1H), 4.46 (br. s, 1H), 4.98-5.09 (m, 1H), 6.87 (dd, 1H), 6.93 (td, 1H), 7.26 (dd, 1H), 7.31 (td, 1H), 7.51 (d, 2H), 7.60 (d, 1H), 7.82 (dd, 1H), 7.99 (d, 2H), 8.84 (d, 1H). Example 32 (3-Chlor-6-methoxypyridin-2-yl)(7-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)methanon

[0288]

[0289] 43 mg (0.23 mmol) 3-Chlor-6-methoxypyridin-2-carbonsäure wurden in 1.4 ml DMF gelöst, mit 119 mg (0.31 mmol) 2-(7-Aza-1 H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 100 mg (0.21 mmol) of 7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo-[3.3.1]nonane dihydrochloride and 182 µl (1.05 mmol) of N,N- Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC (Method 6). 86 mg (0.16 mmol, 76% of theory) of the title compound were obtained.

[0290] LC-MS (Method 2): R t = 1.39 min; m / z = 538 / 539 / 540 (M+H) +< .

[0291] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 2.46-2.60 (m, 2H, partially obscured by DMSO signal), 2.86 (br. d, 1H), 3.04 (br. d, 1H), 3.34 (br. s, 1H), 3.59-3.76 (m, 3H), 3.82 (s, 3H), 3.88 (d, 1H), 3.94 (s, 2H), 4.46 (br. s, 1H), 6.89-6.98 (m, 2H), 7.30 (d, 1H), 7.52 (d, 2H), 7.60 (d, 1H), 7.90 (d, 1H), 7.97 (d, 2H), 8.81 (d, 1H). Example 33 (3-{[2-(5-Chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(6-methoxypyridin-2-yl)methanone

[0292]

[0293] 39 mg (0.26 mmol) of 6-methoxypyridine-2-carboxylic acid were dissolved in 1.5 ml of DMF, with 134 mg (0.35 mmol) of 2-(7-aza-1 H -benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) was added and stirred at room temperature for 30 min. Subsequently, 100 mg (0.23 mmol) of 3-{[2-(5-chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octane dihydrochloride and 200 µl (1.17 mmol) of N,N-Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC (Method 6). 93 mg (0.19 mmol, 81% of theory) of the title compound were obtained.

[0294] LC-MS (Method 2): R t = 1.31 min; m / z = 489 / 491 (M+H) +< .

[0295] 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.62-1.80 (m, 4H), 2.40 (br. d, 1H), 2.46-2.69 (m, 2H, partially obscured by DMSO signal), 2.76 (br. d, 1H), 3.72 (s, 3H), 4.44-4.64 (m, 4H), 6.91 (d, 1H), 7.02 (dd, 1H), 7.30-7.39 (m, 2H), 7.62 (d, 1H), 7.80 (dd, 1H), 8.00 (dd, 1H), 8.19 (d, 1H), 8.57 (d, 1H), 8.66 (d, 1H).

[0296] Analogously to Examples 21 and 33, the following compounds were prepared from the respective starting materials: Beispiel Name / Struktur / Edukte Analytische Daten 34 (+)-[(1 R ,4 R )-5-{[2-(4-Chlorphenyl)imidazo[1,2-a]-pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl](6-methoxypyridin-2-yl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.48-2.00 (m, 4H), 2.64 (br. s, 0.25H), 2.71 (dd, 0.75H), 2.81-2.93 (m, 2H), 3.38 (dd, 0.75H), 3.47 (dd, 0.25H), 3.70-3.78 (m, 3H), 3.80 (s, 0.75H), 3.92 (br. d, 0.25H), 3.98 (br. s, 0.75H), 4.21-4.32 (m, 2H), 4.38 (br. s, 0.25H), 6.85-7.02 (m, 2H), 7.17 (d, 0.75H), 7.25-7.35 (m, 1.25H), 7.46-7.56 (m, 2H), 7.60 (d, 1H), 7.75-7.92 (m, 3H), 8.55-8.63 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 2) und 6-Methoxypyridin-2-carbonsäure [α] D 20< = +46.13° (c = 0.250, Methanol). LC-MS (Methode 1): R t = 0.73 min; m / z = 488 / 490 (M+H) +< . Die Absolutkonfiguration wurde mittels VCD-Spektroskopie bestimmt (vgl. Beispiel 21) 35 (-)-(5-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(2-fluorphenyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.48-1.97 (m, 4H), 2.63-2.71 (m, 1H), 2.74-2.88 (m, 1.25H), 2.90 (br. s, 0.75H), 3.01 (d, 0.25H), 3.27-3.36 (m, 0.75H, teilweise verdeckt durch H 2 O-Signal), 3.42 (br. d, 1H), 3.76 (br. d, 0.75H), 4.17-4.32 (m, 2H), 4.39 (br. s, 0.25H), 6.93-7.02 (m, 1H), 7.20-7.39 (m, 4H), 7.42-7.63 (m, 4H), 7.84 (d, 0.5H), 7.88 (d, 1.5H), 8.54-8.63 (m, 1H). from 2-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride (Enantiomer 1) and 2-fluorobenzoic acid [α] D 20< = -29.87° (c = 0.250, Methanol). LC-MS (Methode 1): R t = 0.75 min; m / z = 475 / 477 (M+H) +< . 36 (+)-(5-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(2-fluorphenyl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.48-1.97 (m, 4H), 2.62-2.71 (m, 1H), 2.74-2.88 (m, 1.25H), 2.90 (br. s, 0.75H), 3.01 (d, 0.25H), 3.27-3.36 (m, 0.75H, teilweise verdeckt durch H 2 O-Signal), 3.42 (br. d, 1H), 3.76 (br. d, 0.75H), 4.17-4.32 (m, 2H), 4.39 (br. s, 0.25H), 6.93-7.02 (m, 1H), 7.20-7.39 (m, 4H), 7.41-7.63 (m, 4H), 7.83 (d, 0.5H), 7.88 (d, 1.5H), 8.54-8.63 (m, 1H). from 2-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride (Enantiomer 2) and 2-fluorobenzoic acid [α] D 20< = +19.64° (c = 0.275, Methanol). LC-MS (Methode 1): R t = 0.74 min; m / z = 475 / 477 (M+H) +< . 37 (5- { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(cyclopentyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.39-1.79 (m, 11H), 1.81-1.95 (m, 1H), 2.63-2.86 (m, 4H), 3.18 (dd, 0.5H), 3.36 (br. d, 0.5H), 3.54 (br. d, 0.5H), 3.73 (br. d, 0.5H), 3.93 (br. s, 0.5H), 4.15-4.29 (m, 2.5H), 6.97 (t, 1H), 7.25-7.36 (m, 1H), 7.53 (d, 2H), 7.59 (d, 1H), 7.86 (d, 2H), 8.54-8.62 (m, 1H). LC-MS (Methode 1): aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1) und Cyclopentancarbonsäure R t = 0.74 min; m / z = 449 / 451 (M+H) +< . 38 (5- { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(cyclopentyl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.38-1.78 (m, 11H), 1.80-1.95 (m, 1H), 2.64-2.86 (m, 4H), 3.18 (dd, 0.5H), 3.36 (br. d, 0.5H), 3.54 (br. d, 0.5H), 3.73 (br. d, 0.5H), 3.93 (br. s, 0.5H), 4.16-4.30 (m, 2.5H), 6.97 (t, 1H), 7.25-7.35 (m, 1H), 7.53 (d, 2H), 7.59 (d, 1H), 7.86 (d, 2H), 8.53-8.62 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 2) und Cyclopentancarbonsäure LC-MS (Methode 1): R t = 0.75 min; m / z = 449 / 451 (M+H) +< . 39 (-)-(5-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(3-methoxyphenyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.46-1.67 (m, 1.75H), 1.69-1.98 (m, 2.25H), 2.68 (br. d, 1H), 2.81 (br. d, 1H), 2.88 (br. s, 0.75H), 2.92 (br. d, 0.25H), 3.17 (br. d, 0.25H), 3.37 (br. d, 0.75H), 3.53 (br. s, 0.75H), 3.62 (br. d, 0.25H), 3.67-3.82 (m, 3.75H), 4.19-4.32 (m, 2.25H), 6.80-6.87 (m, 1.5H), 6.91-7.06 (m, 2.5H), 7.26-7.40 (m, 2H), 7.46-7.64 (m, 3H), 7.83-7.92 (m, 2H), 8.56-8.63 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1) und 3-Methoxybenzoesäure [α] D 20< = -36.15° (c = 0.260, Methanol). LC-MS (Methode 1): R t = 0.75 min; m / z = 487 / 489 (M+H) +< . 40 (+)-(5-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(3-methoxyphenyl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.46-1.67 (m, 1.75H), 1.70-1.97 (m, 2.25H), 2.68 (br. d, 1H), 2.81 (br. d, 1H), 2.88 (br. s, 0.75H), 2.92 (br. d, 0.25H), 3.17 (br. d, 0.25H), 3.37 (br. d, 0.75H), 3.53 (br. s, 0.75H), 3.62 (br. d, 0.25H), 3.68-3.82 (m, 3.75H), 4.20-4.32 (m, 2.25H), 6.80-6.87 (m, 1.5H), 6.92-7.06 (m, 2.5H), 7.26-7.39 (m, 2H), 7.47-7.63 (m, 3H), 7.84-7.92 (m, 2H), 8.56-8.64 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 2) und 3-Methoxybenzoesäure [α] D 20< = +43.73° (c = 0.250, Methanol). LC-MS (Methode 1): R t = 0.75 min; m / z = 487 / 489 (M+H) +< . 41 (2-Chlor-5-fluorphenyl)(5-{[2-(4-chlorphenyl)-imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.46-1.99 (m, 4H), 2.56-3.01 (m, 3.6H), 3.14 (br. s, 0.4H), 3.23 (br. s, 0.4H), 3.41 (br. t, 0.6H), 3.77 (br. t, 0.6H), 4.17-4.33 (m, 2H), 4.39 (br. s, 0.4H), 6.92-7.03 (m, 1H), 7.14-7.38 (m, 3H), 7.46-7.64 (m, 4H), 7.77-7.93 (m, 2H), 8.53-8.64 (m, 1H). LC-MS (Methode 1): R t = 0.79 min; m / z = 509 / 511 (M+H) +< . aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1 ) und 2-Chlor-5-fluorbenzoesäure 42 (5-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(cyclohexyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.04-1.38 (m, 5H), 1.42-1.78 (m, 8H), 1.79-1.94 (m, 1H), 2.23-2.45 (m, 1H), 2.61-2.84 (m, 3H), 3.16 (dd, 0.6H), 3.27-3.39 (m, 0.4H, teilweise verdeckt durch H 2 O-Signal), 3.51 (d, 0.6H), 3.72 (d, 0.4H), 3.89 (br. s, 0.6H), 4.15-4.29 (m, 2.4H), 6.97 (t, 1H), 7.31 (t, 1H), 7.52 (d, 2H), 7.59 (d, 1H), 7.82-7.90 (m, 2H), 8.57 (d, 1H). from 2-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride (Enantiomer 1) and cyclohexanecarboxylic acid LC-MS (Methode 1): R t = 0.77 min; m / z = 463 / 465 (M+H) +< . 43 (5- { [2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(cyclobutyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.41-1.55 (m, 1H), 1.56-2.18 (m, 9H), 2.64-2.83 (m, 3H), 3.10-3.24 (m, 2H), 3.48-3.60 (m, 1H), 3.63 (br. s, 0.6H), 4.15-4.28 (m, 2.4H), 6.97 (t, 1H), 7.31 (t, 1H), 7.53 (d, 2H), 7.59 (d, 1H), 7.81-7.90 (m, 2H), 8.57 (d, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1) und Cyclobutancarbonsäure LC-MS (Methode 1): R t = 0.69 min; m / z = 435 / 437 (M+H) +< . 44 (5- { [2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(2-methoxyphenyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.45-1.67 (m, 2.2H), 1.69-1.95 (m, 1.8H), 2.46-2.84 (m, 3H, partially obscured by DMSO signal), 2.90 (br. s, 1H), 3.18 (br. s, 0.8H), 3.28-3.47 (m, 1H, partially obscured by H 2 O signal), 3.58 (br. s, 1.2H), 3.74 (br. s, 1.8H), 4.17-4.30 (m, 2H), 4.33-4.39 (m, 0.2H), 6.86-7.14 (m, 4H), 7.26-7.41 (m, 2H), 7.47-7.63 (m, 3H), 7.79-7.94 (m, 2H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl} -2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1) und 2-Methoxybenzoesäure LC-MS (Methode 2): R t = 1.33 min; m / z = 487 / 489 (M+H) +< . 45 (5- { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(5-fluor-2-methoxyphenyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, 0DMSO- d 6 ): δ [ppm] = 1.47-1.97 (m, 4H), 2.69 (br. d, 1H), 2.77-2.92 (m, 2H), 3.03 (br. d, 0.25H), 3.34-3.48 (m, 1.75H), 3.68-3.80 (m, 3.75H), 4.17-4.30 (m, 2H), 4.38 (br. s, 0.25H), 6.80-6.91 (m, 1H), 6.93-7.05 (m, 2H), 7.13-7.25 (m, 1H), 7.27-7.35 (m, 1H), 7.46-7.57 (m, 2H), 7.57-7.63 (m, 1H), 7.81-7.92 (m, 2H), 8.54-8.63 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1) und 5-Fluor-2-methoxybenzoesäure LC-MS (Methode 2): R t = 1.41 min; m / z = 505 / 507 (M+H) +< . 46 (5- { [2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(2-methylphenyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.46-1.97 (m, 4H), 2.00-2.22 (m, 3H), 2.56-2.69 (m, 1.5H), 2.73-2.80 (m, 0.5H), 2.86 (br. t, 0.5H), 2.94 (br. s, 0.75H), 3.12-3.27 (m, 1H), 3.40 (d, 0.75H), 3.80 (br. d, 0.75H), 4.16-4.30 (m, 2H), 4.40 (br. s, 0.25H), 6.91-7.02 (m, 1.3H), 7.09-7.36 (m, 4.7H), 7.46-7.63 (m, 3H), 7.79-7.91 (m, 2H), 8.52-8.62 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1) und 2-Methylbenzoesäure LC-MS (Methode 2): R t = 1.40 min; m / z = 471 / 473 (M+H) +< . 47 (5- { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(5-fluor-2-methylphenyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.48-1.96 (m, 4H), 1.97-2.20 (m, 3H), 2.57-2.69 (m, 1.4H), 2.74-3.01 (m, 2H), 3.13-3.29 (m, 1H), 3.40 (dd, 0.7H), 3.78 (br. d, 0.6H), 4.16-4.31 (m, 2H), 4.39 (br. s, 0.3H), 6.90-7.17 (m, 3H), 7.21-7.35 (m, 2H), 7.47-7.56 (m, 2H), 7.56-7.63 (m, 1H), 7.81-7.92 (m, 2H), 8.53-8.63 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1 ) und 5-Fluor-2-methylbenzoesäure LC-MS (Methode 2): R t = 1.45 min; m / z = 489 / 491 (M+H) +< . 48 (5- { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-[3-(trifluormethoxy)phenyl]methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.46-1.99 (m, 4H), 2.63-2.72 (m, 1H), 2.84 (br. d, 1H), 2.87-2.97 (m, 1H), 3.18 (br. d, 0.3H), 3.39 (dd, 0.7H), 3.47 (br. s, 0.7H), 3.63 (br. d, 0.3H), 3.74 (br. d, 0.7H), 4.20-4.35 (m, 2.3H), 6.92-7.02 (m, 1H), 7.26-7.37 (m, 2.4H), 7.40-7.63 (m, 5.6H), 7.83-7.92 (m, 2H), 8.56-8.64 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1 ) und 3-(Trifluormethoxy)benzoesäure LC-MS (Methode 4): R t = 2.09 min; m / z = 541 / 543 (M+H) +< . 49 (3-Chlorphenyl)(5-{[2-(4-chlorphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.48-1.98 (m, 4H), 2.62-2.70 (m, 1H), 2.83 (br. d, 1H), 2.87-2.95 (m, 1H), 3.17 (br. d, 0.3H), 3.38 (dd, 0.7H), 3.49 (br. s, 0.7H), 3.65 (br. d, 0.3H), 3.73 (br. d, 0.7H), 4.19-4.32 (m, 2.3H), 6.93-7.02 (m, 1H), 7.22-7.63 (m, 8H), 7.84-7.92 (m, 2H), 8.56-8.64 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1 ) und 3-Chlorbenzoesäure LC-MS (Methode 4): R t = 2.00 min; m / z = 491 / 493 (M+H) +< . 50 (5- { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-[3-(trifluormethyl)phenyl]methanon (Enantiomer 1) 1< H-NMR (400 MHz, 0DMSO- d 6 ): δ [ppm] = 1.47-1.99 (m, 4H), 2.63-2.71 (m, 1H), 2.80-2.99 (m, 2H), 3.19 (br. d, 0.3H), 3.41 (d, 0.7H), 3.47 (br. s, 0.7H), 3.63 (br. d, 0.3H), 3.75 (br. d, 0.7H), 4.19-4.36 (m, 2.3H), 6.92-7.03 (m, 1H), 7.26-7.35 (m, 1H), 7.45-7.73 (m, 5H), 7.76-7.92 (m, 4H), 8.56-8.65 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1 ) und 3-(Trifluormethyl)benzoesäure LC-MS (Methode 4): R t = 2.05 min; m / z = 525 / 527 (M+H) +< . 51 (5- { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(pyridin-2-yl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.47-1.99 (m, 4H), 2.68 (dd, 1H), 2.81-2.94 (m, 2H), 3.34-3.45 (m, 1H), 3.71-3.81 (m, 1H), 3.87 (br. s, 0.75H), 4.20-4.33 (m, 2H), 4.39 (br. s, 0.25H), 6.92-7.02 (m, 1H), 7.26-7.35 (m, 1H), 7.41-7.66 (m, 5H), 7.81-7.97 (m, 3H), 8.50-8.64 (m, 2H). LC-MS (Methode 1): R t = 0.64 min; m / z = 458 / 460 (M+H) +< . aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1) und Pyridin-2-carbonsäure 52 (5- { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(1-methyl-1 H -imidazol-2-yl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.48-1.98 (m, 4H), 2.64-2.93 (m, 3H), 3.36 (dd, 1H), 3.66-3.81 (m, 3.75H), 4.09 (d, 0.25H), 4.19-4.31 (m, 2H), 4.38 (br. s, 0.25H), 4.74 (br. s, 0.75H), 6.87-7.02 (m, 2H), 7.23-7.35 (m, 2H), 7.46-7.56 (m, 2H), 7.60 (d, 1H), 7.82-7.92 (m, 2H), 8.60 (d, 1H). LC-MS (Methode 1): R t = 0.61 min; m / z = 461 / 463 (M+H) +< . aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 1) und 1-Methyl-1 H- imidazol-2-carbonsäure 53 (5- { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(3-methylphenyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.45-1.98 (m, 4H), 2.30 (s, 2H), 2.35 (s, 1H), 2.62-2.69 (m, 1H), 2.75-2.84 (m, 1H), 2.86-2.94 (m, 1H), 3.16 (br. d, 0.3H), 3.37 (br. d, 0.7H), 3.52 (br. d, 0.7H), 3.62 (br. d, 0.3H), 3.74 (br. d, 0.7H), 4.20-4.32 (m, 2.3H), 6.92-7.13 (m, 2.4H), 7.18-7.36 (m, 3.6H), 7.46-7.64 (m, 3H), 7.83-7.92 (m, 2H), 8.56-8.63 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 1 ) und 3-Methylbenzoesäure LC-MS (Methode 2): R t = 1.41 min; m / z = 471 / 473 (M+H) +< . 54 (5- { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-(3-ethoxyphenyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.22-1.38 (m, 3H), 1.44-1.96 (m, 4H), 2.62-2.97 (m, 3H), 3.16 (br. d, 0.3H), 3.36 (br. d, 0.7H), 3.52 (br. s, 0.7H), 3.63 (br. d, 0.3H), 3.73 (br. d, 0.7H), 3.95-4.10 (m, 2H), 4.17-4.32 (m, 2.3H), 6.77-6.85 (m, 1.4H), 6.91-7.03 (m, 2.6H), 7.23-7.38 (m, 2H), 7.46-7.63 (m, 3H), 7.82-7.92 (m, 2H), 8.55-8.64 (m, 1H). aus 2-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 1 ) und 3-Ethoxybenzoesäure LC-MS (Methode 2): R t = 1.43 min; m / z = 501 / 503 (M+H) +< . 55 (5- { [2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(pyridin-4-yl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.47-1.99 (m, 4H), 2.61-2.70 (m, 1H), 2.78-2.87 (m, 1H), 2.91 (br. s, 1H), 3.14 (br. d, 0.3H), 3.36-3.46 (m, 1.4H), 3.58 (br. d, 0.3H), 3.74 (br. d, 0.7H), 4.18-4.36 (m, 2.3H), 6.92-7.02 (m, 1H), 7.25 (m, 2.5H), 7.38-7.44 (m, 0.5H), 7.47-7.63 (m, 3H), 7.81-7.91 (m, 2H), 8.55-8.64 (m, 2.5H), 8.65-8.70 (m, 0.5H). from 2-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride (Enantiomer 1 ) and isonicotinic acid LC-MS (Methode 2): R t = 1.06 min; m / z = 458 / 460 (M+H) +< . 56 (-)-(2-Fluorphenyl)(5-{[2-(4-isopropylphenyl)-imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.20-1.30 (m, 6H), 1.49-1.99 (m, 4H), 2.65-2.73 (m, 1H), 2.76-2.88 (m, 1.25H), 2.88-3.06 (m, 2H), 3.27-3.36 (m, 0.75H, teilweise verdeckt durch H 2 O-Signal), 3.39-3.49 (m, 1H), 3.77 (br. d, 0.75H), 4.22 (s, 0.5H), 4.26 (s, 1.5H), 4.40 (br. s, 0.25H), 6.91-7.00 (m, 1H), 7.18-7.39 (m, 6H), 7.41-7.53 (m, 1H), 7.55-7.62 (m, 1H), 7.73 (d, 0.5H), 7.76 (d, 1.5H), 8.52-8.61 (m, 1H). [α] D 20< = -27.07° (c = 0.250, Methanol). aus 2-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 1 ) und 2-Fluorbenzoesäure LC-MS (Methode 1): R t = 0.81 min; m / z = 483 (M+H) +< . 57 (+)-(2-Fluorphenyl)(5-{[2-(4-isopropylphenyl)-imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.20-1.30 (m, 6H), 1.48-1.97 (m, 4H), 2.63-2.74 (m, 1H), 2.75-2.88 (m, 1.25H), 2.89-3.05 (m, 2H), 3.25-3.36 (m, 0.75H, teilweise verdeckt durch H 2 O-Signal), 3.38-3.51 (m, 1H), 3.77 (br. d, 0.75H), 4.22 (s, 0.5H), 4.26 (s, 1.5H), 4.40 (br. s, 0.25H), 6.90-7.00 (m, 1H), 7.17-7.40 (m, 6H), 7.40-7.53 (m, 1H), 7.54-7.61 (m, 1H), 7.73 (d, 0.5H), 7.76 (d, 1.5H), 8.51-8.61 (m, 1H). aus 2-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 2) und 2-Fluorbenzoesäure [α] D 20< = +26.29° (c = 0.265, Methanol). LC-MS (Methode 4): R t = 2.02 min; m / z = 483 (M+H) +< . 58 (-)-(5-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(3-methoxyphenyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.20-1.30 (m, 6H), 1.47-1.69 (m, 1.75H), 1.71-1.98 (m, 2.25H), 2.66-2.74 (m, 1H), 2.82 (br. d, 1H), 2.88-3.01 (m, 2H), 3.17 (br. d, 0.25H), 3.37 (br. d, 0.75H), 3.54 (br. s, 0.75H), 3.64 (br. d, 0.25H), 3.70-3.82 (m, 3.75H), 4.22 (s, 0.5H), 4.26 (s, 1.5H), 4.31 (br. s, 0.25H), 6.80-6.87 (m, 1.5H), 6.90-7.06 (m, 2.5H), 7.24-7.39 (m, 4H), 7.54-7.62 (m, 1H), 7.73-7.80 (m, 2H), 8.53-8.62 (m, 1H). aus 2-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 1 ) und 3 -Methoxybenzoesäure [α] D 20< = -27.50° (c = 0.280, Methanol). LC-MS (Methode 1): R t = 0.81 min; m / z = 495 (M+H) +< . 59 (+)-(5-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(3-methoxyphenyl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.19-1.30 (m, 6H), 1.47-1.69 (m, 1.75H), 1.71-1.98 (m, 2.25H), 2.66-2.74 (m, 1H), 2.82 (br. d, 1H), 2.87-3.02 (m, 2H), 3.17 (br. d, 0.25H), 3.37 (br. d, 0.75H), 3.54 (br. s, 0.75H), 3.64 (br. d, 0.25H), 3.69-3.82 (m, 3.75H), 4.22 (s, 0.5H), 4.26 (s, 1.5H), 4.31 (br. s, 0.25H), 6.80-6.87 (m, 1.5H), 6.89-7.05 (m, 2.5H), 7.23-7.39 (m, 4H), 7.53-7.61 (m, 1H), 7.71-7.82 (m, 2H), 8.53-8.62 (m, 1H). aus 2-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 2) und 3 -Methoxybenzoesäure [α] D 20< = +30.79° (c = 0.275, Methanol). LC-MS (Methode 4): R t = 2.02 min; m / z = 495 (M+H) +< . 60 (-)-(5-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(6-methoxypyridin-2-yl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.24 (d, 6H), 1.49-2.00 (m, 4H), 2.67-2.78 (m, 1H), 2.84-3.01 (m, 3H), 3.39 (dd, 0.75H), 3.46 (d, 0.25H), 3.71-3.78 (m, 3H), 3.82 (s, 0.75H), 3.94-4.03 (m, 1H), 4.21-4.31 (m, 2H), 4.39 (br. s, 0.25H), 6.85-7.00 (m, 2H), 7.17 (d, 0.75H), 7.24-7.38 (m, 3.25H), 7.58 (d, 1H), 7.70-7.86 (m, 3H), 8.54-8.61 (m, 1H). aus 2-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 1 ) und 6-Methoxypyridin-2-carbonsäure [α] D 20< = -32.98° (c = 0.285, Methanol). LC-MS (Methode 2): R t = 1.34 min; m / z = 496 (M+H) +< . 61 (+)-(5-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(6-methoxypyridin-2-yl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.24 (d, 6H), 1.49-2.01 (m, 4H), 2.68-2.78 (m, 1H), 2.84-3.01 (m, 3H), 3.39 (dd, 0.75H), 3.46 (d, 0.25H), 3.71-3.78 (m, 3H), 3.82 (s, 0.75H), 3.94-4.03 (m, 1H), 4.22-4.31 (m, 2H), 4.39 (br. s, 0.25H), 6.85-7.00 (m, 2H), 7.17 (d, 0.75H), 7.23-7.38 (m, 3.25H), 7.58 (d, 1H), 7.70-7.85 (m, 3H), 8.54-8.61 (m, 1H). aus 2-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 2) und 6-Methoxypyridin-2-carbonsäure [α] D 20< = +36.23° (c = 0.265, Methanol). LC-MS (Methode 4): R t = 2.02 min; m / z = 496 (M+H) +< . 62 Cyclopentyl(5-{[2-(4-isopropylphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanon (Enantiomer 1 ) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.25 (d, 6H), 1.39-1.79 (m, 11H), 1.80-1.96 (m, 1H), 2.64-2.86 (m, 4H), 2.88-3.01 (m, 1H), 3.19 (dd, 0.5H), 3.27-3.38 (m, 0.5H, teilweise verdeckt durch HzO-Signal), 3.55 (br. d, 0.5H), 3.73 (br. d, 0.5H), 3.94 (br. s, 0.5H), 4.17-4.30 (m, 2.5H), 6.95 (t, 1H), 7.28 (t, 1H), 7.34 (d, 2H), 7.58 (dd, 1H), 7.71-7.79 (m, 2H), 8.56 (d, 1H). aus 2- {[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 1 ) und Cyclopentancarbonsäure LC-MS (Methode 2): R t = 1.44 min; m / z = 457 (M+H) +< . 63 Cyclopentyl(5-{[2-(4-isopropylphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.25 (d, 6H), 1.38-1.80 (m, 11H), 1.80-1.96 (m, 1H), 2.64-2.86 (m, 4H), 2.88-3.01 (m, 1H), 3.19 (dd, 0.5H), 3.27-3.38 (m, 0.5H, teilweise verdeckt durch HzO-Signal), 3.55 (br. d, 0.5H), 3.73 (br. d, 0.5H), 3.94 (br. s, 0.5H), 4.17-4.30 (m, 2.5H), 6.95 (t, 1H), 7.28 (t, 1H), 7.34 (d, 2H), 7.58 (dd, 1H), 7.70-7.79 (m, 2H), 8.56 (d, 1H). aus 2-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 2) und Cyclopentancarbonsäure LC-MS (Methode 4): R t = 2.10 min; m / z = 457 (M+H) +< . 64 (-)-(5-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(2-fluorphenyl)methanon (Enantiomer 1) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.49-1.93 (m, 3.3H), 1.94-2.07 (m, 0.7H), 2.65-2.73 (m, 0.3H), 2.87 (br. d, 0.7H), 2.91-3.09 (m, 2.3H), 3.36 (br. s, 0.7H), 3.43 (dd, 0.7H), 3.73 (br. d, 0.3H), 3.85 (br. d, 0.7H), 4.43 (br. s, 0.3H), 4.53-4.75 (m, 2H), 6.94-7.05 (m, 1H), 7.21-7.40 (m, 3.7H), 7.41-7.57 (m, 1.3H), 7.58-7.66 (m, 1H), 7.94-8.05 (m, 1H), 8.19 (d, 0.3H), 8.22 (d, 0.7H), 8.41 (d, 0.3H), 8.45-8.52 (m, 1H), 8.66 (d, 0.7H). aus 2-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid ( Enantiomer 1 ) und 2-Fluorbenzoesäure [α] D 20< = -55.55° (c = 0.270, Methanol). LC-MS (Methode 2): R t = 1.13 min; m / z = 476 / 478 (M+H) +< . 65 (+)-(5-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(6-methoxypyridin-2-yl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.50-2.07 (m, 4H), 2.68-2.72 (m, 0.3H), 2.85-2.95 (m, 1.4H), 3.00-3.09 (m, 1.3H), 3.37 (dd, 0.7H), 3.49 (dd, 0.3H), 3.77 (s, 2.3H), 3.81-3.89 (m, 1.4H), 4.01 (br. s, 0.7H), 4.08 (br. d, 0.3H), 4.42 (br. s, 0.3H), 4.57-4.76 (m, 2H), 6.89 (d, 0.7H), 6.94 (d, 0.3H), 6.96-7.04 (m, 1H), 7.21 (d, 0.7H), 7.31-7.39 (m, 1.3H), 7.57-7.65 (m, 1H), 7.77-7.89 (m, 1H), 7.97-8.04 (m, 1H), 8.17-8.25 (m, 1H), 8.43 (d, 0.3H), 8.47-8.53 (m, 1H), 8.63 (d, 0.7H). aus 2-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 2) und 6-Methoxypyridin-2-carbonsäure [α] D 20< = +76.24° (c = 0.275, Methanol). LC-MS (Methode 2): R t = 1.16 min; m / z = 489 / 491 (M+H) +< . 66 (5-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(3-fluor-6-methoxypyridin-2-yl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.53-2.08 (m, 4H), 2.76 (br. s, 0.3H), 2.87 (dd, 0.7H), 2.91-3.09 (m, 2H), 3.15 (br. d, 0.3H), 3.42 (dd, 0.7H), 3.50 (br. s, 0.7H), 3.72-3.89 (m, 4H), 4.42 (br. s, 0.3H), 4.58-4.76 (m, 2H), 6.93 (dd, 0.7H), 6.96-7.04 (m, 1.3H), 7.31-7.39 (m, 1H), 7.59-7.65 (m, 1H), 7.76 (t, 0.7H), 7.84 (t, 0.3H), 7.96-8.04 (m, 1H), 8.16-8.25 (m, 1H), 8.44-8.52 (m, 1.3H), 8.65 (d, 0.7H). aus 2-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 2) und 3-Fluor-6-methoxypyridin-2-carbonsäure LC-MS (Methode 2): R t = 1.13 min; m / z = 507 / 509 (M+H) +< . 67 (3-Chlor-6-methoxypyridin-2-yl)(5-{[2-(5-chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanon (Enantiomer 2) 1< H-NMR (400 MHz, DMSO- d 6 ): δ [ppm] = 1.51-2.08 (m, 4H), 2.74 (br. s, 0.3H), 2.83 (dd, 0.7H), 2.91-3.08 (m, 2.3H), 3.24 (br. s, 0.7H), 3.44 (br. d, 0.7H), 3.66 (br. d, 0.3H), 3.76 (s, 2.3H), 3.82-3.90 (m, 1.4H), 4.43 (br. s, 0.3H), 4.62-4.74 (m, 2H), 6.90 (d, 0.7H), 6.93-7.06 (m, 1.3H), 7.30-7.39 (m, 1H), 7.58-7.67 (m, 1H), 7.85 (d, 0.7H), 7.95 (d, 0.3H), 7.97-8.05 (m, 1H), 8.16-8.27 (m, 1H), 8.44 (d, 0.3H), 8.46-8.53 (m, 1H), 8.65 (d, 0.7H). aus 2-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-Dihydrochlorid (Enantiomer 2) und 3-Chlor-6-methoxypyridin-2-carbonsäure LC-MS (Methode 2): R t = 1.21 min; m / z = 523 / 524 / 525 (M+H) +< . 68 (2-Fluorphenyl)(5- { [2-(6-isopropylpyridin-3-yl)-imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanon (Racemat) LC-MS (Methode 2): R t = 1.19 min; m / z = 484 (M+H) +< . aus 2-{[2-(6-Isopropylpyridin-3-yl)imidazo-[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octan-Dihydrochlorid (Racemat) und 2-Fluorbenzoesäure 69 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(2-fluorphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 2.45 (br. d, 1H), 2.57 (br. d, 1H, teilweise verdeckt durch DMSO-Signal), 2.86 (br. d, 1H), 3.00 (br. d, 1H), 3.39 (br. s, 1H), 3.59 (br. d, 1H), 3.70 (br. t, 2H), 3.86 (d, 1H), 3.93 (s, 2H), 4.49 (br. s, 1H), 6.93 (td, 1H), 7.25-7.35 (m, 3H), 7.41-7.55 (m, 4H), 7.59 (d, 1H), 7.96 (d, 2H), 8.82 (d, 1H). aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 2-Fluorbenzoesäure LC-MS (Methode 1): R t = 0.73 min; m / z = 491 / 493 (M+H) +< . 70 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(3-methoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 2.46-2.57 (m, 1H, verdeckt durch DMSO-Signal), 2.61 (br. d, 1H), 2.83 (br. d, 1H), 2.96 (br. d, 1H), 3.56-3.75 (m, 4H), 3.77 (s, 3H), 3.84 (d, 1H), 3.94 (s, 2H), 4.41 (br. s, 1H), 6.88-7.06 (m, 4H), 7.30 (t, 1H), 7.36 (t, 1H), 7.52 (d, 2H), 7.59 (d, 1H), 7.98 (d, 2H), 8.83 (d, 1H). LC-MS (Methode 1): R t = 0.74 min; m / z = 503 / 505 (M+H) +< . aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 3-Methoxybenzoesäure 71 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(cyclopentyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.43-1.81 (m, 8H), 2.40 (br. d, 1H), 2.45-2.57 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.83-2.96 (m, 3H), 3.51 (br. d, 1H), 3.60 (br. d, 1H), 3.76 (dd, 2H), 3.85-3.95 (m, 2H), 4.05 (br. s, 1H), 4.34 (br. s, 1H), 6.93 (td, 1H), 7.30 (ddd, 1H), 7.51 (d, 2H), 7.60 (d, 1H), 7.98 (d, 2H), 8.82 (d, 1H). aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und Cyclopentancarbonsäure LC-MS (Methode 1): R t = 0.74 min; m / z = 465 / 467 (M+H) +< . 72 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl) [3 -(trifluormethoxy)phenyl]methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 2.47-2.58 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.64 (br. d, 1H), 2.83 (br. d, 1H), 2.96 (br. d, 1H), 3.53 (br. s, 1H), 3.63-3.77 (m, 3H), 3.84 (d, 1H), 3.95 (s, 2H), 4.42 (br. s, 1H), 6.93 (td, 1H), 7.30 (dd, 1H), 7.40-7.55 (m, 5H), 7.56-7.64 (m, 2H), 7.97 (d, 2H), 8.82 (d, 1H). LC-MS (Methode 2): R t = 1.60 min; m / z = 557 / 559 (M+H) +< . aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 3-(Trifluormethoxy)benzoesäure 73 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(2-isopropylphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.11-1.26 (m, 6H), 2.26 (br. d, 0.5H), 2.46-2.59 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.62 (br. d, 0.5H), 2.77-2.89 (m, 1H), 2.90-3.05 (m, 2H), 3.25-3.35 (m, 1H, teilweise verdeckt durch H 2 O-Signal), 3.44 (br. d, 0.5H), 3.61-3.76 (m, 2.5H), 3.78-3.88 (m, 1H), 3.88-4.01 (m, 2H), 4.52 (br. s, 1H), 6.94 (td, 1H), 7.15-7.26 (m, 2H), 7.30 (ddd, 1H), 7.35-7.45 (m, 2H), 7.51 (t, 2H), 7.60 (d, 1H), 7.93 (d, 1H), 7.98 (d, 1H), 8.76 (d, 0.5H), 8.83 (d, 0.5H). aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 2-Isopropylbenzoesäure LC-MS (Methode 2): R t = 1.60 min; m / z = 515 / 517 (M+H) +< . 74 (2-Chlor-5-methoxyphenyl)(7-{[2-(4-chlorphenyl)-imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 2.47-2.60 (m, 1.5H, teilweise verdeckt durch DMSO-Signal), 2.65 (br. d, 0.5H), 2.77-2.92 (m, 1H), 2.92-3.04 (m, 1H), 3.26 (br. d, 1H), 3.62-3.98 (m, 9H), 4.46 (br. s, 1H), 6.93 (t, 1H), 7.01 (d, 2H), 7.30 (t, 1H), 7.42 (d, 1H), 7.52 (d, 2H), 7.59 (d, 1H), 7.97 (t, 2H), 8.82 (t, 1H). LC-MS (Methode 2): R t = 1.44 min; m / z = 537 / 538 / 539 (M+H) +< . aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 2-Chlor-5-methoxybenzoesäure 75 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(5-fluor-2-methoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 2.38-2.60 (m, 2H, teilweise verdeckt durch DMSO-Signal), 2.75-2.89 (m, 1H), 2.89-3.04 (m, 1H), 3.26 (br. s, 1H), 3.47-3.97 (m, 9H), 4.44 (br. s, 1H), 6.94 (t, 1H), 7.05-7.18 (m, 2H), 7.23 (tt, 1H), 7.30 (t, 1H), 7.52 (d, 2H), 7.59 (d, 1H), 7.96 (d, 2H), 8.82 (d, 1H). LC-MS (Methode 2): R t = 1.35 min; m / z = 521 / 523 (M+H) +< . aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 5-Fluor-2-methoxybenzoesäure 76 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(3-isopropylphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.19 (d, 6H), 2.47-2.57 (m, 1H, verdeckt durch DMSO-Signal), 2.63 (br. d, 1H), 2.80-3.00 (m, 3H), 3.55-3.75 (m, 4H), 3.84 (br. d, 1H), 3.94 (s, 2H), 4.42 (br. s, 1H), 6.93 (td, 1H), 7.20-7.39 (m, 5H), 7.52 (d, 2H), 7.59 (d, 1H), 7.98 (d, 2H), 8.83 (d, 1H). LC-MS (Methode 2): R t = 1.62 min; m / z = 515 / 517 (M+H) +< . aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 3-Isopropylbenzoesäure 77 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)[6-(2,2,2-trifluorethoxy)pyridin-2-yl]methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 2.58-2.69 (m, 2H), 2.87 (br. d, 1H), 3.07 (br. d, 1H), 3.66-3.76 (m, 3H), 3.87-4.00 (m, 3H), 4.16 (br. s, 1H), 4.47 (br. s, 1H), 4.92 (q, 2H), 6.92 (td, 1H), 7.11 (d, 1H), 7.30 (ddd, 1H), 7.42 (d, 1H), 7.51 (d, 2H), 7.60 (d, 1H), 7.91-8.01 (m, 3H), 8.84 (d, 1H). LC-MS (Methode 2): R t = 1.60 min; m / z = 572 / 574 (M+H) +< . aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 6-(2,2,2-Trifluorethoxy)pyridin-2-carbonsäure 78 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(tetrahydrofuran-3-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.73-2.16 (m, 4H), 2.42 (br. t, 1H), 2.46-2.59 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.91 (br. d, 2H), 3.47-3.58 (m, 1H), 3.64 (br. d, 1H), 3.68-3.82 (m, 4H), 3.84-3.96 (m, 2H), 4.09 (br. s, 1H), 4.28 (br. s, 1H), 4.60 (td, 1H), 6.93 (td, 1H), 7.30 (ddd, 1H), 7.51 (dd, 2H), 7.60 (d, 1H), 7.93-8.02 (m, 2H), 8.82 (d, 1H). aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und Tetrahydrofuran-3-carbonsäure LC-MS (Methode 2): R t = 1.13 min; m / z = 467 / 469 (M+H) +< . 79 (3-Chlorphenyl)(7-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl} -3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 2.46-2.58 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.63 (d, 1H), 2.83 (br. d, 1H), 2.96 (br. d, 1H), 3.56 (br. s, 1H), 3.62-3.76 (m, 3H), 3.84 (d, 1H), 3.95 (s, 2H), 4.41 (br. s, 1H), 6.93 (t, 1H), 7.30 (t, 1H), 7.39 (d, 1H), 7.45-7.56 (m, 5H), 7.60 (d, 1H), 7.97 (d, 2H), 8.83 (d, 1H). aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 3-Chlorbenzoesäure LC-MS (Methode 2): R t = 1.54 min; m / z = 507 / 508 / 509 (M+H) +< . 80 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)[6-(trifluormethoxy)pyridin-2-yl]methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 2.56-2.64 (m, 2H), 2.88 (br. d, 1H), 3.03 (br. d, 1H), 3.64-3.79 (m, 3H), 3.88 (d, 1H), 3.93 (s, 2H), 4.01 (br. s, 1H), 4.46 (br. s, 1H), 6.93 (t, 1H), 7.31 (t, 1H), 7.41 (d, 1H), 7.51 (d, 2H), 7.60 (d, 1H), 7.73 (d, 1H), 7.97 (d, 2H), 8.18 (t, 1H), 8.81 (d, 1H). LC-MS (Methode 2): R t = 1.47 min; m / z = 558 / 560 (M+H) +< . aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 6-(Trifluormethoxy)pyridin-2-carbonsäure 81 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(6-methoxy-3-methylpyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 2.21 (s, 3H), 2.46-2.61 (m, 2H, teilweise verdeckt durch DMSO-Signal), 2.86 (br. d, 1H), 3.03 (br. d, 1H), 3.38 (br. s, 1H), 3.57-3.74 (m, 3H), 3.77 (s, 3H), 3.87 (d, 1H), 3.93 (s, 2H), 4.48 (br. s, 1H), 6.79 (d, 1H), 6.93 (td, 1H), 7.30 (t, 1H), 7.52 (d, 2H), 7.60 (d, 1H), 7.64 (d, 1H), 7.97 (d, 2H), 8.81 (d, 1H). aus 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 6-Methoxy-3-methylpyridin-2-carbonsäure LC-MS ((Methode 1): R t = 0.75 min; m / z = 518 / 520 (M+H) +< . 82 (8-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(2-fluorphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.33-1.60 (m, 2H), 1.78-1.97 (m, 2H), 2.79 (br. d, 1H), 2.99 (br. d, 1H), 3.05 (br. s, 1H), 3.12 (br. d, 1H), 3.21 (br. s, 1H), 3.93-4.05 (m, 2H), 4.16 (br. d, 1H), 6.99 (t, 1H), 7.25 (t, 2H), 7.32 (t, 2H), 7.46 (q, 1H), 7.60 (d, 1H), 7.66 (d, 2H), 7.80 (d, 2H), 8.67 (d, 1H). aus 8-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Fluorbenzoesäure LC-MS (Methode 1): R t = 0.80 min; m / z = 519 / 521 (M+H) +< . 83 (8-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(6-methoxypyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.49-1.60 (m, 1H), 1.62-1.71 (m, 1H), 1.79-1.98 (m, 2H), 2.81 (d, 1H), 3.05 (br. s, 1H), 3.11 (br. d, 1H), 3.23 (br. s, 1H), 3.39 (br. d, 1H), 3.80 (s, 3H), 3.93-4.07 (m, 2H), 4.13 (br. d, 1H), 6.85 (d, 1H), 6.99 (t, 1H), 7.09 (d, 1H), 7.32 (t, 1H), 7.60 (d, 1H), 7.66 (d, 2H), 7.77 (t, 1H), 7.81 (d, 2H), 8.68 (d, 1H). aus 8-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 6-Methoxypyridin-2-carbonsäure LC-MS (Methode 2): R t = 1.41 min; m / z = 532 / 534 (M+H) +< . 84 (8-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(3-methoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.33-1.47 (m, 1H), 1.49-1.63 (m, 1H), 1.77-1.95 (m, 2H), 2.77 (br. d, 1H), 3.05 (br. s, 1H), 3.16 (br. s, 3H), 3.75 (s, 3H), 3.98 (br. s, 2H), 4.16 (br. d, 1H), 6.80-6.89 (m, 2H), 6.92-7.02 (m, 2H), 7.26-7.36 (m, 2H), 7.60 (d, 1H), 7.66 (d, 2H), 7.80 (d, 2H), 8.66 (d, 1H). aus 8-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 3-Methoxybenzoesäure LC-MS (Methode 2): R t = 1.46 min; m / z = 531 / 533 (M+H) +< . 85 (8-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(cyclopentyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.29-1.39 (m, 1H), 1.39-1.92 (m, 11H), 2.44-2.61 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.78-2.90 (m, 1H), 3.01 (br. d, 1H), 3.08 (br. s, 1H), 3.13 (br. s, 1H), 3.58 (br. d, 1H), 3.95 (br. d, 1H), 4.01 (s, 2H), 6.99 (t, 1H), 7.32 (t, 1H), 7.60 (d, 1H), 7.67 (d, 2H), 7.82 (d, 2H), 8.66 (d, 1H). aus 8-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und Cyclopentancarbonsäure LC-MS (Methode 2): R t = 1.48 min; m / z = 493 / 495 (M+H) +< . 86 (8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(cyclopentyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.31-1.38 (m, 1H), 1.41-1.68 (m, 8H), 1.69-1.78 (m, 1H), 1.78-1.89 (m, 2H), 2.57 (br. d, 1H), 2.80-2.88 (m, 1H), 3.01 (br. d, 1H), 3.08 (br. s, 1H), 3.13 (br. s, 1H), 3.58 (br. d, 1H), 3.95 (br. d, 1H), 4.01 (s, 2H), 6.99 (td, 1H), 7.32 (ddd, 1H), 7.53 (d, 2H), 7.60 (d, 1H), 7.87 (d, 2H), 8.66 (d, 1H). aus 8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und Cyclopentancarbonsäure LC-MS (Methode 1): R t = 0.80 min; m / z = 449 / 451 (M+H) +< . 87 (8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(2-fluorphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.38-1.49 (m, 1H), 1.50-1.59 (m, 1H), 1.77-1.95 (m, 2H), 2.79 (br. d, 1H), 2.99 (br. d, 1H), 3.05 (br. s, 1H), 3.12 (br. d, 1H), 3.21 (br. d, 1H), 4.00 (q, 2H), 4.15 (br. d, 1H), 6.99 (td, 1H), 7.25 (br. t, 2H), 7.32 (ddd, 2H), 7.42 (m, 1H), 7.53 (d, 2H), 7.60 (d, 1H), 7.85 (d, 2H), 8.66 (d, 1H). aus 8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Fluorbenzoesäure LC-MS (Methode 1): R t = 0.78 min; m / z = 475 / 477 (M+H) +< . 88 (8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)(5-fluor-2-methylphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.27-1.41 (m, 0.5H), 1.41-1.66 (m, 1.5H), 1.77-1.97 (m, 2H), 2.04 (br. s, 1.5H), 2.21 (br. s, 1.5H), 2.79 (br. d, 1H), 2.87 (br. s, 1H), 3.02 (br. s, 1.5H), 3.09-3.19 (m, 0.5H), 3.22 (br. s, 1H), 3.92-4.07 (m, 2H), 4.14 (br. d, 1H), 6.93-7.06 (m, 2H), 7.10 (td, 1H), 7.20-7.37 (m, 2H), 7.52 (d, 2H), 7.60 (d, 1H), 7.86 (d, 2H), 8.65 (d, 1H). aus 8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Methyl-5-fluorbenzoesäure LC-MS (Methode 1): R t = 0.85 min; m / z = 489 / 491 (M+H) +< . 89 (8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)(5-fluor-2-methoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.32-1.43 (m, 0.5H), 1.53 (br. d, 1H), 1.60-1.70 (m, 0.5H), 1.74-1.95 (m, 2H), 2.75 (br. d, 1H), 2.82-2.94 (m, 1H), 2.95-3.08 (m, 2H), 3.20 (br. s, 1H), 3.70 (br. s, 1.6H), 3.77 (br. s, 1.4H), 3.93-4.02 (m, 2H), 4.05 (br. d, 0.5H), 4.12 (br. d, 0.5H), 6.93-7.11 (m, 3H), 7.13-7.24 (m, 1H), 7.32 (br. t, 1H), 7.53 (d, 2H), 7.60 (d, 1H), 7.81-7.90 (m, 2H), 8.65 (d, 1H). LC-MS (Methode 1): aus 8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Methoxy-5-fluorbenzoesäure R t = 0.81 min; m / z = 505 / 506 (M+H) +< . 90 (8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(2-methylphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.28-1.42 (m, 0.5H), 1.42-1.65 (m, 1.5H), 1.76-1.97 (m, 2H), 2.08 (br. s, 1.5H), 2.24 (br. s, 1.5H), 2.78 (br. d, 1H), 2.88 (br. d, 1H), 2.96-3.15 (m, 2H), 3.22 (br. s, 1H), 3.92-4.07 (m, 2H), 4.17 (br. d, 1H), 6.99 (t, 1H), 7.02-7.29 (m, 4H), 7.32 (t, 1H), 7.52 (d, 2H), 7.60 (d, 1H), 7.85 (d, 2H), 8.65 (d, 1H). aus 8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Methylbenzoesäure LC-MS (Methode 1): R t = 0.82 min; m / z = 471 / 473 (M+H) +< . 91 (8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(2-methoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.27-1.41 (m, 0.5H), 1.53 (br. t, 1H), 1.61-1.72 (m, 0.5H), 1.73-1.95 (m, 2H), 2.69-2.80 (m, 1H), 2.82-3.08 (m, 3H), 3.19 (br. s, 1H), 3.71 (s, 1.7H), 3.78 (s, 1.3H), 3.92-4.05 (m, 2H), 4.08 (br. d, 0.5H), 4.18 (br. d, 0.5H), 6.89-7.08 (m, 3.5H), 7.18 (br. d, 0.5H), 7.27-7.39 (m, 2H), 7.52 (d, 2H), 7.60 (d, 1H), 7.80-7.90 (m, 2H), 8.65 (d, 1H). aus 8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Methoxybenzoesäure LC-MS (Methode 1): R t = 0.78 min; m / z = 487 / 489 (M+H) +< . 92 (8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(6-methoxypyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.50-1.60 (m, 1H), 1.62-1.71 (m, 1H), 1.79-1.97 (m, 2H), 2.81 (br. d, 1H), 3.05 (br. s, 1H), 3.11 (br. d, 1H), 3.23 (br. s, 1H), 3.39 (br. d, 1H), 3.80 (s, 3H), 3.96-4.06 (m, 2H), 4.13 (br. d, 1H), 6.85 (d, 1H), 6.99 (t, 1H), 7.09 (d, 1H), 7.32 (t, 1H), 7.53 (d, 2H), 7.60 (d, 1H), 7.77 (t, 1H), 7.87 (d, 2H), 8.68 (d, 1H). aus 8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl} -3,8 -diazabicyclo [3.2.1] octan-Dihydrochlorid und 6-Methoxypyridin-2-carbonsäure LC-MS (Methode 1): R t = 0.75 min; m / z = 488 / 490 (M+H) +< . 93 (8- f [2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(cyclohexyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.04-1.41 (m, 6H), 1.42-1.55 (m, 2H), 1.55-1.72 (m, 4H), 1.76-1.89 (m, 2H), 2.39-2.48 (m, 1H), 2.48-2.58 (br. d, 1H, teilweise verdeckt durch DMSO-Signal), 3.03 (br. d, 1H), 3.10 (br. d, 2H), 3.55 (br. d, 1H), 3.94 (br. d, 1H), 4.01 (s, 2H), 6.99 (td, 1H), 7.32 (ddd, 1H), 7.53 (d, 2H), 7.61 (d, 1H), 7.87 (d, 2H), 8.66 (d, 1H). aus 8-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und Cyclohexancarbonsäure LC-MS (Methode 1): R t = 0.81 min; m / z = 463 / 465 (M+H) +< . 94 (2-Fluorphenyl)(8-{[2-(4-isopropylphenyl)-imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diaza-bicyclo[3.2.1]oct-3-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.24 (d, 6H), 1.36-1.61 (m, 2H), 1.76-1.97 (m, 2H), 2.80 (br. d, 1H), 2.87-3.04 (m, 2H), 3.05-3.18 (m, 2H), 3.20-3.27 (m, 1H), 3.93-4.06 (m, 2H), 4.16 (br. d, 1H), 6.97 (td, 1H), 7.20-7.39 (m, 6H), 7.42-7.51 (m, 1H), 7.58 (d, 1H), 7.73 (d, 2H), 8.66 (d, 1H). LC-MS (Methode 2): R t = 1.46 min; m / z = 483 (M+H) +< . aus 8-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Fluorbenzoesäure 95 (8-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)-(6-methoxypyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.24 (d, 6H), 1.50-1.60 (m, 1H), 1.63-1.72 (m, 1H), 1.79-1.97 (m, 2H), 2.81 (br. d, 1H), 2.87-3.00 (m, 1H), 3.06-3.15 (m, 2H), 3.22-3.28 (m, 1H), 3.40 (br. d, 1H), 3.80 (s, 3H), 4.01 (s, 2H), 4.13 (br. d, 1H), 6.95 (dd, 1H), 6.97 (td, 1H), 7.09 (dd, 1H), 7.26-7.37 (m, 3H), 7.34 (d, 2H), 7.59 (d, 1H), 7.74 (d, 2H), 7.78 (d, 1H), 8.67 (d, 1H). aus 8-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 6-Methoxypyridin-2-carbonsäure LC-MS (Methode 2): R t = 1.45 min; m / z = 496 (M+H) +< . 96 (3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(cyclopentyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.43-1.67 (m, 7H), 1.67-1.80 (m, 5H), 2.27 (br. dd, 2H), 2.55 (br. d, 1H, teilweise verdeckt durch DMSO-Signal), 2.61 (br. d, 1H), 2.80-2.91 (m, 1H), 3.92-4.04 (m, 2H), 4.29 (br. s, 1H), 4.42 (br. d, 1H), 6.99 (td, 1H), 7.31 (ddd, 1H), 7.60 (d, 1H), 7.67 (d, 2H), 7.87 (d, 2H), 8.61 (d, 1H). aus 3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und Cyclopentancarbonsäure LC-MS (Methode 1): R t = 0.89 min; m / z = 493 / 495 (M+H) +< . 97 (3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(2-fluorphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.63-1.80 (m, 4H), 2.26 (br. d, 1H), 2.43 (br. d, 1H), 2.55 (br. d, 1H, teilweise verdeckt durch DMSO-Signal), 2.66 (br. d, 1H), 3.67 (br. s, 1H), 4.02 (s, 2H), 4.60 (br. d, 1H), 6.99 (td, 1H), 7.24-7.34 (m, 3H), 7.41-7.54 (m, 2H), 7.60 (d, 1H), 7.67 (d, 2H), 7.86 (d, 2H), 8.60 (d, 1H). aus 3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Fluorbenzoesäure LC-MS (Methode 1): R t = 0.86 min; m / z = 519 / 521 (M+H) +< . 98 (3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(6-methoxypyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.65-1.84 (m, 4H), 2.46 (br. d, 1H), 2.60 (s, 2H), 2.73 (dd, 1H), 3.77 (s, 3H), 4.04 (s, 2H), 4.67 (br. d, 2H), 6.93 (d, 1H), 6.99 (td, 1H), 7.27-7.38 (m, 2H), 7.61 (d, 1H), 7.67 (d, 2H), 7.82 (t, 1H), 7.87 (d, 2H), 8.62 (d, 1H). LC-MS (Methode 1): R t = 0.86 min; m / z = 532 / 534 (M+H) +< . aus 3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 6-Methoxypyridin-2-carbonsäure 99 (3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(3-methoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.64-1.79 (m, 4H), 2.36-2.69 (m, 4H, teilweise verdeckt durch DMSO-Signal), 3.78 (s, 3H), 3.94 (br. s, 1H), 4.03 (s, 2H), 4.56 (br. s, 1H), 6.94-7.06 (m, 4H), 7.27-7.39 (m, 2H), 7.60 (d, 1H), 7.67 (d, 2H), 7.87 (d, 2H), 8.62 (d, 1H). LC-MS (Methode 1): R t = 0.86 min; m / z = 531 / 533 (M+H) +< . aus 3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 3-Methoxybenzoesäure 100 (3- f [2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(2-methylphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.62-1.80 (m, 4H), 2.20-2.29 (m, 4H), 2.24 (s, 3H), 2.43 (br. d, 1H), 2.53 (br. d, 1H), 2.66 (br. d, 1H), 3.52 (br. s, 1H), 4.02 (s, 2H), 4.60 (br. s, 1H), 6.99 (t, 1H), 7.19-7.33 (m, 5H), 7.54 (d, 2H), 7.60 (d, 1H), 7.92 (d, 2H), 8.60 (d, 1H). LC-MS (Methode 1): R t = 0.83 min; m / z = 471 / 473 (M+H) +< . aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Methylbenzoesäure 101 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(cyclobutyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.51-1.79 (m, 5H), 1.81-1.96 (m, 1H), 1.97-2.13 (m, 3H), 2.17-2.30 (m, 3H), 2.48-2.63 (m, 2H, partially obscured by DMSO signal), 3.21-3.34 (m, 1H, partially obscured by H 2 O signal), 3.92-4.03 (m, 2H), 4.06 (br. s, 1H), 4.38 (br. d, 1H), 6.98 (td, 1H), 7.31 (ddd, 1H), 7.53 (d, 2H), 7.60 (d, 1H), 7.92 (d, 2H), 8.59 (d, 1H). aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und Cyclobutancarbonsäure LC-MS (Methode 2): R t = 1.46 min; m / z = 435 / 437 (M+H) +< . 102 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(2-fluorphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.63-1.79 (m, 4H), 2.26 (br. d, 1H), 2.43 (br. d, 1H), 2.46-2.59 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.66 (br. d, 1H), 3.66 (br. s, 1H), 4.03 (s, 2H), 4.60 (br. s, 1H), 6.99 (td, 1H), 7.23-7.35 (m, 3H), 7.40-7.51 (m, 2H), 7.54 (d, 2H), 7.60 (d, 1H), 7.92 (d, 2H), 8.60 (d, 1H). aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Fluorbenzoesäure LC-MS (Methode 2): R t = 1.50 min; m / z = 475 / 477 (M+H) +< . 103 (3- f [2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(5-fluor-2-methoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.61-1.77 (m, 4H), 2.26 (br. d, 1H), 2.40 (br. d, 1H), 2.46-2.54 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.63 (br. d, 1H), 3.54 (br. s, 1H), 3.75 (s, 3H), 4.01 (s, 2H), 4.55 (br. s, 1H), 6.99 (td, 1H), 7.05-7.16 (m, 2H), 7.22 (td, 1H), 7.31 (ddd, 1H), 7.54 (d, 2H), 7.60 (d, 1H), 7.92 (d, 2H), 8.59 (d, 1H). aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 5-Fluor-2-methoxybenzoesäure LC-MS (Methode 1): R t = 0.81 min; m / z = 505 / 507 (M+H) +< . 104 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(6-methoxypyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.62-1.82 (m, 4H), 2.45 (br. d, 1H), 2.57-2.64 (m, 2H), 2.73 (dd, 1H), 3.78 (s, 3H), 4.04 (s, 2H), 4.67 (br. d, 2H), 6.93 (d, 1H), 6.99 (td, 1H), 7.32 (ddd, 1H), 7.35 (d, 1H), 7.54 (d, 2H), 7.60 (d, 1H), 7.82 (dd, 1H), 7.93 (d, 2H), 8.62 (d, 1H). LC-MS (Methode 2): R t = 1.52 min; m / z = 488 / 490 (M+H) +< . aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 6-Methoxypyridin-2-carbonsäure 105 (3- f [2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(cyclohexyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.02-1.46 (m, 5H), 1.50-1.79 (m, 9H), 2.25 (br. dd, 2H), 2.38-2.48 (m, 1H), 2.48-2.65 (m, 2H, teilweise verdeckt durch DMSO-Signal), 3.93-4.06 (m, 2H), 4.26 (br. s, 1H), 4.41 (br. d, 1H), 6.99 (td, 1H), 7.32 (ddd, 1H), 7.53 (d, 2H), 7.60 (d, 1H), 7.93 (d, 2H), 8.61 (d, 1H). aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und Cyclohexancarbonsäure LC-MS (Methode 2): R t = 1.65 min; m / z = 463 / 465 (M+H) +< . 106 (2-Chlor-5-fluorphenyl)(3- { [2-(4-chlorphenyl)-imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diaza-bicyclo[3.2.1]oct-8-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.64-1.86 (m, 4H), 2.34 (br. d, 1H), 2.44 (br. d, 1H), 2.47-2.57 (m, 1H, verdeckt durch DMSO-Signal), 2.64 (br. d, 1H), 3.55 (br. s, 1H), 4.03 (s, 2H), 4.58 (br. s, 1H), 7.00 (t, 1H), 7.27-7.35 (m, 2H), 7.36-7.49 (m, 1H), 7.51-7.63 (m, 4H), 7.91 (d, 2H), 8.59 (d, 1H). aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Chlor-5-fluorbenzoesäure LC-MS (Methode 2): R t = 1.61 min; m / z = 509 / 510 / 511 (M+H) +< . 107 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(5-fluor-2-methylphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.64-1.81 (m, 4H), 2.20 (s, 3H), 2.29 (br. d, 1H), 2.44 (br. d, 1H), 2.54 (br. d, 1H), 2.63 (br. d, 1H), 3.54 (br. s, 1H), 4.03 (s, 2H), 4.58 (br. s, 1H), 7.00 (td, 1H), 7.09-7.18 (m, 2H), 7.27-7.34 (m, 2H), 7.54 (d, 2H), 7.60 (d, 1H), 7.93 (d, 2H), 8.60 (d, 1H). LC-MS (Methode 1): R t = 0.84 min; m / z = 489 / 491 (M+H) +< . aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 5-Fluor-2-methylbenzoesäure 108 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(3-methoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.62-1.79 (m, 4H), 2.35-2.69 (m, 4H, teilweise verdeckt durch DMSO-Signal), 3.78 (s, 3H), 3.94 (br. s, 1H), 4.04 (s, 2H), 4.56 (br. s, 1H), 6.94-7.07 (m, 4H), 7.26-7.38 (m, 2H), 7.54 (d, 2H), 7.60 (d, 1H), 7.94 (d, 2H), 8.62 (d, 1H). LC-MS (Methode 2): R t = 1.51 min; m / z = 487 / 489 (M+H) +< . aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 3-Methoxybenzoesäure 109 (3- f [2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(2-methoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.57-1.80 (m, 4H), 2.17-2.30 (m, 1H), 2.3 9 (br. d, 1H), 2.43-2.57 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.65 (br. d, 1H), 3.52 (br. s, 1H), 3.76 (s, 3H), 4.01 (s, 2H), 4.56 (br. s, 1H), 6.93-7.02 (m, 2H), 7.06 (d, 1H), 7.17-7.26 (m, 1H), 7.27-7.41 (m, 2H), 7.54 (d, 2H), 7.60 (d, 1H), 7.91 (d, 2H), 8.59 (d, 1H). LC-MS (Methode 2): R t = 1.46 min; m / z = 487 / 489 (M+H) +< . aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Methoxybenzoesäure 110 (2-Fluorphenyl)(3-{[2-(4-isopropylphenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.25 (d, 6H), 1.66-1.80 (m, 4H), 2.27 (br. d, 1H), 2.42 (br. d, 1H), 2.58 (br. d, 1H), 2.67 (br. d, 1H), 2.88-3.01 (m, 1H), 3.68 (br. s, lH), 4.02 (s, 2H), 4.60 (br. s, 1H), 6.97 (td, 1H), 7.24-7.32 (m, 3H), 7.35 (d, 2H), 7.42-7.54 (m, 2H), 7.58 (d, 1H), 7.80 (d, 2H), 8.58 (d, 1H). aus 3-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3 - yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Fluorbenzoesäure LC-MS (Methode 2): R t = 1.46 min; m / z = 483 (M+H) +< . 111 (3-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(2-fluorphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.61-1.77 (m, 4H), 2.23 (br. d, 1H), 2.39 (br. d, 1H), 2.57 (br. d, 1H), 2.71 (dd, 1H), 3.63 (br. s, 1H), 4.50 (s, 2H), 4.57 (br. s, 1H), 7.01 (td, 1H), 7.24-7.31 (m, 2H), 7.34 (ddd, 1H), 7.42 (td, 1H), 7.45-7.52 (m, 1H), 7.60 (d, 1H), 7.99 (dd, 1H), 8.20 (d, 1H), 8.53 (d, 1H), 8.68 (d, 1H). aus 3-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 2-Fluorbenzoesäure LC-MS (Methode 2): R t = 1.47 min; m / z = 476 / 478 (M+H) +< . 112 (3-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(3-methoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.60-1.76 (m, 4H), 2.28-2.45 (m, 2H), 2.55-2.76 (m, 2H), 3.77 (s, 3H), 3.91 (br. s, 1H), 4.51 (br. s, 3H), 6.95 dd, 1H), 6.97-7.05 (m, 3H), 7.34 (t, 2H), 7.62 (d, 1H), 7.99 (dd, 1H), 8.20 (d, 1H), 8.55 (d, 1H), 8.68 (d, 1H). LC-MS (Methode 2): R t = 1.45 min; m / z = 488 / 490 (M+H) +< . aus 3-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und 3-Methoxybenzoesäure 113 (3-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(cyclopentyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.43-1.78 (m, 12H), 2.16-2.28 (m, 2H), 2.55-2.67 (m, 2H), 2.83 (quin, 1H), 4.25 (br. s, 1H), 4.38 (br. d, 1H), 4.42-4.52 (m, 2H), 7.02 (td, 1H), 7.35 (ddd, 1H), 7.60 (d, 1H), 7.99 (dd, 1H), 8.20 (d, 1H), 8.56 (d, 1H), 8.66 (d, 1H). LC-MS (Methode 2): R t = 1.39 min; m / z = 450 / 452 (M+H) +< . aus 3-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-Dihydrochlorid und Cyclopentancarbonsäure 114 (3-Chlorphenyl)(3- { [2-(4-chlorphenyl)imidazo-[1,2-a]pyridin-3-yl] methyl}-3,6-diazabicyclo-[3.1.1]hept-6-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.70 (d, 1H), 2.47-2.60 (m, 1H, partially obscured by DMSO signal), 2.73 (br. d, 1H), 2.79 (br. d, 1H), 3.25 (br. d, 1H), 3.28-3.34 (m, 1H, partially obscured by H O signal), 4.20 (s, 2H), 4.32 (br. s, 1H), 4.47 (br. s, 1H), 6.97 (t, 1H), 7.31 (t, 1H), 7.41 (d, 1H), 7.44-7.55 (m, 5H), 7.59 (d, 1H), 7.85 (d, 2H), 8.44 (d, 1H). aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid und 3-Chlorbenzoesäure LC-MS (Methode 1): R t = 0.82 min; m / z = 477 / 479 (M+H) +< . 115 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]hept-6-yl)-(tetrahydrofuran-2-yl)methanon (Racemat) 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.65-2.05 (m, 5H), 2.29-2.42 (m, 1H), 2.70-2.93 (m, 3.5H), 3.01 (br. d, 0.5H), 3.61-3.75 (m, 2H), 4.13-4.22 (m, 3.5H), 4.26 (dd, 0.5H), 4.41-4.50 (m, 1H), 6.96 (td, 1H), 7.31 (t, 1H), 7.49-7.56 (m, 2H), 7.60 (d, 1H), 7.82-7.92 (m, 2H), 8.51 (d, 1H). LC-MS (Methode 1): R t = 0.64 min; m / z = 437 / 439 (M+H) +< . aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid und Tetrahydrofuran-2-carbonsäure (Racemat) 116 (3 - { [2-(4-Chlorphenyl)imidazo [1,2-a]pyridin-3 -yl] - methyl}-3,6-diazabicyclo[3.1.1]hept-6-yl)-(cyclopentyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.34-1.62 (m, 7H), 1.65-1.77 (m, 2H), 2.27-2.36 (m, 1H), 2.41-2.52 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.70-2.82 (m, 3H), 2.97 (br. d, 1H), 4.08-4.24 (m, 3H), 4.29-4.37 (m, 1H), 6.96 (td, 1H), 7.31 (t, 1H), 7.52 (d, 2H), 7.60 (d, 1H), 7.86 (d, 2H), 8.48 (d, 1H). aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid und Cyclopentancarbonsäure LC-MS (Methode 1): R t = 0.76 min; m / z = 435 / 437 (M+H) +< . 117 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]hept-6-yl)-(2-fluorphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.82 (d, 1H), 2.39-2.48 (m, 2H), 2.70 (dd, 1H), 2.89 (dd, 1H), 3.14 (d, 1H), 4.07 (br. s, 1H), 4.15-4.27 (m, 2H), 4.37 (br. s, 1H), 6.98 (t, 1H), 7.15-7.27 (m, 2H), 7.27-7.39 (m, 2H), 7.43-7.56 (m, 3H), 7.60 (d, 1H), 7.85 (d, 2H), 8.49 (d, 1H). LC-MS (Methode 1): R t = 0.75 min; m / z = 461 / 463 (M+H) +< . aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid und 2-Fluorbenzoesäure 118 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]hept-6-yl)-(cyclohexyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.01-1.40 (m, 6H), 1.52-1.67 (m, 4H), 1.71 (d, 1H), 1.95-2.06 (m, 1H), 2.28 (q, 1H), 2.65 (br. d, 1H), 2.74-2.83 (m, 2H), 2.91 (br. d, 1H), 4.09 (br. s, 1H), 4.12-4.25 (m, 2H), 4.33 (br. s, 1H), 6.96 (td, 1H), 7.31 (t, 1H), 7.52 (d, 2H), 7.60 (d, 1H), 7.85 (d, 2H), 8.48 (d, 1H). aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid und Cyclohexancarbonsäure LC-MS (Methode 1): R t = 0.80 min; m / z = 449 / 451 (M+H) +< . 119 (2-Chlor-5-fluorphenyl)(3- { [2-(4-chlorphenyl)-imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diaza-bicyclo[3.1.1]hept-6-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.92 (d, 1H), 2.40-2.52 (m, 2H, teilweise verdeckt durch DMSO-Signal), 2.74 (dd, 1H), 2.95 (dd, 1H), 3.09 (d, 1H), 3.99 (br. s, lH), 4.25 (s, 2H), 4.41 (br. s, 1H), 6.97 (t, 1H), 7.26-7.36 (m, 3H), 7.49-7.58 (m, 3H), 7.60 (d, 1H), 7.88 (d, 2H), 8.52 (d, 1H). LC-MS (Methode 1): R t = 0.79 min; m / z = 495 / 497 (M+H) +< . aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid und 2-Chlor-5-fluorbenzoesäure 120 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]hept-6-yl)-[3-(trifluormethoxy)phenyl]methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.73 (d, 1H), 2.47-2.60 (m, 2H, teilweise verdeckt durch DMSO-Signal), 2.74 (br. d, 1H), 2.82 (br. d, 1H), 3.26 (br. d, 1H), 4.14-4.25 (m, 2H), 4.35 (br. s, 1H), 4.47 (br. s, 1H), 6.95 (t, 1H), 7.30 (t, 1H), 7.41-7.61 (m, 7H), 7.85 (d, 2H), 8.46 (d, 1H). aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid und 3-(Trifluormethoxy)benzoesäure LC-MS (Methode 1): R t = 0.90 min; m / z = 527 / 529 (M+H) +< . 121 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]hept-6-yl)-(cyclobutyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.62-1.89 (m, 4H), 1.91-2.13 (m, 3H), 2.31 (q, 1H), 2.66 (dd, 1H), 2.70-2.81 (m, 2H), 2.87-3.02 (m, 2H), 4.08-4.24 (m, 4H), 6.95 (t, 1H), 7.30 (t, 1H), 7.52 (d, 2H), 7.60 (d, 1H), 7.86 (d, 2H), 8.46 (d, 1H). LC-MS (Methode 1): R t = 0.71 min; m / z = 421 / 423 (M+H) +< . aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid und Cyclobutancarbonsäure 122 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]hept-6-yl)-(3 -ethoxyphenyl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.30 (t, 3H), 1.72 (d, 1H), 2.47-2.61 (m, 2H, teilweise verdeckt durch DMSO-Signal), 2.73 (br. d, 1H), 2.81 (br. d, 1H), 3.27 (br. d, 1H), 3.83-3.99 (dq, 2H), 4.11-4.23 (m, 2H), 4.31 (br. s, 1H), 4.43 (br. s, 1H), 6.91-7.02 (m, 3H), 7.07 (d, 1H), 7.23-7.33 (m, 2H), 7.50 (d, 2H), 7.58 (d, 1H), 7.87 (d, 2H), 8.49 (d, 1H). aus 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid und 3-Ethoxybenzoesäure LC-MS (Methode 2): R t = 1.56 min; m / z = 487 / 489 (M+H) +< . 123 Cyclopentyl(3-{[2-(4-isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]hept-6-yl)methanon 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.25 (d, 6H), 1.35-1.63 (m, 7H), 1.66-1.79 (m, 2H), 2.31 (q, 1H), 2.42-2.57 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.70-2.83 (m, 3H), 2.87-3.01 (m, 2H), 4.07-4.24 (m, 3H), 4.34 (br. s, 1H), 6.93 (t, 1H), 7.28 (t, 1H), 7.33 (d, 2H), 7.58 (d, 1H), 7.75 (d, 2H), 8.44 (d, 1H). LC-MS (Methode 2): R t = 1.48 min; m / z = 443 (M+H) +< . aus 3-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]heptan-Dihydrochlorid und Cyclopentancarbonsäure Beispiel 124 und Beispiel 125 (5-{[2-(6-Isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(6-methoxypyridin-2-yl)methanone (Enantiomer 1 und 2)

[0297]

[0298] 139 mg (0.28 mmol) of the racemic (5-{[2-(6-Isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]-methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(6-methoxypyridin-2-yl)methanone (Example 27) was separated into the enantiomers by preparative HPLC on a chiral phase [column: YMC Cellulose SC, 5 µm, 250 mm x 20 mm; eluent: n-heptane / isopropanol 25:75 + 0.2% diethylamine; flow rate: 15 ml / min; UV detection: 220 nm; temperature: 55°C]: Example 124 ( Enantiomer 1 ):

[0299] Ausbeute: 65 mg R t = 14.77 min; chemische Reinheit >99%; >99% ee [Säule: Daicel Chiralpak IC, 5 µm, 250 mm x 4.6 mm; Elutionsmittel: Isohexan / Isopropanol 25:75 + 0.2% Diethylamin; Fluss: 1 ml / min; Temperatur: 55°C; UV-Detektion: 235 nm]. 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.28 (d, 6H), 1.47-2.00 (m, 4H), 2.74 (br. d, 1H), 2.82-2.95 (m, 2H), 3.07 (dt, 1H), 3.39 (br. d, 0.7H), 3.50 (br. d, 0.3H), 3.71-3.81 (m, 3H), 3.84 (s, 0.7H), 3.99 (br. s, 1H), 4.22-4.34 (m, 2H), 4.39 (br. s, 0.3H), 6.84-7.03 (m, 2H), 7.17 (d, 0.7H), 7.27-7.41 (m, 2.3H), 7.62 (d, 1H), 7.73-7.85 (m, 1H), 8.09-8.18 (m, 1H), 8.55-8.65 (m, 1H), 8.88-8.98 (m, 1H). LC-MS (Methode 2): R t = 1.19 min; m / z = 497 (M+H) +< . Example 125 (Enantiomer 2):

[0300] Ausbeute: 66 mg R t = 19.54 min; chemische Reinheit >99%; >99% ee [Säule: Daicel Chiralpak IC, 5 µm, 250 mm x 4.6 mm; Elutionsmittel: Isohexan / Isopropanol 25:75 + 0.2% Diethylamin; Fluss: 1 ml / min; Temperatur: 55°C; UV-Detektion: 235 nm]. 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.28 (d, 6H), 1.48-2.00 (m, 4H), 2.74 (br. d, 1H), 2.82-2.96 (m, 2H), 3.08 (dt, 1H), 3.39 (br. d, 0.7H), 3.50 (br. d, 0.3H), 3.71-3.81 (m, 3H), 3.84 (s, 0.7H), 4.00 (br. s, 1H), 4.22-4.34 (m, 2H), 4.39 (br. s, 0.3H), 6.85-7.03 (m, 2H), 7.17 (d, 0.7H), 7.27-7.42 (m, 2.3H), 7.62 (d, 1H), 7.74-7.85 (m, 1H), 8.08-8.18 (m, 1H), 8.56-8.65 (m, 1H), 8.88-8.98 (m, 1H). LC-MS (Methode 2): R t = 1.19 min; m / z = 497 (M+H) +< . Example 126 and Example 127 (3-Fluor-6-methoxypyridin-2-yl)(5-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]-methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanon (Enantiomers 1 and 2)

[0301]

[0302] 134 mg (0.26 mmol) of the racemic (3-fluoro-6-methoxypyridin-2-yl)(5-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanone (Example 28) was separated into the enantiomers by preparative HPLC on a chiral phase [column: YMC Cellulose SC, 5 µm, 250 mm x 20 mm; eluent: n-heptane / isopropanol 25:75 + 0.2% diethylamine; flow rate: 15 ml / min; UV detection: 220 nm; temperature: 55°C]: Example 126 (Enantiomer 7):

[0303] Yield: 60 mg R t = 15.10 min; chemical purity >99%; >99% ee [Column: Daicel Chiralpak IC, 5 µm, 250 mm x 4.6 mm; eluent: isohexane / isopropanol 25:75 + 0.2% diethylamine; flow: 1 ml / min; temperature: 55°C; UV detection: 235 nm]. 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.22-1.31 (m, 6H), 1.50-1.99 (m, 4H), 2.65-2.77 (m, 1H), 2.77-2.87 (m, 1.3H), 2.94 (br. s, 0.7H), 3.01-3.18 (m, 1.3H), 3.39-3.51 (m, 1.4H), 3.60 (br. d, 0.3H), 3.68-3.85 (m, 3.7H), 4.20-4.35 (m, 2H), 4.40 (br. s, 0.3H), 6.87-7.03 (m, 2H), 7.27-7.42 (m, 2H), 7.62 (d, 1H), 7.70-7.83 (m, 1H), 8.07-8.18 (m, 1H), 8.55-8.64 (m, 1H), 8.86-8.98 (m, 1H). LC-MS (Methode 2): R t = 1.22 min; m / z = 515 (M+H) +< . Example 127 (Enantiomer 2):

[0304] Ausbeute: 57 mg R t = 20.80 min; chemische Reinheit >99%; >99% ee [Säule: Daicel Chiralpak IC, 5 µm, 250 mm x 4.6 mm; Elutionsmittel: Isohexan / Isopropanol 25:75 + 0.2% Diethylamin; Fluss: 1 ml / min; Temperatur: 55°C; UV-Detektion: 235 nm]. 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.21-1.33 (m, 6H), 1.50-1.99 (m, 4H), 2.65-2.77 (m, 1H), 2.77-2.88 (m, 1.3H), 2.94 (br. s, 0.7H), 3.01-3.18 (m, 1.3H), 3.39-3.51 (m, 1.4H), 3.60 (br. d, 0.3H), 3.69-3.86 (m, 3.7H), 4.19-4.34 (m, 2H), 4.39 (br. s, 0.3H), 6.88-7.04 (m, 2H), 7.27-7.41 (m, 2H), 7.62 (d, 1H), 7.70-7.83 (m, 1H), 8.07-8.18 (m, 1H), 8.56-8.64 (m, 1H), 8.87-8.98 (m, 1H). LC-MS (Method 2): R t = 1.22 min; m / z = 515 (M+H) +< .

[0305] The enantiomerically pure compound from Example 126 (Enantiomer 1) could also be obtained using an alternative method as follows: 80 mg (0.47 mmol) of 3-fluoro-6-methoxypyridine-2-carboxylic acid was dissolved in 2 ml of DMF, treated with 242 mg (0.64 mmol) of 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU), and stirred at room temperature for 30 min. Subsequently, 200 mg (0.43 mmol) of 2-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octane dihydrochloride (enantiomer 1; Example 32A) and 370 µl (2.12 mmol) of N,N Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components by preparative HPLC (Method 6). This yielded 126 mg (0.24 mmol, 57% of theory) of the title compound. [α] D 20< = -92.16° (c = 0.285, methanol). LC-MS (Method 2): R t = 1.27 min; m / z = 515 (M+H) +< . Example 128 and Example 129 (2-Fluorophenyl)(5-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diaza-bicyclo[2.2.2]oct-2-yl)methanone (Enantiomers 1 and 2)

[0306]

[0307] 121 mg (0.25 mmol) of the racemic (2-fluorophenyl)(5-{[2-(6-isopropylpyridin-3-yl)imidazo-[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)methanone (Example 68) was separated into the enantiomers by preparative HPLC on a chiral phase [column: YMC Cellulose SC, 5 µm, 250 mm x 20 mm; eluent: n-heptane / isopropanol 25:75 + 0.2% diethylamine; flow rate: 15 ml / min; UV detection: 220 nm; temperature: 55°C]: Example 128 (Enantiomer 1 ):

[0308] Yield: 57 mg R t = 14.26 min; chemical purity >99%; >99% ee [Column: Daicel Chiralpak IC, 5 µm, 250 mm x 4.6 mm; eluent: isohexane / isopropanol 25:75 + 0.2% diethylamine; flow: 1 ml / min; temperature: 55°C; UV detection: 235 nm]. 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.24-1.32 (m, 6H), 1.48-1.98 (m, 4H), 2.65-2.89 (m, 2.3H), 2.94 (br. s, 0.7H), 3.00-3.16 (m, 1.3H), 3.28-3.36 (m, 0.7H, partially obscured by water signal), 3.39-3.50 (m, 1H), 3.78 (br. d, 0.7H), 4.20-4.33 (m, 2H), 4.39 (br. s, 0.3H), 6.94-7.03 (m, 1H), 7.19-7.53 (m, 6H), 7.58-7.65 (m, 1H), 8.08-8.18 (m, 1H), 8.55-8.64 (m, 1H), 8.90 (d, 0.3H), 8.94 (d, 0.7H). LC-MS (Method 1): R t = 0.68 min; m / z = 484 (M+H) +< . Example 129 (Enantiomer 2 ):

[0309] Yield: 60 mg R t = 23.23 min; chemical purity >99%; >99% ee [Column: Daicel Chiralpak IC, 5 µm, 250 mm x 4.6 mm; eluent: isohexane / isopropanol 25:75 + 0.2% diethylamine; flow: 1 ml / min; temperature: 55°C; UV detection: 235 nm]. 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.22-1.32 (m, 6H), 1.52-1.97 (m, 4H), 2.65-2.89 (m, 2.3H), 2.94 (br. s, 0.7H), 3.01-3.14 (m, 1.3H), 3.27-3.36 (m, 0.7H, partially obscured by water signal), 3.39-3.49 (m, 1H), 3.78 (br. d, 0.7H), 4.21-4.33 (m, 2H), 4.39 (br. s, 0.3H), 6.93-7.04 (m, 1H), 7.18-7.53 (m, 6H), 7.58-7.65 (m, 1H), 8.08-8.18 (m, 1H), 8.55-8.64 (m, 1H), 8.90 (d, 0.3H), 8.94 (d, 0.7H). LC-MS (Method 1): R t = 0.67 min; m / z = 484 (M+H) +< .

[0310] Analogous to Examples 1-4, the following compounds were also prepared from the indicated starting materials: Example Name / Structure / Educts Analytical data 130 tert. -Butyl-7-{[2-(5-chlorpyridin-2-yl)imidazo[1,2-a]-pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-carboxylat 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.39 (s, 9H), 2.38 (br. s, 2H), 2.85 (br. d, 2H), 3.49-3.59 (m, 2H), 3.60-3.70 (m, 2H), 3.83 (br. d, 2H), 4.42 (s, 2H), 6.93 (dd, 1H), 7.33 (ddd, 1H), 7.61 (d, 1H), 8.00 (dd, 1H), 8.21 (d, 1H), 8.67 (dd, 1H), 8.83 (d, 1H). aus 2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3-oxa-7,9-di-azabicyclo[3.3.1]nonan-9-carboxylat LC-MS (Method 2): R t = 1.22 min; MS (ESIpos): m / z = 470 [M+H] +< . 131 tert . -Butyl-3-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat LC-MS (Method 2): R t = 1.68 min; MS (ESIpos): m / z = 462 [M+H] +< . aus 2-(6-Isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert .-Butyl-3,8-diazabicyclo[3.2.1]octan-3-carboxylat 132 tert. -Butyl-5-{[2-(4-bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octan-2-carboxylat ( Racemate ) 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.13-1.25 (m, 1H), 1.33-1.40 (m, 9H), 1.50 (br. d, 1H), 1.66 (br. s, 2H), 1.85 (br. s, 1H), 2.52-2.55 (m, 4H), 2.62-2.77 (m, 3H), 3.13 (br. t, 1H), 3.46-3.54 (m, 1H), 4.17-4.25 (m, 2H), 6.97 (t, 1H), 7.31 (t, 1H), 7.58-7.69 (m, 3H), 7.74-7.83 (m, 2H), 8.57 (d, 1H). aus 2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-carbaldehyd und tert.-Butyl-2,5-diazabicyclo[2.2.2]octan-2-carboxylat ( Racemate ) LC-MS (Methode 5): R t = 1.16 min; MS (ESIpos): m / z = 497 [M+H] +< . Beispiel 133 und Beispiel 134 tert . - Butyl 5-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo-[2.2.2]octane-2-carboxylate (Enantiomer 1 und 2)

[0311]

[0312] 4700 mg (10.38 mmol) of the racemic tert .-Butyl-5-{[2-(6-isopropylpyridin-3-yl)imidazo[1,2-a]-pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane-2-carboxylate (Example 3) was separated into the enantiomers by preparative HPLC on a chiral phase [column: Daicel Chiralpak IG, 5 µm, 250 mm x 20 mm; eluent: isohexane / isopropanol 50:50 + 0.2% diethylamine; flow rate: 15 ml / min; UV detection: 220 nm; temperature: 50°C]: Example 133 (Enantiomer 1 ):

[0313] Yield: 2310 mg R t = 8.97 min; chemical purity >99%; >99% ee [Column: Daicel Chiralpak IF, 5 µm, 250 mm x 4.6 mm; eluent: isohexane / isopropanol 60:40 + 0.2% diethylamine; flow: 1 ml / min; temperature: 40°C; UV detection: 235 nm]. 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.28 (d, 6H), 1.36 (2s, 9H), 1.43-1.56 (m, 1H), 1.57-1.74 (m, 2H), 1.79-1.92 (m, 1H), 2.65-2.82 (m, 3H), 3.01-3.19 (m, 2H), 3.53 (dd, 1H), 3.81 (br. d, 1H), 4.17-4.28 (m, 2H), 6.98 (t, 1H), 7.31 (t, 1H), 7.38 (d, 1H), 7.61 (d, 1H), 8.09-8.16 (m, 1H), 8.58 (d, 1H), 8.92 (dd, 1H). LC-MS (Methode 2): R t = 1.44 min; m / z = 462 (M+H) +< . [α] D 20< = +8.89° (c = 0.270, Methanol). Example 134 (Enantiomer 2):

[0314] Ausbeute: 2110 mg R t = 7.28 min; chemische Reinheit >99%; >99% ee [Säule: Daicel Chiralpak IF, 5 µm, 250 mm x 4.6 mm; Elutionsmittel: Isohexan / Isopropanol 60:40 + 0.2% Diethylamin; Fluss: 1 ml / min; Temperatur: 40°C; UV-Detektion: 235 nm]. 1< H-NMR (400 MHz, DMSO- d 6 , δ / ppm): 1.28 (d, 6H), 1.36 (2s, 9H), 1.43-1.56 (m, 1H), 1.57-1.74 (m, 2H), 1.79-1.92 (m, 1H), 2.65-2.82 (m, 3H), 3.01-3.19 (m, 2H), 3.53 (dd, 1H), 3.81 (br. d, 1H), 4.17-4.28 (m, 2H), 6.98 (t, 1H), 7.31 (t, 1H), 7.38 (d, 1H), 7.61 (d, 1H), 8.09-8.16 (m, 1H), 8.58 (d, 1H), 8.92 (dd, 1H). LC-MS (Method 2): R t = 1.44 min; m / z = 462 (M+H) +< . [α] D 20< = -10.53° (c = 0.285, methanol).

[0315] Analogously to examples 21 and 33, the following compounds were also prepared from the respective starting materials: Beispiel Name / Struktur / Edukte Analytische Daten 135 (7-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)[6-(trifluormethoxy)pyridin-2-yl]methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 2.87 (br. d, 1H), 3.07 (br. d, 1H), 3.59-3.73 (m, 3H), 3.84 (d, 1H), 3.95 (br. s, 1H), 4.39-4.53 (m, 3H), 6.94 (t, 1H), 7.33 (t, 1H), 7.39 (d, 1H), 7.61 (d, 1H), 7.71 (d, 1H), 7.96-8.03 (m, 1H), 8.11-8.24 (m, 2H), 8.66 (d, 1H), 8.82 (d, 1H). aus 7-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 6-(Trifluormethoxy)pyridin-2-carbonsäure LC-MS (Methode 2): R t = 1.36 min; MS (ESIpos): m / z = 559 [M+H] +< . 136 (3-Chlor-6-methoxypyridin-2-yl)(7-{[2-(5-chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 3.57 (br. t, 1H), 3.67 (br. t, 1H), 3.74-3.85 (m, 3H), 3.88 (s, 3H), 3.92-4.02 (m, 2H), 4.10 (br. d, 1H), 4.25 (br. d, 1H), 4.82 (br. s, 1H), 4.93-5.10 (m, 2H), 7.02 (d, 1H), 7.20 (t, 1H), 7.48 (t, 1H), 7.78 (d, 1H), 7.96 (d, 1H), 8.19-8.31 (m, 2H), 8.72 (d, 1H), 8.90 (d, 1H). aus 7-{[2-(5-Chlorpyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-Dihydrochlorid und 3-Chlor-6-methoxypyridin-2-carbonsäure LC-MS (Methode 2): R t = 1.21 min; MS (ESIpos): m / z = 539 [M+H] +< . 137 5-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl](6-methoxy-3-methylpyridin-2-yl)methanon ( Enantiomer 1 ) LC-MS (Methode 2): R t = 1.49 min; MS (ESIpos): m / z = 510 [M+H] +< . aus 3-[2,5-Diazabicyclo[2.2.2]oct-2-ylmethyl]-2-(4-isopropylphenyl)imidazo[1,2-a]pyridin-Dihydrochlorid (Enantiomer 1 ) und 6-Methoxy-3-methylpyridin-2-carbonsäure 138 5-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl](6-methoxy-3-methylpyridin-2-yl)methanon ( Enantiomer 1 ) 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.50-1.97 (m, 4H), 2.02-2.11 (m, 3H), 2.59-2.86 (m, 2.3H), 2.89-3.00 (m, 1H), 3.23 (br. s, 0.7H), 3.33-3.45 (m, 1H), 3.66-3.82 (m, 3.75H), 4.16-4.31 (m, 2H), 4.39 (m, 0.25H), 6.71-6.80 (m, 1H), 6.92-7.02 (m, 1H), 7.26-7.35 (m, 1H), 7.45-7.65 (m, 4H), 7.79-7.91 (m, 2H), 8.53-8.62 (m, 1H). aus 2-(4-Chlorphenyl)-3-(2,5-diazabicyclo[2.2.2]oct-2-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid (Enantiomer 1 ) und 6-Methoxy-3-methylpyridin-2-carbonsäure LC-MS (Methode 2): R t = 1.39 min; MS (ESIpos): m / z = 502 / 504 [M+H] +< . 139 (3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(3-chlor-6-methoxypyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.62-1.82 (m, 4H), 2.37-2.55 (m, 3H, teilweise verdeckt durch DMSO-Signal), 2.73 (m, 1H), 3.63 (br. s, 1H), 3.79 (s, 3H), 4.04 (s, 2H), 4.60 (br. s, 1H), 6.92 (d, 1H), 6.99 (t, 1H), 7.31 (dd, 1H), 7.60 (d, 1H), 7.67 (d, 2H), 7.86 (t, 3H), 8.59 (d, 1H). aus 2-(4-Bromphenyl)-3-(3,8-diazabicyclo[3.2.1]oct-3-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid und 3-Chlor-6-methoxypyridin-2-carbonsäure LC-MS (Methode 2): R t = 1.58 min; MS (ESIpos): m / z = 566 / 568 / 569 [M+H] +< . 140 (3- f [2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(3-fluor-6-methoxypyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.25 (br. d, 1H), 1.63-1.82 (m, 4H), 2.41-2.54 (m, 3H, teilweise verdeckt durch DMSO-Signal), 2.70-2.79 (m, 1H), 3.76 (s, 3H), 3.92 (br. s, 1H), 3.99-4.10 (m, 2H), 4.61 (br. s, 1H), 6.93-7.01 (m, 2H), 7.31 (t, 1H), 7.60 (d, 1H), 7.65-7.70 (m, 2H), 7.77 (t, 1H), 7.83-7.88 (m, 2H), 8.61 (d, 1H). from 2-(4-bromophenyl)-3-(3,8-diazabicyclo[3.2.1]oct-3-ylmethyl)imidazo[1,2-a]pyridine dihydrochloride and 3-fluoro-6-methoxypyridine-2-carboxylic acid LC-MS (Methode 2): R t = 1.50 min; MS (ESIpos): m / z = 550 [M+H] +< . 141 (3-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(2-isopropylphenyl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.16 (br. d, 6H), 1.51-1.83 (m, 4H), 2.25-2.57 (m, 3H, teilweise verdeckt durch DMSO-Signal), 2.67 (br. s, 1H), 2.78-3.15 (m, 1H), 3.50 (br. s, 1H), 4.02 (br. s, 2H), 4.62 (br. s, 1H), 6.99 (t, 1H), 7.22 (br. s, 1H), 7.25-7.42 (m, 4H), 7.57-7.72 (m, 3H), 7.84 (br. s, 2H), 8.59 (br. d, 1H). aus 2-(4-Bromphenyl)-3-(3,8-diazabicyclo[3.2.1]oct-3-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid und 2-Isopropylbenzoesäure LC-MS (Methode 1): R t = 0.92 min; MS (ESIpos): m / z = 545 [M+H] +< . 142 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,6-diazabicyclo[3.1.1]hept-6-yl)(6-methoxy-3-methylpyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.89 (d, 1H), 2.26 (s, 3H), 2.32-2.47 (m, 1H), 2.71-2.79 (m, 1H), 2.81-2.88 (m, 1H), 2.96-3.04 (m, 2H), 3.63 (s, 3H), 4.17-4.26 (m, 2H), 4.34-4.41 (m, 2H), 6.80 (d, 1H), 6.93 (t, 1H), 7.29 (t, 1H), 7.50 (d, 2H), 7.59 (d, 2H), 7.84 (d, 2H), 8.52 (d, 1H). aus 2-(4-Chlorphenyl)-3-(3,6-diazabicyclo[3.1.1]hept-3-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid und 6-Methoxy-3-methylpyridin-2-carbonsäure LC-MS (Methode 1): R t = 0.77 min; MS (ESIpos): m / z = 488 / 490 [M+H] +< . 143 (8- { [2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)(6-methoxy-3-methylpyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.49-1.70 (m, 2H), 1.79-1.97 (m, 2H), 2.09 (s, 3H), 2.78-2.92 (m, 2H), 2.98-3.07 (m, 2H), 3.24 (br. d, 1H), 3.76 (s, 3H), 3.94-4.05 (m, 2H), 4.14 (br. d, 1H), 6.74 (d, 1H), 6.99 (td, 1H), 7.32 (ddd, 1H), 7.53 (d, 2H), 7.56-7.63 (m, 2H), 7.86 (d, 2H), 8.66 (d, 1H). aus 2-(4-Chlorphenyl)-3-(3,8-diazabicyclo[3.2.1]oct-8-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid und 6-Methoxy-3-methylpyridin-2-carbonsäure LC-MS (Methode 1): R t = 0.78 min; MS (ESIpos): m / z = 502 / 504 [M+H] +< . 144 (8-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-3-yl)(6-methoxy-3-methylpyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.24 (d, 6H), 1.49-1.70 (m, 2H), 1.80-1.97 (m, 2H), 2.09 (s, 3H), 2.81 (br. d, 1H), 2.87-2.97 (m, 2H), 3.01-3.08 (m, 2H), 3.27 (m, 1H), 3.76 (s, 3H), 3.94-4.05 (m, 2H), 4.14 (br. d, 1H), 6.74 (d, 1H), 6.97 (td, 1H), 7.25-7.37 (m, 3H), 7.58 (d, 2H), 7.73 (d, 2H), 8.66 (d, 1H). aus 3-(3,8-Diazabicyclo[3.2.1]oct-8-ylmethyl)-2-(4-isopropylphenyl)imidazo[1,2-a]pyridin-Dihydrochlorid und 6-Methoxy-3-methylpyridin-2-carbonsäure LC-MS (Methode 1): R t = 0.81 min; MS (ESIpos): m / z = 510 [M+H] +< . 145 (3-{[2-(4-Isopropylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(6-methoxy-3-methylpyridin-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.25 (d, 6H), 1.61-1.84 (m, 4H), 2.17 (s, 3H), 2.43 (br. d, 2H), 2.47-2.56 (m, 1H, verdeckt durch DMSO-Signal), 2.75 (dd, 1H), 2.88-3.01 (m, 1H), 3.70 (s, 1H), 3.97-4.09 (m, 2H), 4.62 (br. s, 1H), 6.77 (d, 1H), 6.97 (td, 1H), 7.34 (d, 2H), 7.60 (t, 2H), 7.80 (d, 2H), 8.57 (d, 1H). aus 3-(3,8-Diazabicyclo[3.2.1]oct-3-ylmethyl)-2-(4-isopropylphenyl)imidazo[1,2-a]pyridin-Dihydrochlorid und 6-Methoxy-3-methylpyridin-2-carbonsäure LC-MS (Methode 1): R t = 0.82 min; MS (ESIpos): m / z = 510 [M+H] +< . 146 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(4-isopropyl-1,3-thiazol-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.24 (d, 6H), 1.67-1.78 (m, 2H), 1.79-1.90 (m, 2H), 2.44 (br. d, 1H), 2.48-2.56 (m, 1H, verdeckt durch DMSO-Signal), 2.64 (br. d, 1H), 2.74 (br. d, 1H), 2.98-3.12 (m, 1H), 4.03 (s, 2H), 4.60 (br. s, 1H), 5.59 (br. s, 1H), 6.99 (t, 1H), 7.32 (t, 1H), 7.52 (d, 2H), 7.57 (s, 1H), 7.61 (d, 1H), 7.94 (d, 2H), 8.63 (d, 1H). aus 2-(4-Chlorphenyl)-3-(3,8-diazabicyclo[3.2.1]oct-3-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid und 4-Isopropyl-1,3-thiazol-2-carbonsäure LC-MS (Methode 2): R t = 1.93 min; MS (ESIpos): m / z = 506 / 508 [M+H] +< . 147 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(1,3-thiazol-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.67-1.92 (m, 4H), 2.42-2.57 (m, 1H, teilweise verdeckt durch DMSO-Signal), 2.70 (br. t, 2H), 4.03 (s, 2H), 4.62 (br. s, 1H), 5.62 (br. s, 1H), 6.99 (t, 1H), 7.32 (t, 1H), 7.53 (d, 2H), 7.61 (d, 1H), 7.95 (d, 2H), 8.02 (q, 2H), 8.63 (d, 1H). from 2-(4-chlorophenyl)-3-(3,8-diazabicyclo[3.2.1]oct-3-ylmethyl)imidazo[1,2-a]pyridine dihydrochloride and 1,3-thiazole-2-carboxylic acid LC-MS (Methode 2): R t = 1.49 min; MS (ESIpos): m / z = 464 / 466 [M+H] +< . 148 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(4-methyl-1,3-thiazol-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.67-1.77 (m, 2H), 1.79-1.92 (m, 2H), 2.41 (s, 3H), 2.42- 2.57 (m, 2H, teilweise verdeckt durch DMSO-Signal), 2.64 (br. d, 1H), 2.72 (br. d, 1H), 4.03 (s, 2H), 4.59 (br. s, 1H), 5.64 (br. s, 1H), 6.99 (t, 1H), 7.32 (t, 1H), 7.53 (d, 2H), 7.57 (s, 1H), 7.61 (d, 1H), 7.95 (d, 2H), 8.63 (d, 1H). aus 2-(4-Chlorphenyl)-3-(3,8-diazabicyclo[3.2.1]oct-3-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid und 4-Methyl-1,3-thiazol-2-carbonsäure LC-MS (Methode 2): R t = 1.69 min; MS (ESIpos): m / z = 478 / 480 [M+H] +< . 149 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(5-methyl-1,3-thiazol-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.64-1.90 (m, 4H), 2.40-2.57 (m, 5H, teilweise verdeckt durch DMSO-Signal), 2.68 (br. t, 2H), 4.02 (s, 2H), 4.59 (br. s, 1H), 5.59 (br. s, 1H), 6.99 (td, 1H), 7.32 (t, 1H), 7.53 (d, 2H), 7.61 (d, 1H), 7.69 (d, 1H), 7.95 (d, 2H), 8.62 (d, 1H). aus 2-(4-Chlorphenyl)-3-(3,8-diazabicyclo[3.2.1]oct-3-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid und 5-Methyl-1,3-thiazol-2-carbonsäure LC-MS (Methode 2): R t = 1.68 min; MS (ESIpos): m / z = 478 / 480 [M+H] +< . 150 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(4,5-dimethyl-1,3-thiazol-2-yl)methanon 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.65-1.89 (m, 4H), 2.29 (s, 3H), 2.38 (s, 3H), 2.43 (br. d, 2H), 2.60-2.75 (m, 2H), 4.02 (s, 2H), 4.57 (br. s, 1H), 5.62 (br. s, 1H), 6.99 (t, 1H), 7.32 (t, 1H), 7.53 (d, 2H), 7.61 (d, 1H), 7.95 (d, 2H), 8.63 (d, 1H). aus 2-(4-Chlorphenyl)-3-(3,8-diazabicyclo[3.2.1]oct-3-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid und 4,5-Dimethyl-1,3-thiazol-2-carbonsäure LC-MS (Methode 2): R t = 1.75 min; MS (ESIpos): m / z = 492 / 494 [M+H] +< . 151 5-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl](6-methoxypyridin-2-yl)methanon (Racemat) 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.46-1.99 (m, 4H), 2.62-2.75 (m, 1H), 2.81-2.93 (m, 2H), 3.35-3.50 (m, 1H), 3.70-3.82 (m, 3.75H), 3.89-4.01 (m, 1H), 4.20- 4.41 (m, 2.25H), 6.83-7.02 (m, 2H), 7.17 (d, 0.75H), 7.25-7.35 (m, 1.25H), 7.55-7.70 (m, 3H), 7.73-7.86 (m, 3H), 8.54-8.64 (m, 1H). aus 2-(4-Bromphenyl)-3-(2,5-diazabicyclo[2.2.2]oct-2-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid ( Racemat ) und 6-Methoxypyridin-2-carbonsäure LC-MS (Methode 2): R t = 1.39 min; MS (ESIpos): m / z = 532 / 534 [M+H] +< . 152 5-{[2-(4-Bromphenyl)imidazo[l,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl](2-fluorphenyl)methanon ( Racemat ) 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.48-1.97 (m, 4H), 2.61-3.04 (m, 4H), 3.42 (br. d, 1H), 3.76 (br. d, 0.75H), 4.16-4.29 (m, 2H), 4.39 (br. s, 0.25H), 6.92-7.02 (m, 1H), 7.20-7.39 (m, 4H), 7.41-7.54 (m, 1H), 7.56-7.72 (m, 3H), 7.74-7.86 (m, 2H), 8.54-8.63 (m, 1H). from 2-(4-bromophenyl)-3-(2,5-diazabicyclo[2.2.2]oct-2-ylmethyl)imidazo[1,2-a]pyridine dihydrochloride ( Racemat ) and 2-fluorobenzoic acid LC-MS (Methode 5): R t = 1.06 min; MS (ESIpos): m / z = 519 [M+H] +< . 153 5-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl](3-fluor-6-methoxypyridin-2-yl)methanon ( Racemat ) 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.51-2.00 (m, 4H), 2.63-2.73 (m, 1H), 2.77-2.85 (m, 1H), 2.91 (br. s, 0.75H), 3.14 (br. d, 0.25H), 3.38-3.59 (m, 2H), 3.69-3.83 (m, 3.75H), 4.17-4.32 (m, 2H), 4.39 (br. s, 0.25H), 6.87-7.03 (m, 2H), 7.31 (dd, 1H), 7.56-7.69 (m, 3H), 7.71-7.86 (m, 3H), 8.54-8.64 (m, 1H). from 2-(4-bromophenyl)-3-(2,5-diazabicyclo[2.2.2]oct-2-ylmethyl)imidazo[1,2-a]pyridine dihydrochloride ( Racemat ) and 3-fluoro-6-methoxypyridine-2-carboxylic acid LC-MS (Methode 5): R t = 1.07 min; MS (ESIpos): m / z = 550 / 552 [M+H] +< . Beispiel 154 3-{[2-(4-Chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N -isopropyl-3,8-diazabicyclo[3.2.1]-octane-8-carboxamide

[0316]

[0317] 8.5 mg (0.10 mmol) of isopropyl isocyanate were placed in a well of a 96-well multititer plate and cooled to 0°C. Separately, 42.6 mg (0.10 mmol) of 3-{[2-(4-chlorophenyl)imidazo-[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octane dihydrochloride were dissolved in 0.8 ml of 1,2-dichloroethane, with 0.052 ml (0.3 mmol) N,N Diisopropylethylamine was added and cooled to 8°C. The two solutions were combined on the multititer plate and shaken at 0°C for 1 h. The solution was then allowed to warm to RT and shaken at RT overnight. The solvent was then completely removed using a centrifuge dryer. The residue was dissolved in 0.6 ml of DMF, filtered, and the filtrate was separated into its components by preparative LC-MS using one of the following methods: MS instrument: Waters, HPLC instrument: Waters; Column: Waters X-Bridge C18, 19 mm x 50 mm, 5 µm; Eluent A: water + 0.375% ammonia, Eluent B: acetonitrile + 0.375% ammonia, with eluent gradient; Flow: 40 ml / min; UV detection: DAD, 210-400 nm or MS instrument: Waters, HPLC instrument: Waters; Column: Phenomenex Luna 5µ C18(2) 100A, AXIA Tech., 50 mm x 21.2 mm; Eluent A: water + 0.0375% formic acid, Eluent B: acetonitrile + 0.0375% formic acid, with eluent gradient; Flow: 40 ml / min; UV detection: DAD, 210-400 nm. This yielded 2.8 mg (6% of theory, 100% purity) of the title compound. LC-MS (Method 7, ESIpos): R t = 0.85 min; m / z = 438 (M+H) +< .

[0318] In a parallel synthetic manner analogous to Example 154, the following compounds were prepared starting from 3-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octane dihydrochloride (in Examples 155-167 and 170-187) or 7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonane dihydrochloride (in Examples 168, 169 and 188-198) and the corresponding isocyanate, carbamoyl chloride or chloroformate: Beispiel Name / Struktur (Ausbeute; Reinheit) LC-MS (Methode 7) 155 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N -(2-fluorphenyl)-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.91 min; m / z = 490 (M+H) +< (38% d. Th.; Reinheit 97%) 156 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- (2,6-dichlorphenyl)-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.93 min; m / z = 540 (M+H) +< (8% d. Th.; Reinheit 96%) 157 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- (2,6-dimethylphenyl)-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.92 min; m / z = 500 (M+H) +< (14% d. Th.; Reinheit 100%) 158 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- pentyl-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.93 min; m / z = 466 (M+H) +< (15% d. Th.; Reinheit 100%) 159 3- {[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N -(2-methylphenyl)-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.92 min; m / z = 486 (M+H) +< (8% d. Th.; Reinheit 96%) 160 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N -[2-chlor-5-(trifluormethyl)phenyl]-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 1.06 min; m / z = 574 (M+H) +< (45% d. Th.; Reinheit 92%) 161 N-(4-Chlorphenyl)-3- f [2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.98 min; m / z = 506 (M+H) +< (50% d. Th.; Reinheit 100%) 162 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N -(2-ethyl-6-methylphenyl)-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.96 min; m / z = 514 (M+H) +< (15% d. Th.; Reinheit 97%) 163 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- (2,5-dimethylphenyl)-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.96 min; m / z = 500 (M+H) +< (19% d. Th.; Reinheit 100%) 164 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- cyclohexyl-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.93 min; m / z = 478 (M+H) +< (35% d. Th.; Reinheit 100%) 165 N -(2-Chlor-6-methylphenyl)-3-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.93 min; m / z = 520 (M+H) +< (37% d. Th.; Reinheit 97%) 166 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- (2,6-difluorphenyl)-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.90 min; m / z = 508 (M+H) +< (23% d. Th.; Reinheit 100%) 167 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- (2,4-dimethylphenyl)-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.96 min; m / z = 500 (M+H) +< (5% d. Th.; Reinheit 100%) 168 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- isopropyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-carboxamid R t = 0.77 min; m / z = 454 (M+H) +< (16% d. Th.; Reinheit 94%) 169 N-(2-Chlor-6-methylphenyl)-7- f [2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-carboxamid R t = 0.82 min; m / z = 536 (M+H) +< (2% d. Th.; Reinheit 93%) 170 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- cyclopropyl-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.79 min; m / z = 436 (M+H) +< (4% d. Th.; Reinheit 100%) 171 N-(2-Chlorphenyl)-3- f [2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.93 min; m / z = 506 (M+H) +< (6% d. Th.; Reinheit 97%) 172 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- methyl- N -phenyl-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.95 min; m / z = 486 (M+H) +< (38% d. Th.; Reinheit 100%) 173 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(morpholin-4-yl)methanon R t = 0.81 min; m / z = 466 (M+H) +< (6% d. Th.; Reinheit 98%) 174 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N,N- diisopropyl-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.98 min; m / z = 480 (M+H) +< (20% d. Th.; Reinheit 100%) 175 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- cyclohexyl- N -ethyl-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 1.04 min; m / z = 506 (M+H) +< (44% d. Th.; Reinheit 100%) 176 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(pyrrolidin-1-yl)methanon R t = 0.87 min; m / z = 450 (M+H) +< (6% d. Th.; Reinheit 93%) 177 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- ethyl- N -phenyl-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.98 min; m / z = 500 (M+H) +< (40% d. Th.; Reinheit 100%) 178 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- isopropyl- N -methyl-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.90 min; m / z = 452 (M+H) +< (2% d. Th.; Reinheit 100%) 179 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(piperidin-1-yl)methanon R t = 0.92 min; m / z = 464 (M+H) +< (19% d. Th.; Reinheit 97%) 180 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N,N- dimethyl-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 0.83 min; m / z = 424 (M+H) +< (11% d. Th.; Reinheit 100%) 181 3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- ethyl- N -(4-methylphenyl)-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 1.02 min; m / z = 514 (M+H) +< (38% d. Th.; Reinheit 95%) 182 N -(4-Chlorphenyl)-3- f [2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N -isopropyl-3,8-diazabicyclo[3.2.1]octan-8-carboxamid R t = 1.05 min; m / z = 548 (M+H) +< (19% d. Th.; Reinheit 99%) 183 (3-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)(thiomorpholin-4-yl)methanon R t = 0.89 min; m / z = 482 (M+H) +< (22% d. Th.; Reinheit 100%) 184 Methyl-3-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat R t = 0.85 min; m / z = 411 (M+H) +< (7% d. Th.; Reinheit 100%) 185 Ethyl-3-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat R t = 0.89 min; m / z = 425 (M+H) +< (15% d. Th.; Reinheit 100%) 186 Cyclopcntyl-3-{[2-(4-chlorphcnyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat R t = 0.98 min; m / z = 465 (M+H) +< (12% d. Th.; Reinheit 99%) 187 Cyclohexyl-3-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]octan-8-carboxylat R t = 1.02 min; m / z = 479 (M+H) +< (8% d. Th.; Reinheit 100%) 188 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N,N- diethyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-carboxamid R t = 0.78 min; m / z = 468 (M+H) +< (35% d. Th.; Reinheit 100%) 189 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(morpholin-4-yl)methanon R t = 0.72 min; m / z = 482 (M+H) +< (27% d. Th.; Reinheit 97%) 190 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N , N- diisopropyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-carboxamid R t = 0.84 min; m / z = 496 (M+H) +< (27% d. Th.; Reinheit 100%) 191 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- cyclohexyl-7V-ethyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-carboxamid R t = 0.90 min; m / z = 522 (M+H) +< (43% d. Th.; Reinheit 100%) 192 (7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(pyrrolidin-1-yl)methanon R t = 0.76 min; m / z = 466 (M+H) +< (27% d. Th.; Reinheit 96%) 193 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-N-ethyl- N -phenyl-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-carboxamid R t = 0.86 min; m / z = 516 (M+H) +< (30% d. Th.; Reinheit 99%) 194 7-{[2-(4-Chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}- N- isopropyl- N -methyl-3-oxa-7,9-diazabicyclo[33.1]nonan-9-carboxamid R t = 0.78 min; m / z = 468 (M+H) +< (44% d. Th.; Reinheit 100%) 195 Ethyl-7-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-carboxylat R t = 0.79 min; m / z = 441 (M+H) +< (9% d. Th.; Reinheit 100%) 196 Cyclopentyl-7-{[2-(4-chlorphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonan-9-carboxylat R t = 0.87 min; m / z = 481 (M+H) +< (6% d. Th.; Reinheit 100%) 197 Propyl-7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]nonane-9-carboxylate R t = 0.83 min; m / z = 455 (M+H) +< (7% of theory; purity 100%) 198 (7-{[2-(4-chlorophenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-3-oxa-7,9-diazabicyclo[3.3.1]non-9-yl)(piperidin-1-yl)methanone R t = 0.79 min; m / z = 480 (M+H) +< (7% of theory; purity 98%)

[0319] Analogously to Examples 21 and 33, the following compound was prepared from the indicated starting materials: Example Name / Structure / Educts Analytical data 199 (5-{[2-(4-Bromphenyl)imidazo[1,2-a]pyridin-3-yl]-methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)(3-chlor-6-methoxypyridin-2-yl)methanon (Racemate) 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.51-1.98 (m, 4H), 2.60 (dd, 0.75H), 2.69-2.77 (m, 1H), 2.80 (br. s, 0.5H), 2.92-3.00 (m, 1H), 3.20 (br. s, 0.5H), 3.35-3.46 (m, 1.25H), 3.71-3.85 (m, 3.75H), 4.18-4.35 (br. s, 2H), 4.38 (br. s, 0.25H), 6.85-7.02 (m, 2H), 7.27-7.35 (m, 1H), 7.56-7.70 (m, 3H), 7.72-7.94 (m, 3H), 8.53-8.62 (m, 1H). LC-MS (Method 2): aus 2-(4-Bromphenyl)-3-(2,5-diazabicyclo[2.2.2]oct-2-ylmethyl)imidazo[1,2-a]pyridin-Dihydrochlorid (Racemate) und 3-Chlor-6-methoxypyridin-2-carbonsäure R t = 1.54 min; MS (ESIpos): m / z = 566 / 567 / 568 / 569 [M+H] +< . Example 200 (5-{[2-(5-Chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]oct-2-yl)-[6-(difluoromethoxy)pyridin-2-yl]methanone (Enantiomer 1 )

[0320]

[0321] 45 mg (0.24 mmol) of 6-(difluoromethoxy)pyridine-2-carboxylic acid was dissolved in 1.5 ml of DMF, treated with 123 mg (0.32 mmol) of 2-(7-aza-1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU), and stirred at room temperature for 30 min. Subsequently, 100 mg of 2-{[2-(5-chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-2,5-diazabicyclo[2.2.2]octane dihydrochloride (enantiomer 1) and 190 µl (1.08 mmol) of N,N Diisopropylethylamine was added, and the mixture was stirred overnight at room temperature. The reaction mixture was then separated into its components directly by preparative HPLC (Method 6). 79 mg (0.15 mmol, 70% of theory) of the title compound were obtained.

[0322] LC-MS (Method 2): R t = 1.29 min; m / z = 525 / 527 [M+H] +< .

[0323] 1< H-NMR (400 MHz, DMSO-d 6 ): δ [ppm] = 1.51-2.08 (m, 4H), 2.73 (br. s, 0.25H), 2.85-2.94 (m, 1.5H), 2.98-3.10 (m, 1.25H), 3.38 (dd, 0.75H), 3.49 (d, 0.25H), 3.78-4.05 (m, 1.75H), 4.41 (br. s, 0.25H), 4.56-4.79 (m, 2H), 6.94-7.05 (m, 1H), 7.15-7.25 (m, 1H), 7.30-7.39 (m, 1.25H), 7.45-7.87 (m, 2.75H), 7.95-8.12 (m, 2H), 8.17-8.26 (m, 1H), 8.45 (d, 0.25H), 8.47-8.53 (m, 1H), 8.65 (d, 0.75H). B. Assessment of pharmacological efficacy

[0324] The pharmacological activity of the compounds according to the invention can be in vitro and in In vivo studies, as known to those skilled in the art, demonstrate this. The following application examples describe the biological effect of the compounds according to the invention. B-1. In Vitro-electrophysiological analysis of human TASK-1 and TASK-3 channels via Two-electrode voltage clamp technique in Xenopus laevis oocytes

[0325] Xenopus laevis oocyteswere selected as described elsewhere [Decher et al., FEBS Lett. 492, 84-89 (2001)]. Subsequently, the oocytes were injected with 0.5-5 ng of cRNA encoding TASK-1 or TASK-3. The two-electrode voltage clamp technique was used for electrophysiological analysis of the channel proteins expressed in the oocytes [Stühmer, Methods Enzymol. 207, 319-339 (1992)]. The measurements were performed as described [Decher et al., FEBS Lett. 492, 84-89 (2001)] at room temperature (21-22°C) with a Turbo-TEC-10CD amplifier (NPI), recorded at 2 kHz, and filtered at 0.4 kHz. The substance was administered using a gravity-driven perfusion system. The oocyte is placed in a measuring chamber and exposed to a solution flow of 10 ml / min. The level in the measuring chamber is controlled and regulated by aspirating the solution with a peristaltic pump.

[0326] The following Table 1 lists the half-maximal inhibition of human TASK-1 and TASK-3 channels (IC 50 value) determined in this test by representative embodiments of the invention: Table 1 Example No. TASK-1 IC50 [nM] TASK-3 IC50 [nM] 21 27.3 ± 5.4 16.3 ± 0.9 24 31.2 ± 5.8 26 54.0 ± 16.1 12.0 ± 3.3 34 18.6 ± 4.3 10.3 ± 0.9 86 17.1 ± 3.5 58.4 ± 12.1 92 13.5 ± 1.2 5.9 ± 1.8 102 8.7 ± 3.6 4.3 ± 3.5 104 60.7 ± 12.0 4.2 ± 1.0 115 22.8 ± 3.7 186.2 ± 5.4 126 127.4 ± 8.5 714.2 ± 0.9

[0327] The data in Table 1 demonstrate that blockade is achieved at both TASK-1 and TASK-3. The results in Table 1 thus demonstrate the mechanism of action of the compounds of the invention as dual TASK-1 / 3 inhibitors. B-2. Inhibition of recombinant TASK-1 and TASK-3 in vitro

[0328] The inhibition studies of recombinant TASK-1 and TASK-3 channels were carried out on stably transfected CHO cells. The compounds of the invention were tested using 40 mM potassium chloride in the presence of a voltage-sensitive dye according to the method described in detail in the following references [Whiteaker et al., Validation of FLIPR membrane potential dye for high-throughput screening of potassium channel modulators, J. Biomol. Screen. 6 (5), 305-312 (2001); Molecular Devices FLIPR Application Note: Measuring membrane potential using the FLIPR ®< membrane potential assay kit on Fluorometric Imaging Plate Reader (FLIPR ®< ) systems, http: / / www.moleculardevices.com / reagentssupplies / assay-kits / ion-channels / flipr-membrane-potential-assay-kits]. The activity of the test substances was determined as their ability to inhibit depolarization induced in the recombinant cells by 40 mM potassium chloride.The concentration that can block half of this depolarization is called IC 50.

[0329] The following Table 2 lists the IC 50 values ​​determined for individual embodiments of the invention from this assay (partly as averages from several independent individual determinations): Table 2 Example No. TASK-1 IC50 [nM] TASK-3 IC50 [nM] 4 560 43 5 200 150 6 394 410 10 1090 230 11 1400 940 12 3000 8300 14 5100 860 15 397 82 16 1300 600 21 240 60 22 170 13 23 790 170 24 140 4.5 25 120 5.6 26 690 42 29 460 50 30 770 21 31 310 26 32 270 9.6 33 140 26 34 855 84 35 350 200 36 670 250 37 350 63 38 790 380 39 640 370 40 533 104 41 76 3.9 42 880 17 43 320 8.9 44 130 3.3 45 340 13 46 73 5 47 70 15 48 390 17 49 740 12 51 290 34 52 170 10 53 140 34 54 470 76 55 2000 320 57 1400 240 60 610 61 680 87 62 2800 760 63 490 140 64 280 17 65 2000 460 66 1100 110 67 990 220 69 870 101 70 1900 160 71 130 24 72 2000 120 73 160 9.6 74 330 23 75 380 30 76 240 14 77 810 44 78 1600 65 79 1000 190 80 310 15 81 520 25 82 230 420 83 134 14 84 1100 400 85 520 53 86 331 126 87 583 160 88 766 210 89 827 220 90 958 79 91 1350 89 92 895 29 93 2300 510 94 530 130 95 1700 350 96 240 4.5 97 390 7.8 98 450 14 99 470 16 100 250 17 101 370 7.2 102 277 56 103 540 20 104 255 32 105 830 20 106 870 110 107 1000 33 108 1100 95 109 693 92 110 780 300 111 110 25 112 200 29 113 89 21 114 480 340 115 4240 2400 116 535 340 117 635 520 118 860 1000 119 1100 1500 120 1100 180 121 1700 2800 122 1100 120 123 2000 1600 126 17900 713 127 9450 670 135 4100 160 136 9300 44 137 190 14 138 75 6.8 139 290 18 140 160 21 141 250 59 142 240 98 143 130 14 144 180 27 145 280 27 146 920 340 147 12 15 148 23 2.7 149 3000 300 150 2700 210 151 72 1.8 152 2900 75 153 1000 34 154 130 29 155 610 210 156 1200 15 157 24 7.4 158 760 110 159 2900 220 160 7600 1000 161 7700 1000 162 53 13 163 1400 160 164 3100 1000 165 25 166 990 44 167 3000 350 168 1400 130 169 3600 110 170 1200 64 171 1800 26 172 5200 80 173 1700 32 174 91 13 175 43 200 176 49 10 177 4000 130 178 290 17 179 270 2.9 180 220 23 181 4100 1000 182 6100 1000 183 450 26 184 2900 72 185 120 186 730 44 187 3800 200 188 60 5.9 189 8300 520 190 170 19 191 9500 190 192 870 73 193 7100 100 194 3000 290 195 230 8.1 196 440 52 197 150 13 198 810 60 199 33 1.8 200 877 75

[0330] The data in Table 2 demonstrate that blockade is achieved at both TASK-1 and TASK-3. The results in Table 2 thus demonstrate the mechanism of action of the compounds of the invention as dual TASK-1 / 3 inhibitors. B-3. Animal model of obstructive sleep apnea in pigs

[0331] The use of negative pressure can induce collapse and thus closure of the upper airway in anesthetized, spontaneously breathing pigs [Wirth et al., Sleep 36, 699-708 (2013)].

[0332] German Landpigs are used for the model. The pigs are anesthetized and tracheotomy performed. A cannula is inserted into the rostral and caudal portions of the trachea. The rostral cannula is connected to a device that generates negative pressures and to the caudal cannula via a T-piece. The caudal cannula is connected to the rostral cannula via a T-piece and to a tube that allows spontaneous breathing while bypassing the upper airways. By appropriately closing and opening the tubes, the pig can switch from normal nasal breathing to breathing via the caudal cannula, while the upper airways are isolated and connected to the device that generates negative pressures. The muscle activity of the Genioglossus muscle is recorded using an electromyogram (EMG).

[0333] At specific time points, the collapsibility of the upper airway is tested by having the pig breathe through the caudal cannula and applying negative pressures of -50, -100, and -150 cm water column (cmH2O) to the upper airway. This causes the upper airway to collapse, which is indicated by an interruption of airflow and a drop in pressure in the tubing system. This test is performed before administration of the test substance and at specific intervals after administration of the test substance. A sufficiently effective test substance can prevent this collapse of the airways during the inspiratory phase.

[0334] After switching from nasal breathing to breathing through the caudal cannula, no EMG activity of the Genioglossus musclemeasurable in an anesthetized pig. A further test is then used to determine the negative pressure at which EMG activity resumes. This threshold is shifted to more positive values ​​if a test substance is effective. The test is also performed before administration of the test substance and at specific times after administration. The test substance can be administered intranasally, intravenously, subcutaneously, intraperitoneally, or intragastrically. B-4. In vitro -electrophysiological determination of the washout rate of compounds after binding to the human TASK-1 channel via Two-electrode voltage clamp technique in Xenopus laevis -Oocytes

[0335] Xenopus laevis oocyteswere obtained from animals anesthetized with tricaine. Ovaries were treated with collagenase (1 mg / ml, Worthington, type II), stored in OR2 solution (82.5 mM NaCl, 2 mM KCl, 1 mM MgCl 2 , 5 mM HEPES; pH 7.4) for 120 min, and then stored in the measuring solution ND96 (96 mM NaCl, 2 mM KCl, 1.8 mM CaCl 2 , 1 mM MgCl 2 , 5 mM HEPES; pH 7.5) with additional sodium pyruvate (275 mg / l), theophylline (90 mg / l), and gentamicin (50 mg / l) at 18°C. hTASK-1 and hTASK-3 were subcloned into the pSGEM vector, and cRNA was extracted after linearization with NHEI and inIn vitro transcription with T7 polymerase was performed. Oocytes were individually injected with 5–20 ng of cRNA solution encoding hTASK-1. Standard two-electrode voltage-clamp recordings [Stühmer, Methods Enzymol. 207, 319–339 (1992)] were performed at room temperature (21–22°C) using a Turbo-TEC-10CD amplifier (NPI) as previously described [Decher et al., FEBS Lett. 492, 84–89 (2001)]. The recording interval was 2 kHz, and the data were filtered at 0.4 kHz. The substance application was gravity-driven via the bath solution, using ND96. In summary, Xenopus laevis oocytes selected as described above, injected with TASK-1 cRNA and subjected to electrophysiological analysis via Two-electrode voltage clamp technique.

[0336] Previously, the TASK-1 channels were inhibited by approximately 40% by administering one of the compounds of the invention. The concentrations shown in Table 3 below were adjusted, which had previously been determined by determining the respective IC 50 values. The recovery of the TASK-1-induced membrane current was then recorded in a voltage clamp for at least one hour. This recovery is due to the washout of the respective compound from the TASK-1 channel.

[0337] At least 6 oocytes were examined per compound. The voltage-clamp measurements lasted a total of at least 1.5 hours (administration of the inhibitor plus a subsequent washout measurement of at least one hour). Oocytes that showed leakage during the measurement were discarded; the results presented in Table 3 only include those oocytes that remained stable throughout the measurement. Table 3 Example No. Concentration [nM] Proportion of measurements used Washout rate [% h -1< ] 21 30 6 / 6 40 26 60 6 / 7 17 29 45 5 / 6 17 33 80 5 / 6 55 C. Examples of pharmaceutical compositions

[0338] The compounds according to the invention can be converted into pharmaceutical preparations as follows: Tablet: Composition:

[0339] 100 mg of the compound according to the invention, 50 mg lactose (monohydrate), 50 mg corn starch (native), 10 mg polyvinylpyrrolidone (PVP 25) (BASF, Ludwigshafen, Germany) and 2 mg magnesium stearate.

[0340] Tablet weight 212 mg. Diameter 8 mm, curvature radius 12 mm. Production:

[0341] The mixture of the compound of the invention, lactose, and starch is granulated with a 5% w / w solution of PVP in water. After drying, the granules are mixed with the magnesium stearate for 5 minutes. This mixture is compressed using a standard tablet press (see tablet format above). A compression force of 15 kN is used as a guideline for compression. Oral suspension: Composition:

[0342] 1000 mg of the compound according to the invention, 1000 mg ethanol (96%), 400 mg Rhodigel ®< (xanthan gum from FMC, Pennsylvania, USA) and 99 g water.

[0343] A single dose of 100 mg of the compound according to the invention corresponds to 10 ml of oral suspension. Production:

[0344] The Rhodigel is suspended in ethanol, and the compound of the invention is added to the suspension. The water is added while stirring. Stirring is continued for approximately 6 hours until the Rhodigel has completely swelled. Oral solution: Composition:

[0345] 500 mg of the compound according to the invention, 2.5 g polysorbate and 97 g polyethylene glycol 400. A single dose of 100 mg of the compound according to the invention corresponds to 20 g of oral solution. Production:

[0346] The compound of the invention is suspended in the mixture of polyethylene glycol and polysorbate while stirring. Stirring is continued until the compound of the invention is completely dissolved. iv solution:

[0347] The compound according to the invention is dissolved at a concentration below saturation solubility in a physiologically acceptable solvent (e.g., isotonic saline solution, 5% glucose solution, and / or 30% PEG 400 solution). The solution is sterile filtered and filled into sterile, pyrogen-free injection containers. Nasal solution:

[0348] The compound according to the invention is dissolved in a physiologically acceptable solvent (e.g., purified water, phosphate buffer, citrate buffer) at a concentration below saturation solubility. The solution may contain further additives for isotonication, preservation, pH adjustment, solubility improvement, and / or stabilization.

Claims

1. Compound of the formula (I) in which the ring Q is a diazaheterobicyclic system of the formula or in which * denotes the bond to the adjacent methylene group and ** the bond to the carbonyl group, A and D are each CH or one of these ring members is CH and the other is N, R1 is halogen, cyano, (C1-C4)-alkyl, cyclopropyl or cyclobutyl, where (C1-C4)-alkyl may be up to trisubstituted by fluorine and cyclopropyl and cyclobutyl may be up to disubstituted by fluorine, and R2 is (C4-C6) -cycloalkyl in which a ring CH2 group may be replaced by -O-, or R2 is a phenyl group of the formula (a), a pyridyl group of the formula (b) or (c) or an azole group of the formula (d) in which *** marks the bond to the adjacent carbonyl group and R3 is hydrogen, fluorine, chlorine, bromine or methyl, R4 is hydrogen, fluorine, chlorine, bromine, cyano, (C1-C3)-alkyl or (C1-C3)-alkoxy, where (C1-C3)-alkyl and (C1-C3)-alkoxy may be up to trisubstituted by fluorine, R5 is hydrogen, fluorine, chlorine, bromine or methyl, R6 is hydrogen, (C1-C3)-alkoxy, cyclobutyloxy, oxetan-3-yloxy, tetrahydrofuran-3-yloxy or tetrahydro-2H-pyran-4-yloxy, where (C1-C3)-alkoxy may be up to trisubstituted by fluorine, R7 is hydrogen, fluorine, chlorine, bromine, (C1-C3)-alkyl or (C1-C3)-alkoxy, R8A and R8B are the same or different and are independently hydrogen or (C1-C3)-alkyl and Y is N(R9), O or S, in which R9 is hydrogen or (C1-C3)-alkyl, or R2 is an -OR10 or -NR11R12 group, in which R10 is (C1-C4)-alkyl or (C4-C6)-cycloalkyl, R11 is hydrogen or (C1-C3)-alkyl and R12 is (C1-C6)-alkyl, (C3-C6)-cycloalkyl, phenyl or benzyl, where (C1-C6)-alkyl may be up to trisubstituted by fluorine, and where phenyl and the phenyl group in benzyl may be up to disubstituted, identically or differently, by a radical selected from the group of fluorine, chlorine, methyl, ethyl and trifluoromethyl, or R11 and R12 are joined to one another and, together with the nitrogen atom to which they are bonded, form a pyrrolidine, piperidine, morpholine or thiomorpholine ring, and the salts, solvates and solvates of the salts thereof.

2. Compound of the formula (I) according to Claim 1, in which the ring Q is a diazaheterobicyclic system of the formula in which * denotes the bond to the adjacent methylene group and ** the bond to the carbonyl group, A and D are each CH or one of these ring members is CH and the other is N, R1 is fluorine, chlorine, bromine, methyl, isopropyl, tert-butyl, cyclopropyl or cyclobutyl, and R2 is cyclobutyl, cyclopentyl or cyclohexyl, or R2 is a phenyl group of the formula (a), a pyridyl group of the formula (b) or an azole group of the formula (d), in which *** marks the bond to the adjacent carbonyl group and R3 is hydrogen, fluorine or chlorine, R4 is fluorine, chlorine, cyano, (C1-C3)-alkyl, (C1-C3)-alkoxy or trifluoromethoxy, R5 is hydrogen, fluorine, chlorine, bromine or methyl, R6 is (C1-C3)-alkoxy which may be up to trisubstituted by fluorine, or cyclobutyloxy, R8A and R8B are independently hydrogen or methyl and Y is N(CH3), O or S, or R2 is an -NR11R12 group in which R11 is hydrogen or (C1-C3)-alkyl and R12 is (C1-C6)-alkyl or phenyl, where phenyl may be up to disubstituted, identically or differently, by a radical selected from the group of fluorine, chlorine, methyl, ethyl and trifluoromethyl, or R11 and R12 are joined to one another and, together with the nitrogen atom to which they are bonded, form a pyrrolidine, piperidine or thiomorpholine ring, and the salts, solvates and solvates of the salts thereof.

3. Compound of the formula (I) according to Claim 1 or 2, in which the ring Q is a diazaheterobicyclic system of the formula in which * denotes the bond to the adjacent methylene group and ** the bond to the carbonyl group, A is CH or N, D is CH, R1 is fluorine, chlorine, bromine, methyl, isopropyl, tert-butyl, cyclopropyl or cyclobutyl, and R2 is cyclobutyl, cyclopentyl or cyclohexyl, or R2 is a phenyl group of the formula (a), a pyridyl group of the formula (b) or an azole group of the formula (d), in which *** marks the bond to the adjacent carbonyl group and R3 is hydrogen, fluorine or chlorine, R4 is fluorine, chlorine, cyano, (C1-C3)-alkyl, (C1-C3)-alkoxy or trifluoromethoxy, R5 is hydrogen, fluorine, chlorine, bromine or methyl, R6 is (C1-C3)-alkoxy which may be up to trisubstituted by fluorine, or cyclobutyloxy, R8A and R8B are independently hydrogen or methyl and Y is N(CH3), O or S, or R2 is an -NR11R12 group in which R11 is hydrogen or (C1-C3)-alkyl and R12 is (C1-C6)-alkyl or phenyl, where phenyl may be up to disubstituted, identically or differently, by a radical selected from the group of fluorine, chlorine, methyl, ethyl and trifluoromethyl, or R11 and R12 are joined to one another and, together with the nitrogen atom to which they are bonded, form a pyrrolidine, piperidine or thiomorpholine ring, and the salts, solvates and solvates of the salts thereof.

4. Compound of the formula (I) according to Claim 1 or 2, in which the ring Q is a diazaheterobicyclic system of the formula in which * denotes the bond to the adjacent methylene group and ** the bond to the carbonyl group, A and D are each CH or one of these ring members is CH and the other is N, R1 is chlorine, bromine, isopropyl or cyclopropyl, and R2 is cyclobutyl, cyclopentyl or cyclohexyl, or R2 is a phenyl group of the formula (a), a pyridyl group of the formula (b) or an azole group of the formula (d), in which *** marks the bond to the adjacent carbonyl group and R3 is hydrogen, fluorine or chlorine, R4 is fluorine, chlorine, methyl, isopropyl, methoxy or ethoxy, R5 is hydrogen, fluorine, chlorine, bromine or methyl, R6 is methoxy, difluoromethoxy, trifluoromethoxy, isopropoxy or cyclobutyloxy, R8A and R8B are each hydrogen and Y is N(CH3), and the salts, solvates and solvates of the salts thereof.

5. Compound of the formula (I) according to Claim 1, 2, 3 or 4, in which the ring Q is a diazaheterobicyclic system of the formula in which * denotes the bond to the adjacent methylene group and ** the bond to the carbonyl group, A is CH or N, D is CH, R1 is chlorine, bromine, isopropyl or cyclopropyl, and R2 is cyclobutyl, cyclopentyl or cyclohexyl, or R2 is a phenyl group of the formula (a), a pyridyl group of the formula (b) or an azole group of the formula (d), in which *** marks the bond to the adjacent carbonyl group and R3 is hydrogen, fluorine or chlorine, R4 is fluorine, chlorine, methyl, isopropyl, methoxy or ethoxy, R5 is hydrogen, fluorine, chlorine, bromine or methyl, R6 is methoxy, difluoromethoxy, trifluoromethoxy, isopropoxy or cyclobutyloxy, R8A and R8B are each hydrogen and Y is N(CH3), and the salts, solvates and solvates of the salts thereof.

6. Compound of the formula (I) according to Claim 1, with the systematic name ((3-{ [2-(5-chloropyridin-2-yl)imidazo[1,2-a]pyridin-3-yl]methyl}-3,8-diazabicyclo[3.2.1]oct-8-yl)-(6-methoxypyridin-2-yl)methanone and the structural formula 7. Process for preparing a compound of the formula (I) as defined in Claims 1 to 5, characterized in that a compound of the formula (II) in which A, D and R1 have the definitions given in Claims 1 to 5 is reacted in the presence of a suitable reducing agent either [A] with a compound of the formula (III) in which R2 and the ring Q have the definitions given in Claims 1 to 5 to give a compound of the formula (I) or [B] with a protected diazaheterobicyclic system of the formula (IV) in which the ring Q has the definition given in Claims 1 to 5 and PG is a suitable amino protecting group, for example tert-butoxycarbonyl, benzyloxycarbonyl or (9H-fluoren-9-ylmethoxy)carbonyl, at first to give a compound of the formula (V) in which A, D, PG, R1 and the ring Q have the definitions given above, then the protecting group PG is removed and the resulting compound of the formula (VI) in which A, D, R1 and the ring Q have the definitions given above, is then reacted, depending on the specific definition of the R2 radical, [B-1] with a carboxylic acid of the formula (VII) in which R2A is (C4-C6) -cycloalkyl in which a ring CH2 group may be replaced by -O-, or is a phenyl group of the formula (a), a pyridyl group of the formula (b) or (c) or an azole group of the formula (d), as described in Claims 1 to 5, with activation of the carboxylic acid function in (VII), or is reacted with the corresponding acid chloride of the formula (VIII) in which R2A has the definition given above to give a compound of the formula (I-A) in which A, D, R1, R2A and the ring Q have the definitions given above, or [B-2] with a chloroformate or carbamoyl chloride of the formula (IX) in which R2B is the -OR10 or -NR11AR12 group, in which R10 and R12 have the definitions given in Claims 1 to 5 and R11A has the definition of R11 given in Claims 1 to 5, but is not hydrogen, to give a compound of the formula (I-B) in which A, D, R1, R2B and the ring Q have the definitions given above, or [B-3] with an isocyanate of the formula (X)         R12-N=C=O     (X) in which R12 has the definition given in Claims 1 to 5 to give a compound of the formula (I-C) in which A, D, R1, R12 and the ring Q have the definitions given above, and the compounds of the formulae (I), (I-A), (I-B) or (I-C) thus obtained are optionally separated into their enantiomers and / or diastereomers and / or optionally converted with the appropriate (i) solvents and / or (ii) acids to the solvates, salts and / or solvates of the salts thereof.

8. Compound as defined in any of Claims 1 to 6 for treatment and / or prevention of diseases.

9. Compound as defined in any of Claims 1 to 6 for use in a method for treatment and / or prevention of respiratory disorders, sleep-related respiratory disorders, obstructive sleep apnoeas, central sleep apnoeas, snoring, cardiac arrhythmias, neurodegenerative disorders, neuroinflammatory disorders and neuroimmunological disorders.

10. Medicament comprising a compound as defined in any of Claims 1 to 6 in combination with one or more inert, nontoxic, pharmaceutically suitable excipients.

11. Medicament comprising a compound as defined in any of Claims 1 to 6 in combination with one or more further active compounds selected from the group consisting of respiratory stimulants, psychostimulating compounds, serotonin reuptake inhibitors, noradrenergic, serotonergic and tricyclic antidepressants, sGC stimulators, mineralocorticoid receptor antagonists, antiinflammatory drugs, immunomodulators, immunosuppressives and cytotoxic drugs.

12. Medicament according to Claim 10 or 11 for use in treatment and / or prevention of respiratory disorders, sleep-related respiratory disorders, obstructive sleep apnoeas, central sleep apnoeas, snoring, cardiac arrhythmias, neurodegenerative disorders, neuroinflammatory disorders and neuroimmunological disorders.