Substituted chroman-6-yloxy-cycloalkanes and their use as pharmaceuticals

The present invention relates to substituted chroman-6-yloxy-cycloalkanes of the formula I,

in which Ar, R1 to R4, p and q are as defined below. The compounds of the formula I are inhibitors of the sodium-calcium exchanger (NCX), especially of the sodium-calcium exchanger of subtype 1 (NCX1 ), and are suitable for the treatment of diverse disorders in which intracellular calcium homeostasis is disturbed, such as arrhythmias, heart failure and stroke. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use as pharmaceuticals, and pharmaceutical compositions comprising them.

Over the last decade major pharmacologic advances have been realized in the management of heart failure (HF), or congestive heart failure (CHF). Beta-blockers and inhibitors of the renin-angiotensin-aldosterone system have been found to have a favorable effect in CHF with regard to mortality and improvement of symptoms (K. Dickstein et al., Eur. J. Heart Fail. 10 (2008): 933-989). Nevertheless, morbidity and mortality have remained unacceptably high. The number of patients with CHF, and in particular more severe forms of CHF, is even growing, in part paradoxically because of the success of these treatment approaches. Thus, there is still a need for agents that can help improve CHF outcome and enhance quality of life. Blockers of the sodium-calcium exchanger (NCX), a transport protein which is involved in the regulation of cellular calcium and sodium levels, have the potential to improve the prognosis of CHF and quality of life.

The function of the NCX is to extrude calcium in cardiomyocytes and other cell types such as neurons. In CHF, the NCX was shown to be upregulated, thus unloading the cell from calcium and further decreasing myocardial contractility (M. Flesch et al., Circulation 94 (1996): 992-1002; G. Hasenfuss et al., Circulation 99 (1999): 641 -648). Pump failure in CHF is not only due to irreversible structural changes and loss of myocardium, but also due to adverse functional changes including a disturbance of the intracellular calcium homeostasis. The latter can be treated by inhibition of the NCX. Three subtypes of the NCX have been described. In the heart, predominantly subtype 1 is expressed.

Through the NCX, calcium is exchanged for sodium, and extracellular sodium is the driving force for the exchanger. The stoichiometry of the exchanger is that three sodium ions enter the cell for the extrusion of one calcium ion. This stoichiometry causes a positive inward current which is depolarizing in nature. The depolarizing current, if of a sufficient size, could induce afterdepolarizations of the ventricular and atrial action potential. Afterdepolarizations are oscillations of the electric membrane potential and can occur during (early afterdepolarizations, EADs) or after (delayed afterdepolarizations, DADs) the cardiac action potential. The occurrence of EADs is associated with a prolonged ventricular action potential (visible as prolonged QT interval in the electrocardiogram (ECG)), which is a common feature of the failing heart. Afterdepolarizations are believed to be the major trigger of cardiac arrhythmias, which therefore are also called triggered activity (D. M. Bers et al., Ann. N. Y. Acad. Sci. 1080 (2006): 165-177; K. R. Sipido et al., Pflugers Arch. 430 (1995): 871 -878; A. O. Verkerk et al., Circulation 104 (2001 ): 2728-2733; C. Pott et al., Current Drug Targets 12 (201 1 ): 737-747; G. Antoons et al., Pharmacol. Ther. 134 (2012): 26-42). The premature beats arising from the NCX-induced depolarizing currents can cause more complex and irreversible arrhythmias such as episodes of tachycardia, ventricular flutter or ventricular fibrillation.

Patients with pump failure, or heart failure, typically suffer from arrhythmias and arrhythmic death. About 50% of the cardiac mortality in CHF is due to arrhythmic death. NCX blockade is therefore a means of improving pump failure and associated

symptoms as well as of reducing arrhythmic death. Current positive inotropic drugs are associated with proarrhythmic effects that either increase mortality, such as in the case of phosphodiesterase inhibitors, or annihilate the positive effects achieved by an improvement of pump failure by the positive inotropic effect (J. T. Parissis et al., Curr. Opin. Crit. Care 16 (2010): 432-441 ). On the other hand, a number of clinically useful antiarrhythmic drugs have a negative inotropic effect on the heart worsening the symptoms of heart failure. NCX blockers are therapeutically unique in that they can address the two major problems of CHF, pump failure and arrhythmias.

NCX blockade is particularly interesting for advanced stages of CHF, like NYHA Classes III and IV according to the New York Heart Association Functional

Classification of heart failure, in which the therapeutic options, i.e. beta-blockers, inhibitors of the renin angiotensin-aldosterone system, diuretics and vasodilators, already are fully exploited. Elderly patients progressing to end-stage HF present a new emerging population. In this late stage a vasodilator effect is no more desirable in a considerable part of the patients because blood pressure is already lowered as a consequence of pump failure. Phosphodiesterase inhibitors as positive inotropic drugs not only suffer from the drawback of being proarrhythmic, but also from a vasodilator effect.

Atrial fibrillation (AF) is the most frequent arrhythmia. AF affects about 6.8 million patients in the US and the European Union, and its prevalence is strongly rising because of the aging of the population and of the successful treatment of myocardial infarction, coronary artery disease and congestive heart failure. AF causes about 25% of all strokes, and increases mortality. Also in AF, upregulation of the NCX has been demonstrated (U. Schotten et al., Cardiovasc. Res. 53 (2002): 192-201 ).

Upregulation of the NCX can be involved in the induction of AF by the

arrhythmogenic activity of the NCX and in its maintenance, and hence NCX blockers have therapeutically favorable effects in the therapy and prevention of AF. Since AF is an increasing disease in the aging population and is frequently associated with heart failure in up to about 45% of patients (I. Savelieva et al., Europace 5 Suppl 1 (2004): S5-S19), NCX blockers would be particularly favorable in patients with AF and CHF.

Since NCX blockers also exert a positive inotropic effect in the atria, they may be particularly favorable in diastolic heart failure where ventricular filling is the major problem as a consequence of ventricular stiffening. A more vigorous atrial contraction would improve ventricular filling in diastolic heart failure.

Since a reduced cardiac output has deleterious effects on the perfusion of organs such as the kidney, brain and heart, inhibition of the NCX, which increases the contractility of the heart, is able to improve perfusion of the brain, heart and kidney for a therapy or prevention of stroke, dementia and Alzheimer's disease, renal failure and cardiac ischemia. Since the NCX is also involved in salt sensitive hypertension, its inhibition is also suited for the treatment of hypertension.

Inhibitors of the NCX are also suited for the therapy and prevention of life threatening conditions in which inotropic support is required to maintain a sufficient level of blood supply. This includes all forms of shock, hemodynamic shock, cardiogenic shock and septic shock. Inhibitors of the NCX are particularly suited to treat these conditions because they are neutral on heart rate and lack the proarrhythmic or vasodilator or vasoconstrictor properties of other inotropic drugs.

In stroke, NCX blockers have the potential of improving the outcome since in neuronal hypoxia, as occurs in stroke, the NCX reverses its transport direction to reverse mode, and loads the cells with calcium leading to a calcium overload. This leads to accelerated cell death due to excessive intracellular calcium concentrations. Moreover, a low cardiac output can lead to brain ischemia favoring stroke. NCX blockers will increase cardiac output and raise brain perfusion. Hence, NCX blockers have a potential in the therapy and prevention of stroke (T. Matsuda et al., J.

Pharmacol. Exp. Ther. 298 (2001 ): 249-256).

Certain compounds capable of inhibiting the NCX have already been described, e.g. in EP 0978506, JP 2008/189592, WO 2004/000813, WO 2004/063191 , WO

03/006452, WO 02/32883, WO 97/09306. However, there still is a need for further compounds which inhibit the NCX and are suitable for use as pharmaceuticals in the treatment of the mentioned disease states. It has now been found that the

compounds of the formula I are excellent inhibitors of the sodium-calcium exchanger (NCX), especially of the sodium-calcium exchanger of subtype 1 (NCX1 ), and have a favorable property profile for such use.

Thus, a subject of the present invention are the compounds of the formula I, in any of their stereoisomeric forms and mixtures of stereoisomeric forms in any ratio, and the pharmaceutically acceptable salts thereof,

wherein

Ar is phenyl which is unsubstituted or substituted by one or more identical or different substituents R0;

R0 is selected from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O- and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-O-, and two groups R0 bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 7-membered mono-unsaturated ring which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R1 is hydrogen or one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R2 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl, HO-, (C1-C-6)-alkyl-O-, (Ci-C6)-alkyl-C(O)-O-, phenyl-C(O)-O-, Het1-C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, wherein (d-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20;

R3 is selected from the series consisting of hydrogen and (Ci-C6)-alkyl, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or two identical or different

substituents selected from the series consisting of (C3-C7)-cycloalkyl, phenyl, HO-and (Ci-C4)-alkyl-O-;

or the groups R2 and R3 together are oxo;

R4 is hydrogen or one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-;

R5 and R6 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl, phenyl, Het1 and Het2, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl, (C6-C10)-bicydoalkyi and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and phenyl and Het1 all are unsubstituted or substituted by one or more identical or different substituents R22,

or the groups R5 and R6, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic, saturated or partially unsaturated

heterocycle which, in addition to the nitrogen atom carrying R5 and R6, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R21 ;

R7 is selected from the series consisting of (CrC6)-alkyl, (C3-C7)-cycloalkyl, phenyl, Het1 and Het2, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and phenyl and Het1 all are unsubstituted or substituted by one or more identical or different substituents R22;

R8 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl;

R9 is selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, phenyl-(Ci-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-;

R10 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-> phenyl-(Ci-C4)-alkyl- and Het1 -(d-C4)-alkyl-;

R20 is selected from the series consisting of R24, fluorine, HO-, oxo, (Ci-C-6)-alkyl-0-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, (C3-C7)-cycloalkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-;

R21 is selected from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, R34-0-C(0)-(Ci-C4)-alkyl-, R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-,

(HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, (C3-C7)-cycloalkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-;

R22 is selected from the series consisting of halogen, (CrC4)-alkyl, HO-(CrC4)-alkyl-, (C3-C7)-cycloalkyl, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, (C3-C7)-cycloalkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, R33-O-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, NC-, R33-C(O)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-;

R24 is a 3-membered to 10-membered, monocyclic or bicydic ring which is saturated, partially unsaturated or aromatic and comprises 0, 1 , 2, 3 or 4 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R22;

R30 and R33 are independently of one another selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, phenyl-(d-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-;

R31 and R32 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, phenyl-(Ci-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-,

or the groups R31 and R32, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic saturated heterocycle which, in addition to the nitrogen atom carrying R31 and R32, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R34 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, phenyl-(Ci-C4)-alkyl- and Het1 -(d-C4)-alkyl-;

Het1 is a 5-membered or 6-mennbered, monocyclic, aromatic heterocycle which comprises 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-, unless specified otherwise;

Het2 is a 4-membered to 10-membered, monocyclic or bicyclic, saturated or partially unsaturated heterocycle which comprises 1 or 2 identical or different ring

heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur;

n is selected from the series consisting of 0, 1 and 2, wherein all numbers n are independent of one another;

p and q are independently of one another selected from the series consisting of 0 and 1 ;

wherein all phenyl groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-, unless specified otherwise;

wherein all cycloalkyl and bicycloalkyl groups, independently of any other

substituents which can be present on a cycloalkyl or bicycloalkyl group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

If the group R1 is hydrogen, the carbon atoms of the cycloalkane ring in the compounds of the formula I and all other compounds in which R1 occurs, carry hydrogen atoms only, apart from the groups R2 and R3 and the oxygen atom linking the cycloalkane ring to the chroman ring. Groups R1 in the compounds of the formula I and all other compounds in which R1 occurs, which are different from hydrogen, i.e. fluorine and (Ci-C4)-alkyl substituents representing R1 , can be bonded to any of the ring carbon atoms of the cycloalkane ring depicted in formula I which has a free binding site, i.e. to any ring carbon atom of the cycloalkane ring except for the ring carbon atom carrying the groups R2 and R3, as is indicated by the bond originating at R1 which is not directed to a specific carbon atom. Likewise, if the group R4 is hydrogen, the chroman ring in the compounds of the formula I and all other compounds in which R4 occurs, carries hydrogen atoms only, apart from the group Ar and the oxygen atom linking the chroman ring to the cycloalkane ring. Groups R4 in the compounds of the formula I and all other compounds in which R4 occurs, which are different from hydrogen, i.e. halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-substituents representing R4, can be bonded to any of the carbon atoms of the chroman ring depicted in formula I which have a free binding site, i.e. to the carbon atoms in ring positions 2, 3, 4, 5, 7 and 8 of the chroman ring as identified in formula Γ, as is indicated by the bond originating at R4 which is not directed to a specific carbon atom of the chroman ring.

In all free binding sites of the carbon atoms in ring positions 2, 3, 4, 5, 7 and 8 of the chroman ring which are not occupied by groups R4 different from hydrogen, as well as in all free binding sites of the cycloalkane ring which are not occupied by groups R1 different from hydrogen, hydrogen atoms are present. I.e., if in a compound of the formula I no group R4 is present which is different from hydrogen, the carbon atoms in ring positions 2, 5, 7 and 8 of the chroman ring carry one hydrogen atom, and the carbon atoms in ring positions 3 and 4 of the chroman ring carry two hydrogen atoms If in a compound of the formula I no group R1 is present which is different from hydrogen, the ring carbon atom of the cycloalkane ring which carries the oxygen

atom linked to the chroman ring, carries one hydrogen atom, and the other ring carbon atoms apart from the atom carrying R2 and R3 carry two hydrogen atoms. Compounds of the formula I in which no group R4 and/or no group R1 is present which is different from hydrogen, may alternatively be represented by a modified formula I in which R4 and/or R1 and the bond originating at them are omitted. If substituents R4 and/or R1 are present, i.e. atoms or groups representing R4 and/or R1 which are different from hydrogen, one or more of the said hydrogen atoms are replaced by the substituents.

If structural elements such as groups, substituents or numbers, for example, can occur several times in the compounds of the formula I, they are all independent of each other and can in each case have any of the indicated meanings, and they can in each case be identical to or different from any other such element. In a

dialkylamino group, for example, the alkyl groups can be identical or different.

Alkyl groups, i.e. saturated hydrocarbon residues, can be linear (straight-chain) or branched. This also applies if these groups are substituted or are part of another group, for example an alkyl-O- group (alkyloxy group, alkoxy group) or an HO-substituted alkyl group (HO-alkyl-, hydroxyalkyl group). Depending on the respective definition, the number of carbon atoms in an alkyl group can be 1 , 2, 3, 4, 5 or 6, or 1 , 2, 3 or 4, or 1 , 2 or 3, or 1 or 2, or 1 . Examples of alkyl are methyl, ethyl, propyl including n-propyl and isopropyl, butyl including n-butyl, sec-butyl, isobutyl and tert-butyl, pentyl including n-pentyl, 1 -methylbutyl, isopentyl, neopentyl and tert-pentyl, and hexyl including n-hexyl, 3,3-dimethylbutyl and isohexyl. Examples of

alkyl-O- groups are methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, tert-butoxy, n-pentoxy. Examples of alkyl-S(O)n- are methylsulfanyl- (CH3-S-), methanesulfinyl- (CH3-S(O)-), methanesulfonyl (CH3-S(O)2-), ethylsulfanyl-(CH3-CH2-S-), ethanesulfinyl- (CH3-CH2-S(O)-), ethanesulfonyl (CH3-CH2-S(O)2-), 1 -methylethylsulfanyl- ((CH3)2CH-S-), 1 -methylethanesulfinyl- ((CH3)2CH-S(O)-), 1 -methylethanesulfonyl ((CH3)2CH-S(O)2-). In one embodiment of the invention, the number n is selected from the series consisting of 0 and 2, wherein all numbers n are independent of each other and can be identical or different. In another embodiment

the number n in any of its occurrences, independent of its meaning in other occurrences, is 0. In another embodiment the number n in any of its occurrences, independent of its meaning in other occurrences, is 2.

A substituted alkyl group can be substituted in any positions, provided that the respective compound is sufficiently stable and is suitable as a pharmaceutical active compound. The prerequisite that a specific group and a compound of the formula I are sufficiently stable and suitable as a pharmaceutical active compound, applies in general with respect to the definitions of all groups in the compounds of the formula I. As examples of substituted alkyl groups, specifically of HO-(Ci-C4)-alkyl- groups, for example, hydroxymethyl, 1 -hydroxyethyl, 2-hydroxyethyl, 1 -hydroxypropyl, 2-hydroxypropyl, 3-hydroxypropyl, 1 -hydroxy-1 -methylethyl, 2-hydroxy-1 -methylethyl, 1 -hydroxybutyl, 4-hydroxybutyl, 2-hydroxy-1 -methylpropyl or 2-hydroxy-1 -methylpropyl may be mentioned.

Independently of any other substituents which can be present on an alkyl group, and unless specified otherwise, alkyl groups can be substituted by one or more fluorine substituents, for example by 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10 or 1 1 fluorine substituents, or by 1 , 2, 3, 4 or 5 fluorine substituents, or by 1 , 2 or 3 fluorine substituents, which can be located in any positions. I.e., independently of any other substituents which can be present on an alkyl group, an alkyl group can be unsubstituted by fluorine substituents, i.e. not carry fluorine substituents, or substituted by fluorine substituents, wherein all alkyl groups in the compounds of the formula I are independent of one another with regard to the optional substitution by fluorine substituents. For example, in a fluoro-substituted alkyl group one or more methyl groups can carry three fluorine substituents each and be present as trifluoromethyl groups, and/or one or more methylene groups (CH2) can carry two fluorine substituents each and be present as difluoromethylene groups. The explanations with respect to the substitution of a group by fluorine also apply if the group additionally carries other substituents and/or is part of another group, for example of an alkyl-O- group. Examples of fluoro-substituted alkyl groups are trifluoromethyl, 2-fluoroethyl, 1 -fluoroethyl, 1 ,1 -difluoroethyl, 2,2,2-trifluoroethyl, pentafluoroethyl, 3,3,3-trifluoropropyl, 2,2,3,3,3- pentafluoropropyl, 4,4,4-trifluorobutyl and heptafluoroisopropyl. Examples of fluoro-substituted alkyl-O- groups are trifluoromethoxy, 2,2,2-trifluoroethoxy,

pentafluoroethoxy and 3,3,3-trifluoropropoxy. Examples of fluoro-substituted alkyl-S(O)n- groups are trifluoromethylsulfanyl- (CF3-S-), trifluoromethanesulfinyl-(CF3-S(O)-) and trifluoromethanesulfonyl (CF3-S(O)2-). With respect to all groups or substituents in the compounds of the formula I which can be an alkyl group which can generally contain one or more fluorine substituents, as an example of groups or substituents containing fluorine-substituted alkyl which may be included in the definition of the group or substituent, the group CF3 (trifluoromethyl), or respective groups such as CF3-O- or CF3-S-, may be mentioned.

The above explanations with respect to alkyl groups apply correspondingly to alkyl groups which in the definition of a group in the compounds of the formula I are bonded to two adjacent groups, or linked to two groups, and may be regarded as divalent alkyl groups (alkanediyl groups), like in the case of the alkyl part of a substituted alkyl group. Thus, such groups can also be linear or branched, the bonds to the adjacent groups can be located in any positions and can start from the same carbon atom or from different carbon atoms, and they can be unsubstituted or substituted by fluorine substituents independently of any other substituents.

Examples of such divalent alkyl groups are -CH2-, -CH2-CH2-, -CH2-CH2-CH2-, -CH2-CH2-CH2-CH2-, -CH(CH3)-, -C(CH3)2-, -CH(CH3)-CH2-, -CH2-CH(CH3)-,

-C(CH3)2-CH2-, -CH2-C(CH3)2-. Examples of fluoro-substituted alkanediyl groups, which can contain 1 , 2, 3, 4, 5 or 6 fluorine substituents, for example, are -CHF-, -CF2-, -CF2-CH2-, -CH2-CF2-, -CF2-CF2-, -CF(CH3)-, -C(CF3)2-, -C(CH3)2-CF2-,

-CF2-C(CH3)2-.

The above explanations with respect to alkyl groups apply correspondingly to unsaturated hydrocarbon residues, i.e. alkenyl groups, which in one embodiment of the invention contain one double bond. Thus, for example, alkenyl groups can likewise be linear or branched. Double bonds can be present in any positions. The number of carbon atoms in an alkenyl group can be 2, 3, 4, 5 or 6, or 2, 3, 4 or 5, or 3, 4 or 5, for example. Examples of alkenyl are ethenyl (vinyl), prop-1 -enyl, prop-2-enyl (allyl), but-2-enyl, but-3-enyl, 2-methylprop-2-enyl, 3-methylbut-2-enyl, hex-3-enyl, hex-4-enyl, 4-methylpent-3-enyl. In one embodiment of the invention, an alkenyl group contains at least three carbon atoms and is bonded to the remainder of the molecule via a carbon atom which is not part of a double bond.

The number of ring carbon atoms in a (C3-C7)-cycloalkyl group can be 3, 4, 5, 6 or 7. Examples of cycloalkyl are cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl. The number of ring carbon atoms in a (C6-Cio)-bicycloalkyl group can be 6, 7, 8, 9 or 10. The two cycles in a bicycloalkyi group can have one, two or more ring carbon atoms in common and can be fused or form a bridged bicycle or a spirocycle. Examples of bicycloalkyi are bicyclo[2.1 .1 ]hexyl, bicyclo[2.2.1 ]heptyl,

bicyclo[3.1 .1 ]heptyl, bicyclo[2.2.2]octyl, bicyclo[3.2.1 ]octyl, bicyclo[3.2.2]nonyl and bicyclo[4.4.0]decyl. Bicycloalkyi groups can be bonded via any ring carbon atom. Independently of any other substituents which can be present on a cycloalkyl group or bicycloalkyi group, and unless specified otherwise, cycloalkyl groups and bicycloalkyi groups can be substituted by one or more (Ci-C4)-alkyl substituents, for example by 1 , 2, 3 or 4 identical or different (Ci-C4)-alkyl substituents, for example by methyl groups, which can be located in any positions. I.e., independently of any other substituents which can be present on a cycloalkyl group or bicycloalkyi group, cycloalkyl groups and bicycloalkyi groups can be unsubstituted by (Ci-C4)-alkyl substituents, i.e. not carry (Ci-C4)-alkyl substituents, or substituted by (Ci-C4)-alkyl substituents, wherein all cycloalkyl groups and bicycloalkyi groups in the compounds of the formula I are independent of one another with regard to the optional

substitution by (Ci-C4)-alkyl substituents. Examples of such alkyl-substituted cycloalkyl groups and bicycloalkyi groups are 1 -methylcyclopropyl, 2,2-dimethylcyclopropyl, 1 -methylcyclopentyl, 2,3-dimethylcyclopentyl, 1 -methylcyclohexyl, 4-methylcyclohexyl, 4-isopropylcyclohexyl, 4-tert-butylcyclohexyl, 3,3,5,5-tetramethylcyclohexyl, 7,7-dimethylbicyclo[2.2.1]heptyl, 6,6-dimethylbicyclo[3.1 .1 ]heptyl and 1 ,7,7-trimethylbicyclo[2.2.1 ]heptyl.

Independently of any other substituents including (Ci-C4)-alkyl substituents which can be present on a cycloalkyl group or bicycloalkyi group, and unless specified

otherwise, cycloalkyi groups and bicydoalkyi groups can further be substituted by one or more fluorine substituents, for example by 1 , 2, 3, 4, 5, 6, 7, 8, 9, 10 or 1 1 fluorine substituents, or by 1 , 2, 3, 4 or 5 fluorine substituents, or by 1 , 2 or 3 fluorine substituents, which can be located in any positions and can also be present in a (Ci-C4)-alkyl substituent. I.e., independently of any other substituents which can be present on a cycloalkyi group or bicydoalkyi group, cycloalkyi groups and bicydoalkyi groups can be unsubstituted by fluorine substituents, i.e. not carry fluorine

substituents, or substituted by fluorine substituents, wherein all cycloalkyi groups and bicydoalkyi groups in the compounds of the formula I are independent of one another with regard to the optional substitution by fluorine substituents. Examples of fluoro-substituted cycloalkyi groups and bicydoalkyi groups are 1 -fluorocyclopropyl, 2,2-difluorocyclopropyl, 3,3-difluorocyclobutyl, 1 -fluorocyclohexyl, 4,4-difluorocyclohexyl, 3,3,4,4,5,5-hexafluorocyclohexyl, 1 -fluorobicyclo[2.2.2]octyl and 1 ,4-difluorobicyclo[2.2.2]octyl. Cycloalkyi groups can also be substituted simultaneously by fluorine and alkyl. Examples of the group (C3-C7)-cycloalkyl-(Ci-C4)-alkyl- are cyclopropylmethyl-, cyclobutylmethyl-, cyclopentylmethyl-, cyclohexylmethyl-, cycloheptylmethyl-, 1 -cyclopropylethyl-, 2-cyclopropylethyl-, 1 -cyclobutylethyl-, 2-cyclobutylethyl-, 1 -cyclopentylethyl-, 2-cyclopentylethyl-, 1 -cyclohexylethyl-, 2-cyclohexylethyl-, 1 -cycloheptylethyl-, 2-cycloheptylethyl-. In one embodiment of the invention, a (C3-C7)-cycloalkyl-(Ci-C4)-alkyl- group in any one or more occurrences of such a group, independently of any other occurrences, is a (C3-C7)-cycloalkyl-(Ci-C2)-alkyl- group, in another embodiment a (C3-C7)-cycloalkyl-CH2- group. In the group (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, and likewise in all other groups, the terminal hyphen denotes the free bond via which the group is bonded, and thus indicates via which subgroup a group composed of subgroups is bonded.

In substituted phenyl groups, including phenyl groups representing Ar and R24, the substituents can be located in any positions. In monosubstituted phenyl groups, the substituent can be located in position 2, in position 3 or in position 4. In disubstituted phenyl groups, the substituents can be located in positions 2 and 3, in positions 2 and 4, in positions 2 and 5, in positions 2 and 6, in positions 3 and 4, or in positions 3 and 5. In trisubstituted phenyl groups, the substituents can be located in positions 2,

3 and 4, in positions 2, 3 and 5, in positions 2, 3 and 6, in positions 2, 4 and 5, in positions 2, 4 and 6, or in positions 3, 4 and 5. If a phenyl group carries four substituents, some of which can be fluorine atoms, for example, the substituents can be located in positions 2, 3, 4 and 5, in positions 2, 3, 4 and 6, or in positions 2, 3, 5 and 6. If a polysubstituted phenyl group or any other polysubstituted group carries different substituents, each substituent can be located in any suitable position, and the present invention comprises all positional isomers. The number of substituents in a substituted phenyl group can be 1 , 2, 3, 4 or 5. In one embodiment of the invention, the number of substituents in a substituted phenyl group, and likewise in other embodiments the number of substituents in any other substituted group which can carry one or more substituents, is 1 , 2, 3 or 4, in another embodiment 1 , 2 or 3, in another embodiment 1 or 2, in another embodiment 1 , wherein the number of substituents in any occurrence of such a substituted group is independent of the number of substituents in other occurrences.

In heterocyclic groups, including the groups Het1 and Het2 and heterocyclic groups R24, and other heterocyclic rings which can be present in the compounds of the formula I, such as rings formed by two groups together with the atom or atoms carrying them, the hetero ring members can be present in any combination and located in any suitable ring positions, provided that the resulting group and the compound of the formula I are suitable and sufficiently stable as a pharmaceutical active compound. In one embodiment of the invention, two oxygen atoms in any heterocyclic ring in the compounds of the formula I cannot be present in adjacent ring positions. In another embodiment of the invention, two hetero ring members selected from the series consisting of oxygen atoms and sulfur atoms cannot be present in adjacent ring positions in any heterocyclic ring in the compounds of the formula I. In another embodiment of the invention, two hetero ring members selected from the series consisting of nitrogen atoms carrying an exocyclic group like a hydrogen atom or a substituent, sulfur atoms and oxygen atoms cannot be present in adjacent ring positions in any heterocyclic ring in the compounds of the formula I. In an aromatic heterocyclic ring the choice of hetero ring members is limited by the prerequisite that the ring is aromatic, i.e. it comprises a cyclic system of six delocalized pi electrons.

Monocyclic aromatic heterocycles are 5-membered or 6-membered rings and, in the case of a 5-membered ring, comprise one ring heteroatom selected from the series consisting of oxygen, sulfur and nitrogen, wherein this ring nitrogen carries an exocyclic group like a hydrogen atom or a substituent, and optionally one or more further ring nitrogen atoms, and, in the case of a 6-membered ring, comprise one or more nitrogen atoms as ring heteroatoms, but no oxygen atoms and sulfur atoms as ring heteroatoms. Unless specified otherwise in the definition of the group,

heterocyclic groups can be bonded via any suitable ring atom, i.e. any ring atom which carries a hydrogen atom or a substituent, including ring carbon atoms and ring nitrogen atoms. In one embodiment of the invention, any of the heterocyclic groups occurring in the compounds of the formula I in any of its occurrences, is

independently of its other occurrences and independently of any other heterocyclic group, bonded via a ring carbon atom, and in another embodiment via a ring nitrogen atom, if applicable. In substituted heterocyclic groups, the substituents can be located in any positions.

The number of ring heteroatoms which can be present in a heterocyclic group in the compounds of the formula I, the number of cycles, i.e. whether the heterocyclic group can be monocyclic and/or bicydic, the number of ring members which can be present, and the degree of saturation, i.e. whether the heterocyclic group is saturated and does not contain a double bond within the ring, or whether it is partially unsaturated and contains one or more, for example one or two, double bonds within the ring but is not aromatic, or whether it is aromatic and thus contains two double bonds within the ring in the case of a 5-membered monocyclic aromatic heterocycle, three double bonds within the ring in the case of a 6-membered monocyclic aromatic heterocycle, four double bonds within the ring in the case of 9-membered bicydic aromatic heterocycle, and five double bonds within the ring in the case of 10-membered aromatic heterocycle, is specified in the definitions of the individual groups in the compounds of the formula I. The two cycles in a bicydic heterocyclic group can have one, two or more ring atoms in common and can be fused or form a bridged bicycle or a spirocycle. As examples of heterocyclic ring systems, from which heterocyclic groups in the compounds of the formula I can be derived, and from any one or more of which any of the heterocyclic groups in the compounds of the formula I, independently of any other heterocyclic group, is selected in one embodiment of the invention, provided that the ring system is comprised by the definition of the group, oxetane, thietane, azetidine, furan, tetrahydrofuran, thiophene, tetrahydrothiophene, pyrrole, pyrroline, pyrrolidine, 1 ,3-dioxole, 1 ,3-dioxolane, isoxazole ([1 ,2]oxazole), isoxazoline, isoxazolidine, oxazole ([1 ,3]oxazole), oxazoline, oxazolidine, isothiazole ([1 ,2]thiazole), isothiazoline, isothiazolidine, thiazole ([1 ,3]thiazole), thiazoline, thiazolidine, pyrazole, pyrazoline, pyrazolidine, imidazole, imidazoline, imidazolidine, [1 ,2,3]triazole, [1 ,2,4]triazole, [1 ,2,4]oxadiazole, [1 ,3,4]oxadiazole, [1 ,2,5]oxadiazole, [1 ,2,4]thiadiazole, 1 H-tetrazole, pyran, tetrahydropyran, thiopyran,

tetrahydrothiopyran, 2,3-dihydro[1 ,4]dioxine, 1 ,4-dioxane, pyridine, 1 ,2,5,6-tetrahydropyridine, piperidine, morpholine, thiomorpholine, piperazine, pyridazine, pyrimidine, pyrazine, [1 ,2,4]triazine, oxepane, thiepane, azepane, [1 ,3]diazepane, [1 ,4]diazepane, [1 ,4]oxazepane, [1 ,4]thiazepane, azocane, 3-azabicyclo[3.1 .0]hexane, octahydrocyclopenta[b]pyrrole,

octahydrocyclopenta[c]pyrrole, 2-azaspiro[4.4]nonane, 7-azabicyclo[2.2.1 ]heptane,

2.7- diazaspiro[4.4]nonane, octahydropyrrolo[3,4-b]pyrrole, 6,7-dihydro-5H-pyrrolo[2,1 -c][1 ,2,4]triazole, imidazo[2,1 -b]thiazole, 6,7-dihydro-5H-thiazolo[3,2-a]pyrimidine, benzofuran, isobenzofuran, benzothiophene (benzo[b]thiophene), 1 H-indole, 2,3-dihydro-1 H-indole, octahydroindole, 2H-isoindole, octahydroisoindole, benzo[1 ,3]dioxole, benzoxazole, benzthiazole, 1 H-benzimidazole, imidazo[1 ,2-a]pyridine, [1 ,2,4]triazolo[4,3-a]pyridine, chroman, isochroman, thiochroman, benzo[1 ,4]dioxane, 3,4-dihydro-2H-benzo[1 ,4]oxazine, 3,4-dihydro-2H-benzo[1 ,4]thiazine, 2-azaspiro[4.5]decane, 3-azabicyclo[3.2.2]nonane, quinoline, 1 ,2,3,4-tetrahydroquinoline, 5,6,7,8-tetrahydroquinoline, isoquinoline, 1 ,2,3,4-tetrahydroisoquinoline, 5,6,7,8-tetrahydroisoquinoline, 2,7-diazaspiro[4.5]decane,

2.8- diazaspiro[4.5]decane, cinnoline, quinazoline, quinoxaline, phthalazine and

[1 ,8]naphthyridine may be mentioned, which can all be unsubstituted or substituted in any suitable positions as specified in the definition of the respective group in the compounds of the formula I, wherein the given degree of unsaturation is by way of example only, and in the individual groups also ring systems with a higher or lower

degree of saturation, or hydrogenation, or of unsaturation can be present as specified in the definition of the group.

As mentioned, the heterocyclic groups can be bonded via any suitable ring atom. For example, among others can an oxetane and a thietane ring be bonded via positions 2 and 3, an azetidine ring via positions 1 , 2 and 3, a furan ring, a tetrahydrofuran ring, a thiophene ring and a tetrahydrothiophene via positions 2 and 3, a pyrrole ring and a pyrrolidine ring via positions 1 , 2 and 3, an isoxazole ring and an isothiazole ring via positions 3, 4 and 5, a pyrazole ring via positions 1 , 3, 4 and 5, an oxazole ring and a thiazole ring via positions 2, 4 and 5, an imidazole ring and an imidazolidine ring via positions 1 , 2, 4 and 5, a 1 H-tetrazole ring via positions 1 and 5, a tetrahydropyran and a tetrahydrothiopyran ring via positions 2, 3 and 4, a 1 ,4-dioxane ring via position 2, a pyridine ring via positions 2, 3 and 4, a piperidine ring via positions 1 , 2, 3 and 4, a morpholine ring and a thiomorpholine ring via positions 2, 3 and 4, a piperazine ring via positions 1 and 2, a pyrimidine ring via positions 2, 4 and 5, a pyrazine ring via position 2, an azepane ring via positions 1 , 2, 3 and 4, a 3-azabicyclo[3.1 .0]hexane ring via positions 3 and 6, an octahydrocyclopenta[b]pyrrole and an

octahydrocyclopenta[c]pyrrole ring via position 1 , a 2-azaspiro[4.4]nonane ring via position 2, a 7-azabicyclo[2.2.1]heptane ring via position 7, an octahydropyrrolo[3,4-b]pyrrole ring via positions 1 and 5, a 6,7-dihydro-5H-pyrrolo[2,1 -c][1 ,2,4]triazole ring via position 3, an imidazo[2,1 -b]thiazole ring via positions 2, 5 and 6, a 6,7-dihydro-5H-thiazolo[3,2-a]pyrimidine via position 3, a benzofuran ring and a benzothiophene ring via positions 2, 3, 4, 5, 6 and 7, a 1 H-indole ring, a 2,3-dihydro-1 H-indole and an octahydroindole ring via positions 1 , 2, 3, 4, 5, 6 and 7, a benzo[1 ,3]dioxole ring via positions 4, 5, 6 and 7, a benzoxazole ring and a benzthiazole ring via positions 2, 4, 5, 6 and 7, a 1 H-benzimidazole ring via positions 1 , 2, 4, 5, 6 and 7, an imidazo[1 ,2-a]pyridine ring via positions 2 and 3, a [1 ,2,4]triazolo[4,3-a]pyridine ring via position 3, a benzo[1 ,4]dioxane ring via positions 5, 6, 7 and 8, a 3-azabicyclo[3.2.2]nonane ring via position 3, a quinoline ring via positions 2, 3, 4, 5, 6, 7 and 8, a 1 ,2,3,4-tetrahydroquinoline ring via positions 1 , 5, 6, 7 and 8, a 5,6,7,8-tetrahydroquinoline via positions 2, 3 and 4, an isoquinoline ring via positions 1 , 3, 4, 5, 6, 7 and 8, a 1 ,2,3,4-tetrahydroisoquinoline ring via positions 2, 5, 6, 7 and 8, a 5,6,7,8-

tetrahydroisoquinoline ring via positions 1 , 3, 4 and 5, a 2,7-diazaspiro[4.5]decane ring via positions 2 and 7, a 2,8-diazaspiro[4.5]decane ring via positions 2 and 8, for example, wherein the resulting residues of the heterocyclic groups can all be unsubstituted or substituted in any suitable positions as specified for the respective group in the definition of the compounds of the formula I.

Halogen is fluorine, chlorine, bromine or iodine. In one embodiment of the invention, in any of its occurrences halogen is fluorine, chlorine or bromine, in another embodiment fluorine or chlorine, in another embodiment fluorine, in another embodiment chlorine, wherein all occurrences of halogen are independent of each other.

An oxo group, i.e. a doubly bonded oxygen atom, when occurring as a substituent on a carbon atom, replaces two hydrogen atoms on a carbon atom of the parent system. Thus, if a CH2 group is substituted by oxo, it becomes a carbonyl group (C(O), C=O). Just so, if the groups R2 and R3 together are oxo, the group C(R2)-R3 in the cycloalkane ring depicted in formula I becomes a carbonyl group. Oxo groups can also occur on sulfur atoms, such as on ring sulfur atoms in saturated and partially unsaturated heterocydes in which generally, besides a ring sulfur atom, also an S(O) group (S(=O)) and an S(O)2 group (S(=O)2) can be present as hetero ring members. An oxo group cannot occur as a substituent on a carbon atom in an aromatic ring such as in a phenyl group.

The present invention comprises all stereoisomeric forms of the compounds of the formula I, for example all enantiomers and diastereomers including cis/trans isomers. The invention likewise comprises mixtures of two or more stereoisomeric forms, for example mixtures of enantiomers and/or diastereomers including cis/trans isomers, in all ratios. Asymmetric centers contained in the compounds of the formula I, for example the carbon atom in position 2 of the chroman ring or in unsubstituted or substituted alkyl groups, can all independently of each other have S configuration or R configuration. The invention relates to enantiomers, both the levorotatory and the dextrorotatory antipode, in enantiomerically pure form and essentially

enantiomerically pure form, for example with a molar ratio of the two enantiomers of 98:2, or 99:1 , or greater, and in the form of their racemate, i.e. a mixture of the two enantiomers in molar ratio of 1 : 1 , and in the form of mixtures of the two enantiomers in all ratios. The invention likewise relates to diastereomers in the form of pure and essentially pure diastereomers and in the form of mixtures of two or more

diastereomers in all ratios. The invention also comprises all cis/trans isomers of the compounds of the formula I in pure form and essentially pure form, for example with a molar ratio of the cis/trans isomers of 98:2, or 99:1 , or greater, and in the form of mixtures of the cis isomer and the trans isomer in all ratios. Cis/trans isomerism can occur in substituted rings, for example. The preparation of individual stereoisomers, if desired, can be carried out by resolution of a mixture according to customary methods, for example, by chromatography or crystallization, or by use of

stereochemically uniform starting compounds in the synthesis, or by stereoselective reactions. Optionally, before a separation of stereoisomers a derivatization can be carried out. The separation of a mixture of stereoisomers can be carried out at the stage of the compound of the formula I or at the stage of an intermediate in the course of the synthesis. For example, in the case of a compound of the formula I containing an asymmetric center the individual enantiomers can be prepared by preparing the racemate of the compound of the formula I and resolving it into the enantiomers by high pressure liquid chromatography on a chiral phase according to standard procedures, or resolving the racemate of any intermediate in the course of its synthesis by such chromatography or by crystallization of a salt thereof with an optically active amine or acid and converting the enantiomers of the intermediate into the enantiomeric forms of the final compound of the formula I, or by performing an enantioselective reaction in the course of the synthesis. The invention also comprises all tautomeric forms of the compounds of the formula I.

Besides the free compounds of the formula I, i.e. compounds in which acidic and basic groups are not present in the form of a salt, the present invention comprises also salts of the compounds of the formula I, in particular their physiologically acceptable salts, or toxicologically acceptable salts, or pharmaceutically acceptable salts, which can be formed on one or more acidic or basic groups in the compounds

of the formula I, for example on basic heterocyclic moieties. The compounds of the formula I may thus be deprotonated on an acidic group and be used for example as alkali metal salts, for example sodium or potassium salts, or as ammonium salts, for example as salts with ammonia or organic amines or amino acids. Compounds of the formula I comprising at least one basic group may also be prepared and used in the form of their acid addition salts, for example in the form of pharmaceutically acceptable salts with inorganic acids and organic acids, such as salts with

hydrochloric acid and thus be present in the form of the hydrochlorides, for example. Salts can in general be prepared from acidic and basic compounds of the formula I by reaction with an acid or base in a solvent or diluent according to customary procedures. If the compounds of the formula I simultaneously contain an acidic and a basic group in the molecule, the invention also includes internal salts (betaines, zwitterions) in addition to the salt forms mentioned. The present invention also comprises all salts of the compounds of the formula I which, because of low physiological tolerability, are not directly suitable for use as a pharmaceutical, but are suitable as intermediates for chemical reactions or for the preparation of

physiologically acceptable salts, for example by means of anion exchange or cation exchange.

In one embodiment of the invention, the group Ar is phenyl which is unsubstituted or substituted by 1 , 2, 3 or 4, in another embodiment by 1 , 2 or 3, in another

embodiment by 1 or 2 identical or different substituents RO. In another embodiment, Ar is phenyl which is unsubstituted or substituted by 1 substituent RO. In another embodiment Ar is unsubstituted phenyl. In another embodiment, Ar is phenyl which is substituted by 1 , 2, 3 or 4, in another embodiment by 1 , 2 or 3, in another

embodiment by 1 or 2 identical or different substituents RO. In another embodiment, Ar is phenyl which is substituted by 1 substituent RO. If one substituent RO is present in Ar, in one embodiment it is located in position 2, in another embodiment in position 3, in another embodiment in position 4 of the phenyl group. If two substituents RO are present which do not form a ring together with the carbon atoms carrying them, in one embodiment they are located in positions 2 and 3, in another embodiment in positions 2 and 4, in another embodiment in positions 2 and 5, in another

embodiment in positions 2 and 6, in another embodiment in positions 3 and 4, and in another embodiment in positions 3 and 5 of the phenyl group.

The double bond which is present in the mono-unsaturated ring which can be formed by two substituents RO bonded to adjacent ring carbon atoms in Ar together with the carbon atoms carrying them, is present between the said two adjacent ring carbon in the aromatic ring Ar which are common to the ring Ar and the ring formed by the two groups RO, and because of the rules of nomenclature for fused rings is regarded as a double bond present in both rings. The case that two groups RO bonded to adjacent carbon atoms in Ar together with the carbon atoms carrying them form a 5-membered to 7-membered mono-unsaturated ring, which is a monocyclic ring, can in other words be regarded as two groups RO together forming a divalent residue comprising a chain of 3 to 5 atoms of which 0, 1 or 2 are identical or different heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, the terminal atoms of which, which are bonded to the two adjacent ring carbon atoms in Ar, are separated from each other by 1 to 3 atoms. Examples of such divalent residues, from any one or more of which two groups RO bonded to adjacent ring carbon atoms in Ar are selected in one embodiment of the invention, are the residues -CH2-CH2-CH2-, -CH2-CH2-CH2-CH2-, -CH2-CH2-CH2-CH2-CH2-, -O-CH2-CH2_,-CH2-CH2-O-, -O-CH2-O-, -O-CH2-CH2-O-, -O-CH2-CH2-CH2-O-, -NH-CH2-CH2-O-, -O-CH2-CH2-NH-, -S-CH2-CH2-NH- and -NH-CH2-CH2-S-, which can all be substituted on carbon atoms and nitrogen atoms by substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl, for example fluorine and methyl, and can thus also be present, for example, as the divalent residues -O-CF2-O-, -O-C(CH3)2-O-, -N(CH3)-CH2-CH2-O-, -O-CH2-CH2-N(CH3)-, -S-CH2-CH2-N(CH3)- and -N(CH3)-CH2-CH2-S-. In one embodiment of the invention, the ring which can be formed by two groups RO bonded to adjacent ring carbon atoms in Ar together with the carbon atoms carrying them, is a 5-membered or 6-membered, in another embodiment a 5-membered, in another embodiment a 6-membered ring. In one embodiment of the invention, the number of substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl, which can be present in a ring formed by two groups RO bonded to adjacent ring carbon atoms in Ar together with the carbon atoms carrying them, is 1 , 2 or 3, in another embodiment 1 or 2, in another embodiment 1 . In one embodiment of the invention, substituents which can be present in a ring formed by two groups R0 bonded to adjacent ring carbon atoms in Ar together with the carbon atoms carrying them, are fluorine substituents, and in another embodiment they are (Ci-C4)-alkyl substituents, for example methyl substituents, and in another embodiment are substituents in such a ring bonded to a ring nitrogen atom selected from the series consisting of (Ci-C4)-alkyl.

In one embodiment of the invention, the group R0 is selected from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, HO- and (Ci-C6)-alkyl-O-, in another embodiment from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, HO- and (Ci-C6)-alkyl-O-, in another embodiment from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl- and (Ci-C6)-alkyl-O-, in another embodiment from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (Ci-C6)-alkyl-O-and (C3-C7)-cycloalkyl-O-, in another embodiment from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (Ci-C6)-alkyl-O-, in another

embodiment from the series consisting of halogen, (Ci-C6)-alkyl, HO- and (Ci-Ce)-alkyl-O-, in another embodiment from the series consisting of halogen, (Ci-Ce)-alkyl and (Ci-C6)-alkyl-O-, in another embodiment from the series consisting of halogen and (Ci-C6)-alkyl, in another embodiment from the series consisting of halogen, in another embodiment from the series consisting of (Ci-C6)-alkyl, and in another embodiment from the series consisting of (Ci-C6)-alkyl-O-, and in all these

embodiments two groups R1 bonded to adjacent carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 7-membered mono-unsaturated ring which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl.

In one embodiment, R0 is selected from the series consisting of halogen, (C1-C-6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, HO-, (Ci-C6)-alkyl-O-, (C3- C7)-cycloalkyl-O- and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-O-, in another embodiment from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, HO- and (Ci-C6)-alkyl-O-, in another embodiment from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, HO- and (Ci-Ce)-alkyl-O-, in another embodiment from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl- and (Ci-C6)-alkyl-O-, in another embodiment from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (Ci-C6)-alkyl-O- and (C3-C7)-cycloalkyl-O-, in another embodiment from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (Ci-C6)-alkyl-O-, in another embodiment from the series consisting of halogen, (Ci-C6)-alkyl, HO- and (Ci-C6)-alkyl-O-, in another embodiment from the series consisting of halogen, (Ci-Ce)-alkyl and (Ci-C6)-alkyl-O-, in another embodiment from the series consisting of halogen and (Ci-C6)-alkyl, in another embodiment from the series consisting of halogen, in another embodiment from the series consisting of (Ci-C6)-alkyl, and in another embodiment from the series consisting of (Ci-C6)-alkyl-O-.

In one embodiment, a (Ci-Ce)-alkyl group which represents RO or is present in the group (Ci-C6)-alkyl-O- representing RO, is a (Ci-C4)-alkyl group, in another embodiment a (Ci-Cs)-alkyl group, in another embodiment a (Ci-C2)-alkyl group, in another embodiment a methyl group. In one embodiment of the invention, a (C3-C7)-cycloalkyl group which represents RO or is present in RO, is a (C3-C6)-cycloalkyl group, in another embodiment a (C3-C4)-cycloalkyl group, in another embodiment a cyclopropyl group. In one embodiment, halogen representing RO is selected from the series consisting of fluorine and chlorine, in another embodiment it is fluorine.

Examples of groups Ar including the optional substituents RO, from any one or more of which Ar is selected in one embodiment of the invention, are phenyl, i.e.

unsubstituted phenyl, 2-fluoro-phenyl, 3-fluoro-phenyl, 4-fluoro-phenyl, 2-chloro-phenyl, 3-chloro-phenyl, 4-chloro-phenyl, 2-methyl-phenyl (o-tolyl), 3-methyl-phenyl (m-tolyl), 4-methyl-phenyl (p-tolyl), 2-ethyl-phenyl, 3-ethyl-phenyl, 4-ethyl-phenyl, 2-methoxy-phenyl, 3-methoxy-phenyl, 4-methoxy-phenyl, 2-ethoxy-phenyl, 3-ethoxy-phenyl, 4-ethoxy-phenyl, 2-propoxy-phenyl, 3-propoxy-phenyl, 4-propoxy-phenyl, 2-

isopropoxy-phenyl, 3-isopropoxy-phenyl, 4-isopropoxy-phenyl, 2,3-difluoro-phenyl, 2,4-difluoro-phenyl, 2,5-difluoro-phenyl, 2,6-difluoro-phenyl, 3,4-difluoro-phenyl, 3,5-difluoro-phenyl, 2,3-dichloro-phenyl, 2,4-dichloro-phenyl, 2,5-dichloro-phenyl, 2,6-dichloro-phenyl, 3,4-dichloro-phenyl, 3,5-dichloro-phenyl, 2-chloro-3-fluoro-phenyl, 2-chloro-4-fluoro-phenyl, 2-chloro-5-fluoro-phenyl, 2-chloro-6-fluoro-phenyl, 3-chloro-2-fluoro-phenyl, 3-chloro-4-fluoro-phenyl, 3-chloro-5-fluoro-phenyl, 4-chloro-2-fluoro-phenyl, 4-chloro-3-fluoro-phenyl, 5-chloro-2-fluoro-phenyl, 2,3-dimethyl-phenyl, 2,4-di methyl -phenyl, 2,5-dimethyl-phenyl, 2,6-dimethyl-phenyl, 3,4-dimethyl-phenyl, 3,5-dimethyl-phenyl, 2-fluoro-3-methyl-phenyl, 2-fluoro-4-methyl-phenyl, 2-fluoro-5-methyl-phenyl, 2-fluoro-6-methyl-phenyl, 3-fluoro-2-methyl-phenyl, 3-fluoro-4-methyl-phenyl, 3-fluoro-5-methyl-phenyl, 4-fluoro-2-methyl-phenyl, 4-fluoro-3-methyl-phenyl, 5-fluoro-2-methyl-phenyl, 2-chloro-3-methyl-phenyl, 2-chloro-4-methyl-phenyl, 2-chloro-5-methyl-phenyl, 2-chloro-6-methyl-phenyl, 3-chloro-2-methyl-phenyl, 3-chloro-4-methyl-phenyl, 3-chloro-5-methyl-phenyl, 4-chloro-2-methyl-phenyl, 4-chloro-3-methyl-phenyl, 5-chloro-2-methyl-phenyl, 2-fluoro-3-methoxy-phenyl, 2-fluoro-4-methoxy-phenyl, 2-fluoro-5-methoxy-phenyl, 2-fluoro-6-methoxy-phenyl, 3-fluoro-2-methoxy-phenyl, 3-fluoro-4-methoxy-phenyl, 3-fluoro-5-methoxy-phenyl, 4-fluoro-2-nnethoxy-phenyl, 4-fluoro-3-methoxy-phenyl, 5-fluoro-2-methoxy-phenyl, 2-methoxy-3-nnethyl-phenyl, 2-methoxy-4-nnethyl-phenyl, 2-methoxy-5-nnethyl-phenyl, 2-methoxy-6-nnethyl-phenyl, 3-methoxy-2-nnethyl-phenyl, 3-methoxy-4-nnethyl-phenyl, 3-methoxy-5-nnethyl-phenyl, 4-methoxy-2-nnethyl-phenyl, 4-methoxy-3-nnethyl-phenyl, 5-methoxy-2-nnethyl-phenyl .

In one embodiment of the invention, the group R1 is hydrogen or one or more fluorine substituents. I.e., in this embodiment the cycloalkane ring depicted in formula I is unsubstituted or substituted by one or more fluorine substituents, apart from the groups R2 and R3 and the oxygen atom linking the cycloalkane ring to the chroman ring. In another embodiment, the group R1 is hydrogen or one or more (Ci-C4)-alkyl substituents. I.e., in this embodiment the cycloalkane ring depicted in formula I is unsubstituted or substituted by one or more (Ci-C4)-alkyl substituents, apart from the groups R2 and R3 and the oxygen atom linking the cycloalkane ring to the chroman ring. In another embodiment, the group R1 is hydrogen. I.e., in this embodiment the cydoalkane ring depicted in formula I is unsubstituted, or in other words carries hydrogen atoms only, apart from the groups R2 and R3 and the oxygen atom linking the cydoalkane ring to the chroman ring. In one embodiment, the number of fluorine atoms and/or (Ci-C4)-alkyl groups representing R1 is 1 , 2, 3 or 4, in another embodiment 1 , 2 or 3, in another embodiment 1 or 2, in another embodiment 1 . In one embodiment, (Ci-C4)-alkyl representing R1 is (Ci-C3)-alkyl, in another

embodiment (Ci-C2)-alkyl, in another embodiment methyl. In one embodiment, the ring carbon atom of the cydoalkane ring depicted in formula I which carries the oxygen atom linking the ring to the chroman ring, does not carry a group R1 which is fluorine or (Ci-C4)-alkyl, i.e. this embodiment the said ring carbon atom carries a hydrogen atom.

In one embodiment of the invention, the group R2 is selected from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-O-, (Ci-C6)-alkyl-C(O)-O-, phenyl-C(O)-O-, Het1 -C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-O-, (Ci-C6)-alkyl-C(O)-O-, Het1 -C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-C(O)-O-, Het1 -C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-C(O)-O-, Het1 -C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (d-C6)-alkyl, HO-, (Ci-C6)-alkyl-O-, (Ci-C6)-alkyl-C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-O-, (Ci-C6)-alkyl-C(O)-O-, Het1 -C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)-and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-Ce)-alkyl, HO-, (Ci-C6)-alkyl-C(O)-O-, Het1 -C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-0-, R5-N(R6)-, R7-C(0)-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, R5-N(R6)-, R7-C(0)-N(R8)-, R7-S(O)2-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, R5-N(R6)-, R7-C(0)-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (d-C6)-alkyl, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, R5-N(R6)-, R7-C(0)-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (CrC6)-alkyl, R5-N(R6)-, R7-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-O-, (Ci-C6)-alkyl-C(O)-O-, phenyl-C(O)-O- and Het1 -C(O)-O-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-C(0)-0 and Het1 -C(O)-O-, in another embodiment from the series consisting of HO-, (Ci-C6)-alkyl-O-, (Ci-C6)-alkyl-C(0)-0- and Het1 -C(O)-O-, in another embodiment from the series consisting of HO-, (Ci-C6)-alkyl-C(O)-O- and Het1 -C(O)-O-, wherein in all these embodiments (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, or in all these embodiments R2 and R3 together are oxo.

In one embodiment, R2 is selected from the series consisting of (CrC6)-alkyl, HO-, (Ci-C6)-alkyl-C(0)-0-, Het1 -C(0)-0-, R5-N(R6)-, R7-C(0)-N(R8)-, R7-S(O)2-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, R5-N(R6)-, R7-C(0)-N(R8)-, R7-S(O)2-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-C(0)-0-, Het1 -C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, HO-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)-and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (C1-C-6)-alkyl, HO-, R5-N(R6)-, R7-C(0)-N(R8)-, R7-S(O)2-N(R8)- and R5-N(R6)-C(0)-, in another embodiment from the series consisting of (CrC6)-alkyl, HO-, R5-N(R6)-, R7-C(O)-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2- N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-C6)-alkyl, R5-N(R6)-, R7-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another

embodiment from the series consisting of (CrC6)-alkyl, R5-N(R6)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of R5-N(R6)-, R7-C(O)-N(R8)- and R7-S(O)2-N(R8)-, in another embodiment from the series consisting of R5-N(R6)-, R7-C(O)-N(R8)- and R5-N(R6)-C(O)-, in another embodiment from the series consisting of (Ci-Ce)-alkyl and R5-N(R6)-, in another embodiment from the series consisting of (Ci-Ce)-alkyl and R5-N(R6)-C(O)-, in another embodiment from the series consisting of R5-N(R6)- and R5-N(R6)-C(O)-, wherein in all these embodiments (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20.

In one embodiment, R2 is (Ci-Ce)-alkyl which is unsubstituted or substituted by one or more identical or different substituents R20. In another embodiment, R(2) is R5-N(R6)- and the compounds of the formula I thus are compounds of the formula la.

In another embodiment, R(2) is R7-C(O)-N(R8)- and the compounds of the formula I thus are compounds of the formula lb.

In another embodiment, R(2) is R7-S(O)2-N(R8)- and the compounds of the formula I thus are compounds of the formula lc.

In another embodiment, R(2) is R5-N(R6)-C(O)- and the compounds of the formula I thus are compounds of the formula Id.

The groups Ar, R1 , R3 to R8 and the numbers p and q in the compounds of the formulae la, lb, Ic and Id are defined as in the compounds of the formula I.

In one embodiment, the number of substituents R20 in a substituted (Ci-C6)-alkyl group which represents R2 or is present in the groups (Ci-C6)-alkyl-O- or (d-Ce)-alkyl-C(O)-O- representing R2, is 1 , 2, 3 or 4, in another embodiment 1 , 2 or 3, in another embodiment 1 or 2, in another embodiment 1. In one embodiment, a (Ci-Ce)-alkyl group which represents R2, is substituted by one or more identical or different substituents R20, i.e. it is not unsubstituted. In one embodiment, a (Ci-Ce)-alkyl group which represents R2 is substituted by one or more identical or different substituents R20, one of which is bonded to the carbon atom of the alkyl group which is bonded to the cycloalkane ring depicted in formula I, i.e. in position 1 of the alkyl group. In one embodiment, a (Ci-Ce)-alkyl group which represents R2 or is present in the groups (Ci-C6)-alkyl-O- or (Ci-C6)-alkyl-C(O)-O- representing R2, is a (d-C4)-alkyl group, in another embodiment a (Ci-Cs)-alkyl group, in another embodiment a (Ci-C2)-alkyl group, in another embodiment a methyl group, which are all

unsubstituted or substituted by one or more identical or different substituents R20, and in one embodiment are substituted by one or more identical or different substituents R20, wherein in one embodiment the number of substituents R20 is 1 , 2 or 3, in another embodiment 1 or 2, and in another embodiment 1. In one

embodiment, a (Ci-C6)-alkyl group which represents R2 is a methyl group which is substituted by one substituent R20, and in this embodiment the group R2 thus is the group R20-CH2-.

In one embodiment of the invention, the group R3 is hydrogen, in another

embodiment it is (Ci-C6)-alkyl, which is unsubstituted or substituted by one or two identical or different substituents selected from the series consisting of (C3-C7)-cycloalkyl, phenyl, HO- and (Ci-C4)-alkyl-O-, wherein alkyl groups representing R3, like alkyl groups in general, can independently of these specified substituents be substituted by one or more fluorine substituents. In one embodiment, the number of substituents selected from the series consisting of (C3-C7)-cycloalkyl, phenyl, HO-and (Ci-C4)-alkyl-O- in a substituted alkyl group representing R3 is one. In one embodiment, an alkyl group representing R3 is not substituted by substituents selected from the series consisting of (C3-C7)-cycloalkyl, phenyl, HO- and (Ci-C4)-alkyl-O-. In one embodiment, the substituents in an alkyl group representing R3 are selected from the series consisting of (C3-C7)-cycloalkyl, phenyl and (Ci-C4)-alkyl-O-, in another embodiment from the series consisting of (C3-C7)-cycloalkyl and phenyl, and in another embodiment they are phenyl groups. In one embodiment, a (C1-C6)-alkyl group representing R3 is a (Ci-C4)-alkyl group, in another embodiment a (Ci-Cs)-alkyl group, in another embodiment a (Ci-C2)-alkyl group, in another embodiment a methyl group. In one embodiment, R2 and R3 have their individual meanings, but together are not oxo. In another embodiment, R2 and R3 together are oxo.

As indicated above, in the free binding sites of the chroman ring, i.e. binding sites in positions 2, 3, 4, 5, 7 and 8 of the chroman ring which are not occupied by bonds within the ring or the bond to the group Ar, hydrogen atoms or substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O- can be present which represent groups R4. In one embodiment of the invention, in the free binding site in position 2 of the chroman ring, i.e. the free binding site of the ring carbon atom which carries the group Ar, a hydrogen atom is present, and in the free binding sites in positions 3, 4, 5, 7 and 8 of the chroman ring hydrogen atoms or substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O- are present. In another embodiment of the invention, in the free binding sites in positions 2, 3 and 4 of the chroman ring hydrogen atoms are present, and in the free binding sites in positions 5, 7 and 8 of the chroman ring hydrogen atoms or substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O- are present. In another embodiment of the invention, in the free binding sites in positions 2 and 5 of the chroman ring hydrogen atoms are present, and in the free binding sites in positions 3, 4, 7 and 8 of the chroman ring hydrogen atoms or substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O- are present. In another embodiment of the invention, in the free binding sites in positions 2, 5, 7 and 8 of the chroman ring hydrogen atoms are present, and in the free binding sites in positions 3 and 4 of the chroman ring hydrogen atoms or substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O- are present. In one embodiment, the number of groups R4 which are different from hydrogen, i.e. the number of substituents R4 which are selected from halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-, is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , and in another embodiment it is 0, and in the latter embodiment thus no groups R4 which are different from hydrogen are present in the chroman ring, and hydrogen atoms are present in all its free binding sites. In one embodiment, R4 is hydrogen or one or more identical or different substituents selected from the series consisting of halogen and (Ci-C4)-alkyl, in another embodiment R4 is hydrogen or one or more identical or different substituents selected from the series consisting of fluorine, chlorine and (Ci-C4)-alkyl. In one embodiment, R4 in the free binding sites in positions 2, 3 and 4 of the chroman ring is hydrogen or one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl, in another embodiment R4 in the free binding sites in positions 2, 3 and 4 of the chroman ring is hydrogen or one or more identical or different substituents selected from the series consisting of (Ci-C4)-alkyl, and R4 in the free binding sites in positions 5, 7 and 8 of the chroman ring is hydrogen or one or more identical or different substituents selected from the series consisting of

halogen, (Ci-C4)-alkyl and (CrC4)-alkyl-O-, in another embodiment R4 in the free binding sites in positions 5, 7 and 8 of the chroman ring is hydrogen or one or more identical or different substituents selected from the series consisting of halogen and (Ci-C4)-alkyl, in another embodiment R4 in the free binding sites in positions 5, 7 and 8 of the chroman ring is hydrogen or one or more identical or different substituents selected from the series consisting of halogen. In one embodiment of the invention, a (Ci-C4)-alkyl group representing R4 or present in R4 is (Ci-C2)-alkyl, in another embodiment it is methyl.

In one embodiment of the invention, R5 and R6 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C6-Cio)-bicycloalkyl, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of hydrogen and (Ci-C6)-alkyl, wherein in all these embodiments (C1-C6)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and Het1 is unsubstituted or substituted by one or more identical or different substituents R22, or the groups R5 and R6, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic, saturated or partially unsaturated

heterocycle which, in addition to the nitrogen atom carrying R5 and R6, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R21 .

In one embodiment, R5 and R6 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, (Ce-Cio)-bicycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C6-Cio)-bicycloalkyl, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, in another embodiment from the series consisting of hydrogen, (Ci-Ce)-alkyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of hydrogen and (Ci-C6)-alkyl, wherein in all these embodiments (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and Het1 is unsubstituted or substituted by one or more identical or different substituents R22.

In one embodiment of the invention, one of the groups R5 and R6 is selected from the series consisting of hydrogen and (Ci-C6)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C4)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C2)-alkyl, in another embodiment from the series consisting of hydrogen and methyl, and in another embodiment is hydrogen, and the other of the groups R5 and R6 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl, phenyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C6-Cio)-bicycloalkyl, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, in another embodiment from the series consisting of hydrogen, (Ci-Ce)-alkyl and (C3-C7)-

cycloalkyl, in another embodiment from the series consisting of hydrogen and (Ci-C6)-alkyl, wherein in all these embodiments (Ci-C6)-alkyl, (Ci-C4)-alkyl, (Ci-C2)-alkyl and methyl representing R5 or R6 is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and Het1 is unsubstituted or substituted by one or more identical or different substituents R22, or the groups R5 and R6, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic, saturated or partially unsaturated heterocycle which, in addition to the nitrogen atom carrying R5 and R6, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R21 .

In one embodiment of the invention, one of the groups R5 and R6 is selected from the series consisting of hydrogen and (Ci-C6)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C4)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C2)-alkyl, in another embodiment from the series consisting of hydrogen and methyl, and in another embodiment is hydrogen, and the other of the groups R5 and R6 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-C6)-alkenyl, (C3-C7)-cycloalkyl, (C6-Ci0)-bicycloalkyl, phenyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C6-Cio)-bicycloalkyl, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, in another embodiment from the series consisting of hydrogen, (Ci-Ce)-alkyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of hydrogen and (Ci-C6)-alkyl, wherein in all these embodiments (Ci-C6)-alkyl, (Ci-C4)-alkyl, (Ci-C2)-alkyl and methyl representing R5 or R6 is unsubstituted or substituted by one or more

identical or different substituents R20, and (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and Het1 is unsubstituted or substituted by one or more identical or different substituents R22. In one embodiment, R5 and R6 both are hydrogen.

In one embodiment of the invention, one of the groups R5 and R6 is selected from the series consisting of hydrogen and (Ci-C6)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C4)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C2)-alkyl, in another embodiment from the series consisting of hydrogen and methyl, and in another embodiment is hydrogen, and the other of the groups R5 and R6 is selected from the series consisting of (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl, phenyl, Het1 and Het2, in another embodiment from the series consisting of (Ci-C6)-alkyl, (C2-C6)-alkenyl, (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl, Het1 and Het2, in another

embodiment from the series consisting of (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of (Ci-Ce)-alkyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C6-Cio)-bicycloalkyl, in another embodiment from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, in another embodiment from the series consisting of (Ci-Ce)-alkyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of (Ci-C6)-alkyl, wherein in all these embodiments (Ci-C6)-alkyl, (Ci-C4)-alkyl, (Ci-C2)-alkyl and methyl representing R5 or R6 is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and Het1 is unsubstituted or substituted by one or more identical or different substituents R22, or the groups R5 and R6, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic, saturated or partially unsaturated heterocycle which, in addition to the nitrogen atom carrying R5 and R6, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R21 .

In one embodiment of the invention, one of the groups R5 and R6 is selected from the series consisting of hydrogen and (CrC6)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C4)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C2)-alkyl, in another embodiment from the series consisting of hydrogen and methyl, and in another embodiment is hydrogen, and the other of the groups R5 and R6 is selected from the series consisting of (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl, phenyl, Het1 and Het2, in another embodiment from the series consisting of (Ci-C6)-alkyl, (C2-C6)-alkenyl, (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl, Het1 and Het2, in another

embodiment from the series consisting of (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of (Ci-Ce)-alkyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C6-Cio)-bicycloalkyl, in another embodiment from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, in another embodiment from the series consisting of (Ci-Ce)-alkyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of (Ci-C6)-alkyl, wherein in all these embodiments (Ci-C6)-alkyl, (Ci-C4)-alkyl, (Ci-C2)-alkyl and methyl representing R5 or R6 is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl, (C6-Ci0)-bicycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and Het1 is unsubstituted or substituted by one or more identical or different substituents R22.

In one embodiment of the invention, a (Ci-Ce)-alkyl group representing R5 or R6 is a (Ci-C4)-alkyl group, in another embodiment a (Ci-Cs)-alkyl group, in another embodiment a (Ci-C2)-alkyl group, in another embodiment any one or more groups selected from the series consisting of butyl, propyl, isopropyl, ethyl and methyl, for example selected from the series consisting of methyl, ethyl and propyl, which are all unsubstituted or substituted by one or more, for example 1 , 2 or 3, or 1 or 2, or 1 , identical or different substituents R20, which substituents can be present in any positions, for example in position 1 and/or in position 2 of an ethyl group representing R5 or R6, or in position 1 and/or in position 2 and/or in position 3 of a propyl group representing R5 or R6.

In one embodiment of the invention, the number of identical or different substituents R20 which are optionally present in a (Ci-C6)-alkyl group representing R5 or R6, is 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of groups R24 representing substituents R20, which are optionally present in a (Ci-C6)-alkyl group representing R5 or R6 besides any other substituents R20, is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0 (zero), i.e., in the latter embodiment R20 is as defined, but is not R24. In one embodiment, the number of oxo groups representing substituents R20, which are optionally present in a (Ci-Ce)-alkyl group representing R5 or R6 besides any other substituents R20, is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of groups selected from the series consisting of R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2- representing substituents R20, which are optionally present in a (Ci-Ce)-alkyl group representing R5 or R6 besides any other substituents R20, is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0.

In one embodiment of the invention, the number of identical or different substituents R21 which are optionally present in (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl and Het2 groups representing R5 or R6, is independently of each other 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 . In one embodiment, the number of groups R24 representing substituents R21 , which are optionally present in (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl and Het2 groups representing R5 or R6 besides any other substituents R21 , is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of oxo groups representing substituents R21 , which are optionally present in (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl and Het2 groups representing R5 or R6 besides any other substituents R21 , is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of groups selected from the series consisting of R34-O-C(O)-(Ci-C4)-alkyl-, R31 -N(R32)-C(O)-, R34-O-C(O)-

and R31 -N(R32)-S(O)2- representing substituents R21 , which are optionally present in (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl and Het2 groups representing R5 or R6 besides any other substituents R21 , is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0.

In one embodiment of the invention, the number of identical or different substituents R22 which are optionally present in phenyl and Het1 groups representing R5 or R6, is independently of each other 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , in another

embodiment it is 0. In one embodiment, the number of groups selected from the series consisting of R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-representing substituents R22, which are optionally present in phenyl and Het1 groups representing R5 or R6 besides any other substituents R22, is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0.

The monocyclic heterocycle which can be formed by the groups R5 and R6 together with the nitrogen atom carrying them, which heterocycle is thus bonded via a ring nitrogen atom, can be 4-membered, 5-membered, 6-membered or 7-membered. In one embodiment of the invention, this heterocycle is 4-membered to 6-membered, in another embodiment it is 5-membered to 6-membered, in another embodiment it is 5-membered, in another embodiment it is 6-membered. In one embodiment, a heterocycle formed by the groups R5 and R6 together with the nitrogen atom carrying them, is saturated or contains one double bond within the ring, in another embodiment it is saturated. In one embodiment, the further ring heteroatom which is optionally present in a heterocycle formed by the groups R5 and R6 together with the nitrogen atom carrying them, is selected from the series consisting of nitrogen and oxygen, in another embodiment it is a nitrogen atom, and in another embodiment it is an oxygen atom. Examples of heterocyclic groups, from any one or more of which the heterocyclic groups formed by the groups R5 and R6 together with the nitrogen atom carrying them is selected in one embodiment of the invention, are azetidin-1 -yl, pyrrolidin-1 -yl, piperidin-1 -yl, azepan-1 -yl, imidazolidin-1 -yl, oxazolidin-3-yl, thiazolidin-3-yl, piperazin-1 -yl, morpholin-4-yl and thiomorpholin-4-yl, which can all be unsubstituted or substituted by one or more identical or different substituents R21 .

In one embodiment of the invention, the number of identical or different substituents R21 which are optionally present in a heterocycle formed by R5 and R6 together with the nitrogen atom carrying them, is 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of groups R24 representing substituents R21 , which are optionally present in a heterocycle formed by R5 and R6 together with the nitrogen atom carrying them besides any other substituents R21 , is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one

embodiment, the number of oxo groups representing substituents R21 , which are optionally present in a heterocycle formed by R5 and R6 together with the nitrogen atom carrying them besides any other substituents R21 , is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of groups selected from the series consisting of R34-O-C(O)-(CrC4)-alkyl-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(0)2- representing substituents R21 , which are optionally present in a heterocycle formed by R5 and R6 together with the nitrogen atom carrying them besides any other substituents R21 , is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0.

In one embodiment of the invention, R7 is in any of its occurrences, independently of other occurrences, selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of (Ci-Ce)-alkyl, (C3-C7)-cycloalkyl and Het2, in another embodiment from the series consisting of (Ci-C6)-alkyl, Het1 and Het2, in another embodiment from the series consisting of (C3-C7)-cycloalkyl, Het1 and Het2, in another embodiment from the series consisting of (Ci-Ce)-alkyl and Het2, in another embodiment from the series consisting of (C3-C7)-cycloalkyl and Het2, in another embodiment from the series consisting of phenyl and Het1 , in another embodiment it is (Ci-C6)-alkyl, in another embodiment it is (C3-C7)-cycloalkyl, in another embodiment is phenyl, in another embodiment is Het1 , and in another embodiment is Het2, wherein all groups (C1-C6)-

alkyl are unsubstituted or substituted by one or more identical or different substituents R20, all groups (C3-C7)-cycloalkyl and Het2 are unsubstituted or substituted by one or more identical or different substituents R2, and all groups phenyl and Het1 are unsubstituted or substituted by one or more identical or different substituents R22.

In one embodiment of the invention, the number of identical or different substituents R20 which are optionally present in a (Ci-Ce)-alkyl group representing R7, is 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of groups R24 representing substituents R20, which are optionally present in a (Ci-C6)-alkyl group representing R7 besides any other substituents R20, is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0 (zero), i.e., in the latter embodiment R20 is as defined, but is not R24. In one embodiment, the number of oxo groups representing substituents R20, which are optionally present in a (Ci-Ce)-alkyl group representing R7 besides any other substituents R20, is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of groups selected from the series consisting of R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2- representing substituents R20, which are optionally present in a (Ci-C6)-alkyl group representing R7 besides any other substituents R20, is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0.

In one embodiment of the invention, the number of identical or different substituents R21 which are optionally present in (C3-C7)-cycloalkyl and Het2 groups representing R7, is independently of each other 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of groups R24 representing substituents R21 , which are optionally present in (C3-C7)-cycloalkyl and Het2 groups representing R7 besides any other substituents R21 , is 1 or 2, in another

embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of oxo groups representing substituents R21 , which are optionally present in (C3-C7)-cycloalkyl and Het2 groups representing R7 besides any other substituents R21 , is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0. In one embodiment, the number of groups selected from the series consisting of R34-O-C(O)-(Ci-C4)-alkyl-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2- representing substituents R21 , which are optionally present in (C3-C7)-cycloalkyl and Het2 groups representing R7 besides any other substituents R21 , is 1 or 2, in another

embodiment it is 1 , in another embodiment it is 0.

In one embodiment of the invention, the number of identical or different substituents R22 which are optionally present in phenyl and Het1 groups representing R7, is independently of each other 1 , 2, 3 or 4, in another embodiment it is 1 , 2 or 3, in another embodiment it is 1 or 2, in another embodiment it is 1 , in another

embodiment it is 0. In one embodiment, the number of groups selected from the series consisting of R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-representing substituents R22, which are optionally present in phenyl and Het1 groups representing R7 besides any other substituents R22, is 1 or 2, in another embodiment it is 1 , in another embodiment it is 0.

In one embodiment of the invention, R8 is in any of its occurrences, independently of its other occurrences, selected from the series consisting of hydrogen and (C1-C3)-alkyl, in another embodiment from the series consisting of hydrogen and (C1-C2)-alkyl, in another embodiment from the series consisting of hydrogen and methyl, and in another embodiment R8 is hydrogen.

In one embodiment of the invention, R9 is selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-, in another embodiment from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, in another embodiment from the series consisting of (Ci-Ce)-alkyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of (Ci-C6)-alkyl, and in another embodiment from the series consisting of (Ci-C4)-alkyl.

In one embodiment of the invention, R10 is selected from the series consisting of hydrogen, (CrC6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-, in another embodiment from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, in another embodiment from the series consisting of hydrogen, (Ci-Ce)-alkyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of hydrogen and (Ci-Ce)-alkyl, in another embodiment from the series consisting of hydrogen and (Ci-C4)-alkyl, in another embodiment from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-, in another embodiment from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, in another embodiment from the series consisting of (Ci-Ce)-alkyl and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of (Ci-C6)-alkyl, and in another embodiment from the series consisting of (Ci-C4)-alkyl.

In one embodiment of the invention, R20 is selected from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, (C3-C7)-cycloalkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-, in another embodiment from the series consisting of R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl- O-, HO-S(O)2-O-, (ΗΟ)2Ρ(Ο)-Ο-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)- and R31 -N(R32)-S(O)2-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)- and R31 -N(R32)-C(O)-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-and R34-O-C(O)-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)- and (Ci-C6)-alkyl-S(O)2-N(R32)-, in another embodiment from the series consisting of R31 -N(R32)-, R33-C(O)-N(R32)- and (Ci-C6)-alkyl-S(O)2-N(R32)-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n- and R31 -N(R32)-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O- and (HO)2P(O)-O-, in another embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O- and (HO)2P(O)-O-CH2-O-C(O)-O-, in another

embodiment from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, HO-S(O)2-O- and (HO)2P(O)-O-, in another embodiment from the series consisting of HO-, (Ci-C6)-alkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O- and (HO)2P(O)-O-, in another embodiment from the series consisting of HO-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O- and (HO)2P(O)-O-, in another embodiment from the series consisting of HO-, HO-S(O)2-O- and (HO)2P(O)-O-, in another embodiment from the series consisting of HO- and (HO)2P(O)-O-, in another embodiment from the series consisting of R24, HO- and (HO)2P(O)-O-, in another embodiment from the series consisting of R24 and HO-, and in another embodiment R20 is HO-, and in another

embodiment R20 is R24, wherein in case that more than one substituent R20 is present, the substituents R20 are independently of one another defined as in any of these embodiments.

In one embodiment of the invention, R21 is selected from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-> R34-O-C(O)-(Ci-C4)-alkyl-, R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, (C3-C7)-cycloalkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-, in another embodiment from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (d-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)- and R34-O-C(O)-, in another embodiment from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, R31 -N(R32)-, R33-C(O)-N(R32)- and (Ci-C6)-alkyl-S(O)2-N(R32)-, in another embodiment from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O- and R31 -N(R32)-, in another embodiment from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, HO-S(O)2-O-,

(HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O- and R31 -N(R32)-, in another

embodiment from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O- and (HO)2P(O)-O-CH2-O-C(O)-O-, in another embodiment from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, R34-O-C(O)-(Ci-C4)-alkyl-, R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-,

HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)- and R31 -N(R32)-C(O)-, in another embodiment from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, R34- O-C(O)-(Ci-C4)-alkyl-, R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-and R31 -N(R32)-C(O)-, in another embodiment from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, R31 -N(R32)-, R33-C(O)-N(R32)-and R31 -N(R32)-C(O)-, in another embodiment from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, R31 -N(R32)-, R33-C(O)-N(R32)-and R31 -N(R32)-C(O)-, in another embodiment from the series consisting of (Ci-C4)-alkyl, fluorine, HO-, oxo, HO-S(O)2-O-, (HO)2P(O)-O- and (HO)2P(O)-O-CH2-O-C(O)-O-, in another embodiment from the series consisting of (Ci-C4)-alkyl, fluorine, HO-, oxo, HO-S(O)2-O- and (HO)2P(O)-O-, in another embodiment from the series consisting of (Ci-C4)-alkyl, fluorine, HO-, oxo and (HO)2P(O)-O-, in another embodiment from the series consisting of (Ci-C4)-alkyl, fluorine, HO- and oxo, in another embodiment from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, fluorine, HO-, (Ci-C6)-alkyl-O-, HO-S(O)2-O- and (HO)2P(O)-O-, in another

embodiment from the series consisting of (Ci-C4)-alkyl, fluorine, HO-, HO-S(O)2-O-and (HO)2P(O)-O-, in another embodiment from the series consisting of (Ci-C4)-alkyl, fluorine, HO-, HO-S(O)2-O- and (HO)2P(O)-O-, in another embodiment from the series consisting of (Ci-C4)-alkyl, fluorine, HO- and (HO)2P(O)-O-, in another embodiment from the series consisting of (Ci-C4)-alkyl, fluorine and HO-, wherein in case that more than one substituent R21 is present, the substituents R21 are independently of one another defined as in any of these embodiments. In one embodiment, substituents R21 which are bonded to a ring nitrogen atom, as can occur in the case of the group Het2 or the ring which can be formed by R5 and R6 together with the nitrogen atom carrying them, are selected from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl- and R24, wherein R24 is bonded via a ring carbon atom, in another embodiment from the series consisting of (Ci-C4)-alkyl.

In one embodiment of the invention, R22 is selected from the series consisting of halogen, (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, (C3-C7)-cycloalkyl, HO-, oxo, (Ci-C6)-alkyl- O-, HO-S(O)2-O-, (ΗΟ)2Ρ(Ο)-Ο-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, R33-O-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, NC-, R31 -N(R32)-C(O)- and R31 -N(R32)-S(O)2-, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, (C3-C7)-cycloalkyl, HO-, oxo, (Ci-C6)-alkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, NC- and R31 -N(R32)-C(O)-, in another

embodiment from the series consisting of halogen, (Ci-C4)-alkyl, HO-, oxo, (Ci-Ce)-alkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, NC- and R31 -N(R32)-C(O)-, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, HO-, (Ci-C6)-alkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, R31 -N(R32)-, NC- and R31 -N(R32)-C(O)-, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, (C3-C7)-cycloalkyl, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, R33-O-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, NC-, R33-C(O)- and R31 -N(R32)-C(O)-, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, (C3-C7)-cycloalkyl, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, NC-, R33-C(O)- and R31 -N(R32)-C(O)-, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, (C3-C7)-cycloalkyl, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)- and R31 -N(R32)-C(O)-, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, HO-, (Ci-C6)-alkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, R31 -N(R32)- and NC-, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, HO-, (Ci-C6)-alkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O- and NC-, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, HO-, (Ci-C6)-alkyl-O-, (HO)2P(O)-O- and NC-, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl, (Ci-C6)-alkyl-O- and NC-, in another embodiment from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-Ce)-alkyl-O-, in another embodiment from the series consisting of halogen and (Ci-C4)-alkyl, wherein in case that more than one substituent R22 is present, the substituents R22 are independently of one another defined as in any of these embodiments. In

one embodiment, substituents R22 which are bonded to a ring nitrogen atom, as can occur in the case of the group Het1 and R24, are selected from the series consisting (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl- and (C3-C7)-cycloalkyl, in another embodiment from the series consisting of (Ci-C4)-alkyl.

The monocyclic or bicyclic group R24 can be 3-membered, 4-membered, 5-membered, 6-membered, 7-membered, 8-membered, 9-membered or 10-membered. In one embodiment of the invention, a monocyclic group R24 is 3-membered, 4-membered, 5-membered, 6-membered or 7-membered, and a bicyclic group R24 is 6-membered, 7-membered, 8-membered, 9-membered or 10-membered. In one embodiment of the invention, R24 is a monocyclic ring, in another embodiment a 3-membered to 7-membered monocyclic ring, in another embodiment a 3-membered to 6-membered monocyclic ring, in another embodiment a 4-membered to 6-membered monocyclic ring, in another embodiment a 5-membered or 6-membered monocyclic ring, in another embodiment a bicyclic ring, in another embodiment a 6-membered to 10-membered bicyclic ring, in another embodiment a 7-membered to 10-membered bicyclic ring, in another embodiment a 7-membered to 9-membered bicyclic ring. The two cycles in a bicyclic group R24 can be fused or form a bridged bicycle or a spirocycle. The monocyclic or bicyclic ring R24 can be saturated, i.e. not contain any double bonds within the ring system, or be partially unsaturated, i.e. contain one or more double bonds within the ring system, for example, one two, three or four double bonds, or one, two or three double bonds, or one or two double bonds, or one double bond, but is not fully aromatic, i.e. it does not contain a cyclic system of six

delocalized pi electrons in the case of a monocycle or of ten delocalized pi electrons in the case of a bicycle, or it can be aromatic. The number of double bonds which can be present in a ring, depends on the type of the ring system and the ring size. Partially unsaturated rings R24 include also bicyclic ring systems in which one of the two cycles is aromatic and the other is not aromatic. In one embodiment, R24 is a saturated or aromatic ring, in another embodiment a saturated ring, in another embodiment an aromatic ring.

The ring R24 can be carbocyclic, i.e. contain 0 (zero) ring heteroatoms, or heterocyclic, i.e. contain 1 , 2, 3 or 4 identical or different ring heteroatoms. In one embodiment, the number of ring heteroatoms which are present in R24 is 0, 1 , 2 or 3, in another embodiment 0, 1 or 2, in another embodiment 0 or 1 . In one embodiment of the invention, R24 is in any of its occurrences, independently of its other

occurrences, a carbocyclic ring, and in another embodiment it is a heterocyclic ring. In a bicyclic ring R24, ring heteroatoms can be present in one of the two rings or in both rings in any suitable positions. In bridged and fused bicyclic rings, ring nitrogen atoms can also be present in bridgehead positions and fusion positions. In one embodiment of the invention, a 3-membered ring R24 is carbocyclic ring, specifically a cyclopropane ring, i.e., in this case the group R24 is a cyclopropyl group. In one embodiment, ring heteroatoms which are present in R24, are selected from the series consisting of nitrogen and oxygen, in another embodiment from the series consisting of nitrogen and sulfur, and in another embodiment they are nitrogen atoms. R24 can be bonded via any ring carbon atom and any ring nitrogen atom which has a free binding position. In a bicyclic group R24, the ring atom via which R24 is bonded, can be present in a saturated ring, a partially unsaturated ring or in an aromatic ring. In one embodiment of the invention, R24 is bonded in any of its occurrences, independently of its other occurrences, via a ring carbon atom, in another

embodiment via a ring nitrogen atom.

Types of cyclic groups which are comprised by the definition of R24, are cycloalkyl groups, bicycloalkyl groups, phenyl groups, naphthyl groups including naphthalen-1 -yl groups and naphthalen-2-yl groups, partially hydrogenated naphthyl groups such as 1 ,2,3,4-tetrahydronaphthalenyl groups, monocyclic and bicyclic aromatic

heterocyclic groups such as the group Het1 , for example, and saturated and partially unsaturated monocyclic and bicyclic heterocyclic groups such as the group Het2. The explanations given above and below with respect to such groups apply

correspondingly to such groups representing R24, as do the explanations given above with respect to heterocyclic groups in general. Examples of groups, from any one or more of which the group R24 is selected in one embodiment of the invention, are the groups of the following formulae,

50

Claims

1 . A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof,

wherein

Ar is phenyl which is unsubstituted or substituted by one or more identical or different substituents RO;

RO is selected from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O- and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-O-, and two groups RO bonded to adjacent ring carbon atoms in Ar, together with the carbon atoms carrying them, can form a 5-membered to 7-membered mono-unsaturated ring which comprises 0, 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R1 is hydrogen or one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R2 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl, HO-, (Ci-Ce)-alkyl-O-, (Ci-C6)-alkyl-C(O)-O-, phenyl-C(O)-O-, Het1 -C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, wherein (d-

C6)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20;

R3 is selected from the series consisting of hydrogen and (Ci-C6)-alkyl, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or two identical or different

substituents selected from the series consisting of (C3-C7)-cycloalkyl, phenyl, HO-and (Ci-C4)-alkyl-O-;

or the groups R2 and R3 together are oxo;

R4 is hydrogen or one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-;

R5 and R6 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-Ce)-alkenyl, (C3-C7)-cycloalkyl, (C6-Cio)-bicycloalkyl, phenyl, Het1 and Het2, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl, (C6-C10)-bicycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and phenyl and Het1 all are unsubstituted or substituted by one or more identical or different substituents R22,

or the groups R5 and R6, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic, saturated or partially unsaturated

heterocycle which, in addition to the nitrogen atom carrying R5 and R6, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R21 ;

R7 is selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, phenyl, Het1 and Het2, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and phenyl and Het1 all are unsubstituted or substituted by one or more identical or different substituents R22;

R8 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl;

R9 is selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, phenyl-(Ci-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-;

R10 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-> phenyl-(Ci-C4)-alkyl- and Het1 -(d-C4)-alkyl-;

R20 is selected from the series consisting of R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, (C3-C7)-cycloalkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-;

R21 is selected from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, R34-O-C(O)-(Ci-C4)-alkyl-, R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-,

(HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, (C3-C7)-cycloalkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-;

R22 is selected from the series consisting of halogen, (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, (C3-C7)-cycloalkyl, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, (C3-C7)-cycloalkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, R33-O-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, NC-, R33-C(O)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-;

R24 is a 3-membered to 10-membered, monocyclic or bicydic ring which is saturated, partially unsaturated or aromatic and comprises 0, 1 , 2, 3 or 4 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R22;

R30 and R33 are independently of one another selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, phenyl-(d-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-;

R31 and R32 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, phenyl-(Ci-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-,

or the groups R31 and R32, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic saturated heterocycle which, in addition to the nitrogen atom carrying R31 and R32, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R34 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, phenyl-(Ci-C4)-alkyl- and Het1 -(d-C4)-alkyl-;

Het1 is a 5-membered or 6-membered, monocyclic, aromatic heterocycle which comprises 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-, unless specified otherwise;

Het2 is a 4-membered to 10-mennbered, monocyclic or bicyclic, saturated or partially unsaturated heterocycle which comprises 1 or 2 identical or different ring

heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur;

n is selected from the series consisting of 0, 1 and 2, wherein all numbers n are independent of one another;

p and q are independently of one another selected from the series consisting of 0 and 1 ;

wherein all phenyl groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-, unless specified otherwise;

wherein all cycloalkyl and bicycloalkyl groups, independently of any other

substituents which can be present on a cycloalkyl or bicycloalkyl group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

2. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to claim 1 , wherein

Ar is phenyl which is unsubstituted or substituted by one or more identical or different substituents RO;

R0 is selected from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O- and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-O;

R1 is hydrogen or one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R2 is selected from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-O-, (Ci-C6)-alkyl-C(O)-O-, Het1 -C(O)-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R7-S(O)2-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, wherein (Ci-C6)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20;

R3 is selected from the series consisting of hydrogen and (Ci-C6)-alkyl, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or two identical or different substituents selected from the series consisting of (C3-C7)-cycloalkyl and phenyl;

or the groups R2 and R3 together are oxo;

R4 is hydrogen or one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-;

R5 and R6 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C2-C6)-alkenyl, (C3-C7)-cycloalkyl, Het1 and Het2, wherein (Ci-C6)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and Het1 is unsubstituted or substituted by one or more identical or different substituents R22,

or the groups R5 and R6, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic, saturated or partially unsaturated

heterocycle which, in addition to the nitrogen atom carrying R5 and R6, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R21 ;

R7 is selected from the series consisting of (CrC6)-alkyl, (C3-C7)-cycloalkyl, phenyl, Het1 and Het2, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 , and phenyl and Het1 all are unsubstituted or substituted by one or more identical or different substituents R22;

R8 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl;

R9 is selected from the series consisting of (Ci-Ce)-alkyl and (C3-C7)-cycloalkyl;

R10 is selected from the series consisting of hydrogen, (Ci-Ce)-alkyl and (C3-C7)-cycloalkyl;

R20 is selected from the series consisting of R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (HO)2P(O)-O-CH2-O-C(O)-O-, (Ci-C6)-alkyl-S(O)n-, (C3-C7)-cycloalkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-;

R21 is selected from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, R34-O-C(O)-(Ci-C4)-alkyl-, R24, fluorine, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-,

(HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)- and R31 -N(R32)-C(O)-;

R22 is selected from the series consisting of halogen, (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, (C3-C7)-cycloalkyl, HO-, oxo, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, R33-O-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, NC-, R33-C(O)- and R31 -N(R32)-C(O)-;

R24 is a 3-membered to 7-membered, monocyclic ring which is saturated, partially unsaturated or aromatic and comprises 0, 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R22;

R30 and R33 are independently of one another selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, phenyl-(d-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-;

R31 and R32 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, phenyl-(Ci-C4)-alkyl- and Het1 -(Ci-C4)-alkyl-;

R34 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-;

Het1 is a 5-membered or 6-membered, monocyclic, aromatic heterocycle which comprises 1 , 2 or 3 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-, unless specified otherwise;

Het2 is a 4-membered to 7-membered, monocyclic, saturated or partially unsaturated heterocycle which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur;

n is selected from the series consisting of 0, 1 and 2, wherein all numbers n are independent of one another;

p and q are independently of one another selected from the series consisting of 0 and 1 ;

wherein all phenyl groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (CrC4)-alkyl-O-, unless specified otherwise;

wherein all cycloalkyi groups, independently of any other substituents which can be present on a cycloalkyi group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

3. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 and 2, wherein

Ar is phenyl which is unsubstituted or substituted by one or more identical or different substituents R0;

R0 is selected from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O- and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-O-;

R1 is hydrogen or one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R2 is selected from the series consisting of (Ci-C6)-alkyl, HO-, (Ci-C6)-alkyl-O-, R5-N(R6)-, R7-C(O)-N(R8)-, R9-N(R10)-C(O)-N(R8)- and R5-N(R6)-C(O)-, wherein (d-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20;

R3 is selected from the series consisting of hydrogen and (Ci-C6)-alkyl, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or two identical or different

substituents selected from the series consisting of (C3-C7)-cycloalkyl and phenyl;

or the groups R2 and R3 together are oxo;

R4 is hydrogen or one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-;

R5 and R6 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 ,

or the groups R5 and R6, together with the nitrogen atom carrying them, form a 4-membered to 7-membered, monocyclic, saturated or partially unsaturated

heterocycle which, in addition to the nitrogen atom carrying R5 and R6, comprises 0 or 1 further ring heteroatom selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R21 ;

R7 is selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 ;

R8 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl;

R9 is selected from the series consisting of (Ci-Ce)-alkyl and (C3-C7)-cycloalkyl;

R10 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl and (C3-C7)-cycloalkyl-;

R20 is selected from the series consisting of R24, fluorine, HO-, oxo, (CrC6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, R30-C(O)-O-, R30-NH-C(O)-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)-, R34-O-C(O)- and R31 -N(R32)-S(O)2-;

R21 is selected from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, R34-O-C(O)-(Ci-C4)-alkyl-, R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)- and R31 -N(R32)-C(O)-;

R22 is selected from the series consisting of halogen, (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, (C3-C7)-cycloalkyl, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-,

(HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, NC-, R33-C(O)- and R31 -N(R32)-C(O)-;

R24 is a 3-membered to 7-membered, monocyclic ring which is saturated, partially unsaturated or aromatic and comprises 0, 1 , 2 or 3 identical or different ring

heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R22;

R30 and R33 are independently of one another selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-;

R31 and R32 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-;

R34 is selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-;

Het2 is a 4-membered to 7-mennbered, monocyclic, saturated or partially unsaturated heterocycle which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur;

n is selected from the series consisting of 0, 1 and 2, wherein all numbers n are independent of one another;

p and q are independently of one another selected from the series consisting of 0 and l ;

wherein all phenyl groups are unsubstituted or substituted by one or more identical or different substituents selected from the series consisting of halogen, (Ci-C4)-alkyl and (Ci-C4)-alkyl-O-, unless specified otherwise;

wherein all cycloalkyi groups, independently of any other substituents which can be present on a cycloalkyi group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

4. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 3,

Ar is phenyl which is unsubstituted or substituted by one or more identical or different substituents R0;

R0 is selected from the series consisting of halogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl, (Ci-C6)-alkyl-O- and (C3-C7)-cycloalkyl-O-;

R1 is hydrogen or one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

R2 is selected from the series consisting of (d-C6)-alkyl, HO-, R5-N(R6)-, R7-C(O)-N(R8)- and R5-N(R6)-C(O)-, wherein (Ci-C6)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20;

R3 is hydrogen;

R4 is hydrogen or one or more identical or different substituents selected from the series consisting of halogen and (Ci-C4)-alkyl;

one of the groups R5 and R6 is selected from the series consisting of hydrogen and (CrC6)-alkyl, and the other of the groups R5 and R6 is selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, wherein (Ci-Ce)-alkyl all are unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 ;

R7 is selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, wherein (Ci-Ce)-alkyl is unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 ;

R8 is selected from the series consisting of hydrogen and (Ci-C4)-alkyl;

R20 is selected from the series consisting of R24, fluorine, HO-, (CrC6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)-, R31 -N(R32)-C(O)- and R31 -N(R32)-S(O)2-;

R21 is selected from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, fluorine, HO-, (Ci-C6)-alkyl-0-, (C3-C7)-cycloalkyl-O-,

HO-S(O)2-O-, (HO)2P(O)-O-, R31 -N(R32)-, R33-C(O)-N(R32)- and R31 -N(R32)-C(O)-;

R22 is selected from the series consisting of halogen, (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, (C3-C7)-cycloalkyl, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-,

(HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)- and R31 -N(R32)-C(O)-;

R24 is a 3-membered to 7-membered, monocyclic ring which is saturated, partially unsaturated or aromatic and comprises 0, 1 , 2 or 3 identical or different ring

heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R22;

R33 is selected from the series consisting of (Ci-C6)-alkyl;

R31 and R32 are independently of one another selected from the series consisting of hydrogen, (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and (C3-C7)-cycloalkyl-(Ci-C4)-alkyl-;

Het2 is a 4-membered to 7-membered, monocyclic, saturated or partially unsaturated heterocycle which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur;

n is selected from the series consisting of 0, 1 and 2, wherein all numbers n are independent of one another;

p and q are 1 ;

wherein all cycloalkyi groups, independently of any other substituents which can be present on a cycloalkyi group, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

5. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 4, wherein R2 is selected from the series consisting of R5-N(R6)- and R7-C(O)-N(R8)-.

6. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 4, wherein R2 is R5-N(R6)-C(O)-.

7. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 6, wherein R3 is hydrogen.

8. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 4, 6 and 7, wherein

Ar is phenyl which is unsubstituted or substituted by one or two identical or different substituents R0;

R0 is selected from the series consisting of halogen, (Ci-Ce)-alkyl and (Ci-Ce)-alkyl-O-;

R1 is hydrogen;

R2 is R5-N(R6)-C(0)-;

R3 is hydrogen;

R4 is hydrogen;

one of the groups R5 and R6 is selected from the series consisting of hydrogen and (Ci-C6)-alkyl, and the other of the groups R5 and R6 is selected from the series consisting of (Ci-C6)-alkyl, (C3-C7)-cycloalkyl and Het2, wherein (Ci-Ce)-alkyl all are unsubstituted or substituted by one or more identical or different substituents R20, and (C3-C7)-cycloalkyl and Het2 all are unsubstituted or substituted by one or more identical or different substituents R21 ;

R20 is selected from the series consisting of R24, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-, (HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)-, (Ci-C6)-alkyl-S(O)2-N(R32)- and R31 -N(R32)-C(O)-;

R21 is selected from the series consisting of (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, R31 -N(R32)-(Ci-C4)-alkyl-, fluorine, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-,

HO-S(O)2-O-, (HO)2P(O)-O-, R31 -N(R32)-, R33-C(O)-N(R32)- and R31 -N(R32)-C(O)-;

R22 is selected from the series consisting of halogen, (Ci-C4)-alkyl, HO-(Ci-C4)-alkyl-, (C3-C7)-cycloalkyl, HO-, (Ci-C6)-alkyl-O-, (C3-C7)-cycloalkyl-O-, HO-S(O)2-O-,

(HO)2P(O)-O-, (Ci-C6)-alkyl-S(O)n-, R31 -N(R32)-, R33-C(O)-N(R32)- and R31 -N(R32)-C(O)-;

R24 is a 3-membered to 7-membered, monocyclic ring which is saturated, partially unsaturated or aromatic and comprises 0, 1 or 2 identical or different ring

heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur, and which is unsubstituted or substituted by one or more identical or different substituents R22;

R33 is selected from the series consisting of (Ci-C6)-alkyl;

R31 and R32 are independently of one another selected from the series consisting of hydrogen and (Ci-C6)-alkyl;

Het2 is a 4-membered to 7-membered, monocyclic, saturated or partially unsaturated heterocycle which comprises 1 or 2 identical or different ring heteroatoms selected from the series consisting of nitrogen, oxygen and sulfur;

n is selected from the series consisting of 0, 1 and 2, wherein all numbers n are independent of one another;

p and q are 1 ;

wherein all cycloalkyl groups independently of any other substituents which can be present on a cycloalkyl, can be substituted by one or more identical or different substituents selected from the series consisting of fluorine and (Ci-C4)-alkyl;

wherein all alkyl groups, independently of any other substituents which can be present on an alkyl group, can be substituted by one or more fluorine substituents.

9. A compound of the formula I according to any of claims 1 to 8, which is selected from the series consisting of:

trans-4-(2-o-Tolyl-chroman-6-yloxy)-cyclohexylamine,

N-(lsoxazol-5-ylmethyl)-4-(2-o-tolyl-chroman-6-yloxy)-cyclohexanecarboxamide, 2-Amino-N-[trans-4-((S)-2-phenyl-chroman-6-yloxy)-cyclohexyl]-acetamide,

4-(2-o-Tolyl-chroman-6-yloxy)-N-(1 ,3,5-trimethylpyrazol-4-ylmethyl)-cyclohexylamine, (S)-N-[trans-4-(2-Phenyl-chroman-6-yloxy)-cyclohexyl]-pyrrolidine-2-carboxamide, trans-4-((R)-2-o-tolyl-chroman-6-yloxy)-cyclohexanecarboxylic acid (2-hydroxy-ethyl)-amide,

trans-4-((S)-2-o-tolyl-chroman-6-yloxy)-cyclohexanecarboxylic acid (2-hydroxy-ethyl)-amide,

cis-4-((R)-2-o-tolyl-chroman-6-yloxy)-cyclohexanecarboxylic acid (2-hydroxy-ethyl)-amide,

cis-4-((S)-2-o-tolyl-chroman-6-yloxy)-cyclohexanecarboxylic acid (2-hydroxy-ethyl)-amide, and

Phosphoric acid mono-(2-{[trans-4-((S)-2-o-tolyl-chroman-6-yloxy)-cyclohexanecarbonyl]-amino}-ethyl) ester disodium salt,

or a pharmaceutically acceptable salt thereof.

10. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 9, for use as a pharmaceutical.

1 1 . A pharmaceutical composition, comprising a compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 9, and a pharmaceutically acceptable carrier.

12. A compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 9, for use as an inhibitor of the sodium-calcium-exchanger (NCX) or in the treatment of heart failure, cardiac arrhythmias, stroke, dementia, hypertension, cardiac ischemia, renal failure, shock or age-related disorders.

13. Use of a compound of the formula I, in any of its stereoisomeric forms or a mixture of stereoisomeric forms in any ratio, or a pharmaceutically acceptable salt thereof, according to any of claims 1 to 9, for the manufacture of a medicament for the inhibition of the sodium-calcium-exchanger (NCX) or for the treatment of heart failure, cardiac arrhythmias, stroke, dementia, hypertension, cardiac ischemia, renal failure, shock or age-related disorders.