RU2779618C2 - Oxadiazaspiro-compounds for treatment of drug abuse and addiction - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to compounds with the general formula (I), as well as to a method for their production, a pharmaceutical composition based on them, and the use for the treatment of conditions mediated by a sigma receptor.

EFFECT: new compounds are obtained, providing binding to sigma receptors, especially sigma-1, which can be used for the treatment of mediated diseases.

16 cl, 113 ex

Description

FIELD OF TECHNOLOGY

The present invention relates to new oxadiazaspiro compounds having affinity for sigma receptors, in particular sigma-1 (σ ₁ ) receptors, as well as to a method for their preparation, to compositions containing them and to their use as drugs against drug abuse and depending on them.

BACKGROUND OF THE INVENTION

In recent years, the search for new therapeutics has been greatly facilitated by a better understanding of the structure of proteins and other biomolecules associated with targeted diseases. One important class of these proteins is the sigma (σ) receptors, cell surface receptors of the central nervous system (CNS), which may be associated with the dysphoric, hallucinogenic, and cardiac stimulant effects of opioids. Evidence has been provided from studies on the biology and action of sigma receptors that sigma receptor ligands may be useful in the treatment of psychosis and movement disorders such as dystonia and tardive dyskinesia, as well as movement disorders associated with Huntington's chorea or Tourette's syndrome and Parkinson's disease. (Walker, J.M. et al, Pharmacological Reviews, 1990, 42, 355). A known sigma receptor ligand, rimcasol, has been reported to be clinically effective in the treatment of psychosis (Snyder, S.H., Largent, B.L. J. Neuropsychiatry 1989, 1, 7).

The sigma receptor has at least two subtypes, a sigma-1 site (σ ₁ ) and a sigma-2 site (σ ₂ ).

The σ1 receptor is a non-opiate-type receptor expressed in a variety of adult mammalian tissues (e.g., central nervous system, ovary, testicle, placenta, adrenal gland, spleen, liver, kidney, gastrointestinal tract), as well as in the development of the fetus from its earliest stages, and is apparently involved in a large number of physiological functions. Its high affinity for various pharmaceuticals has been described, for example, for (+)SKF-10047, (+)-pentazocine, haloperidol and rimcasol, among others known ligands with analgesic, anxiolytic, antidepressant, antiamnesic, antipsychotic and neuroprotective activity.

The σ ₂ receptor is also expressed in a variety of adult mammalian tissues (eg, nervous system, immune system, endocrine system, liver, kidneys). σ ₂ receptors may be components in a novel apoptosis pathway that may play an important role in the regulation of cell proliferation or in cell development. This pathway appears to consist of σ ₂ receptors attached to intracellular membranes located in calcium storage organelles such as the endoplasmic reticulum and mitochondria, which also have the ability to release calcium from these organelles. Calcium signals can be used in the normal cell signaling pathway and/or in the induction of apoptosis.

Endogenous sigma ligands are not known, although it has been suggested that progesterone is one of them. Possible sigma site-mediated effects of drugs include modulation of glutamate receptor function, neurotransmitter response, neuroprotective effects, behavior and recognition (Quirion, R. et al. Trends Pharmacol. Sci., 1992, 13:85-86). Most studies have implied that sigma-binding sites (receptors) are elements of the plasmolemma of the signal transduction cascade. Drugs listed as selective sigma ligands have been evaluated as antipsychotics (Hanner, M. et al. Proc. Natl. Acad. Sci., 1996, 93:8072-8077). The existence of sigma receptors in the CNS, immune and endocrine systems suggested the possibility that they could serve as a link between the three systems.

In view of the potential therapeutic applications of sigma receptor agonists or antagonists, great efforts have been directed to the search for selective ligands. Thus, various sigma receptor ligands are disclosed in the prior art.

For example, international patent application WO 2007/098961 describes 4,5,6,7-tetrahydrobenzo[b]thiophene derivatives having pharmacological activity against the sigma receptor.

Spiro[benzopyran] or spiro[benzofuran] derivatives have also been disclosed in EP 1847542, as well as pyrazole derivatives (EP 1634873) with pharmacological activity for sigma receptors.

WO 2009/071657 discloses certain tricyclic triazole compounds with activity against sigma receptors, although they differ in structure from the compounds of the present invention.

In addition, the σ ₁ receptor has become a promising target for the development of new therapies aimed at treating the effects of various drugs (Robson et al., Curr Pharm Des. 2012;18(7):902-19). The σ ₁ receptor is known to be expressed in brain regions involved in addiction processes, eg, the hippocampus, nucleus striate, nucleus accumbens, and amygdala (Alonso et al., Neuroscience. 2000;97(1): 155-70). It is also expressed in organs such as the heart (Ela et al., J Pharmacol Exp Ther 1994; 269: 1300-9), the liver (Samovilova and Vinogradov, Eur J Pharmacol 1992; 225: 69-74.) or the gastrointestinal tract (Roman et al, Gastroenterology 1989; 97:76-82.), organs involved in some side effects and many drug toxicities. Narcotic drugs such as cocaine (Matsumoto et al., Neuropharmacology 2001; 41: 878-86, 2007), methamphetamine (Nguyen et al., Neuropharmacology 2005; 49: 638-45) or phencyclidine (Morris et al., Curr Opin Pharmacol 2005;5:101-6.) interact directly with the σ ₁ receptor, which is involved in some of the effects of these substances. However, the σ ₁ receptor can also modulate the effects of other drugs, even if they do not have affinity for the σ ₁ receptor. This occurs with opiates such as morphine (Chen et al., Drug Alcohol Depend 2011; 117: 164-9), ethanol (Blasio et al., Behav Brain Res 2015; 287:315-22) or nicotine (Horan et al., Eur J Pharmacol 2001;426:Rl-2).

Modulation of the σ ₁ receptor is known to be effective in blocking the enhancing effects of cocaine (Romieu et al., Neuroreport 2000; 11: 2885-8), ethanol (Maurice et al., Pharmacol Biochem Behav 2003; 74: 869-76) or nicotine ( Horan et al., Eur J Pharmacol 2001; 426: R1-2.) in rodents, which was assessed in the place preference test and may also reduce nicotine replacement (Martin-Fardon et al., Neuropsychopharmacology. 2007 Sep;32 (9): 1967-73) or ethanol (Martin-Fardon et al., Neuroreport. 2012 Oct 3;23(14):809-13) in response to self-administration. It also inhibits the stimulatory effect on locomotor activity induced by cocaine (McCracken et al., Eur J Pharmacol 1999; 370(3):225-32) or methamphetamine (Okuyama et al., Life Sci. 1993;53(18):PL285 -90).

The exact mechanisms by which σ ₁ receptor ligands influence the observed effects are not fully elucidated. It is well known that the σ ₁ receptor modulates the neurotransmitter system such as dopaminergic, serotonergic and glutamatergic, as well as ion channel activity, signaling pathways and the expression of several genes, all of which are involved in drug action (Matsumoto, Expert Rev Clin Pharmacol. 2009 Jul; 2(4):351-8).

Drug addiction is one of the most serious health problems worldwide, affecting society on multiple levels. Drug dependence is responsible for significant medical, economic, and social health costs. The ineffectiveness, in some cases, of modern pharmacological treatment, or even the lack of treatment, also exacerbates the problem. All of this together confirms the need for a deeper understanding of the neurobiological effects of the mechanisms of drug abuse and dependence, in order to discover new therapeutic targets for the development of alternative treatments.

In addition, there is still a need to find compounds with sigma receptor pharmacological activity that are both potent and selective and/or have good "drug use" properties, i.e. good pharmaceutical properties relating to administration, distribution, metabolism and excretion.

Surprisingly, the novel oxadiazaspiro compounds of general formula (I) have been found to exhibit good to excellent affinity for the σ ₁ receptor. These compounds are thus particularly useful as pharmacologically active agents in medicaments for the prevention and/or treatment of disorders or diseases associated with sigma receptors, in particular against drug abuse and dependence.

DISCLOSURE OF THE INVENTION

The present invention discloses novel compounds with good sigma receptor affinity and high physiological solubility that can be used in the treatment of sigma receptor related disorders or diseases, in particular against drug abuse and dependence.

Since the present invention is directed to providing a compound or a chemically linked series of compounds that act as σ ₁ receptor ligands, it is highly preferred if the compound has a binding expressed as K _i , which is preferably < 1000 nM, more preferably < 500 nM, even more preferably < 100 nM.

The present invention in its main aspect is directed to a compound of general formula (I),

where R ₁ , R ₂ , R ₃ , R _3' , R ₄ , R _4' , R ₅ , R _5' , R ₆ , R _6' , X, Y, m, n and p are as defined below in the detailed description.

Another object of the present invention relates to processes for the preparation of compounds of general formula (I).

Another object of the present invention relates to the use of intermediates for the preparation of a compound of general formula (I).

In addition, the aim of the present invention is a pharmaceutical composition containing a compound of formula (I).

Finally, an object of the present invention is the use of the compound as a drug and, more particularly, for the treatment of pain and disease conditions.

DETAILED DESCRIPTION OF THE PRESENT INVENTION

The present invention discloses novel compounds with sigma receptor affinity and high physiological solubility that can be used to treat sigma receptor related disorders or diseases.

Since the present invention is directed to providing a compound or a chemically linked series of compounds that act as σ ₁ receptor ligands, it is highly preferred if the compound has a binding expressed as K _i , which is preferably < 1000 nM, more preferably < 500 nM, even more preferably < 100 nM.

Preferably, the compounds of the present invention will furthermore exhibit one or more of the following functionalities: σ ₁ receptor antagonism. It should be noted, however, that "antagonism" and "agonism" functionality is also subdivided according to their effect into additional functionality such as partial agonism or reversible agonism. Therefore, the functionality of the connection should be considered in a relatively wide range.

An antagonist blocks or dampens agonist-mediated responses. Known additional functionality are neutral antagonists or reversible agonists.

The agonist increases the activity of the receptor above its baseline. Known additional functionality are full agonists or partial agonists.

The present invention in its main aspect is directed to a compound of general formula (I).

In a specific aspect, the present invention is directed to compounds of general formula (I):

where

p is 0, or 1, or 2; preferably p is 0 or 1;

m is 1, 2 or 3;

n is 0, 1 or 2;

Y represents -CH ₂ - or -C(O)-;

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

where R _{x is} selected from halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

where said cycloalkyl in R ₁ , if substituted, is substituted with one or more substituents/s selected from halo, -R ₁₁ , -OR ₁₁ , -NO ₂ , -NR ₁₁ R _11''' , NR ₁₁ C(O) R _11' , -NR ₁₁ S(O) ₂ R _11' , -S(O) ₂ NR ₁₁ R _11' , -NR ₁₁ C(O)NR _11' R _11'' , -SR ₁₁ , -S( O)R ₁₁ , S(O) ₂ R ₁₁ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₁ , -C(O)NR ₁₁ R _11' , -OCH ₂ CH ₂ OH, -NR ₁₁ S (O) ₂ NR _11' R _11'' and C(CH ₃ ) ₂ OR ₁₁ ;

или =O;in addition, the cycloalkyl in R ₁ , if substituted, may also be substituted with

or =O;

where alkyl, alkenyl or alkynyl in R ₁ , if substituted, is substituted with one or more substituent(s) selected from -OR ₁₁ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₁ R _11''' ;

where R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

and where R _11''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

where the specified cycloalkyl, aryl or heterocyclyl in R ₂ if substituted, is substituted with one or more substituent(s) selected from halogen, -R ₁₂ , -OR ₁₂ , -NO ₂ , -NR ₁₂ R ₁₂ ''', NR ₁₂ C(O)R _12' , -NR ₁₂ S(O) ₂ R _12' , -S(O) ₂ NR ₁₂ R _12' , -NR ₁₂ C(O)NR _12' R _12'' , -SR ₁₂ , -S(O)R ₁₂ , S(O) ₂ R ₁₂ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₂ , -C(O)NR ₁₂ R _12' , -OCH ₂ CH ₂ OH, -NR ₁₂ S(O) ₂ NR _12' R _12'' and C(CH ₃ ) ₂ OR ₁₂ ;

или =O;in addition, the cycloalkyl or non-aromatic heterocyclyl in R ₂ , if substituted, may also be substituted with

or =O;

where alkyl, alkenyl or alkynyl in R ₂ , if substituted, is substituted with one or more substituent(s) selected from -OR ₁₂ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₂ R _12''' ;

where R ₁₂ , R _12' and R _12'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

and where R _12''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

R ₃ and R _3' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₃ and R _3' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl;

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

where R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl and substituted or unsubstituted C _2-9 alkynyl;

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

R ₆ and R _6' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -OR ₁₀ , -CHOR ₁₀ and -C(O )OR ₁₀ ;

where R ₁₀ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate;

In a specific aspect, the present invention is directed to compounds of general formula (I):

where

p is 0 or 1;

m is 1, 2 or 3;

n is 0, 1 or 2;

Y represents -CH ₂ - or -C(O)-;

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

where R _{x is} selected from halo or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl;

R ₃ and R _3' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₃ and R _3' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl;

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

where R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl and substituted or unsubstituted C _2-9 alkynyl;

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

R ₆ and R _6' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -OR ₁₀ , -CHOR ₁₀ and -C(O )OR ₁₀ ;

where R ₁₀ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

These compounds according to the present invention are optionally present as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their corresponding salt, or their the corresponding solvate.

In another embodiment, these compounds of the present invention are optionally present as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their corresponding salt.

In yet another implementation, the following condition applies:

when Y is -C(O)- and R ₂ is substituted or unsubstituted aryl or substituted or unsubstituted heterocyclyl, then m is 1, X is a bond, n is 0, and R ₃ is not hydrogen.

In yet another implementation, the following condition applies:

when Y is -C(O)- and R ₂ is a substituted or unsubstituted monocyclic aryl or a substituted or unsubstituted monocyclic heterocyclyl, then m is 1, X is a bond, n is 0, and R ₃ is not hydrogen.

In yet another implementation, the following condition applies:

when Y is -C(O)- and R ₂ is substituted or unsubstituted aryl or substituted or unsubstituted heterocyclyl, then m is 1, X is a bond, and n is 0.

In yet another implementation, the following condition applies:

when Y is -C(O)- and R ₂ is a substituted or unsubstituted monocyclic aryl or a substituted or unsubstituted monocyclic heterocyclyl, then m is 1, X is a bond, and n is 0.

In yet another implementation, the following condition applies:

when Y is -C(O)- and R ₂ is substituted or unsubstituted aryl or substituted or unsubstituted heterocyclyl, then -[CR ₅ R _5' ] _m -X-[CR ₆ R _6' ] _n - is not neither -CH ₂ CH ₂ - nor -CH ₂ CH(OH)-, and R ₃ is not hydrogen.

For reasons of clarity with respect to -CH ₂ CH(OH)-, this would mean that when Y is -C(O)- and R ₂ is substituted or unsubstituted aryl or substituted or unsubstituted heterocyclyl, then -[CR ₅ R _5' ] _m -X-[CR ₆ R _6' ] _n -

cannot be -CH ₂ CH(OH)-, reading in the direction from the "N" spiro part of the core in the direction of R ₂ .

In yet another implementation, the following connection is also excluded:

In yet another implementation, the following connection is excluded:

In another embodiment, both of the following compounds are also excluded:

и

and

In yet another embodiment, a compound of the present invention of general formula (I) is a compound of general formula (I')

where R ₁ , R ₂ , R ₃ , R _3' , R ₄ , R _4' , R ₅ , R _5' , X, Y, m and p are as defined in the description.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound of general formula (I ^a ')

where R ₁ , R ₂ , R ₃ , R _3' , R ₄ , R _4' , R ₅ , R _5' , X, Y, m and p are as defined in the description.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound of general formula (I ^b ')

where R ₁ , R ₂ , R ₄ , R _4' , R ₅ , R _5' , X, Y, m and p are as defined in the description.

In yet another embodiment, a compound of the present invention of general formula (I) is a compound of general formula (I ^c ')

where R ₁ , R ₂ , R ₄ , R _4' , R ₅ , R _5' , X, Y, m and p are as defined in the description.

In yet another embodiment, a compound of the present invention of general formula (I) is a compound of general formula (I ² ')

where R ₁ , R ₂ , R ₄ , R _4' , R ₅ , R _5' , X, Y, m and p are as defined in the description.

In yet another embodiment, compounds of general formula (I) are compounds of general formula (I ^3' )

where R ₁ , R ₂ , R ₄ , R _4' , R ₅ , R _5' , X, m and p are as defined in the description.

In yet another embodiment, compounds of general formula (I) are compounds of general formula (I ^4' )

where R ₁ , R ₂ , m and p are as defined in the description.

In yet another embodiment, compounds of general formula (I) are compounds of general formula (I ^5' )

where R ₁ , R ₂ and m are as defined in the description.

In yet another embodiment, a compound of the present invention of general formula (I) is a compound of general formula (I ⁶ ')

where R ₁ , R ₂ , R ₃ , R _3' , R ₅ , R _5' , X, Y and m are as defined in the description.

For reasons of clarity, reference is also made to the following statements below in the definitions of substitutions on alkyl, etc. or aryl, etc., consisting in the fact that "moreover, when different radicals R ₁ -R _14'''' and R _x , R _x' are present simultaneously in the formula I, they may be identical or different." This statement is reflected in the general formula (I ⁷ ') below, derived from and falling within the general formula (I).

where R ₁ , R ₂ , R ₃ , R _3' , R ₄ , R _4' , R ₅ , R _5' , X, Y and p are as defined in the description. In addition, m' (equal to 0 or 1), R _5'' and R _5''' are added. As stated above, this statement is thus reflected in the fact that R _5'' and R _5''' are or may be different from R ₅ and R _5' or not, and therefore m' equal to 0 or 1, naturally derived from m (in general formulas (I)-(I ^6' ) equal to 1 or 2).

The same will apply mutatis mutandis for general formulas such as general formula (I) as well as other general formulas (I')-(I ^6' ) above, as well as for all synthetic intermediates.

For reasons of clarity, all groups and definitions described in the description and referring to compounds of general formula (I) also apply to compounds of general formula (I'), (I ^a' ), (1 ^b' ), (I ^c' ), (I ² '), (I ³ '), (I ⁴ '), (I ⁵ ') or (I ⁶ '), as well as (I ^7' ), as well as to all intermediate compounds of the synthesis, when these groups are in these general Markush formulas, since the compounds of general formula (I'), (I ^a' ), (1 ^b' ), (I ^c' ), (I ² '), (I ³ '), (I ⁴ ') , (I ^5' ) or (I ⁶ '), or (I ⁷ ') are included in the general formula (I).

For reasons of clarity, the general Markush formula (I)

is equivalent to

where only -C(R ₄ R _4' )-, -C(R ₅ R _5' )- and -C(R ₆ R _6' )- are bracketed and p, m and n are the number of times that - C(R ₄ R _4' )-, -C(R ₅ R _5' )- and -C(R ₆ R _6' )- are repeated, respectively. The same will apply to the general Markush formulas (I'), (I ^a' ), (1 ^b' ), (I ^c' ), (I ² '), (I ³ '), (I ⁴ '), (I ^5' ) or (I ^6' ), as well as to all intermediate compounds of the synthesis.

Thus, the general formula (I') can also be expressed as the general formula (IZ'), etc.:

In addition, and for reasons of clarity, it should also be understood that, of course, if p, m or n is 0, then R ₁ , X or R ₂ are still in the general Markush formulas (I'), (I ^a' ) , (1 ^b' ), (I ^c' ), (I ² '), (I ³ '), (I ⁴ '), (I ^5' ) or (I ^6' ), as well as in all synthetic intermediates .

In the context of the present invention, alkyl should be understood as meaning saturated, linear or branched hydrocarbons, which may be unsubstituted or substituted one or more times. It covers, for example, -CH ₃ and -CH ₂ -CH ₃ . In these radicals C _1-2 -alkyl is C1- or C2-alkyl, C _1-3 -alkyl is C1-, C2- or C3-alkyl, C _1-4 -alkyl is C1-, C2-, C3- or C4-alkyl, _C1-5 -alkyl is C1-, C2-, C3-, C4- or C5-alkyl, _C1-6 -alkyl is C1-, C2-, C3-, C4- , C5- or C6-alkyl, _C1-7 -alkyl is C1-, C2-, C3-, C4-, C5-, C6- or C7-alkyl, _C1-8 -alkyl is C1-, C2 -, C3-, C4-, C5-, C6-, C7- or C8-alkyl, C _1-10 -alkyl is C1-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C9- or C10-alkyl and _C1-8 -alkyl is C1-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C9-, C10-, C11 -, C12-, C13-, C14-, C15-, C16-, C17- or C18-alkyl. The alkyl radicals are preferably methyl, ethyl, propyl, methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl , 1-methylpentyl, if substituted, also CHF ₂ , CF ₃ or CH ₂ OH, etc. Preferably, alkyl is to be understood in the context of the present invention as C _1-8 alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl or octyl; preferably it is C _1-6 alkyl such as methyl, ethyl, propyl, butyl, pentyl or hexyl; more preferably it is C _1-4 alkyl such as methyl, ethyl, propyl or butyl.

Alkenyl is to be understood as meaning unsaturated, linear or branched hydrocarbons which may be unsubstituted or substituted one or more times. It covers such groups as, for example, -CH=CH-CH ₃ . Alkenyl radicals are preferably vinyl (ethenyl), allyl (2-propenyl). Preferably, in the context of the present invention, alkenyl is C _2-10 alkenyl or C _2-8 alkenyl such as ethylene, propylene, butylene, pentylene, hexylene, heptylene or octylene; or is C _2-6 alkenyl such as ethylene, propylene, butylene, pentylene or hexylene; or is C _2-4 alkenyl such as ethylene, propylene or butylenes.

Alkynyl is to be understood as meaning unsaturated, linear or branched hydrocarbons which may be unsubstituted or substituted one or more times. It covers such groups as, for example, -C = C-CH ₃ (1-propynyl). Preferably, alkynyl in the context of the present invention is C _2-10 alkynyl or C _2-8 alkynyl such as ethyne, propyne, butyne, pentyne, hexine, heptine or octyne; or is C _2-6 alkynyl such as ethyne, propyne, butyne, pentyne or hexine; or is a C _2-4 alkynyl such as ethyne, propyne, butyne, pentyne or hexine.

When applied to alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl), alkenyl, alkynyl and O-alkyl - unless otherwise indicated - the term "substituted" in the context of the present invention should be understood as meaning the replacement of at least one hydrogen radical on a carbon atom with a halogen ( F, Cl, Br, I), -NR _c R _c''' , -SR _c , -S(O)R _c , -S(O) ₂ R _c , -OR _c , -C(O)OR _c , -CN, -C(O)NR _c R _c' ; heloalkyl, haloalkoxy or —OC _1-6 alkyl, being R _c represented by R ₁₁ , R ₁₂ , R ₁₃ , (being R _c' represented by R _11' , R _12' , R _13' ; being R _c'' represented by R _11'' , R _12'' , R _13'' ; being R _c''' represented by R _11''' , R _12''' , R _13''' , being R _c'''' represented by R _11'''' , R _12'''' -, R _13'''' ), where R ₁ -R _14'''' and R _x , R _{x '} and R _n are as defined in the description, and moreover, when different radicals R ₁ -R _14'''' and R _x , R _x' and R _n are simultaneously present in formula I, they may be identical or different.

Most preferably, when applied to alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl), alkenyl, alkynyl or O-alkyl, "substituted" is to be understood in the context of this invention such that any alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl), alkenyl, alkynyl or O-alkyl which is substituted by one or more of halogen (F, Cl, Br, I), -OR _c , -CN, -NR _c R _c''' , haloalkyl, haloalkoxy or -OC _1-6 alkyl, being R _c represented by R ₁₁ , R ₁₂ , R ₁₃ , (being R _c' represented by R _11' , R _12' , R _13' ; being R _c'' represented by R _11'' , R _12'' , R _13'' ; being R _c''' represented by R _11''' , R _12''' , R _13''' , being R _c'''' represented by R _11'''' , R _12'''' , R _13'''' ), where R ₁ -R _14'''' and R _x , R _x ' and R _n are as defined in the description, and moreover, when different radicals R ₁ -R _14'''' and R _x , R _x' and R _n are simultaneously present in formula I, they m may be identical or different.

More than one substitution on the same molecule and also on the same carbon atom, possibly with the same or different substituents. This includes, for example, the substitution of 3 hydrogens on the same C atom, as in the case of CF ₃ , or in different places in the same molecule, as in the case, for example, with -CH(OH)-CH=CH- _CHCl2 .

In the context of the present invention, haloalkyl is to be understood as meaning alkyl substituted one or more times with halogen (selected from F, Cl, Br, I). It covers, for example, -CH ₂ Cl, -CH ₂ F, -CHCl ₂ , -CHF ₂ , -CCl ₃ , -CF ₃ and -CH ₂ -CHCl ₂ . Preferably, haloalkyl is to be understood in the context of the present invention as halo-substituted C _1-4 alkyl, which is C 1-, C2-, C3- or C4-alkyl substituted with halo. Halogenated alkyl radicals are thus preferably methyl, ethyl, propyl and butyl. Preferred examples include -CH ₂ Cl, -CH ₂ F, -CHCl ₂ , -CHF ₂ and -CF ₃ .

In the context of the present invention, haloalkoxy is to be understood as meaning -O-alkyl substituted one or more times with halogen (selected from F, Cl, Br, I). It covers, for example, -OCH ₂ Cl, -OCH ₂ F, -OCHCl ₂ , -OCHF ₂ , -OCCl ₃ , -OCF ₃ and -OCH ₂ -CHCl ₂ . Preferably, haloalkyl is to be understood in the context of the present invention as halo-substituted -OC _1-4 alkyl, which is C1-, C2-, C3- or C4-alkoxy substituted with halo. Halogenated alkyl radicals are thus preferably O-methyl, O-ethyl, O-propyl and O-butyl. Preferred examples include -OCH ₂ Cl, -OCH ₂ F, -OCHCl ₂ , -OCHF ₂ and -OCF ₃ .

In the context of the present invention, cycloalkyl is to be understood as meaning saturated and unsaturated (but not aromatic) cyclic hydrocarbons (without a ring heteroatom) which may be unsubstituted or substituted one or more times. In addition, C _3-4 cycloalkyl is C3 or C4 cycloalkyl, C _3-5 cycloalkyl is C3, C4 or C5 cycloalkyl, C _3-6 cycloalkyl is C3-, C4-, C5- or C6-cycloalkyl, _C3-7 -cycloalkyl is C3-, C4-, C5-, C6- or C7-cycloalkyl, _C3-8 -cycloalkyl is C3-, C4-, C5-, C6- , C7 or C8 cycloalkyl, _{C4-5 cycloalkyl is C4 or C5 cycloalkyl, C4-6 cycloalkyl is C4, C5 or C6 cycloalkyl, C4-7 cycloalkyl is} C4 -, C5-, C6- or C7-cycloalkyl, _C5-6 -cycloalkyl is C5- or C6-cycloalkyl, and _C5-7 -cycloalkyl is C5-, C6- or C7-cycloalkyl. Examples are cyclopropyl, 2-methylcyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cycloheptyl, cyclooctyl and also adamantyl. Preferably, in the context of the present invention, cycloalkyl is C _3-8 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; or is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; or is C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, in particular cyclopentyl or cyclohexyl.

Aryl is to be understood as meaning 5-18 membered mono- or polycyclic ring systems with at least one aromatic ring but no heteroatoms even in only one of the rings. Examples are phenyl, naphthyl, fluoroanthenyl, fluorenyl, tetralinyl or indanyl, 9H-fluorenyl or anthracenyl radicals which may be unsubstituted or substituted one or more times. Most preferably, aryl is to be understood in the context of the present invention as phenyl, naphthyl or anthracenyl, preferably it is phenyl.

A heterocyclyl radical or group (also referred to hereinafter as heterocyclyl) is to be understood as meaning/meaning 5-18 membered mono- or polycyclic heterocyclic ring systems with at least one saturated or unsaturated ring which contains one or more heteroatoms from the group consisting of nitrogen , oxygen and/or sulfur in the ring. The heterocyclic group may also be substituted once or more than once.

Examples include non-aromatic heterocyclyls such as tetrahydropyran, oxazepane, morpholine, piperidine, pyrrolidine, as well as heteroaryls such as furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, thiazole, benzothiazole, indole , benzotriazole, carbazole and quinazoline.

Subgroups within heterocyclyls as used herein include heteroaryls and non-aromatic heterocyclyls.

- heteroaryl (which is equivalent to heteroaromatic radicals or aromatic heterocyclyls) is an aromatic 5-18-membered mono- or polycyclic heterocyclic ring system, and from one or more rings of which at least one aromatic ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably, it is an aromatic 5-18-membered mono- or polycyclic heterocyclic ring system, wherein at least one aromatic ring of one or two rings contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in ring, more preferably it is selected from furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, benzothiazole, indole, benzotriazole, carbazole, quinazoline, thiazole, imidazole, pyrazole, oxazole, thiophene and benzimidazole;

- non-aromatic heterocyclyl is a 5-18-membered mono- or polycyclic heterocyclic ring system, and from one or more rings of which at least one ring - and this (or these) ring(s) are then not aromatic - contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably, it is a 5 to 18-membered mono- or polycyclic heterocyclic ring system, wherein of one or two rings of which at least one or both rings - this one or two rings then being non-aromatic - contain one or more heteroatoms from a group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably it is selected from oxazepam, pyrrolidine, piperidine, piperazine, tetrahydropyran, morpholine, indoline, oxopyrrolidine, benzodioxane, oxetane, in particular it is benzodioxane, morpholine, tetrahydropyran , piperidine, oxopyrrolidine, oxetane and pyrrolidine.

Preferably, in the context of the present invention, heterocyclyl is defined as a 5 to 18 membered mono- or polycyclic heterocyclic ring system, wherein at least one of the one or more saturated or unsaturated rings contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring.

Preferred examples of heterocyclyls include oxetane, oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzodiazole, thiazole, benzothiazol, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline, in in particular, it is pyridine, pyrazine, indazole, benzodioxane, thiazole, benzothiazole, morpholine, tetrahydropyran, pyrazole, imidazole, piperidine, thiophene, indole, benzimidazole, pyrrolo[2,3b]pyridine, benzoxazole, oxopyrrolidine, pyrimidine, oxazepane, oxetane and pyrrolidine.

In the context of the present invention, oxopyrrolidine is to be understood as meaning pyrrolidin-2-one.

For aromatic heterocyclyls (heteroaryls), non-aromatic heterocyclyls, aryls and cycloalkyls, when a ring system falls within two or more of the above ring definitions at the same time, then the ring system is defined first as an aromatic heterocyclyl (heteroaryl) if at least one aromatic ring contains heteroatom. If none of the aromatic rings contains a heteroatom, then the ring system is defined as a non-aromatic heterocyclyl if at least one non-aromatic ring contains a heteroatom. If none of the non-aromatic rings contains a heteroatom, then the ring system is defined as aryl if it contains at least one aryl ring. If aryl is absent, then the ring system is defined as cycloalkyl if at least one non-aromatic cyclic hydrocarbon is present.

In the context of the present invention, alkylaryl is to be understood as meaning an aryl group (see above) connected to another atom via a C _1-6 alkyl (see above) which may be branched or linear and is unsubstituted or substituted one or more times . Preferably, alkylaryl is to be understood as meaning an aryl group (see above) connected to another atom via 1-4 (-CH ₂ -) groups. Most preferably, alkylaryl is benzyl (ie -CH ₂ -phenyl).

In the context of the present invention, alkylheterocyclyl should be understood as meaning a heterocyclyl group connected to another atom via C _1-6 -alkyl (see above), which may be branched or linear and is unsubstituted or substituted one or more times. Preferably, alkylheterocyclyl is to be understood as meaning a heterocyclyl group (see above) connected to another atom via 1-4 (-CH ₂ -) groups. Most preferably, the alkylheterocyclyl is -CH ₂ -pyridine.

In the context of the present invention, alkylcycloalkyl should be understood as meaning a cycloalkyl group connected to another atom via C _1-6 -alkyl (see above), which may be branched or linear and is unsubstituted or substituted one or more times. Preferably, alkylcycloalkyl is to be understood as meaning a cycloalkyl group (see above) connected to another atom via 1-4 (-CH ₂ -) groups. Most preferably, the alkylcycloalkyl is -CH ₂ -cyclopropyl.

Preferably, the aryl is a monocyclic aryl. More preferably, aryl is a 5-, 6-, or 7-membered monocyclic aryl. Even more preferably, the aryl is a 5- or 6-membered monocyclic aryl.

Preferably, the heteroaryl is a monocyclic heteroaryl. More preferably, heteroaryl is a 5-, 6-, or 7-membered monocyclic heteroaryl. Even more preferably, the heteroaryl is a 5- or 6-membered monocyclic heteroaryl.

Preferably, the non-aromatic heterocyclyl is a monocyclic non-aromatic heterocyclyl. More preferably, the non-aromatic heterocyclyl is a 4-, 5-, 6- or 7-membered monocyclic non-aromatic heterocyclyl. Even more preferably, the non-aromatic heterocyclyl is a 5- or 6-membered monocyclic non-aromatic heterocyclyl.

Preferably, the cycloalkyl is a monocyclic cycloalkyl. More preferably, cycloalkyl is a 3-, 4-, 5-, 6-, 7-, or 8-membered monocyclic cycloalkyl. Even more preferably, the cycloalkyl is a 3-, 4-, 5- or 6-membered monocyclic cycloalkyl.

When applied to aryl (including alkylaryl), cycloalkyl (including alkylcycloalkyl) or heterocyclyl (including alkylheterocyclyl), "substituted" should be understood - unless otherwise indicated - as meaning a substitution of the aryl or alkylaryl, cycloalkyl or alkylcycloalkyl ring system; heterocyclyl or alkylheterocyclyl with one or more of halogen (F, Cl, Br, I), -R _c , -OR _c , -CN, -NO ₂ , -NR _c R _c''' , -C(O)OR _c , NR _c C(O)R _c' , -C(O)NR _c R _c' , -NR _c S(O) ₂ R _c' , =O, -OCH ₂ CH ₂ OH, -NR _c C(O) NR _c' R _c'' , -S(O) ₂ NR _c R _c' , -NR _c S(O) ₂ NR _c' Rc _'' , haloalkyl, haloalkoxy, -SR _c , -S(O)R _c , -S(O) ₂ R _c or C(CH ₃ )OR _c ; NR _c R _c''' , wherein R _c , R _c' , R _c'' and R _c''' are independently either H or saturated or unsaturated, linear or branched, substituted or unsubstituted C _1-6 -alkyl ; saturated or unsaturated, linear or branched, substituted or unsubstituted C _1-6 -alkyl; saturated or unsaturated, linear or branched, substituted or unsubstituted -O-C _{1-6 -} alkyl (alkoxy); saturated or unsaturated, linear or branched, substituted or unsubstituted -SC _{1-6 -} alkyl; a saturated or unsaturated, linear or branched, substituted or unsubstituted -C(O)-C _1-6 alkyl group; a saturated or unsaturated, linear or branched, substituted or unsubstituted -C(O)-O-C _1-6 alkyl group; substituted or unsubstituted aryl or alkylaryl; substituted or unsubstituted cycloalkyl or alkylcycloalkyl; substituted or unsubstituted heterocyclyl or alkylheterocyclyl, wherein R _c is one of R ₁₁ , R ₁₂ or R ₁₄ , (wherein R _c' is one of R _11' , R _12' or R _14' ; wherein R _c'' is is one of R _11'' , R _12'' or R _14'' ; wherein R _c''' is one of R _11''' , R _12''' or R _14''' ; wherein R _c'''' is one of R _11'''' , R _12'''' or R _14'''' ), where R ₁ -R _14'''' and R _x , R _x' and R _n are such as defined in the description, and moreover, when different radicals R ₁ -R _14'''' and R _x , R _x' and R _n are present simultaneously in the formula I, they may be identical or different.

Most preferably, when applied to aryl (including alkylaryl), cycloalkyl (including alkylcycloalkyl), or heterocyclyl (including alkylheterocyclyl), "substituted" is to be understood in the context of the present invention such that any aryl, cycloalkyl, and heterocyclyl that is substituted is substituted (also in alkylaryl, alkylcycloalkyl or alkylheterocyclyl) one or more of halogen (F, Cl, Br, I), -R _c , -OR _c , -CN, -NO ₂ , -NR _c R _c''' , NR _c C(O )R _c' , -NRcS(O) ₂ R _c' , =O, haloalkyl, haloalkoxy or C(CH ₃ )OR _c ; wherein -OC _1-4 alkyl is unsubstituted or substituted by one or more of OR _c or halo (F, Cl, I, Br), -CN, or -C _1-4 alkyl is unsubstituted or substituted by one or more of OR _c or halogen (F, Cl, I, Br), and R _c is one of R ₁₁ , R ₁₂ or R ₁₄ , (and R _c' is one of R _11' , R _12' or R _14' ; and R _c'' is one of R _11'' , R _12'' and R _14'' ; wherein R _c''' is one of R _11''' , R _12''' or R _14''' ; wherein R _c'''' is one of R _11'''' , R _12'''' or R _14'''' ), where R ₁ -R _14'''' and R _x , R _x' and R _n are , as defined in the description, and moreover, when different radicals R ₁ -R _14'''' and R _x , R _x' and R _n are present simultaneously in the formula I, they may be identical or different.

или =O.In addition to the above substitutions, in relation to cycloalkyl (including alkylcycloalkyl) or heterocyclyl (including alkylheterocyclyl), namely non-aromatic heterocyclyl (including non-aromatic alkylheterocyclyl), "substituted" should also be understood - unless otherwise indicated - as meaning a substitution of the cycloalkyl or alkylcycloalkyl ring system; non-aromatic heterocyclyl or non-aromatic alkyl heterocyclyl on

or =O.

(что дает спироструктуру) или на =O.When applied to cycloalkyl (including alkylcycloalkyl) or heterocyclyl (including alkylheterocyclyl), namely non-aromatic heterocyclyl (including non-aromatic alkylheterocyclyl), "substituted" should also be understood - unless otherwise indicated - as meaning a substitution of the cycloalkyl or alkylcycloalkyl ring system; non-aromatic heterocyclyl or non-aromatic alkyl heterocyclyl on

(which gives the spiro structure) or on =O.

A ring system is a system consisting of at least one ring of connected atoms, but also including systems in which two or more rings of connected atoms are attached, with "attached" meaning that the respective rings have one (as a spiro structure), two or more common atoms that are a member or members of both attached rings.

The term "leaving group" means a fragment of a molecule that leaves with a pair of electrons upon heterolytic bond cleavage. The leaving groups may be anions or neutral molecules. Common anionic leaving groups are halides such as Cl-, Br- and I- and sulfonate esters such as tosylate (TsO-) or mesylate.

The term "salt" should be understood to mean any form of the active compound used according to the present invention in which it assumes an ionic form, or is charged and associated with a counterion (cation or anion), or is in solution. It should also be understood as complexes of the active compound with other molecules and ions, in particular complexes by means of ionic interactions.

The term "physiologically acceptable salt" means in the context of the present invention any salt that is physiologically tolerable (meaning that most of the time it is not toxic, in particular not caused by a counterion), when used, respectively, for treatment, in particular when used on humans and/or mammals or as applicable to them.

These physiologically acceptable salts can be formed with cations or bases and in the context of the present invention they should be understood as meaning salts of at least one of the compounds used according to the present invention - usually a (deprotonated) acid - as an anion with at least one, preferably inorganic , a cation that is physiologically acceptable - in particular when applied to humans and/or mammals. Alkali metal and alkaline earth metal salts are especially preferred, as well as salts with NH ₄ , but in particular salts of (mono)- or (di)sodium, (mono)- or (di)potassium, magnesium or calcium.

Physiologically acceptable salts can also be formed with anions or acids and in the context of the present invention they should be understood as meaning salts of at least one of the compounds used according to the present invention in the form of a cation with at least one anion, which are physiologically tolerable - in particular, when applied to humans and/or mammals. This is to be understood, in particular in the context of the present invention, as a salt formed with a physiologically tolerable acid, in other words, salts of the particular active compound with inorganic or organic acids which are physiologically tolerable - in particular for use in humans and/or mammals. Examples of physiologically acceptable salts of specific acids are salts of: hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid or citric acid .

The compounds of the present invention may be in crystalline form or as free compounds such as free base or acid.

Any compound which is a solvate of a compound of the present invention, such as a compound of general formula I as defined above, is also to be understood as being included within the scope of the present invention. Solvation methods are generally known in the art. Suitable solvates are pharmaceutically acceptable solvates. The term "solvate", according to this invention, should be understood as meaning any form of the active compound according to the present invention, in which this compound has been attached to it by non-covalent binding with another molecule (most likely with a polar solvent). Particularly preferred examples include hydrates and alcoholates such as methanolates or ethanolates.

Any compound which is a prodrug of a compound of the present invention, such as a compound of general formula I as defined above, is to be understood as also included within the scope of the present invention. The term "prodrug" is used in its broadest sense and includes those derivatives which are converted in vivo to the compounds of the present invention. Such derivatives will be readily apparent to those skilled in the art and include, depending on the functional groups present in the molecule and without limitation, the following derivatives of the compounds of the present invention: esters, amino acid esters, phosphate esters, sulfonate esters of metal salts , carbamates and amides. Examples of well-known methods for producing a prodrug of a given active compound are known to those skilled in the art and can be found, for example, in Krogsgaard-Larsen et al. "Textbook of Drug design and Discovery" Taylor & Francis (April 2002).

Any compound which is the N-oxide of a compound of the present invention, such as a compound of general formula I as defined above, is to be understood as also included within the scope of the present invention.

Unless otherwise indicated, compounds of the present invention are also to be understood as including compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds with these structures, with the exception of replacing hydrogen with deuterium or tritium, or replacing carbon with ¹³ C- or ¹⁴ C-rich carbon, or nitrogen with ¹⁵ N-rich nitrogen, are within the scope of the present invention. This will in particular also apply to the conditions described above, so that any reference to hydrogen or any "H" in the formula will also cover deuterium or tritium.

The compounds of formula (I) as well as their salts or compound solvates are preferably in a pharmaceutically acceptable or substantially pure form. By pharmaceutically acceptable form is meant, inter alia, the presence of a pharmaceutically acceptable level of purity, excluding conventional pharmaceutical additives such as diluents and carriers, and excluding material considered toxic at normal dosage levels. Purity levels for the drug substance are preferably above 50%, more preferably above 70%, most preferably above 90%. In a preferred embodiment, it is greater than 95% of the compound of formula (I) or salts thereof. This also applies to its solvates or prodrugs.

In yet another embodiment, a compound of the present invention of general formula (I)

is a connection where

p is 0 or 1;

m is 1, 2 or 3;

n is 0, 1 or 2;

Y represents -CH ₂ - or -C(O)-;

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

where R _{x is} selected from halo or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

where said cycloalkyl in R ₁ , if substituted, is substituted with one or more substituents/s selected from halo, -R ₁₁ , -OR ₁₁ , -NO ₂ , -NR ₁₁ R _11''' , NR ₁₁ C(O) R _11' , -NR ₁₁ S(O) ₂ R _11' , -S(O) ₂ NR ₁₁ R _11' , -NR ₁₁ C(O)NR _11' R _11'' , -SR ₁₁ , -S( O)R ₁₁ , S(O) ₂ R ₁₁ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₁ , -C(O)NR ₁₁ R _11' , -OCH ₂ CH ₂ OH, -NR ₁₁ S (O) ₂ NR _11' R _11'' and C(CH ₃ ) ₂ OR ₁₁ ;

или =O;in addition, the cycloalkyl in R ₁ , if substituted, may also be substituted with

or =O;

where alkyl, alkenyl or alkynyl in R ₁ , if substituted, is substituted with one or more substituent(s) selected from -OR ₁₁ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₁ R _11''' ;

where R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

and where R _11''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

where the specified cycloalkyl, aryl or heterocyclyl in R ₂ if substituted, is substituted with one or more substituent(s) selected from halogen, -R ₁₂ , -OR ₁₂ , -NO ₂ , -NR ₁₂ R _12''' , NR ₁₂ C(O)R _12' , -NR ₁₂ S(O) ₂ R _12' , -S(O) ₂ NR ₁₂ R _12' , -NR ₁₂ C(O)NR _12' R _12'' , -SR ₁₂ , -S(O)R ₁₂ , S(O) ₂ R ₁₂ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₂ , -C(O)NR ₁₂ R _12' , -OCH ₂ CH ₂ OH, -NR ₁₂ S(O) ₂ NR _12' R _12'' and C(CH ₃ ) ₂ OR ₁₂ ;

или =O;in addition, the cycloalkyl or non-aromatic heterocyclyl in R ₂ , if substituted, may also be substituted with

or =O;

where alkyl, alkenyl or alkynyl in R ₂ , if substituted, is substituted with one or more substituent(s) selected from -OR ₁₂ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₂ R _12''' ;

where R ₁₂ , R _12' and R _12'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

and where R _12''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

R ₃ and R _3' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₃ and R _3' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl;

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

where R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl and substituted or unsubstituted C _2-9 alkynyl;

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

R ₆ and R _6' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -OR ₁₀ , -CHOR ₁₀ and -C(O )OR ₁₀ ;

where R ₁₀ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alkyl, alkenyl or alkynyl other than those defined in R ₁ or R ₂ , if substituted, is substituted with one or more substituent(s) selected from -OR ₁₃ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₃ R _13''';

where R ₁₃ is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

R _13''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

aryl, heterocyclyl or cycloalkyl other than those defined in R ₁ or R ₂ , if substituted, is substituted with one or more substituents/s selected from halogen, -R ₁₄ , -OR ₁₄ , -NO ₂ , -NR ₁₄ R _14''' , NR ₁₄ C(O)R _14' , -NR ₁₄ S(O) ₂ R _14' , -S(O) ₂ NR ₁₄ R _14' , -NR ₁₄ C(O)NR _14' R _14'' , -SR ₁₄ , -S(O)R ₁₄ , S(O) ₂ R ₁₄ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₄ , -C(O)NR ₁₄ R _14' , -OCH ₂ CH ₂ OH, -NR ₁₄ S(O) ₂ NR _14' R _14'' and C(CH ₃ ) ₂ OR ₁₄ ;

или =O;in addition, where cycloalkyl or non-aromatic heterocyclyl other than those defined in R ₁ or R ₂ , if substituted, may also be substituted with

or =O;

where R ₁₄ , R _14' and R _14'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

and where R _14''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _1-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

These preferred compounds according to the present invention are optionally present as one of the stereoisomers, preferably enantiomers or diastereomers, the racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their corresponding salt, or their corresponding solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

m is 1, 2 or 3;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

n is 0, 1 or 2;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

p is 0 or 1;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

X is a bond;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

X is -C(R _x R _x' )-;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

X is -O-;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

X is -C(O)-;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

Y represents -CH ₂ - or -C(O)-;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

Y is -CH ₂ -;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

Y is -C(O)-;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is substituted or unsubstituted C _1-6 alkyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl and substituted or unsubstituted cycloalkyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein R ₃ and R _3' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₃ and R _3' are independently selected from hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₃ and R _3' taken together with the connecting C-atom form a substituted or unsubstituted cycloalkyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, and substituted or unsubstituted C _2-9 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₄ and R _4' are independently selected from hydrogen and substituted or unsubstituted C _1-9 alkyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₅ and R _5' taken together with the connecting C atom form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₅ and R _5' taken together with the connecting C atom form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl, m is 1, X is a bond, n is 0, and R ₂ is hydrogen;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₅ and R _5' taken together with the connecting C atom form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted saturated heterocyclyl, m is 1, X is a bond, n is 0, and R ₂ is hydrogen;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₆ and R _6' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -OR ₁₀ , -CHOR ₁₀ and -C(O )OR ₁₀ ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₆ and R _6' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, and substituted or unsubstituted C _2-9 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₀ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

and where R _11''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R _11''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₂ , R _12' and R _12'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

and where R _12''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₂ , R _12' and R _12'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R _12''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₃ is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

R _13''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₃ is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R _13''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₄ , R _14' and R _14'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

and where R _14''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₄ , R _14' and R _14'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R _14''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R _{x is} selected from halo, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R _{x is} selected from halo, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment, the compound of the present invention of general formula (I) is a compound wherein

p is 0 or 1;

m is 1, 2 or 3;

n is 0, 1 or 2;

Y represents -CH ₂ - or -C(O)-;

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably C _1-6 alkyl is methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, isopentyl or neopentyl;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

and/or

cycloalkyl is C _3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; preferably cycloalkyl is cyclopropyl;

and/or

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably C _1-6 alkyl is methyl, ethyl, propyl, isopropyl, isobutyl, t-butyl or neopentyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

and/or

aryl is selected from phenyl, naphthyl or anthracene; preferably, it is naphthyl or phenyl; more preferably it is phenyl;

and/or

heterocyclyl is a heterocyclic ring system wherein, of one or more saturated or unsaturated rings, at least one ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system, wherein, of one or two saturated or unsaturated rings, at least one ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably selected from imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2, 3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline; more preferably is pyridine;

and/or

cycloalkyl is C _3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; preferably cycloalkyl is cyclopropyl; and/or

R ₃ and R _3' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl; preferably is methyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine; and/or

R ₃ and R _3' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl;

where

cycloalkyl is C _3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; more preferably the cycloalkyl is cyclopropyl;

and/or

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl; preferably is methyl;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

and/or

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine; and/or

R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

where

non-aromatic heterocyclyl is a heterocyclic ring system, wherein one or more saturated or unsaturated rings has at least one ring containing one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring; is preferably a non-aromatic heterocyclic ring system, wherein, of one or two saturated or unsaturated rings, at least one ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably selected from piperidine, piperazine , tetrahydropyran, morpholine, oxopyrrolidine; preferably the non-aromatic heterocyclyl is tetrahydropyran;

and/or

cycloalkyl is C _3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; more preferably it is cyclobutyl, cyclopentyl or cyclohexyl; and/or

R ₆ and R _6' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -OR ₁₀ , -CHOR ₁₀ and -C(O )OR ₁₀ ;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine; and/or

R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butane, pentyne and hexine;

and/or

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

and/or

R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, and substituted or unsubstituted C _2-9 alkynyl;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

and/or

R ₁₀ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine; and/or

R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

R _11''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine; and/or

R ₁₂ , R _12' and R _12'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

R _12''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl; preferably C _1-6 alkyl is methyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine; and/or

R ₁₃ is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

R _13''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butane, pentyne and hexine;

and/or

R ₁₄ , R _14' and R _14'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

R _14''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butane, pentyne and hexine; and/or

aryl is selected from phenyl, naphthyl and anthracene; preferably, it is naphthyl or phenyl;

and/or

heterocyclyl is a heterocyclic ring system wherein, of one or more saturated or unsaturated rings, at least one ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system, wherein, of one or two saturated or unsaturated rings, at least one ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably selected from imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2, 3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline;

and/or

cycloalkyl is C _3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

and/or

R _{x is} selected from halo, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

and/or

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

where

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where in R ₁ as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably C _1-6 alkyl is methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, isopentyl or neopentyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

and/or

cycloalkyl is C _3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; preferably cycloalkyl is cyclopropyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where in R ₂ as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably C _1-6 alkyl is methyl, ethyl, propyl, isopropyl, isobutyl, t-butyl or neopentyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butane, pentyne and hexine;

and/or

aryl is selected from phenyl, naphthyl or anthracene; preferably, it is naphthyl or phenyl; more preferably it is phenyl;

and/or

heterocyclyl is a heterocyclic ring system wherein, of one or more saturated or unsaturated rings, at least one ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system, wherein, of one or two saturated or unsaturated rings, at least one ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably selected from imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2, 3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline; preferably is pyridine;

and/or

cycloalkyl is C _3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; preferably cycloalkyl is cyclopropyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where in R ₃ and R _3' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably is methyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine; and/or

cycloalkyl is C _3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; more preferably the cycloalkyl is cyclopropyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound where in R ₄ and R _4' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl; more preferably is methyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where in R ₅ and R _5' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine; and/or

non-aromatic heterocyclyl is a heterocyclic ring system, wherein one or more saturated or unsaturated rings has at least one ring containing one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring; is preferably a non-aromatic heterocyclic ring system, wherein, of one or two saturated or unsaturated rings, at least one ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably selected from piperidine, piperazine , tetrahydropyran, morpholine, oxopyrrolidine; preferably the non-aromatic heterocyclyl is tetrahydropyran;

and/or

cycloalkyl is C _3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; more preferably it is cyclobutyl, cyclopentyl or cyclohexyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where in R ₆ and R _6' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio

components in the mixture, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where in R ₇ as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound where in R ₈ as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound where in R ₉ as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where in R ₁₀ as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound where in R ₁₁ , R _11' and R _11'' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound where in R _11''' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound where in R ₁₂ , R _12' and R _12'' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl; preferably C _1-6 alkyl is methyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound where in R _12''' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound where in R ₁₃ and R _13''' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound where in R ₁₄ , R _14' and R _14'' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine; and/or

aryl is selected from phenyl, naphthyl and anthracene; preferably, it is naphthyl or phenyl;

and/or

heterocyclyl is a heterocyclic ring system wherein, of one or more saturated or unsaturated rings, at least one ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring; preferably is a heterocyclic ring system, wherein, of one or two saturated or unsaturated rings, at least one ring contains one or more heteroatoms from the group consisting of nitrogen, oxygen and/or sulfur in the ring, more preferably selected from imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2, 3b]pyridine, quinoline, isoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline;

and/or

cycloalkyl is C _3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is C _3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably C _3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound where in R _14''' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where in R _x as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound wherein in R _x' as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl and 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene and hexylene;

and/or

C _2-6 alkynyl is preferably selected from ethyne, propyne, butyne, pentyne and hexine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where

n is 0, 1 or 2; preferably n is 0;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where

m is 1, 2 or 3; preferably m is 1 or 2;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where

p is 0 or 1 or 2;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where

p is 0 or 1;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-; preferably X is a bond or -O-;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where

Y represents -CH ₂ - or -C(O)-;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another preferred embodiment of the present invention according to the general formula (I), the compound is a compound, where

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-; preferably X is a bond or -O- and/or

m is 1, 2 or 3; preferably m is 1 or 2; and/or

n is 0, 1 or 2; preferably n is 0; and/or

p is 0 or 1; preferably p is 0;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I) the compound is a compound of formula (I')

where R ₁ , R ₂ , R ₃ R _3' , R ₄ , R _4' , R ₅ , R _5' , X, Y, m and p are as described above or as described below.

In another preferred embodiment of the present invention according to the general formula (I) the compound is a compound of formula (I')

where

p is 0 or 1;

m is 1, 2 or 3;

Y represents -CH ₂ - or -C(O)-;

X is a bond, -C(RXRX)-, -C(O)- or -O-;

where R _{x is} selected from halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

R ₃ and R _3' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₃ and R _3' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl;

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

where R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl and substituted or unsubstituted C _2-9 alkynyl;

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I) the compound is a compound of formula (I ^a ')

where

p is 0 or 1;

m is 1, 2 or 3;

Y represents -CH ₂ - or -C(O)-;

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

where R _{x is} selected from halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

R ₃ and R _3' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₃ and R _3' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl;

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

where R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl and substituted or unsubstituted C _2-9 alkynyl;

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I) the compound is a compound of formula (I ^b ')

where

p is 0 or 1;

m is 1, 2 or 3;

Y represents -CH ₂ - or -C(O)-;

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

where R _{x is} selected from halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

where R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl and substituted or unsubstituted C _2-9 alkynyl;

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I) the compound is a compound of formula (I ^c ')

where

p is 0 or 1;

m is 1, 2 or 3;

Y represents -CH ₂ - or -C(O)-;

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

where R _{x is} selected from halo, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and —OR ₈ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

where R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl and substituted or unsubstituted C _2-9 alkynyl;

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a further preferred embodiment of the present invention according to the general formula (I), the compound is a compound of formula (I),

where R ₁ , R ₂ , R ₄ , R _4' , R ₅ , R _5' , X, Y, m and p are as described above or as described below.

In an additional preferred embodiment of the present invention according to the general formula (I), the compound is a compound of formula (I ^2' ),

where

p is 0 or 1;

m is 1, 2 or 3;

Y represents -CH ₂ - or -C(O)-;

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

where R _{x is} selected from halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

where R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl and substituted or unsubstituted C _2-9 alkynyl;

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a further preferred embodiment of the present invention according to the general formula (I), the compound is a compound of formula (I ^3' ),

where R ₁ , R ₂ , R ₄ , R _4' , R ₅ , R _5' , X, Y, m and p are as described above or as described below.

In a further preferred embodiment of the present invention according to the general formula (I), the compound is a compound of formula (I ^3' ),

where

p is 0 or 1;

m is 1, 2 or 3;

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

where R _{x is} selected from halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ⁸ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ⁸ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

R ₄ and R _4' are independently selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl, substituted or unsubstituted C _2-9 alkynyl, -CHOR ₉ and -C(O)OR ₉ ;

where R ₉ is selected from hydrogen, substituted or unsubstituted C _1-9 alkyl, substituted or unsubstituted C _2-9 alkenyl and substituted or unsubstituted C _2-9 alkynyl;

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I) the compound is a compound of formula (I ^4' ),

where R ₁ , R ₂ , m and p are as described above or as described below.

In another preferred embodiment of the present invention according to the general formula (I) the compound is a compound of formula (I ^4' ),

where

p is 0 or 1;

m is 1, 2 or 3;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I) the compound is a compound of formula (I ^5' ),

where

m is 1, 2 or 3;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another preferred embodiment of the present invention according to the general formula (I) the compound is a compound of formula (I ^6' )

where

m is 1, 2 or 3;

Y represents -CH ₂ - or -C(O)-;

X is a bond, -C(R _x R _x' )-, -C(O)- or -O-;

where R _{x is} selected from halogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and -OR ₈ ;

R _x' is selected from hydrogen, halogen, or substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₈ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

R ₃ and R _3' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₃ and R _3', taken together with the connecting C-atom, may form a substituted or unsubstituted cycloalkyl;

R ₅ and R _5' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, -CHOR ₇ and -C(O)OR ₇ ;

where R ₇ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₅ and R _5' taken together with the connecting C atom may form a substituted or unsubstituted cycloalkyl or a substituted or unsubstituted non-aromatic heterocyclyl;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment, R ₁ is a substituted or unsubstituted group selected from methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, isopentyl, neopentyl, and cyclopropyl.

In a preferred embodiment, R ₁ is an unsubstituted group selected from methyl, ethyl, propyl, isopropyl, isobutyl, sec-butyl, isopentyl, neopentyl, and cyclopropyl.

In a preferred embodiment, R ₁ is substituted or unsubstituted cyclopropyl, preferably unsubstituted cyclopropyl.

In a preferred embodiment, R ₂ is hydrogen or a substituted or unsubstituted group selected from methyl, ethyl, propyl, isopropyl, isobutyl, t-butyl, neopentyl, cyclopropyl, phenyl, and pyridine; more preferably hydrogen or an unsubstituted group selected from methyl, ethyl, propyl, isopropyl, isobutyl, t-butyl, neopentyl, cyclopropyl, or a substituted or unsubstituted group selected from phenyl and pyridine.

In a preferred embodiment, R ₃ and R _3' taken together with the connecting C-atom can form a substituted or unsubstituted cyclopropyl: preferably an unsubstituted cyclopropyl.

In a preferred embodiment, R ₃ is hydrogen or substituted or unsubstituted methyl, preferably R ₃ is hydrogen or unsubstituted methyl.

In a preferred embodiment, R _3' is hydrogen or substituted or unsubstituted methyl, preferably R _3' is hydrogen or unsubstituted methyl.

In a preferred embodiment, R _3' is hydrogen while R ₃ is substituted or unsubstituted methyl, preferably R _3' is hydrogen while R ₃ is unsubstituted methyl.

In a preferred embodiment, R ₃ is hydrogen while R _3' is substituted or unsubstituted methyl, preferably R ₃ is hydrogen while R _3' is unsubstituted methyl.

In a preferred embodiment, both R ₃ and R _3' are substituted or unsubstituted methyl, preferably both R ₃ and R _3' are unsubstituted methyl.

In a preferred embodiment, both R ₃ and R _3' are hydrogen.

In a preferred embodiment, R ₄ is hydrogen or substituted or unsubstituted methyl, preferably R ₄ is hydrogen or unsubstituted methyl.

In a preferred embodiment, R _4' is hydrogen.

In a preferred embodiment, R _4' is hydrogen while R ₄ is substituted or unsubstituted methyl, preferably R _4' is hydrogen while R ₄ is unsubstituted methyl.

In a preferred embodiment, both R ₄ and R _4' are hydrogen.

In a preferred embodiment, both R ₅ and R _5' are hydrogen.

In a preferred embodiment, R ₅ and R _5' taken together with the connecting C atom form a substituted or unsubstituted group selected from cyclobutyl, cyclopentyl, cyclohexyl or tetrahydropyran, preferably an unsubstituted group selected from cyclobutyl, cyclopentyl, cyclohexyl or tetrahydropyran.

In a preferred embodiment, both R ₆ and R _6' are hydrogen.

In a preferred embodiment, X is a bond.

In a preferred embodiment, X is -O-.

In a preferred embodiment, Y is -CH ₂ -;

In a preferred embodiment, Y is -C(O)-;

In another preferred embodiment, n is 0.

In another preferred embodiment, n is 1.

In another preferred embodiment, n is 2.

In another preferred embodiment, m is 1 or 2;

In another preferred embodiment, p is 0, 1, or 2.

In another preferred embodiment, p is 0 or 1.

In another preferred embodiment, p is 0.

In a particular embodiment, the halogen is fluorine or chlorine.

In yet another preferred embodiment, the compounds of general formula (I) are selected from the following:

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In yet another preferred embodiment, the compounds of general formula (I) are selected from the following:

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment of a compound of the present invention with the general formula (I),

R ₁ is selected from substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and substituted or unsubstituted cycloalkyl;

where said cycloalkyl in R ₁ , if substituted, is substituted with one or more substituents/s selected from halo, -R ₁₁ , -OR ₁₁ , -NO ₂ , -NR ₁₁ R _11''' , NR ₁₁ C(O) R _11' , -NR ₁₁ S(O) ₂ R _11' , -S(O) ₂ NR ₁₁ R _11' , -NR ₁₁ C(O)NR _11' R _11'' , -SR ₁₁ , -S( O)R ₁₁ , S(O) ₂ R ₁₁ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₁ , -C(O)NR ₁₁ R _11' , -OCH ₂ CH ₂ OH, -NR ₁₁ S (O) ₂ NR _11' R _11'' and C(CH ₃ ) ₂ OR ₁₁ ;

или =O;in addition, the cycloalkyl in R ₁ , if substituted, may also be substituted with

or =O;

where alkyl, alkenyl or alkynyl in R ₁ , if substituted, is substituted with one or more substituent(s) selected from -OR ₁₁ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₁ R _11''' ;

where R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

and where R _11''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another embodiment of the present invention, a compound of general formula (I),

R ₂ is selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl,

where the specified cycloalkyl, aryl or heterocyclyl in R ₂ if substituted, is substituted with one or more substituent(s) selected from halogen, -R ₁₂ , -OR ₁₂ , -NO ₂ , -NR ₁₂ R _12''' , NR ₁₂ C(O)R _12' , -NR ₁₂ S(O) ₂ R _12' , -S(O) ₂ NR ₁₂ R _12' , -NR ₁₂ C(O)NR _12' R _12'', SR ₁₂ , -S(O)R ₁₂ , S(O) ₂ R ₁₂ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₂ , -C(O)NR ₁₂ R _12' , -OCH ₂ CH ₂ OH, - NR ₁₂ S(O) ₂ NR _12' R _12'' and C(CH ₃ ) ₂ OR ₁₂ ;

или =O;in addition, the cycloalkyl or non-aromatic heterocyclyl in R ₂ , if substituted, may also be substituted with

or =O;

where alkyl, alkenyl or alkynyl in R ₂ , if substituted, is substituted with one or more substituent(s) selected from -OR ₁₂ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₂ R _12''' ;

where R ₁₂ , R _12' and R _12'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

and where R _12''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another embodiment of the present invention, a compound of general formula (I),

alkyl, alkenyl or alkynyl other than those defined in R ₁ or R ₂ , if substituted, is substituted with one or more substituent(s) selected from -OR ₁₃ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₃ R _13''';

where R ₁₃ is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl;

R _13''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another embodiment of the present invention, a compound of general formula (I),

aryl, heterocyclyl or cycloalkyl other than those defined in R ₁ or R ₂ , if substituted, is substituted with one or more substituents/s selected from halogen, -R ₁₄ , -OR ₁₄ , -NO ₂ , -NR ₁₄ R _14''' , NR ₁₄ C(O)R _14' , -NR ₁₄ S(O) ₂ R _14' , -S(O) ₂ NR ₁₄ R _14' , -NR ₁₄ C(O)NR _14' R _14'' , -SR ₁₄ , -S(O)R ₁₄ , S(O) ₂ R ₁₄ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₄ , -C(O)NR ₁₄ R _14' , -OCH ₂ CH ₂ OH, -NR ₁₄ S(O) ₂ NR _14' R _14'' and C(CH ₃ ) ₂ OR ₁₄ ;

или =O;in addition, where cycloalkyl or non-aromatic heterocyclyl other than those defined in R ₁ or R ₂ , if substituted, may also be substituted with

or =O;

where R ₁₄ , R _14' and R _14'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

and where R _14''' is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, and -Boc;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment of a compound of the present invention with general formula (I), and with respect to R _{1 of} any of the embodiments of the present invention,

cycloalkyl in R ₁ , if substituted, is substituted with one or more substituents/s selected from halogen, -R ₁₁ , -OR ₁₁ , -NO ₂ , -NR ₁₁ R _11''' , NR ₁₁ C(O)R _{11 '} , -NR ₁₁ S(O) ₂ R _11' , -S(O) ₂ NR ₁₁ R _11' , -NR ₁₁ C(O)NR _11' R _11'' , -SR ₁₁ , -S(O) R ₁₁ , S(O) ₂ R ₁₁ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₁ , -C(O)NR ₁₁ R _11' , -OCH ₂ CH ₂ OH, -NR ₁₁ S(O ) ₂ NR _11' R _11'' and C(CH ₃ ) ₂ OR ₁₁ ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment of a compound of the present invention with general formula (I), and with respect to R _{1 of} any of the embodiments of the present invention,

или =O;cycloalkyl in R ₁ , if substituted, may also be substituted with

or =O;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment of a compound of the present invention with general formula (I), and with respect to R _{1 of} any of the embodiments of the present invention,

alkyl, alkenyl or alkynyl in R ₁ , if substituted, is substituted with one or more substituents/s selected from -OR ₁₁ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₁ R _11''' ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment of a compound of the present invention with the general formula (I), and with respect to R _{2 of} any of the embodiments of the present invention,

cycloalkyl, aryl or heterocyclyl in R ₂ , if substituted, is substituted with one or more substituent(s) selected from halo, -R ₁₂ , -OR ₁₂ , -NO ₂ , -NR ₁₂ R _12''' , NR ₁₂ C( O)R _12' , -NR ₁₂ S(O) ₂ R _12' , -S(O) ₂ NR ₁₂ R _12' , -NR ₁₂ C(O)NR _12' R _12'' , -SR ₁₂ , - S(O)R ₁₂ , S(O) ₂ R ₁₂ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₂ , -C(O)NR ₁₂ R _12' , -OCH ₂ CH ₂ OH, -NR ₁₂ S(O) ₂ NR _12' R _12'' . and C(CH ₃ ) ₂ OR ₁₂ ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment of a compound of the present invention with the general formula (I), and with respect to R _{2 of} any of the embodiments of the present invention,

или =O;cycloalkyl or non-aromatic heterocyclyl in R ₂ , if substituted, may also be substituted with

or =O;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment of a compound of the present invention with the general formula (I), and with respect to R _{2 of} any of the embodiments of the present invention,

alkyl, alkenyl or alkynyl in R ₂ , if substituted, is substituted with one or more substituent(s) selected from -OR ₁₂ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₂ R _12''' ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment of a compound of the present invention of general formula (I), and for alkyls other than those defined in R ₁ or R _{2 of} any of the embodiments of the present invention,

alkyl, alkenyl or alkynyl other than those defined in R ₁ or R ₂ , if substituted, is substituted with one or more substituent(s) selected from -OR ₁₃ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₃ R _13''';

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment of a compound of the present invention of general formula (I) and with respect to a cycloalkyl, aryl or heterocyclyl other than those defined in R ₁ or R _{2 of} any of the embodiments of the present invention,

aryl, heterocyclyl or cycloalkyl other than those defined in R ₁ or R ₂ , if substituted, is substituted with one or more substituents/s selected from halogen, -R ₁₄ , -OR ₁₄ , -NO ₂ , -NR ₁₄ R _14''' , NR ₁₄ C(O)R _14' , -NR ₁₄ S(O) ₂ R _14' , -S(O) ₂ NR ₁₄ R _14' , -NR ₁₄ C(O)NR _14' R _14'' , -SR ₁₄ , -S(O)R ₁₄ , S(O) ₂ R ₁₄ , -CN, haloalkyl, haloalkoxy, -C(O)OR ₁₄ , -C(O)NR ₁₄ R _14' , -OCH ₂ CH ₂ OH, -NR ₁₄ S(O) ₂ NR _14' R _14'' and C(CH ₃ ) ₂ OR ₁₄ ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In a preferred embodiment of a compound of the present invention of general formula (I) and with respect to a cycloalkyl, aryl or heterocyclyl other than those defined in R ₁ or R _{2 of} any of the embodiments of the present invention,

или =O;cycloalkyl or non-aromatic heterocyclyl other than those defined in R ₁ or R ₂ , if substituted, may also be substituted with

or =O;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In an embodiment of a compound of the present invention with the general formula (I),

halogen is fluorine, chlorine, iodine or bromine, preferably fluorine or chlorine; more preferably fluorine;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In an embodiment of a compound of the present invention with the general formula (I),

haloalkyl is -CF ₃ ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

In another embodiment of a compound of the present invention with the general formula (I),

haloalkoxy is -OCF ₃ ;

optionally as one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or as a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their respective salt, or their respective solvate.

Since the present invention is directed to providing a compound or a chemically linked series of compounds that act as σ ₁ receptor ligands, a highly preferred embodiment in which compounds are selected that act as σ ₁ receptor ligands and, in particular, compounds that have binding , expressed as K _i , which is preferably <1000 nM, more preferably <500 nM, even more preferably <100 nM.

Hereinafter, the phrase "compound of the present invention" is used. It should be understood as any compound according to the present invention, described above, according to the General formula (I), (I'), (I ^a' ), (I ^b' ), (I ^c' ), (I ² _' ), ( I ³ _' ), (I ⁴ _' ), (I ⁵ _' ), (I ⁶ _' ) or (I ⁷ _' ).

The compounds of the present invention represented by formula (I) above may include enantiomers depending on the presence of chiral centers or isomers depending on the presence of multiple bonds (eg Z, E). Some isomers, enantiomers or diastereoisomers and mixtures thereof are within the scope of the present invention.

The methods are generally described below in the experimental section. Starting materials are commercially available or can be obtained by conventional methods.

A preferred aspect of the present invention is also a process for preparing a compound according to formula (I).

A preferred aspect of the present invention is a process for preparing a compound according to formula (I),

and where R ₁ , R ₂ , R ₃ , R _3' , R ₄ , R _4' , R ₅ , R _5' , R ₆ , R _6' , m, n, p, X and Y are as defined in the description following schemes 1-4.

In all methods and uses described below, the values of R ₁ , R ₂ , R ₃ , R _3' , R ₄ , R _4' , R ₅ , R _5' , R ₆ , R _6' , m, n, p, X and Y are as defined in the description (unless otherwise indicated), LG is a leaving group such as halogen, mesylate, tosylate or triflate provided that when Y=CO it can only be chlorine or bromine , V is an aldehyde or other leaving group (such as halogen, mesylate, tosylate or triflate) and P' is a suitable protecting group (preferably 4-methoxybenzyl or benzyl).

A preferred embodiment of the present invention is a process for the preparation of compounds of general formula (I), said process comprising:

a) intramolecular cyclization of a compound of formula VIIa

or

b) reaction of a compound of formula VIIIH

with a compound of formula IX, X or XI,

or

cl) when Y is CH ₂ by alkylating a compound of formula XIV

with compound of formula XV

wherein the compound of formula XV is an alkylating agent and V is a leaving group, or alternatively by a reductive amination reaction of a compound of formula XIV with a compound of formula XV, wherein the compound of formula XV is an aldehyde and V is C(O)H group;

or

c2) when Y is C(O), by alkylating a compound of formula XIV

with compound of formula XV

wherein the compound of formula XV is an alkylating agent and V is a leaving group.

Another embodiment of the present invention is a process for the preparation of compounds of general formula (I), said process comprising the intramolecular cyclization of a compound of formula VIIa

Another embodiment of the present invention is a process for the preparation of compounds of general formula (I), said process comprising the reaction of a compound of formula VIIIH

with a compound of formula IX, X or XI,

Another embodiment of the present invention is a process for the preparation of compounds of general formula (I) wherein Y is CH ₂ , said process comprising alkylation of a compound of formula XIV

with compound of formula XV

wherein the compound of formula XV is an alkylating agent and V is a leaving group, or alternatively by a reductive amination reaction of a compound of formula XIV with a compound of formula XV, wherein the compound of formula XV is an aldehyde and V is C(O)H group;

Another embodiment of the present invention is a process for preparing compounds of general formula (I) where Y is C(O) by alkylation of a compound of formula XIV

with compound of formula XV

wherein the compound of formula XV is an alkylating agent and V is a leaving group.

Another preferred embodiment of the present invention is a process for the preparation of compounds of general formula (I) wherein Y is CO and R ₃ and R _3' taken together with the connecting C atom form cyclopropyl (compounds of formula Ic),

wherein said method includes

a) treating with a strong base a compound of formula Ib, where R _s =R _s' =H and s=1

or

b) a cyclopropanation reaction on a compound of formula XXI

or

c) alkylation of a compound of formula XXV

with compound of formula XV

wherein the compound of formula XV is an alkylating agent and V is a leaving group;

or

d) reacting a compound of formula XIXH

with a compound of formula IX, X or XI,

Another preferred embodiment of the present invention is a process for the preparation of compounds of general formula (I) wherein Y is CO and R ₃ and R _3' taken together with the connecting C atom form cyclopropyl (compounds of formula Ic),

wherein said method includes

treatment with a strong base of a compound of formula Ib, where R _s =R _s' =H and s=1

Another preferred embodiment of the present invention is a process for the preparation of compounds of general formula (I) wherein Y is CO and R ₃ and R _3' taken together with the connecting C atom form cyclopropyl (compounds of formula Ic),

said process comprising a cyclopropanation reaction on a compound of formula XXI

Another preferred embodiment of the present invention is a process for the preparation of compounds of general formula (I) wherein Y is CO and R ₃ and R _3' taken together with the connecting C atom form cyclopropyl (compounds of formula Ic),

said process comprising alkylating a compound of formula XXV

with compound of formula XV

wherein the compound of formula XV is an alkylating agent and V is a leaving group.

Another preferred embodiment of the present invention is a process for the preparation of compounds of general formula (I) wherein Y is CO and R ₃ and R _3' taken together with the connecting C atom form cyclopropyl (compounds of formula Ic),

said method comprising the reaction of a compound of formula XIXH

с соединением формулы IX, X или XI,

with a compound of formula IX, X or XI,

In another specific embodiment, a compound of formula II, IIP, III, SR, IVa, IVb, Vb, VbP, Va, VaP, VI, VIIa, VIIb, VIIb, VIIbP, VIIIP, VIIIH, IX, X, XI, XII, XIIP , XIII, XIIIP, XIV, XIVP, XIVH, XV, XVI, XVIP, XVIH, Ia, XVIIP, XVIIH, Ib, XVIIIP, Ic, XIXP, XIXH, Id, XXP, XXH, XXI, XXIP, XXIH, XXII, XXIIP , XXIIH, XXIII, XXIIIP, XXIIIH, XXIV, XXIVP, XXIVH, XXV, XXVP, XXVH, Ie, XXVIP, XXVIH, XXVIIa, XXVIIb, XXVIIc, If, XXVIIIP, XXVIIIH, Ig, XXIXP, XXIXH, Ih, XXXP, XXXH , XXXI, XXXIP, XXXIH, XXXII, XXXIIP, XXXIIH, XXXIII, XXXIIIP, XXXIIIH, XXXIV, XXXIVP or XXXIVH,

или

or

used to obtain a compound of formula (I).

If necessary, the resulting reaction products can be purified by conventional methods such as crystallization and chromatography. Where the above methods for preparing the compounds of the present invention give mixtures of stereoisomers, these isomers can be separated using conventional techniques such as preparative chromatography. In the presence of chiral centers, the compounds can be obtained in racemic form, or individual enantiomers can be obtained by enantiospecific synthesis or by resolution.

One preferred pharmaceutically acceptable form of a compound of the present invention is a crystalline form, including such form in a pharmaceutical composition. In the case of salts as well as solvates of the compounds of the present invention, the additional ionic and solvent moieties must also be non-toxic. The compounds of the present invention may have various polymorphic forms, it is intended that the present invention cover all such forms.

Another aspect of the present invention relates to a pharmaceutical composition which comprises a compound of the present invention as described above according to general formula I, or a pharmaceutically acceptable salt or stereoisomer thereof, and a pharmaceutically acceptable carrier, adjuvant or base. The present invention thus provides pharmaceutical compositions comprising a compound of the present invention, or a pharmaceutically acceptable salt or stereoisomers thereof, together with a pharmaceutically acceptable carrier, excipient or vehicle, for administration to a patient.

Examples of pharmaceutical compositions include any solid (tablets, pills, capsules, granules, etc.) or liquid (solutions, suspensions or emulsions) composition for oral, topical or parenteral administration.

In a preferred embodiment, the pharmaceutical compositions are in solid or liquid form for oral administration. Suitable dosage forms for oral administration may be tablets, capsules, syrups or solutions and may contain conventional excipients known in the art such as binders, for example syrup, acacia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone; fillers, for example lactose, sugar, cornstarch, calcium phosphate, sorbitol or glycine; tablet lubricants, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycolate or microcrystalline cellulose; or pharmaceutically acceptable wetting agents such as sodium lauryl sulfate.

Solid oral compositions may be prepared by conventional mixing, filling or tableting methods. Repetitive mixing operations can be used to distribute the active ingredient in these compositions using large amounts of excipients. Such operations are conventional in the art. Tablets can be prepared, for example, by wet or dry granulation and optionally coated by methods well known in conventional pharmaceutical practice, in particular by enteric coating.

Pharmaceutical compositions may also be adapted for parenteral administration, such as sterile solutions, suspensions, or lyophilized products in a suitable unit dosage form. Suitable adjuvants such as bulking agents, buffering agents or surfactants may be used.

Said formulations will be prepared using standard methods such as those described or referred to in the Spanish or US Pharmacopeias and similar reference texts.

Administration of the compounds or compositions of the present invention may be by any suitable route, such as intravenous infusion, oral preparations, and intraperitoneal and intravenous administration. Oral administration is preferred because of the convenience to the patient and the chronic nature of the diseases to be treated.

In general, the effective amount of a compound of the present invention administered will depend upon the relative potency of the compound chosen, the severity of the disorder being treated, and the weight of the patient. However, the active compounds will generally be administered once or several times a day, for example 1, 2, 3 or 4 times a day, with typical total daily doses being in the range of 0.1 to 1000 mg/kg/day.

The compounds and compositions of the present invention may be used with other drugs to provide combination therapy. Other drugs may be part of the same composition or provided as a separate composition for administration at the same time or at a different time.

Another aspect of the present invention relates to the use of a compound of the present invention, or a pharmaceutically acceptable salt or isomer thereof, in the manufacture of a medicament.

Another aspect of the present invention relates to a compound of the present invention according to the above general formula I, or a pharmaceutically acceptable salt or isomer thereof, for use as a drug for the treatment of drug abuse and dependence.

Another aspect of the present invention relates to the use of a compound of the present invention in the manufacture of a medicament for the treatment or prevention of drug abuse and dependence.

Another aspect of the present invention relates to a method for treating or preventing drug abuse and dependence, the method comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound as defined above, or a pharmaceutical composition thereof.

The present invention is shown below by way of examples. These illustrations are provided by way of example only and do not limit the general essence of the present invention.

General experimental part (methods and equipment for synthesis and analysis)

SCHEME 1:

A 4-step process for the preparation of compounds of general formula (I) is described, starting from the ketone of formula II, as shown in the following scheme:

where R_one, R₂, R₃, R_3', R_four, R_four', R₅, R_5', R₆, R_6', X, Y, m, n and p are as defined above for the compound of formula (I), LG is a leaving group such as halogen, mesylate, tosylate or triflate, with the proviso that when Y=CO it may be chlorine or bromine only, V is an aldehyde or other leaving group (such as halogen, mesylate, tosylate or triflate), P is a suitable protecting group (preferably Boc) and P' is an orthogonal protecting group (preferably 4-methoxybenzyl or benzyl).

The 4-step process is performed as described below:

Step 1: A compound of formula III is prepared by treating a compound of formula II with a suitable methyl transfer reagent such as trimethylsulfoxonium iodide or trimethylsulfonium iodide in a suitable aprotic solvent such as dimethylsulfoxide or 1,2-dimethoxyethane or mixtures and in the presence of a strong base such as sodium hydride or potassium tert-butoxide, at a suitable temperature, preferably between 0°C and 60°C.

Step 2: A compound of formula Va is prepared by reacting a compound of formula III with an amine of formula IVa in a suitable solvent such as an alcohol, preferably mixtures of ethanol and water, at a suitable temperature ranging from room temperature to reflux.

Step 3: A compound of formula VIIa is prepared by reacting a compound of formula Va with a compound of formula VI. Depending on the value of Y, the compound of formula VI may be of a different nature and different reaction conditions will be applied:

a) when Y is CO, VI is an acylating agent. The acylation reaction is carried out in a suitable solvent such as dichloromethane or mixtures of ethyl acetate and water; in the presence of an organic base such as triethylamine or diisopropylethylamine or an inorganic base such as K ₂ CO ₃ ; and at a suitable temperature, preferably -78°C to room temperature.

b) when Y is CH₂, VI is an alkylating agent. The alkylation reaction can be carried out in a suitable solvent such as acetonitrile, dichloromethane, tetrahydrofuran, 1,4-dioxane or dimethylformamide; in the presence of an inorganic base such as K₂CO₃, Cs₂CO₃ or NaH, or an organic base such as triethylamine or diisopropylethylamine at a suitable temperature ranging from room temperature to boiling point. It may be necessary to protect the OH group present before the alkylation reaction.

Step 4: Intramolecular cyclization of a compound of formula VIIa gives a compound of formula I. The cyclization reaction is carried out in a suitable solvent such as tetrahydrofuran; in the presence of a strong base such as potassium tert-butoxide or sodium hydride; and at a suitable temperature of -78° C. to boiling point, preferably by cooling.

Alternatively, the group -(CR ₅ R _5' ) _m X(CR ₆ R _6' ) _n R ₂ can be included in the last step of the synthesis by reacting a compound of formula VIIIH with a compound of formula IX, X or XI as shown in Scheme 1. A compound of formula VIIIH is prepared by deprotection of a compound of formula VIIIP, where P is an appropriate protecting group, preferably Boc (tert-butoxycarbonyl). When the protecting group is Boc, deprotection can be carried out by adding a solution of a strong acid such as HCl in a suitable solvent such as diethyl ether, 1,4-dioxane or methanol, or by using trifluoroacetic acid in dichloromethane. A compound of formula VIIIP is prepared from a compound of formula IIP following the same sequence as described for the synthesis of compounds of formula I.

The alkylation reaction between a compound of formula VIIIH (or a suitable salt such as trifluoroacetate or hydrochloride) and a compound of formula IX is carried out in a suitable solvent such as acetonitrile, dichloromethane, 1,4-dioxane or dimethylformamide, preferably acetonitrile; in the presence of an inorganic base such as K ₂ CO ₃ or Cs ₂ CO ₃ or an organic base such as triethylamine or diisopropylethylamine, preferably K ₂ CO ₃ ; at a suitable temperature ranging from room temperature to the boiling point, preferably by heating, or alternatively, the reactions can be carried out in a microwave reactor. An additional activating agent such as NaI may be used.

The reductive amination reaction between a compound of formula VIIIH and a compound of formula X is carried out in the presence of a reducing agent, preferably sodium triacetoxyborohydride, in an aprotic solvent, preferably tetrahydrofuran or dichloroethane, optionally in the presence of an acid, preferably acetic acid.

The condensation reaction between a compound of general formula VIIIH and a compound of formula XI is preferably carried out in a suitable solvent such as ethanol, isopropanol, n-butanol or 2-methoxyethanol, optionally in the presence of an organic base such as triethylamine or diisopropylethylamine, at a suitable temperature, from room temperature temperature to the boiling point, preferably by heating, or, alternatively, the reactions can be carried out in a microwave reactor.

In another alternative approach, the -(CR ₄ R _4' ) _p R ₁ substituent may be incorporated later in the sequence by reacting a compound of formula XIV with a compound of formula XV. Depending on the value of Y, V may have a different nature and different reaction conditions will apply:

a) when Y is CH ₂ , compound XV is an alkylating agent and V is a leaving group such as halo, mesylate, tosylate or triflate. The alkylation reaction is carried out under the same reaction conditions as described above for the reaction of a compound of formula VIIIH and a compound of formula IX.

Alternatively, compound XV may be an aldehyde where V is a C(O)-H group. The reductive amination reaction is carried out under the same reaction conditions as described above for the reaction of a compound of formula VIIIH and a compound of formula X.

b) when Y is C(O), compound XV is an alkylating agent and V is a leaving group such as halo, mesylate, tosylate or triflate. This alkylation reaction is carried out in an aprotic solvent, preferably dimethylformamide, in the presence of an inorganic base such as NaH, at a suitable temperature, preferably from room temperature to 60°C.

The compound of formula XIV is synthesized following a similar sequence as described for the synthesis of compounds of formula I, but performing step 2 using ammonia instead of amine IVa. Alternatively, when Y is C(O), a compound of formula XIV can be prepared by reacting a compound of formula XIVH (derived from a compound of formula XIVP where P is an appropriate protecting group) with a compound of formula IX, X, or XI as described above. .

In addition, a compound of formula XIV can be prepared from a compound of formula XVI where P' is an orthogonal protecting group. When Y is C(O), P' is preferably a 4-methoxybenzyl group and the deprotection reaction is carried out with cerium ammonium nitrate in a suitable solvent such as mixtures of acetonitrile and water or by heating in trifluoroacetic acid or hydrochloric acid . When Y is -CH ₂ -, P' is preferably a 4-methoxybenzyl, benzyl or benzhydryl group, and the deprotection reaction is preferably carried out by hydrogenation under a hydrogen atmosphere and with a metal catalyst, preferably with palladium on charcoal as a catalyst, in a suitable solvent such as methanol or ethanol, optionally in the presence of an acid such as acetic acid or hydrochloric acid.

A compound of formula XVI is synthesized from a compound of formula III following a similar sequence as described for the synthesis of compounds of formula I. Alternatively, a compound of formula XVI may be prepared by reacting a compound of formula XVIH (obtained from a compound of formula XVIP where P is an appropriate protecting group) with a compound of formula IX, X or XI as described above.

Compounds of general formula II, IIP, IVa, IVb, VI, IX, X, XI and XV, where R ₁ , R ₂ , R ₃ , R _3' , R ₄ , R _4' , R ₅ , R _5' , R ₆ , R _6' , X, Y, m, n and p are as defined above, are commercially available, or can be obtained by conventional methods described in the list of used literature.

SCHEME 2

Obtaining compounds of general formula (I), where Y represents CO, aR ₃ andR _{3 '} taken together with the connecting C-atom to give cycloalkyl (compounds of formula Ia), described in the following scheme:

where R ₁ , R ₂ , R ₄ , R _4' , R ₅ , R _5' , R ₆ , R _6' , X, Y, m, n and p are as defined above for the compound of formula (I), s is 1, 2, 3 or 4, R _s and R _s' are hydrogen or alkyl, LG is a leaving group such as halogen, mesylate, tosylate or triflate, V is another leaving group (such as halogen, mesylate, tosylate or triflate), P is a suitable protecting group (preferably Boc), P' is an orthogonal protecting group (preferably 4-methoxybenzyl), and Q is methyl or benzyl.

A compound of formula Ia can be prepared from a compound of formula Ib by treatment with a strong base such as lithium diisopropylamide or potassium t-butoxide in an aprotic solvent such as tetrahydrofuran at a suitable temperature, preferably cooling. And similarly, a compound of formula Ic (where R _S =R _S' =H and s=l) can be obtained from a compound of formula Ib under the same reaction conditions.

Alternatively, compounds of formula Ic may be prepared from compounds of formula XXI. The cyclopropanation reaction is carried out with a suitable methyl transfer reagent such as trimethylsulfoxonium iodide or trimethylsulfonium iodide in a suitable aprotic solvent such as dimethyl sulfoxide and in the presence of a strong base such as sodium hydride or potassium t-butoxide at a suitable temperature, preferably from room temperature to 60°C. Alternatively, typical Simmons-Smith reaction conditions may be used, including treatment of a compound of formula XXI with diiodomethane, a zinc source such as zinc-copper, zinc iodide or diethylzinc in a suitable aprotic solvent such as diethyl ether.

Compounds of formula XXI may be prepared from a compound of formula Id where Q is methyl or benzyl. The elimination reaction is carried out in the presence of a base such as t-butoxide, potassium, in a suitable solvent such as tetrahydrofuran.

In another alternative approach, the -(CR ₄ R _4' ) _p R ₁ substituent may be included later in the synthesis. Thus, compounds of formula Ia and Ic can be prepared from compounds of formula XXIII and XXV, respectively, following the reaction conditions described in Scheme 1 for the preparation of compounds of formula I from compounds of formula XIV. Compounds of formula XXIII and XXV can be prepared from suitable precursors with protecting groups XXII and XXIV, respectively, following the conditions described in Scheme 1.

In addition, the group -(CR ₅ R _5' ) _m X (CR ₆ R _{6 '} ) _n R ₂ can be included in the last stage of the synthesis to obtain compounds of formula Ia and Ic from suitable precursors with protective groups by deprotection followed by reaction with a compound of formula IX or X or XI as described in Scheme 1 to obtain compounds of formula I.

Compounds of general formula Ib and Id can be prepared by the procedures described in Scheme 1 from a compound of formula Va using suitable starting materials. Compounds of general formulas XXII and XXIV can be prepared by following the procedures described in Scheme 2 for the preparation of compounds of formulas Ia and Ic using the appropriate starting materials with protective groups.

SCHEME 3 and SCHEME 4

Compounds of formula (I) can also be prepared starting from other compounds of formula (I) as described in Schemes 3 and 4 below.

Compounds of formula Ia, If and Ig can be prepared from a compound of formula Ie as shown in Scheme 3:

where R ₁ , R ₂ , R ₃ , R _3' , R ₄ , R _4' , R ₅ , R _5' , R ₆ , R _6' , X, m, n and p are as defined above for the compound of formula (I), s is 1, 2, 3 or 4, R _s and R _s' are hydrogen or alkyl, LG, X' and X'' independently represent a leaving group such as halogen, mesylate, tosylate or triflate, and P is a suitable protecting group (preferably Boc).

A compound of formula If can be prepared by treating a compound of formula Ie with an alkylating agent of formula XXVIIa in the presence of a strong base such as lithium diisopropylamide or potassium t-butoxide in an aprotic solvent such as tetrahydrofuran at a suitable temperature, preferably -78°C to room temperature. temperature. A second alkylation can be carried out under the same reaction conditions to give a compound of formula Ig. A similar double alkylation process can be used to prepare compounds of formula Ia by reacting a compound of formula Ie with an alkylating agent of formula XXVIIc, as an alternative to the procedure described in Scheme 2 for the preparation of compounds of formula Ia.

In addition, the group -(CR ₅ R _{5 '} ) _m X (CR ₆ R _{6 '} ) _n R ₂ can be included in the last stage of the synthesis to obtain compounds of formula Ia, Ie, If and Ig from suitable precursors with protective groups by deletion protecting groups followed by reaction with a compound of formula IX or X or XI under the reaction conditions described in Scheme 1 to obtain compounds of formula I.

Compounds of general formula Ie and If can be obtained by the procedures described in scheme 1, using suitable starting materials.

Compounds of general formula XXVIIa, XXVIIb and XXVIIc, where R ₃ , R _3' , R _s , R _s' , X', X'' and s have the meanings defined above, are commercially available or can be obtained by traditional methods described in list of used literature.

Scheme 4 shows the preparation of compounds of formula (I) where Y is CH ₂ from compounds of formula (I) where Y is C(O):

where R ₁ , R ₂ , R ₃ , R _3' , R ₄ , R _4' , R ₅ , R _5' , R ₆ , R _6' , X, m, n and p are as defined above for the compound of formula (I) LG is a leaving group such as halogen, mesylate, tosylate or triflate, V is an aldehyde or other leaving group (such as halogen, mesylate, tosylate or triflate), P is a suitable protecting group (preferably Boc) , and P' represents an orthogonal protecting group (preferably 4-methoxybenzyl or benzyl).

The reduction reaction of a compound of formula Ig to give a compound of formula Ih can be carried out using a suitable reducing agent, such as lithium aluminum hydride, a borane-tetrahydrofuran complex, or a borane-dimethyl sulfide complex, in a suitable solvent, such as tetrahydrofuran or diethyl ether, at a suitable temperature, from room temperature to boiling point, preferably by heating.

The reduction reaction can also be carried out with a suitable precursor (compounds of formula XXXI or XXXII) or derivative with protective groups (compounds of formula XXIXP, XXXIP or XXXIIP, where A=P). When P is Boc, borane is the preferred reducing agent.

Compounds of general formula Ig can be prepared by the procedures described in Schemes 1-3 using suitable starting materials, or they can be prepared from a compound of formula XXXI or XXXII. Deprotection of a compound of formula XXXII to give a compound of formula XXXI and subsequent reaction with a compound of formula XV to give a compound of formula Ig is carried out following the procedures described in Scheme 1.

Compounds of general formula XXXI and XXXII can be obtained according to the procedures described in scheme 1 using suitable starting materials.

Therefore, compounds of general formula Ih can be prepared from a compound of formula XXXIII or XXXIV following a similar procedure.

In addition, the group -(CR ₅ R _5' ) _m X(CR ₆ R _6' ) _n R ₂ can be included at various stages of the synthesis to obtain compounds of formula Ig and Ih from suitable precursors with protective groups, by deprotection from followed by reaction with a compound of formula IX or X or XI as described in Scheme 1 to obtain compounds of formula I.

Moreover, some compounds of the present invention can also be prepared starting from other compounds of formula (I) by suitable functional group conversion reactions, in one or more steps, using well known organic chemistry reactions under standard experimental conditions.

In addition, a compound of formula I which is characterized by chirality can also be obtained by resolution of a racemic compound of formula I by chiral preparative HPLC or by crystallization of a diastereomeric salt or co-crystal. Alternatively, the separation step may be carried out in the previous step using any suitable intermediate.

Examples

Intermediates and examples

The examples use the following abbreviations:

ACN: acetonitrile

AcOH: acetic acid

Boc: tert-butoxycarbonyl

conc.: concentrated

DCM: dichloromethane

DIPEA: N,N-diisopropylethylamine

DMF: dimethylformamide

DMSO: dimethyl sulfoxide

EtOH: ethanol

PR: example

h: h/s

HPLC: high performance liquid chromatography

PROM: intermediate connection

LDA: lithium diisopropylamide

MeOH: methanol

MS: mass spectrometry

Min: minutes

Quantity: quantitative

Hold: Hold

rt: room temperature

Saturation: saturated

i.m.: source material

TFA: trifluoroacetic acid

THF: tetrahydrofuran

Mass: mass

The following methods were used to determine the HPLC-MS spectra:

Method A

Column: Gemini-NX 30×4.6 mm, 3 µm

Temperature: 40°C

Flow rate: 2.0 ml/min

Gradient: NH ₄ HCO ₃ pH 8: ACN (95:5)---0.5 min---(95:5)---6.5 min---(0:100)---1 min ---(0:100)

The sample was dissolved approx. 1 mg/ml in NH ₄ HCO ₃ pH 8/ACN

Method B

Column: Xbridge C ₁₈ XP 30×4.6 mm, 2.5 µm

Temperature: 40°C

Flow rate: 2.0 ml/min

Gradient: NH ₄ HCO ₃ pH 8: ACN (95:5)---0.5 min---(95:5)---6.5 min---(0:100)---1 min ---(0:100)

The sample was dissolved approx. 1 mg/ml inNH _four HCO ₃ pH 8/ACN

Method C

Column: Kinetex EVO 50×4.6 mm 2.6 µm

Temperature: 40°C

Flow rate: 2.0 ml/min

Gradient: NH ₄ HCO ₃ pH 8: ACN (95:5)---0.5 min---(95:5)---6.5 min---(0:100)---1 min ---(0:100)

The sample was dissolved approx. 1 mg/ml in NH ₄ HCO ₃ pH 8/ACN

Method D

Column: Kinetex EVO 50×4.6 mm 2.6 µm

Temperature: 40°C

Flow rate: 1.5 ml/min

Gradient: NH ₄ HCO ₃ pH 8: ACN (95:5)---0.5 min---(95:5)---6.5 min-(0:100)---2 min-- -(0:100)

The sample was dissolved approx. 1 mg/ml in NH ₄ HCO ₃ pH 8/ACN

Synthesis of intermediates

Intermediate 1A: tert-Butyl-1-oxa-6-azaspiro[2.5]octane-6-carboxylate

A solution of tert-butyl-4-oxopiperidine- 1-carboxylate (20.0 g, 100 mmol) in DMSO (140 ml). The reaction mixture was stirred at rt. for 30 min, then heated at 50°C for 1 h. After cooling to rt. ice was added slowly and the reaction mixture was extracted three times with ethyl acetate. The organic phases were combined, washed with water, dried over MgSO ₄ and concentrated in vacuo to give the title compound (17.6 g, 82% yield) as a white solid.

This method was used to prepare Intermediate 1B using the appropriate starting materials:

Intermediate 2A: tert-Butyl 4-hydroxy-4-((methylamino)methyl)piperidine-1-carboxylate

To a solution of intermediate 1A (0.50 g, 2.34 mmol) in a mixture of EtOH and water 5.5:1 (14 ml) was added methylamine (4.1 ml, 40% solution in water, 47 mmol). The reaction mixture was stirred at rt. overnight in a sealed tube. The solvent was removed in vacuo to give the title compound (0.534 g, 93% yield) as a white solid.

This method was used to prepare intermediates 2B-2I using the appropriate starting materials:

Intermediate 3A: tert-Butyl 12-(4-methoxybenzyl)-13-oxo-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane-8-carboxylate

Step 1. tert-Butyl 4-((2-bromo-4-chloro-N-(4-methoxybenzyl)butanamido)methyl)-4-hydroxypiperidine-1-carboxylate: To a solution of Intermediate 2D (9.94 g, 28.4 mmol) and triethylamine (9.5 ml, 68.1 mmol) in DCM (500 ml) was added dropwise a solution of 2-bromo-4-chlorobutanoyl chloride (prepared as described in US 6114541 A1 (2000) Ex 1) (9.35 g, 20.2 mmol) in DCM (200 ml) at 0°C. The reaction mixture was stirred at 0° C. for 3 h. DCM and aq. sat. NaHCO ₃ solution was added and the phases were separated. The aqueous phase was extracted with DCM and the organic phases were combined, dried over MgSO ₄ , filtered and concentrated to dryness to give the title compound (17.6 g, crude product).

Step 2 Named Compound: A solution of the crude product from Step 1 (14.8 g, 27.7 mmol) in THF (185 ml) was cooled under nitrogen to 0°C. After adding a solution of potassium tert-butoxide (111 ml, 1M in THF, 111 mmol), the reaction mixture was stirred at 0° C. for 2 h. Sat. NH ₄ Cl solution was then added and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, dried over MgSO ₄ , filtered and concentrated in vacuo. The residue was purified by flash chromatography, silica gel, with a DCM gradient to MeOH/DCM (1:4) to give the title compound (5.51 g, 48% yield over 2 steps).

This method was used to prepare intermediates 3B-3E using the appropriate starting materials:

Intermediate 4: tert-Butyl 13-oxo-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane-8-carboxylate

Step 1 4-oxa-8,12-diazadispiro[2.1.5.3]tridecan-13-one trifluoroacetate: A solution of intermediate 3A (1.78 g, 4.26 mmol) in TFA (20 mL) was stirred in a sealed tube at 80°C for 4 days. The reaction mixture was concentrated to dryness and water was added to the residue. The acidic aqueous phase was washed with ethyl ether, which was discarded. The aqueous layer was evaporated to dryness to give the title compound (1.17 g).

Step 2 Named Compound: Mixture of crude product from step 1, di-tert-butyl dicarbonate (1.40 g, 6.40 mmol), 1,4-dioxane (40 ml) and 1M aqueous NaOH solution (10 ml) stirred at rt. during the night. Water was added and the resulting mixture was extracted with ethyl acetate. The organic phases were combined, dried over MgSO ₄ , filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, gradient DCM to MeOH/DCM (1:4) to give the title compound (0.872 g, 69% yield over 2 steps).

Intermediate 5A: tert-Butyl 13-oxo-12-propyl-4-oxa-8,12-diazadispiro[2.1.5.3] tridecane-8-carboxylate

To a solution of intermediate 4 (0.200 g, 0.641 mmol) in dry DMF (6.7 mL) was added NaH (54 mg, 60 wt% in mineral oil, 1.35 mmol) at 0°C. The reaction mixture was stirred at 0°C for 30 min, then 1-bromopropane (0.092 mL, 1.012 mmol) was added and the resulting mixture was stirred at rt. within 3 hours. Water sat. NaHCO ₃ solution was added to the reaction mixture and it was extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over MgSO ₄ , filtered and concentrated to dryness to give the title compound as the crude product, which was used as is (229 mg, quant. yield).

This method was used to prepare intermediates 5B-5F using the appropriate starting materials:

Intermediate 6A: (S)-tert-Butyl-4-ethyl-2-methyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

Step 1. (R)-tert-butyl-4-((2-chloro-N-methylpropanamido)methyl)-4-hydroxypiperidine-1-carboxylate: To a solution of intermediate 2B (0.700 g, 2.71 mmol) in ethyl acetate (7 ml) was added a solution of K ₂ CO ₃ (1.05 g, 7.59 mmol) in water (7.7 ml). After cooling to 0° C., a solution of (R)-2-chloropropanoyl chloride (0.461 g, 3.63 mmol) in ethyl acetate (3.5 ml) was added dropwise. The reaction mixture was stirred at 0-5°C for 30 min and then diluted with water. The layers were separated and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, washed with 0.5 M aqueous HCl, and then sat. NaHCO ₃ solution, dried over MgSO ₄ , filtered and concentrated to dryness to give the title compound (0.775 g, 82% yield).

Step 2 Title Compound: A solution of the crude product from Step 1 (0.775 g, 2.22 mmol) in THF (15.5 ml) was cooled to -78° C. using a dry ice/acetone bath. After adding a solution of potassium t-butoxide (2.4 ml, 1M in THF, 2.4 mmol), the reaction mixture was stirred at -78°C for 30 min. Sat. NH ₄ Cl solution was then added and the aqueous phase was extracted with ethyl acetate. The organic phases were combined, dried over MgSO ₄ , filtered and concentrated in vacuo to give the title compound (0.683 g, 98% yield).

This method was used to prepare intermediates 6B-6P using the appropriate starting materials:

Intermediate 7A: tert-Butyl 12-isopropyl-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane-8-carboxylate

To a solution of intermediate 3B (1.00 g, 2.95 mmol) in THF (5 mL) was added a solution of borane-tetrahydrofuran complex (11.8 mL, 1M in THF, 11.8 mmol) dropwise at rt. The reaction mixture was stirred at 65°C for 2 h, then it was cooled to rt. 1M aqueous NaOH sol (5 ml) was carefully added while cooling the mixture in an ice water bath, and then it was heated to 70°C for 2 h. After cooling to rt. it was diluted with ethyl acetate. The phases were separated and the aqueous phase was reversibly extracted with ethyl acetate. The organic phases were combined, dried over MgSO ₄ , filtered and concentrated to dryness to give the title compound as the crude product, which was used as is (960 mg, quant. yield).

This method was used to prepare intermediates 7B-7H using the appropriate starting materials:

Intermediate 8: tert-Butyl 4-oxa-8,12-diazadispiro[2.1.5.3]tridecane-8-carboxylate

Mixture of Intermediate 7E (7.4 g, 19.9 mmol), AcOH (1.14 ml, 19.9 mmol) and palladium (1.31 g, 10 wt% on charcoal, wet) in MeOH (37 ml ) was stirred at 3 bar H ₂ at rt. within 1 day. The solids were filtered off and the solvent was removed in vacuo. The residue was diluted with DCM and 1M NaOH aqueous solution. The phases were separated and the aqueous phase was extracted several times with DCM. The organic phases were combined, dried over MgSO ₄ , filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, DCM to MeOH/DCM (1:4) gradient to give the title compound (3.57 g, 64% yield).

Intermediate 9A: tert-Butyl-4-ethyl-2,2-dimethyl-3-oxo-1-oxa-4,9-diazaspiro[5.5]undecane-9-carboxylate

A solution of intermediate 6B (18.15 g, 58.1 mmol) in dry THF (82 ml) was cooled to 0°C. After slowly adding a solution of LDA (77 ml, 1.5M in THF/h-heptane/ethylbenzene, 115.5 mmol), the reaction mixture was stirred at 0° C. for 30 minutes. Then iodomethane (10.9 ml, 174.2 mmol) was added and the reaction mixture was stirred at 0-5° C. for another 60 minutes. LDA solution (77 ml, 1.5 M in THF/n-heptane/ethylbenzene, 115.5 mmol) was added slowly again and the reaction mixture was stirred at 0° C. for 30 min. Then additional iodomethane (10.9 ml, 174.2 mmol) was added and the reaction mixture was stirred at 0-5°C for another 60 min to achieve complete conversion. Sat. NH ₄ Cl solution was then added and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by flash chromatography, silica gel, gradient DCM to MeOH/DCM (1:4) to give the title compound (8.42 g, 44% yield).

This method was used to prepare intermediates 9B-9C using the appropriate starting materials:

Intermediate 10A: tert-Butyl 12-isobutyl-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane-8-carboxylate

Mixture of intermediate 8 (1.5 g, 5.31 mmol), 1-bromo-2-methylpropane (0.69 ml, 6.37 mmol) and K ₂ CO ₃ (1.468 g, 10.62 mmol) in ACN (18 ml) was heated at 80° C. in a sealed tube overnight. 1M NaOH was added and the reaction mixture was extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over MgSO ₄ , filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, DCM to MeOH/DCM (1:4) gradient to give the title compound (679 mg, 38% yield).

This method was used to prepare Intermediate 10B using the appropriate starting materials:

Intermediate 11A: tert-Butyl-12-neopentyl-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane-8-carboxylate

To a solution of intermediate 8 (0.300 g, 1.06 mmol) in dry THF (7.2 ml) was added trimethylacetic aldehyde (0.15 ml, 1.38 mmol) and acetic acid (0.12 ml, 2.12 mmol). The reaction mixture was stirred at rt. for 15 minutes and then sodium triacetoxyborohydride (0.675 g, 3.19 mmol) was added in portions. The resulting mixture was stirred at rt. during the night. Water and conc.NH ₃ was carefully added and it was extracted with ethyl acetate. The organic phases were combined, washed with brine, dried overNa ₂ SO _four ,filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, DCM to MeOH/DCM gradient (1:4) to give the title compound (184 mg, 49% yield).

This method was used to prepare Intermediate 11B using the appropriate starting materials:

Synthesis of examples

Example 1: 12-ethyl-8-isopentyl-4-oxa-8,12-diazadispiro[2.1.5.3]tridecan-13-one

Step 1. 12-ethyl-4-oxa-8,12-diazadispiro[2.1.5.3]tridecan-13-one trifluoroacetate. To a solution of intermediate 3C (1.75 g, 5.39 mmol) in DCM (65 ml) was added TFA (4.2 ml, 53.9 mmol) and the reaction mixture was heated at 40°C for 2 h. evaporated to dryness to give the title compound as the crude product (3.59 g, 50 wt%, quant. yield) which was used in the next step without further purification.

Step 2 Named Compound: Mixture of crude product from step 1 (0.200 g, 50 wt%, 0.297 mmol), 1-bromo-3-methylbutane (0.043 ml, 0.357 mmol), NaI (0.026 g, 0.178 mmol) and K ₂ CO ₃ (0.205 g, 1.49 mmol) in ACN (2.5 ml) were heated at 80° C. in a sealed tube overnight. Water was added and the reaction mixture was extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over MgSO ₄ , filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, gradient from DCM to MeOH/DCM (1:4) to give the title compound (45 mg, 51% yield).

HPLC retention time (method B): 3.48 min; MS: 295.2 (M+H).

This method was used to prepare examples 2-15 using the appropriate starting materials:

Example 16 12-ethyl-8-(4-fluorobenzyl)-4-oxa-8,12-diazadispiro[2.1.5.3]tridecan-13-one

To a solution of the crude product from Step 1 of Example 1 (0.173 g, 59 wt %, 0.30 mmol) in dry THF (2 mL) was added 4-fluorobenzaldehyde (0.042 mL, 0.39 mmol). The reaction mixture was stirred at rt. for 15 minutes and then sodium triacetoxyborohydride (0.190 g, 0.91 mmol) was added in portions. The resulting mixture was stirred at rt. during the night. Water and conc.NH ₃ was carefully added and it was extracted with ethyl acetate. The organic phases were combined, washed with brine, dried overNa ₂ SO _four ,filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, DCM to MeOH/DCM gradient (1:4) to give the title compound (55 mg, 55% yield).

HPLC retention time (method A): 3.08 min; MS: 333.1 (M+H).

This method was used to prepare examples 17-35 using the appropriate starting materials:

Example 36 8-(2-(3-Fluoropyridin-2-yl)ethyl)-12-isopropyl-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane

Step 1. 12-isopropyl-4-oxa-8,12-diazadispiro[2.1.5.3]tridecane dihydrochloride. To a solution of intermediate 7A (156 mg, 0.48 mmol) in MeOH (2 ml) was added HCl (2M solution in diethyl ether, 2.4 ml, 4.8 mmol) and the mixture was stirred at rt. for 4 h. The solvent was evaporated in vacuo to give the corresponding di-HCl salt (143 mg, quant.).

Step 2 Named Compound: A solution of the crude product from Step 1 (0.125 g, 0.42 mmol), DIPEA (0.366 ml, 2.1 mmol) and 3-fluoro-2-vinylpyridine hydrochloride (0.115 g, 0.72 mmol) in EtOH (1.2 ml) was heated at 90° C. in a sealed tube for 1 day. Additional 3-fluoro-2-vinylpyridine hydrochloride (0.034 g, 0.210 mmol) was added and the mixture was heated at 90° C. for another day. The reaction mixture was allowed to cool to rt. and the solvent was evaporated. It was diluted with DCM and washed twice with 1N NaOH. The organic phase was dried over MgSO ₄ , filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, gradient from DCM to MeOH/DCM (1:4) to give the title compound (yield 44 mg, 30%).

HPLC retention time (method A): 3.70 min; MS: 348.2 (M+H).

This method was used to prepare examples 37-43 using the appropriate starting materials:

The method described in Example 1 was used to prepare Examples 44-65 using the appropriate starting materials:

The method described in Example 16 was used to prepare Examples 67-100 using the appropriate starting materials:

The method described in Example 36 was used to prepare Examples 101-108 using the appropriate starting materials:

Example 109 4-isopropyl-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecane

Step 1. 4-isopropyl-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one. To a solution of intermediate 6L (0.168 g, 0.58 mmol) in dry DMF (5 mL) was added NaH (47 mg, 60 wt% in mineral oil, 1.17 mmol). The reaction mixture was stirred at rt. for 30 min, then 2-bromopropane (0.054 ml, 0.58 mmol) was added and the resulting mixture was stirred at rt. during the night. Water was added and it was extracted with ethyl acetate. The organic phases were combined, washed with brine, dried over MgSO ₄ , filtered and concentrated to dryness. The residue was purified by flash chromatography, silica gel, DCM to MeOH/DCM gradient (1:4) to give the title compound (84 mg, 43% yield).

Step 2 Named Compound: To a solution of the product from step 1 (50 mg, 0.15 mmol) in dry THF (1 ml) cooled at 0°C, was added a solution of lithium aluminum hydride (0.6 ml, 1M in THF, 0.6 mmol). The reaction mixture was stirred at 50°C for 3 h, and then at room temperature. during the night. 1M NaOH was added and the heterogeneous mixture was filtered through a pad of celite, washing with THF. The filtrate was concentrated to dryness and the residue was purified by flash chromatography, silica gel, gradient from DCM to MeOH:DCM (1:4) to give the title compound (36 mg, 76% yield).

HPLC retention time (method B): 4.45 min; MS: 317.2 (M+H).

This method was used to prepare examples 110-111 using the appropriate starting materials:

Example 112 4-ethyl-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecane

Step 1. 4-ethyl-2-methyl-9-phenethyl-1-oxa-4,9-diazaspiro[5.5]undecan-3-one. Following the procedure described for the preparation of Example 1, but starting from intermediate 5F (220 mg, 0.70 mmol), the title compound (162 mg, 73% yield) was obtained.

Step 2 Named Compound: To a solution of the product from step 1 (101 mg, 0.32 mmol) in dry THF (2 ml) cooled at 0°C was added a solution of lithium aluminum hydride (1.28 ml, 1M in THF, 1.28 mmol). The reaction mixture was stirred at 50° C. overnight. 1M NaOH was added and the heterogeneous mixture was filtered through a pad of celite, washing with THF. The filtrate was concentrated to dryness and the residue was purified by flash chromatography, silica gel, gradient from DCM to MeOH:DCM (1:4) to give the title compound (55 mg, 57% yield).

HPLC retention time (method B): 3.91 min; MS: 303.2 (M+H).

This method was used to prepare Example 113 using the appropriate starting materials:

Table of examples with binding to the D ₁ receptor:

BIOLOGICAL ACTIVITY

Pharmacological study

Radioligand analysis σ _one human receptor

HEK-293 transfected membranes and [ ³ H](+)-pentazocine (Perkin Elmer, NET-1056) as the radioligand were used to evaluate the binding properties of test compounds to the human σ ₁ receptor. The assay was performed with 7 μg of membrane suspension, 5 nM [ ³ H](+)-pentazocine in the absence or presence of buffer, or 10 μM haloperidol for general and non-specific binding, respectively. The binding buffer contained 50 mM Tris-HCl at pH 8. The plates were incubated at 37° C. for 120 minutes. After the incubation period, the reaction mixture was then transferred to MultiScreen HTS, FC plates (Millipore), filtered and the plates washed 3 times with ice-cold 10 mM Tris-HCL (pH 7.4). The filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkin-Elmer) using an EcoScint liquid scintillation cocktail.

Results:

Since the present invention is directed to providing a compound or a chemically linked series of compounds that act as σ ₁ receptor ligands, a highly preferred embodiment in which compounds are selected that act as σ ₁ receptor ligands and, in particular, compounds that have binding , expressed as K _i , which is preferably <1000 nM, more preferably <500 nM, even more preferably <100 nM.

The following scale is adapted to represent binding to the σ ₁ receptor, expressed as K ₁ :

All compounds obtained in this application are characterized by binding to the σ ₁ receptor, in particular, the following binding results are demonstrated:

Claims (75)

1. Compound with the general formula (I)

where p is 0 or 1; m is 1 or 2; n is 0 or 1; Y represents -CH ₂ - or -C(O)-; X is a bond or -O-; R ₁ is selected from unsubstituted C _1-6 alkyl and unsubstituted C _3-6 cycloalkyl; R ₂ is selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _3-6 cycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted pyridine, where the specified phenyl or pyridine in R ₂ if substituted, substituted by one or two substituents selected from halogen, -OR ₁₂ , -CN, C _1-2 halogen-alkyl; wherein R ₁₂ is independently selected from hydrogen, unsubstituted C _1-2 alkyl; R ₃ and R _3' are independently selected from hydrogen or unsubstituted C _1-2 alkyl; alternatively, R ₃ and R _3' taken together with the connecting C-atom may form an unsubstituted C _3-6 cycloalkyl; R ₄ and R _4' are independently selected from hydrogen or unsubstituted C _1-2 alkyl; R ₅ and R _5' are independently selected from hydrogen or unsubstituted C _1-2 alkyl; alternatively, R ₅ and R _5' taken together with the connecting C atom may form an unsubstituted C _4-6 cycloalkyl or an unsubstituted non-aromatic 6-membered heterocyclyl containing 1 O heteroatom; R ₆ and R _6' are independently selected from hydrogen or unsubstituted C _1-2 alkyl; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or their corresponding pharmaceutically acceptable salt; subject to the following conditions: when Y is -C(O)- and R ₂ is substituted or unsubstituted aryl or substituted or unsubstituted heterocyclyl then m is 1 and X is a bond, n is 0 and R ₃ is not hydrogen; with the following compounds being further excluded:

2. The compound according to claim 1, in which R ₃ is hydrogen or unsubstituted methyl; R _3' is hydrogen or unsubstituted methyl; alternatively, R ₃ and R _3' taken together with the connecting C-atom may form unsubstituted cyclopropyl; 3. Connection according to paragraphs. 1 or 2, where the compound of formula (I) is a compound of formula (I'), (I ^a' ), (I ^b' ) or (I ^c' )

4. The connection according to any one of paragraphs. 1-3, where the compound of formula (I) is a compound of formula (I ^2' )

5. Connection according to any one of paragraphs. 1-4, where the compound of formula (I) is a compound of formula (I ^3' )

6. The connection according to any one of paragraphs. 1-5 where X is a bond or -O 7. Connection according to any one of paragraphs. 1-6, where the compound of formula (I) is a compound of formula (I ^4' )

8. Connection according to any one of paragraphs. 1-7, where R ₁ is an unsubstituted group selected from methyl, ethyl, isopropyl, isobutyl, sec-butyl, isopentyl, neopentyl, cyclopropyl and propyl. 9. Connection according to any one of paragraphs. 1-8, where R ₂ is selected from an unsubstituted group selected from methyl, ethyl, propyl, isopropyl, t-butyl, neopentyl, cyclopropyl and isobutyl, or a substituted or unsubstituted group selected from phenyl and pyridine. 10. Connection according to any one of paragraphs. 1-9, where the connection is selected from the following list:

11. The method of obtaining compounds with formula (I) according to any one of paragraphs. 1-10, including: a) intramolecular cyclization of a compound of formula VIIa

where LG is a leaving group, and while the cyclization reaction is carried out in a suitable solvent such as tetrahydrofuran; in the presence of a strong base such as potassium tert-butoxide or sodium hydride; and at a suitable temperature, from -78°C to the boiling point, preferably under cooling or b) reaction of a compound of formula VIIIH

with a compound of formula IX, X or XI,

wherein the alkylation reaction between a compound of formula VIIIH or a suitable salt such as trifluoroacetate or hydrochloride and a compound of formula IX is carried out in a suitable solvent such as acetonitrile, dichloromethane, 1,4-dioxane or dimethylformamide, preferably acetonitrile; in the presence of an inorganic base such as K ₂ CO ₃ or Cs ₂ CO ₃ or an organic base such as triethylamine or diisopropylethylamine, preferably K ₂ CO ₃ , at a suitable temperature between room temperature and boiling point, preferably with heating, or alternatively, reactions carried out in a microwave reactor; wherein the reductive amination reaction between a compound of formula VIIIH and a compound of formula X is carried out in the presence of a reducing agent, preferably sodium triacetoxyborohydride, in an aprotic solvent, preferably tetrahydrofuran or dichloroethane, optionally in the presence of an acid, preferably acetic acid; and wherein the condensation reaction between a compound of general formula VIIIH and a compound of formula XI is preferably carried out in a suitable solvent such as ethanol, isopropanol, n-butanol or 2-methoxyethanol, optionally in the presence of an organic base such as triethylamine or diisopropylethylamine, at a suitable temperature between room temperature and the boiling point, preferably under heating or alternatively, reactions carried out in a microwave reactor; or c1) when Y is CH ₂ , by alkylating a compound of formula XIV

with compound with formula XV

wherein the compound of formula XV is an alkylating agent and V is a leaving group, or alternatively by reacting a reductive amination of a compound of formula XIV with a compound of formula XV, wherein the compound of formula XV is an aldehyde and V is a C(O)H group; wherein the alkylation reaction is carried out in a suitable solvent such as acetonitrile, dichloromethane, 1,4-dioxane or dimethylformamide, preferably acetonitrile; in the presence of an inorganic base such as K ₂ CO ₃ or Cs ₂ CO ₃ or an organic base such as triethylamine or diisopropylethylamine, preferably K ₂ CO ₃ at a suitable temperature between room temperature and boiling point, preferably with heating, or, alternatively, reactions carried out in a microwave reactor; or alternatively when compound XV is an aldehyde in which V is a C(O)H group, the reductive amination reaction is carried out in the presence of a reducing agent, preferably sodium triacetoxyborohydride, in an aprotic solvent, preferably tetrahydrofuran or dichloroethane, optionally in the presence of acids, preferably acetic acid; or c2) when Y is C(O), by alkylating a compound of formula XIV with a compound of formula XV

fifteen

wherein the compound of formula XV is an alkylating agent and V is a leaving group; wherein the alkylation reaction is carried out in an aprotic solvent, preferably dimethylformamide, in the presence of an inorganic base such as NaH, at a suitable temperature, preferably from room temperature to 60°C. 12. Use of one or more compounds of formula II, IIP, III, IIIP, IVa, IVb, Vb, VbP, Va, VaP, VI, VIIa, VIIb, VIIb, VIIbP, VIIIP, VIIIH, IX, X, XI, XII , XIIP, XIII, XIIIP, XIV, XIVP, XIVH, XV, XVI, XVIP, XVIH, Ia, XVIIP, XVIIH, Ib, XVIIIP, Ic, XIXP, XIXH, Id, XXP, XXH, XXI, XXIP, XXIH, XXII , XXIIP, XXIIH, XXIII, XXIIIP, XXIIIH, XXIV, XXIVP, XXIVH, XXV, XXVP, XXVH, Ie, XXVIP, XXVIH, XXVIIa, XXVIIb, XXVIIc, If, XXVIIIP, XXVIIIH, Ig, XXIXP, XXIXH, Ih, XXXP , XXXH, XXXI, XXXIP, XXXIH, XXXII, XXXIIP, XXXIIH, XXXIII, XXXIIIP, XXXIIIH, XXXIV, XXXIVP or XXXIVH,

where LG is a leaving group, P is a protecting group, P is an orthogonal protecting group, V is an aldehyde or other leaving group, Rs, Rs' is hydrogen or alkyl, s is 1, 2, 3 or 4, Q represents methyl or benzyl, and X', X'' independently represent a leaving group, to obtain compounds with formula (I), as defined in any of paragraphs. 1-10. 13. A pharmaceutical composition that contains a compound of formula (I), according to any one of paragraphs. 1-10, or a pharmaceutically acceptable salt thereof, providing binding to sigma receptors, especially to the sigma-1 receptor, a pharmaceutically acceptable carrier, adjuvant or binder, while the compound of formula (I) is taken in an effective amount of 0.1 mg /kg/day up to 1000 mg/kg/day. 14. The use of compounds with formula (I) according to any one of paragraphs. 1-10 as a drug for the treatment of pain and disease states mediated by the sigma receptor, especially the sigma-1 receptor. 15. The use of a compound according to any one of paragraphs. 1-10 as a drug for the treatment of drug abuse or dependence mediated by the sigma receptor, especially the sigma-1 receptor. 16. Connection selected from:

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any mixture ratio, or a corresponding pharmaceutically acceptable salt.