New LSD prodrugs for the treatment of depression and PTSD

Abstract

A compound of formula (I), a stereoisomer, a pharmaceutically acceptable salt, a solvate and / or hydrate thereof: where R1 is H, XYZ or where L is a leftist; X is selected from the group consisting of C=O, C=S, C=NH, C=N-Me, C=N-OH, C=NO-Me, S=O, SO2 and CH2; Y is selected from the group consisting of O, S, NH, Aryl, Heteroaryl, Selenophenyl, linear or branched C 1-12 -Alkyl, optionally substituted with one or more R 10 , linear or branched C 1-12 -Alkyl ether, optionally substituted with one or more R 10 , linear or branched C 1-12 -Alkylamine, optionally substituted with one or several R 10 , linear or branched C 1-12 -Thioalkyl, optionally substituted with one or more R 10 , linear or branched C 1-12-Alkyl selenoethers, optionally substituted with one or more R 10 , linear or branched C 1-12 -Alkylcarbonyl, optionally substituted with one or more R 10 , OP(=O)(ORa)2, OP(=O)(ORa)(ORb), OP(=O)(ORa)(Ra), OP(=O)(ORa)(Rb), OP(=O)(Ra)2, OP(=O)(Ra)(Rb), P(=O)(ORa)2, P(=O)(ORa)(ORb), P(=O)(ORa)(Ra), P(=O)(ORa)(Rb), P(=O)(Ra)2 and P(=O)(Ra)(Rb), where Ra and Rb each independently of each other C 3-10 -Cycloalkyl and / or linear or branched C 1-12 -Alkyl groups, optionally substituted with one or more R groups 10 , where R 10 selected from the group consisting of halogens, OH, NH2, SH, linear or branched C 1-6 -Perfluoroalkyl, linear or branched C 1-12 -Alkylthiol, linear or branched C 1-12 -Alkyl selenoethers, linear or branched C 1-12 -Alkylselenol, linear or branched C 1-12-Alkylether, linearem oder verzweigtem C 1-6 Alkylcarbonyl und linearem oder verzweigtem C 1-12 -Thioalkyl; Z abwesend oder ausgewählt ist aus der Gruppe bestehend aus H, O-P(=O)(OR a )2, O-P(=O)(OR a )(OR b ), O-P(=O)(OR a )(OR c ), O-P(=O)(OR c )2, O-P(=O)(OR a )(R a ), O-P(=O)(OR a )(R b ), O-P(=O)(OR a )(R c ), O-P(=O)(OR c )(R c ), O-P(=O)(R a )2, O-P(=O)(R c )2, O-P(=O)(R a )(R b ), O-P(=O)(R a )(R c ), P(=O)(OR a )2, P(=O)(OR a )(OR b ), P(=O)(OR c )2, P(=O)(OR a )(OR c ), P(=O)(OR a )(R a ), P(=O)(OR a )(R b ), P(=O)(OR a )(R c ), P(=O)(OR c )(R c ), P(=O)(R a )2, P(=O)(R a )(R b), P(=O)(R c )2, P(=O)(R a )(R c ), Si(R a )2(Ph), Si(R a )(R b )(Ph), Si(R a )2(CH2Ph), Si(R a )(R b )(CH2Ph), Si(R a )2(R d ), Si(R a )(R b )(R d ), Si(R a )2 (CH2R c ), Si(R a )(R b )(CH2R c ), Si(R c )3, Si(CH2R c )3, linear or branched C 1-12 -Alkyl selenoether, B(OR e )2, B(OCH(CH2)2)2, where R a and R b each linear or branched C 1-12 -Alkyl are; R c is C 3-10 -Cycloalkyl; R d is C 3-10 -Cycloalkenyl; R e is linear or branched C 1-6 -Alkyl and / or wherein C 1-12 -Alkyl selenoether is linear or branched; R2 and R6 are each independently selected from the group consisting of H, B(OH)2, B(OR 11)2 and B(OR 11 )(OR 12 ); where R 11 and R 12 Each is selected independently from the group consisting of linear or branched C 1-12 -Alkyl and linear or branched C 1-12 -Alkylcarbonyl; R3 and R7 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkylmethyl, cycloalkyl, cycloalkylalkyl, carbocycle, heterocycle, methylazetidinyl and (1-methylazetidin-3-yl)methyl, where alkyl is linear or branched C 1-4 -Alkyl is optionally substituted with one or more OH and / or halogen atoms; alkenyl is linear or branched C 2-4 -Alkenyl, optionally substituted with one or more halogen atoms; alkynyl is linear or branched C 2-4 -Alkynyl, optionally substituted with one or more halogen atoms, cycloalkyl is C 3-6-Cycloalkyl, optionally substituted with one or more halogen atoms; R4, R5, R8 and R9 are each independently selected from the group consisting of H, C 3-5 -Cycloalkyl, C 1-5 -Alkyl, where the C 1-5 -Alkyl is linear or branched, optionally substituted with one or more halogen atoms or trifluoromethyl groups; or R4 and R5 together form part of a C 3-6 -Carbocycle or one C 3-6 -Heterocycle; or R8 and R9 together form part of a C 3-6 -Carbocycle or one C 3-6 -Heterocycle; provided that if R1 and R2 are both H, R4 and R5 are not both ethyl groups, and R3 is not a methyl group.

Description

Scope of the invention

[0001] The present invention relates to novel prodrugs of lysergic acid diethylamide (LSD) and structural derivatives functioning as prodrugs, and their manufacturing processes. Furthermore, the invention relates to their use as pharmaceuticals, particularly in the medical and therapeutic treatment of mental disorders, specifically depression, anxiety disorders and post-traumatic stress disorder (PTSD), addiction treatment, eating disorders, cluster headaches and / or migraines. Finally, the present invention also relates to compositions containing the novel prodrugs of LSD and the structural derivatives functioning as prodrugs. Background of the invention

[0002] Mental health conditions such as depression, anxiety disorders, and PTSD, as well as addiction treatment, eating disorders, cluster headaches, and / or migraines, represent a significant global medical challenge. Despite existing therapeutic approaches, there is a high unmet need for innovative, effective, and well-tolerated treatment options. In recent years, the therapeutic use of psychedelics has gained increasing importance due to their potentially rapid and lasting effects on affective and stress-related disorders.

[0003] LSD is a classic psychedelic with strong serotonergic activity. However, its direct use is limited due to regulatory restrictions, abuse potential, intense hallucinogenic profile, short pharmacokinetic half-life, and dosing challenges. The development of prodrugs—pharmacologically inactive or weakly active precursors that are converted in the body into active compounds or metabolites—offers a promising strategy for improving efficacy, safety, and medical applicability. However, currently available LSD prodrugs do not exhibit the desired therapeutic effects and continue to cause hallucinogenic side effects.

[0004] Therefore, there is a need for prodrugs with a slower, more controlled release of the active compound, which could lead to reduced peak plasma concentrations and thus limit hallucinogenic side effects while maintaining therapeutic benefits. Furthermore, prodrugs exhibit an improved pharmacokinetic half-life due to this more controlled release. This pharmacokinetic modulation is thought to enhance safety, tolerability, and therapeutic applicability in clinical settings. The goal is thus to enable controlled, safe, and effective access to LSD-like pharmacological effects, taking into account factors such as bioavailability, half-life, release profile, and regulatory constraints. Summary of the invention

[0005] The present invention aims to solve the aforementioned problems by providing novel compounds that are prodrugs of lysergic acid diethylamide (LSD) and structural derivatives of LSD, which function as serotonin receptor prodrugs. The compounds of the present invention behave as prodrugs that can be used as pharmaceuticals, particularly for the treatment of mental disorders such as depression, anxiety, and post-traumatic stress disorder (PTSD), addiction treatment, eating disorders, cluster headaches, and / or migraines.

[0006] The invention relates to the compound of formula (I), a stereoisomer, a pharmaceutically acceptable salt, a solvate and / or a hydrate thereof.

[0007] The compounds of formula (I) function as prodrugs.

[0008] In a further aspect, the invention relates to the compound of formula I for use as a pharmaceutical, in particular for the treatment of mental disorders such as depression, anxiety and post-traumatic stress disorder, addiction treatment, eating disorders, cluster headaches and / or migraines. The invention further relates to a pharmaceutical composition containing the compound of formula (I). Another aspect of the invention relates to a method for preparing the compound of formula (I). Definitions

[0009] All chemical names of the substituents are to be understood in the sense of the IUPAC.

[0010] The term "alkyl" here refers to a group consisting of carbon and hydrogen that contains no double or triple bonds. An alkyl group can be linear or branched, or optionally modified with one or more substituents, as described here. Examples of alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, and hexyl.

[0011] The term "linker" here refers to a group that joins two molecules together. In the context of the present invention, the molecules are derivatives or analogue compounds of LSD. A linker can be a covalent bond or a linker group. The linker can be linear or branched. An example of a linker group is a linear or branched alkyl group. The linker can be flexible or rigid.

[0012] The term "alkenyl," as used herein, refers to a linear or branched hydrocarbon chain radical group consisting of carbon and hydrogen atoms and containing at least one carbon-carbon double bond. The alkenyl may optionally be substituted with one or more substituents, as described herein. The alkenyl is linked to the rest of the molecule via a single bond. Examples of alkenyl groups include, but are not limited to, ethenyl, prop-1-enyl, but-1-enyl, and pent-1-enyl.

[0013] The term "alkynyl," as used herein, refers to a linear or branched hydrocarbon chain radical group consisting exclusively of carbon and hydrogen atoms and containing at least one carbon-carbon triple bond. The alkynyl may optionally be substituted with one or more substituents as described herein. The alkynyl is linked to the rest of the molecule via a single bond. Examples of alkynyl groups include, but are not limited to, ethynyl, propynyl, butynyl, pentynyl, and hexynyl.

[0014] The term "cycloalkyl," as used herein, refers to a hydrocarbon ring system in which all atoms in the ring are carbon atoms connected to each other by single bonds. The cycloalkyl may optionally be substituted with one or more substituents, as described herein. The cycloalkyl is linked to the rest of the molecule by a single bond. Examples of cycloalkyl groups include, but are not limited to, cyclopropyl, cyclobutyl, and cyclohexyl.

[0015] The term "cycloalkenyl," as used herein, refers to a hydrocarbon ring system containing at least one carbon-carbon double bond. The cycloalkenyl may optionally be substituted with one or more substituents, as described herein. The cycloalkenyl is linked to the rest of the molecule via a single bond. Examples of cycloalkenyl groups include, but are not limited to, cyclopentenyl, cycloheptenyl, and cyclohexenyl.

[0016] The term "cycloalkylmethyl," as used herein, refers to a functional group comprising a methyl group in which one of the hydrogen atoms is replaced by a cycloalkyl. The cycloalkyl may be a C3-6 cycloalkyl, optionally substituted with one or more substituents as described herein. The cycloalkylmethyl is linked to the rest of the molecule via a single bond to the methyl group. Examples of cycloalkylmethyl groups include, but are not limited to, cyclopropylmethyl, cyclobutylmethyl, and cyclohexylmethyl.

[0017] The term "cycloalkylalkyl," as used herein, refers to a functional group comprising a cycloalkyl group substituted onto an alkyl group. The alkyl group may be linear or branched. An example of a cycloalkylalkyl group is an ethyl group substituted with a cyclopropyl group, resulting in cyclopropylethyl. The cycloalkylalkyl group is linked to the rest of the molecule via a single bond to the alkyl group.

[0018] The term “C x-y “, as used herein in conjunction with a chemical unit such as alkyl, alkenyl or alkynyl, comprises groups with x to y carbon atoms in the chain or ring. For example, a “C 1-6 -Alkyl" is an alkyl, linear or branched, substituted or unsubstituted, with 1 to 6 carbon atoms in a chain.

[0019] The term "aryl," as used herein, refers to aromatic carbocycles. Aryl can also be called an "aromatic ring," "aryl group," or "aryl ring." Aryl can comprise monocyclic, bicyclic, or polycyclic ring systems. Examples of aryl groups include phenyl, benzyl, and naphthyl.

[0020] The term "heteroaryl," as used herein, refers to monocyclic, bicyclic, or polycyclic ring systems in which at least one ring in the system is aromatic and contains at least one heteroatom such as N, O, or S. Heteroaryl can also be called a heteroaromatic ring. Each ring of the heteroaryl ring system can contain 3 to 7 ring atoms. Examples of heteroaryl groups include pyrrolyl, furanyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, pyridinyl, pyrazinyl, pyridazinyl, and pyrimidinyl.

[0021] The term "selenophenyl," as used herein, refers to an unsaturated five-membered ring with four carbon atoms and one selenium atom, with the chemical formula C4H4Se. Selenophenyl is the selenium analogue of furanyl and / or thiophenyl. The selenophenyl is linked to the rest of the molecule via a single bond.

[0022] The term "alkyl ether," as used herein, refers to a functional group in which an oxygen atom is covalently bonded to two alkyl groups. The alkyl groups of the alkyl ether can be the same, in which case it is called a symmetrical alkyl ether, or different, in which case it is known as an unsymmetrical alkyl ether. The alkyl groups can be linear or branched. 1-12The alkyl ether is optionally substituted with one or more substituents as described herein. The alkyl ether is linked to the rest of the molecule via a single bond to one of its alkyl groups. Examples of alkyl ethers include dimethyl ether, diethyl ether, and ethyl methyl ether.

[0023] The term "thioalkyl," as used herein, refers to a functional group in which a sulfur atom is covalently bonded to an alkyl group. The alkyl group may be linear or branched, optionally substituted with one or more substituents as described herein. The thioalkyl is linked to the rest of the molecule via a single bond to the sulfur atom. Examples of thioalkyl groups include methyl thioethers, ethyl thioethers, and isopropyl thioethers.

[0024] The term "alkyl thioether," as used herein, refers to a functional group in which a sulfur atom is covalently bonded to two alkyl groups. Alkyl thioethers can also be called "sulfides." The alkyl groups can be the same or different. The alkyl groups can be linear or branched. 1-12 The alkyl thioether is optionally substituted with one or more substituents as described herein. The alkyl thioether is linked to the rest of the molecule via a single bond to one of its two alkyl groups. Examples of alkyl thioethers include dimethyl thioether, ethyl methyl thioether, diethyl thioether, and ethyl isopropyl thioether.

[0025] The term "alkyl selenoether," as used herein, refers to a functional group in which a selenium atom is covalently bonded to two alkyl groups. The alkyl groups can be the same or different. The alkyl groups can be linear or branched. 1-12 The alkyl selenoether is optionally substituted with one or more substituents as described herein. The alkyl selenoether is linked to the rest of the molecule via a single bond to one of its two alkyl groups. Examples of alkyl selenoethers include dimethyl selenoether, ethyl methyl selenoether, diethyl selenoether, and ethyl isopropyl selenoether.

[0026] The term "alkylamine," as used herein, refers to an ammonia derivative in which at least one of the hydrogen atoms is replaced by an alkyl group. Alkylamines can be primary, secondary, or tertiary amines, with one, two, or three of the hydrogen atoms replaced by one, two, or three alkyl groups, respectively. The alkyl groups can be the same or different. The alkyl groups can be linear or branched. 1-12 The alkylamine is an alkyl group, optionally substituted with one or more substituents as described herein. The alkylamine is linked to the rest of the molecule either via a single bond to one of the alkyl groups of the alkylamine or via a single bond to the nitrogen atom. Examples of alkylamines include methylamine, ethylamine, diethylamine, and diisopropylethylamine.

[0027] The term "alkyl carbonyl," as used herein, refers to a functional group in which an alkyl group is bonded to a carbonyl group. The alkyl group may be linear or branched, optionally substituted with one or more substituents as described herein. The alkyl carbonyl is linked to the rest of the molecule via a single bond to the carbonyl group. Examples of alkyl carbonyl groups include methyl carbonyl, ethyl carbonyl, propyl carbonyl, isobutyl carbonyl, and hexyl carbonyl.

[0028] The term “perfluoroalkyl,” as used herein, refers to an alkyl group in which all or the majority (more than 50%) of the hydrogen atoms are replaced by fluorine atoms. The perfluoroalkyl group may be linear or branched, or optionally substituted with one or more substituents as described herein. Examples of perfluoroalkyl groups include perfluoroethyl, perfluorobutyl, and perfluoroisobutyl.

[0029] The term "alkylthiol," as used herein, refers to a functional group in which an alkyl group is bonded to a thiol group (SH). The alkyl group can be linear or branched. The alkylthiol is connected to the rest of the molecule via a single bond to the alkyl group. Examples of alkylthiol groups include methylthiol, ethylthiol, propylthiol, isobutylthiol, and pentylthiol.

[0030] The term "alkylselenol," as used herein, refers to a functional group in which an alkyl group is bonded to a selenol group (SeH). The alkyl group can be linear or branched. The alkylselenol is connected to the rest of the molecule via a single bond to the alkyl group. Examples of alkylselenol groups include methylselenol, ethylselenol, propylselenol, and butylselenol.

[0031] The term "trihalomethyl groups," as used herein, refers to a methyl group in which the three hydrogen atoms are replaced by halogen atoms such as chlorine, bromine, iodine, or fluorine. Examples of trihalomethyl groups are trichloromethane, tribromomethane, triiodomethane, and trifluoromethane.

[0032] The term "carbocycle," as used herein, refers to a saturated, unsaturated, aromatic, or non-aromatic ring in which every atom in the ring is a carbon atom. Examples of carbocycle groups include cyclopentyl, cyclohexyl, cyclohexenyl, and phenyl.

[0033] The term "heterocycle," as used herein, refers to a saturated, unsaturated, or aromatic ring containing one or more heteroatoms such as N, O, and S. Examples of heterocycle groups include aziridine, pyrrole, pyrrolidine, thiophene, and thiomorpholine.

[0034] The term “optionally substituted”, as used herein, means that the group in question may or may not be substituted with one or more additional groups as described herein.

[0035] The term “pharmaceutically acceptable”, as used herein, refers to substances or compositions that are compatible with the intended therapeutic purpose and, when administered to a patient, do not cause adverse reactions, e.g., toxic, allergic, or immunological reactions.

[0036] The term "prodrug," as used herein, refers to a pharmacologically inactive or less active compound that, after administration, undergoes a chemical or metabolic transformation in the body, releasing the active substance and producing the desired pharmacological effect. This transformation occurs via various mechanisms, such as enzymatic or hydrolytic cleavage.

[0037] The term "mental illness," as used herein, refers to pathological psychological conditions characterized by a clinically significant disturbance in a subject's or patient's cognition, emotional regulation, or behavior. Mental illnesses cause significant distress or impairment in personal, social, or occupational life. They are also referred to as "mental health conditions" or "mental disorders." Common examples of mental illnesses include anxiety disorders, depression, bipolar disorder, schizophrenia, and post-traumatic stress disorder (PTSD).

[0038] The term “pharmaceutical composition,” as used herein, refers to a formulation containing the compound or prodrug in combination with pharmaceutically acceptable carriers or excipients and intended for administration to a subject or patient. The pharmaceutical composition may be formulated for systemic use, including oral and / or parenteral administration. The pharmaceutical composition may be in the form of a tablet, capsule, suspension, solution, or intravenous infusion.

[0039] The term “14-BPin-lysergamide”, as used herein, refers to lysergamide derivatives with a pinacolborane group at position C14 of the lysergamide backbone, as shown below. In other words, 14-BPin-lysergamide refers to a lysergamide where R2 of formula (I) corresponds to a pinacolborane group.

[0040] The term “14-boric acid lysergic acid amide”, as used herein, refers to lysergic acid amide derivatives with a boric acid group at position C14 of the lysergic acid amide backbone, as shown below. In other words, 14-boric acid lysergic acid amide refers to a lysergic acid amide in which R2 of formula (I) corresponds to a boric acid group.

[0041] The term "trialkyl orthoformate," as used herein, refers to an ester of orthoformic acid in which the acidic hydrogen atoms or protons are replaced by alkyl groups. The alkyl groups can be linear or branched. 1-12 -Alkyl.

[0042] The term “substituted alkyl acyl halide”, as used herein, refers to an alkyl acyl halide in which the alkyl is a linear or branched C 1-12-Alkyl is a compound substituted with a phosphate group, a borate group, a silyl group, or a selenium atom. The acyl halide can be, for example, an acyl chloride, an acyl iodide, or an acyl bromide. The phosphate, borate, or silyl group can, in turn, be further modified with a linear or branched C 1-12 -Alkyl, a C 3-10 -Cycloalkyl or an aryl substitute.

[0043] The term “substituted alkyl halide”, as used herein, refers to an alkyl halide in which the alkyl is a linear or branched C 1-12 -Alkyl is a compound substituted with a phosphate group, a borate group, a silyl group, or a selenium atom. The halide can be, for example, a chloride, an iodide, or a bromide. The phosphate, borate, or silyl group can, in turn, be further modified with a linear or branched C 1-12 -Alkyl, a C 3-10 -Cycloalkyl or an aryl group substituted.

[0044] The term "lysergamide linker unit," as used herein, refers to a lysergamide molecule linked at position N1, corresponding to substituent R1, to a linker. The linker may be attached at position N1 by forming an amide or carbamate unit. The linker may terminate with a leaving group, such as an ester group or an acyl halide group, which can be substituted by the amine at position N1 of another lysergamide molecule. Detailed description of the invention

[0045] The present invention relates to compounds that represent novel prodrugs of lysergic acid diethylamide (LSD) as well as structural derivatives of LSD that function as prodrugs. The compounds according to the present invention are based on the framework represented by formula (I): where R1, R2, R3, R4, and R5 are substituents, as described below. The substitution at positions N1 and C14 each leads to prodrugs of LSD. Without being bound to any particular theory, the substituents R3, R4, and R5 modulate or influence the affinity of the LSD derivatives thus obtained for serotonin receptors.

[0046] The compounds according to the present invention are prodrugs that are converted in the body into the respective active compound or the corresponding metabolite that exerts the therapeutic effect. The active compounds or metabolites can be LSD or structural derivatives of LSD. The prodrugs according to the present invention enable a controlled release of the active ingredient, which can lead to lower peak plasma concentrations and thus limit the onset of hallucinogenic side effects while maintaining the desired therapeutic effect. Furthermore, due to the controlled release of the active ingredient, prodrugs exhibit an improved pharmacokinetic half-life. Based on in silico data, the compounds of the present invention are therefore expected to improve safety, tolerability, and therapeutic applicability in the clinical setting.The compounds according to the present invention can therefore find valuable therapeutic applications, particularly in the treatment of mental illnesses such as depression, anxiety disorders and post-traumatic stress disorder, addiction treatment, eating disorders, cluster headache and / or migraine.

[0047] The active compounds or metabolites derived from the compounds or prodrugs according to the present invention are expected to act on serotonin receptors. Serotonin receptors, also known as 5-hydroxytryptamine receptors or 5-HT receptors, are G protein-coupled receptors (GPCRs) and ligand-gated ion channels found in the central and peripheral nervous system. Serotonin receptors are divided into seven families of GPCRs, including 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7 receptors. The 5-HT1 family is further subdivided into the subtypes 5-HT1, 5-HT2, 5-HT3, 5-HT4, 5-HT5, 5-HT6, and 5-HT7. 1A , 5-HT 1B , 5-HT 1D, 5-HT 1E and 5-HT 1F The 5-HT2 family is further subdivided into the subtypes 5-HT 2A , 5-HT 2B and 5-HT 2C The 5-HT5 family is further subdivided into the subtypes 5-HT 5A and 5-HT 5B It is known that the psychedelic or hallucinogenic effects of LSD are mediated by the 5-HT receptor. 2A -receptor subtype mediated. The active metabolites derived from the prodrugs according to the present invention showed a lower affinity for 5-HT in docking studies. 2A -receptor subtype compared to LSD. Without being tied to a theory, this reduced affinity for 5-HT is expected. 2A -receptor leads to improved anxiolytic or antidepressant effects with simultaneously reduced hallucinogenic or psychedelic side effects.

[0048] In the broadest sense, the present invention relates to a compound of formula (I), a stereoisomer, a pharmaceutically acceptable salt, a solvate and / or hydrate thereof: wherein R1 is H, XYZ or where L is a leftist.

[0049] X is selected from the group consisting of C=O, C=S, C=NH, C=N-Me, C=N-OH, C=NO-Me, S=O, SO2 and CH2.

[0050] Y is selected from the group consisting of O, S, NH, aryl, heteroaryl, selenophenyl, linear or branched C 1-12 -Alkyl, optionally substituted with one or more R 10 , linear or branched C 1-12 -Alkyl ether, optionally substituted with one or more R 10 , linear or branched C 1-12 -Alkylamine, optionally substituted with one or more R 10 , linear or branched C 1-12 -Thioalkyl, optionally substituted with one or more R 10 , linear or branched C 1-12-Alkyl selenoethers, optionally substituted with one or more R 10 , linear or branched C 1-12 -Alkylcarbonyl, optionally substituted with one or more R 10 , OP(=O)(OR a )2, OP(=O)(OR a )(OR b ), OP(=O)(OR a )(R a ), OP(=O)(OR a )(R b ), OP(=O)(R a )2, OP(=O)(R a )(R b ), P(=O)(OR a )2, P(=O)(OR a )(OR b ), P(=O)(OR a )(R a ), P(=O)(OR a )(R b ), P(=O)(R a )2 and P(=O)(R a )(R b In a preferred embodiment, aryl is phenyl. In another preferred embodiment, heteroaryl is selected from thienyl and furanyl.

[0051] R a and R b are each independent of each other C 3-10 -Cycloalkyl and / or linear or branched C 1-12-Alkyl groups, optionally substituted with one or more R groups 10 .

[0052] R 10 is selected from the group consisting of halogens, OH, NH2, SH, linear or branched C 1-6 -Perfluoroalkyl, linear or branched C 1-12 -Alkylthiol, linear or branched C 1-12 -Alkyl selenoethers, linear or branched C 1-12 -Alkylselenol, linear or branched C 1-12 -Alkyl ether, linear or branched C 1-6 Alkylcarbonyl and linear or branched C 1-12 -Thioalkyl. The halogen can be selected from the group consisting of chlorine, bromine, iodine or fluorine, preferably fluorine.

[0053] Z is absent or selected from the group consisting of H, OP(=O)(OR) a )2, OP(=O)(OR a )(OR b ), OP(=O)(OR a )(OR c ), OP(=O)(OR c )2, OP(=O)(OR a )(R a ), OP(=O)(OR a )(R b), O-P(=O)(OR a )(R c ), O-P(=O)(OR c )(R c ), O-P(=O)(R a )2, O-P(=O)(R c )2, O-P(=O)(R a )(R b ), O-P(=O)(R a )(R c ), P(=O)(OR a )2, P(=O)(OR a )(OR b ), P(=O)(OR c )2, P(=O)(OR a )(OR c ), P(=O)(OR a )(R a ), P(=O)(OR a )(R b ), P(=O)(OR a )(R c ), P(=O)(OR c )(R c ), P(=O)(R a )2, P(=O)(R a )(R b ), P(=O)(R c )2, P(=O)(R a )(R c ), Si(R a )2(Ph), Si(R a )(R b )(Ph), Si(R a )2(CH2Ph), Si(R a )(R b )(CH2Ph), Si(R a )2(R d ), Si(R a )(R b )(R d ), Si(R a )2 (CH2R c ), Si(R a )(R b )(CH2R c ), Si(R c )3, Si(CH2R c)3, linear or branched C 1-12 -Alkyl selenoether, B(OR e )2, B(OCH(CH2)2)2.

[0054] R a and R b are either linear or branched C 1-12 -Alkyl; R c is C 3-10 -Cycloalkyl; R d is C 3-10 -Cycloalkenyl; R e is linear or branched C 1-6 -Alkyl.

[0055] R2 and R6 are each independently selected from the group consisting of H, B(OH)2, B(OR 11 )2 and B(OR 11 )(OR 12 ); where R 11 and R 12 Each is selected independently from the group consisting of linear or branched C 1-12 -Alkyl and linear or branched C 1-12 -Alkylcarbonyl.

[0056] R3 and R7 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkylmethyl, cycloalkyl, cycloalkylalkyl, carbocycle, heterocycle, methylazetidinyl and (1-methylazetidin-3-yl)methyl, where alkyl is linear or branched C 1-4 -Alkyl is optionally substituted with one or more OH and / or halogen atoms; alkenyl is linear or branched C 2-4 -Alkenyl, optionally substituted with one or more halogen atoms; alkynyl is linear or branched C 2-4 -Alkynyl, optionally substituted with one or more halogen atoms, cycloalkyl is C 3-6 -Cycloalkyl, optionally substituted with one or more halogen atoms, preferably fluorine; cycloalkyl is C 3-6-Cycloalkyl, optionally substituted with one or more halogen atoms, preferably fluorine. Preferably, R3 and R7 are each independently selected from the group consisting of 2-fluoroethyl, 1,2-difluoroethyl, methylazetidinyl, trifluoromethyl, 2,2,2-trifluoroethyl, perfluoroethyl, 3,3-difluoroallyl, 2',2'-difluorocyclopropylmethyl and (1-methylazetidin-3-yl)methyl.

[0057] R4, R5, R8 and R9 are each independently selected from the group consisting of H, C 3-5 -Cycloalkyl, C 1-5 -Alkyl, where the C 1-5 -Alkyl is linear or branched, optionally substituted with one or more halogen atoms or trifluoromethyl groups. Fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, and perfluoroethyl are suitable.

[0058] R4 and R5 together form part of a C 3-6 -Carbocycle or one C 3-6 -Heterocycle or R8 and R9 together form part of a C 3-6-Carbocycle or one C 3-6 -Heterocycle.

[0059] It is stipulated that if R1 and R2 are both hydrogen (H), R4 and R5 are not both ethyl groups and R3 is not a methyl group. The compound according to formula (I) is not lysergic acid diethylamide (LSD). Preferably, either R1 is hydrogen and R2 is not hydrogen. In a further preferred embodiment, R1 is not hydrogen and R2 is hydrogen.

[0060] In one or more embodiments, the compound exists as a pharmaceutically acceptable salt form of the compound of formula (I). In one or more embodiments, the compound is a hydrochloride, hydrobromide, sulfate, phosphate, mesylate, acetate, fumarate, maleate, tartrate, citrate, and / or tosylate salt of the compound of formula (I). In one or more embodiments, the compound exists as a solvate of the compound of formula (I). In one or more embodiments, the compound exists as a hydrate of the compound of formula (I). In one or more embodiments, the compound exists as a stereoisomeric form of the compound of formula (I).

[0061] In one or more embodiments, the compound has the formula (II):

[0062] In one or more embodiments, the compound has formula (I) or formula (II), wherein R1 is

[0063] In one or more embodiments, the compound has the formula (I), where R1 is H and R2 is selected from the group consisting of B(OH)2, B(OR 11 )2 and B(OR 11 )(OR 12 ), where R 11 and R 12 a linear or branched C 1-12 -Alkyl, preferably a linear or branched C 1-4 -Alkyl are.

[0064] In one or more embodiments, the compound has the formula (I), where R1 is H and R2 is B(OR 11 )2 or B(OR 11 )(OR 12 ) is, where R 11 and R 12 each a linear or branched C 1-12 -Alkyl, preferably a linear or branched C 1-4 -Alkyl and especially preferably ethyl or isopropyl.

[0065] In one or more embodiments, the compound has the formula (I), wherein R4 and R5 are each independently selected from the group consisting of H, C 3-5-Cycloalkyl, linear or branched C 1-5 -Alkyl, optionally substituted with one or more halogen atoms or trihalomethyl groups, preferably unsubstituted linear C 1-5 -Alkyl.

[0066] In one or more embodiments, the compound has formula (I), wherein R4 and R5 are each independently H. In one or more embodiments, R4 and R5 are each independently H or C. 3-5 -Cycloalkyl. In one or more embodiments, R4 and R5 are each independently H or linear or branched C. 1-5 -Alkyl, optionally substituted with one or more halogen atoms, preferably fluorine atoms, or trihalomethyl groups. In one or more embodiments, R4 and R5 are each independently C 3-5 -Cycloalkyl or linear or branched C 1-5-Alkyl, optionally substituted with one or more halogen atoms, preferably fluorine atoms or trihalomethyl groups. In one or more embodiments, R4 and R5 are each independently linear or branched C 1-5 -Alkyl, optionally substituted with one or more halogen atoms, preferably fluorine atoms or trihalomethyl groups. In one or more embodiments, R4 and R5 are each independently linear or branched unsubstituted C 1-5 -Alkyl or H.

[0067] In one or more embodiments, the compound has the formula (I), where R2 B(OR 11 )2 or B(OR 11 )(OR 12 ) is, where R 11 and R 12 each a linear or branched C 1-12 -Alkyl, preferably a linear or branched C 1-4 -alkyl are, and / or wherein R4 and R5 are each independently linear or branched unsubstituted C 1-5-Alkyl are. In one or more embodiments, the compound has the formula (I), where R1 is H, R2 is B(OR 11 )2 or B(OR 11 )(OR 12 ) is, where R 11 and R 12 each a linear or branched C1. 12 -Alkyl, preferably a linear or branched C 1-4 -alkyl are, and / or wherein R4 and R5 are each independently linear or branched unsubstituted C 1-5 -Alkyl are.

[0068] In one or more embodiments, the compound has the formula (I), wherein R4 and R5 are part of a C 3-6 -Carbocycle or C 3-6 -Heterocycles are, preferably of a C 3-6 -Heterocycle.

[0069] In one or more embodiments, the compound has the formula (I), where R2 B(OR 11 )2 or B(OR 11 )(OR 12 ) is, where R 11 and R 12 each a linear or branched C 1-4-Alkyl are and / or where R4 and R5 are part of a C 3-6 -Carbocycle or C 3-6 -Heterocycles. In one or more embodiments, the compound has the formula (I), where R1 is H, R2 is B(OR 11 )2 or B(OR 11 )(OR 12 ) is, where R 11 and R 12 each a linear or branched C 1-4 -alkyl are, and / or where R4 and R5 are part of a C 3-6 -Carbocycle or C 3-6 -Heterocycles are.

[0070] In one or more embodiments, the compound has the formula (I), where R2 B(OR 11 )2 or B(OR 11 )(OR 12 ) is, where R 11 and R 12 each a linear or branched C 1-4 -Alkyl are and / or where R4 and R5 are part of a C 3-6 -Heterocycles. In one or more embodiments, the compound has the formula (I), where R1 is H, R2 is B(OR 11 )2 or B(OR 11 )(OR 12) is, where R 11 and R 12 each a linear or branched C 1-4 -alkyl are, and / or where R4 and R5 are part of a C 3-6 -Heterocycles are.

[0071] In one or more embodiments, the compound has the formula (I), where R2 is H and R1 is XYZ.

[0072] In one or more embodiments, the compound has formula (I), wherein R2 is H and R1 is XYZ, X is CH2, Y is a phosphate, phosphonate, or phosphinate, wherein the phosphate, phosphonate, or phosphinate is preferably further substituted with alkyl or cycloalkyl groups, and wherein Z is absent. The phosphate can be a dialkyl phosphate, a dicycloalkyl phosphate, or an alkylcycloalkyl phosphate, wherein the alkyl or cycloalkyl groups can be identical or different. The phosphonate can be a dialkylphosphonate, a dicycloalkylphosphonate, or an alkylcycloalkylphosphonate, wherein the alkyl or cycloalkyl groups can be identical or different. The phosphinate can be a dialkyl phosphinate, a dicycloalkyl phosphinate, or an alkylcycloalkyl phosphinate, wherein the alkyl or cycloalkyl groups can be identical or different. The alkyl groups can be linear or branched. 1-12-alkyl, optionally substituted with one or more of the substituents R described above 10 The cycloalkyl groups can form a C 3-10 -Cycloalkyl.

[0073] In one or more embodiments, the compound has the formula (I), where R2 is H and R1 is XYZ, where X is CH2 and Y is selected from the group consisting of OP(=O)(OR) a )2, OP(=O)(OR a )(OR b ), OP(=O)(OR a )(R a ), OP(=O)(OR a )(R b ), OP(=O)(R a )2, OP(=O)(R a )(R b ), P(=O)(OR a )2, P(=O)(OR a )(OR b ), P(=O)(OR a )(R a ), P(=O)(OR a )(R b ), P(=O)(R a )2 and P(=O)(R a )(R b ) and where Z is absent, where R a and R b Each independently linear or branched C 1-12 -Alkyl, preferably linear C 1-5-Alkyl are. In some embodiments, R a and R b Each independently linear or branched C 1-5 -Alkyl. In preferred embodiments, R a and R b Each independently linear C 1-5 -Alkyl.

[0074] In one or more embodiments, the compound has the formula (I), where R2 is H, R1 is XYZ, where XC=O, Y is a linear or branched C 1-12The alkyl group is Z, and Z is a phosphate, phosphonate, or phosphinate group, wherein the phosphate, phosphonate, or phosphinate is preferably additionally substituted with alkyl or cycloalkyl groups. The phosphate can be a dialkyl phosphate, a dicycloalkyl phosphate, or an alkyl cycloalkyl phosphate, wherein the alkyl or cycloalkyl groups can be the same or different. The phosphonate can be a dialkyl phosphonate, a dicycloalkyl phosphonate, or an alkyl cycloalkyl phosphonate, wherein the alkyl or cycloalkyl groups can be the same or different. The phosphinate can be a dialkyl phosphinate, a dicycloalkyl phosphinate, or an alkyl cycloalkyl phosphinate, wherein the alkyl or cycloalkyl groups can be the same or different. The alkyl groups can be linear or branched. 1-12 -alkyl groups, optionally with one or more of the substituents R described above 10 are substituted. The cycloalkyl groups can be a C 3-10-Cycloalkyl residue.

[0075] In one or more embodiments, the compound has the formula (I), where R2 is H and R1 is XYZ, where XC=O, Y is a linear or branched C 1-12 -Alkyl is and Z is selected from the group consisting of OP(=O)(OR a )2, OP(=O)(OR a )(OR b ), OP(=O)(OR a )(R a ), OP(=O)(OR a )(R b ), OP(=O)(R a )2, OP(=O)(R a )(R b ), P(=O)(OR a )2, P(=O)(OR a )(OR b ), P(=O)(OR a )(R a ), P(=O)(OR a )(R b ), P(=O)(R a )2, P(=O)(R a )(R b ), where R a and R b Each independently a linear or branched C 1-12 -Alkyl are, preferably linear C 1-5 -Alkyl.

[0076] In one or more embodiments, the compound has the formula (I), where R2 is H and R1 is XYZ, where XC=O, Y is a linear C 1-12 -Alkyl is and Z is selected from the group consisting of OP(=O)(OR a )2, OP(=O)(OR a )(OR b ), OP(=O)(OR a )(R a ), OP(=O)(OR a )(R b ), OP(=O)(R a )2, OP(=O)(R a )(R b ), P(=O)(OR a )2, P(=O)(OR a )(OR b ), P(=O)(OR a )(R a ), P(=O)(OR a )(R b ), P(=O)(R a )2, P(=O)(R a )(R b ), where R a and R b Each independently a linear or branched C 1-12 -Alkyl are, preferably linear C 1-5 -Alkyl.

[0077] In one or more embodiments, the compound has the formula (I), where R2 is H and R1 is XYZ, where XC=O, Y is a linear C 1-12-Alkyl is and Z is selected from the group consisting of OP(=O)(OR a )2, OP(=O)(OR a )(OR b ), OP(=O)(OR a )(R a ), OP(=O)(OR a )(R b ), OP(=O)(R a )2, OP(=O)(R a )(R b ), P(=O)(OR a )2, P(=O)(OR a )(OR b ), P(=O)(OR a )(R a ), P(=O)(OR a )(R b ), P(=O)(R a )2, P(=O)(R a )(R b ), where R a and R b Each independently linear or branched C 1-12 -Alkyl are, preferably linear C 1-5 -Alkyl.

[0078] In one or more embodiments, the compound has the formula (I), where R2 is H and R1 is XYZ, where XC=O, Y is a linear C 1-12 -Alkyl is and Z is a C 1-12 -Alkyl selenoethers, preferably a C 1-6-Alkyl selenoether. In one or more embodiments, the compound has formula (I) and / or any stereoisomeric form and / or diastereomeric form thereof, wherein R2 is H and R1 has formula (A), where L is a linker. In some embodiments, the linker L is a covalent bond.

[0079] In one or more embodiments, L is a linker selected from the group consisting of: where R 13 and R 14 Each are independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkylmethyl, cycloalkyl, cycloalkylalkyl, carbocycle, heterocycle, methylazetidinyl and (1-methylazetidin-3-yl)methyl, where alkyl is a linear or branched C 1-4 -Alkyl is optionally substituted with one or more OH and / or halogen atoms; alkenyl is a linear or branched C 2-4-Alkenyl is optionally substituted with one or more halogen atoms; alkynyl is a linear or branched C 2-4 -Alkynyl is optionally substituted with one or more halogen atoms; cycloalkyl is a C 3-6 -Cycloalkyl is optionally substituted with one or more halogen atoms. The halogen can be selected from the group consisting of chlorine, bromine, iodine or fluorine, preferably fluorine.

[0080] In preferred embodiments, the linker L is selected from the group consisting of

[0081] Preferably, the compound according to formula (I) is one of the compounds 1 to 30 and / or any stereoisomer thereof and / or any diastereomer thereof, as shown below in Table 1. Table 1: Structures of compounds 1 to 30 Connection number structure 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30

[0082] In one or more embodiments, the compound according to formula (I) is a prodrug.

[0083] Another aspect of the present invention relates to the use of the compound according to formula (I) as a pharmaceutical. A further aspect of the present invention relates to the use of the compound according to formula (I) for the treatment of mental disorders such as depression, anxiety disorders and / or post-traumatic stress disorder (PTSD), addiction treatment, eating disorders, cluster headache and / or migraine.

[0084] Another aspect of the present invention relates to a pharmaceutical composition containing the compound according to formula (I), a pharmaceutically acceptable salt, a stereoisomer, a hydrate, and / or a solvate thereof. The pharmaceutical composition containing the compound according to formula (I) can be prepared in any form suitable for systemic administration, including oral and parenteral routes. The pharmaceutical composition containing the compound according to formula (I) can be provided in the form of a tablet, capsule, elixir, saline solution, and / or suspension. The pharmaceutical composition may further contain pharmaceutically acceptable excipients or carriers.

[0085] Another aspect of the present invention relates to a method for producing the compound according to formula (I).

[0086] Lysergic acid amide can be obtained by known methods, such as those described in David E. Nichols: “Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)” in ACS Chemical Neuroscience 2018, Volume 9, Issue 10; and in Aaron P. Monte, Danuta Marona-Lewicka, Arthi Kanthasamy, Elaine Sanders-Bush, David E. Nichols: “Stereoselective LSD-like Activity in a Series of d-Lysergic Acid Amides of (R)- and (S)-2-Aminoalkanes” in Journal of Medicinal Chemistry 1995, Volume 38, Issue 6.

[0087] In one embodiment, the method for producing the compound according to formula (I) consists of method (A), comprising the steps: a. Provision of a lysergic acid amide, b. Preparation of a 14-BPin lysergic acid amide by reacting the lysergic acid amide from step (a) with B2 pin, c. Reaction of the 14-BPin-lysergic acid amide obtained from step (b) with alkylboronic acid, preferably methylboronic acid, to prepare 14-boric acid-lysergic acid amide, followed by a reaction with trialkyl orthoformate to obtain the compound according to formula (I).

[0088] The reaction in step b can be carried out analogously to the method described in Andrew S. Eastabrook, Jonathan Sperry: “Synthetic Access to 3,5,7-Trisubstituted Indoles Enabled by Iridium-Catalyzed CH Borylation” in Synthesis 2017, 49, AG, (DOI: 10.1055 / s-0036-1589018). Me4Phen can be replaced by 4,4'-di-tert-butyl-2,2'-dipyridyl (dtbpy) for improved selectivity and yield.

[0089] The reaction in step c can be carried out according to the method described in Stephan PA Hinkes, Christian DP Klein: “Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids” in Organic Letters 2019, Volume 21, Issue 9 (DOI: 10.1021 / acs.orglett.9b00584).

[0090] In one or more embodiments, the compound prepared according to method (A) according to formula (I) is one of compounds 1, 2, or 3 and / or any stereoisomer thereof. In one embodiment, the lysergic acid amide from step (a) of method (A) is LSD and / or any stereoisomer thereof. In one embodiment, the lysergic acid amide from step (a) of method (A) is compound 31 and / or any stereoisomer thereof.

[0091] In one embodiment, the method for producing the compound according to formula (I) consists of method (B), comprising the steps: a. Provision of a lysergic acid amide, b. Reaction of the lysergic acid amide from step (a) with a suitable substituted alkyl acyl halide or a suitable substituted alkyl halide to obtain the compound according to formula (I).

[0092] In one or more embodiments, the compound prepared according to method (B) according to formula (I) is one of compounds 4 to 19 and / or any stereoisomer thereof. In one or more embodiments, the lysergic acid amide from step (a) of method (B) is LSD and / or any stereoisomer thereof. In one or more embodiments, the lysergic acid amide from step (a) of method (B) is compound 32 and / or any stereoisomer thereof. In one or more embodiments, the lysergic acid amide from step (a) of method (B) is compound 33 and / or any stereoisomer thereof. In one or more embodiments, the lysergic acid amide from step (a) of method (B) is compound 34 and / or any stereoisomer thereof.

[0093] In one or more embodiments, the suitably substituted alkyl acyl halide from step (b) of process (B) is an alkyl acyl halide wherein the alkyl is a linear or branched C 1-12 -Alkyl, preferably a linear C 1-6 -Alkyl is substituted with a phosphate, phosphonate, or phosphinate. Preferably, the phosphate, phosphonate, or phosphinate is further modified with a linear or branched C 1-12 -Alkyl, preferably a linear C 1-6 -Alkyl, or a C 3-10 -Cycloalkyl substituted. In preferred embodiments, the suitably substituted alkyl-acyl halide from step (b) of process (B) is selected from the group consisting of: where X is a halide, such as Cl, I or Br.

[0094] In one or more embodiments, the suitably substituted alkyl acyl halide from step (b) of process (B) is an alkyl acyl halide wherein the alkyl is a linear or branched C 1-12 -Alkyl, preferably a linear C 1-6 -Alkyl is substituted with a selenium atom. In one or more embodiments, the suitably substituted alkyl acyl halide from step (b) of process (B) is X, where X is a halide such as Cl, I, or Br.

[0095] In one or more embodiments, the suitably substituted alkyl halide from step (b) of process (B) is an alkyl halide wherein the alkyl is a linear or branched C 1-12 -Alkyl, preferably a linear C 1-6 -Alkyl is substituted with a phosphate, phosphonate, or phosphinate. Preferably, the phosphate, phosphonate, or phosphinate is further modified with a linear or branched C 1-12-Alkyl, preferably a linear C 1-6 -Alkyl, or a C 3-10 -Cycloalkyl substituted. In preferred embodiments, the suitably substituted alkyl halide from step (b) of process (B) is selected from the group consisting of: where X is a halide, such as Cl, I or Br.

[0096] In one or more embodiments, the method for producing the compound according to formula (I) consists of method (C), comprising the steps: a. Provision of a lysergic acid amide, b. Reaction of the lysergic acid amide from step (a) with linker L to obtain a lysergic acid amide linker fragment / unit, wherein the linker L is linked to the lysergic acid amide via an amide and / or carbamate unit and wherein the linker L has a terminal leaving group, such as an ester, a halide, including bromide, iodide, fluoride, a sulfate, a mesylate, a triflate, a tosylate, preferably an ester. c. Reaction of the lysergic acid amide linker fragment / unit from step (b) with another lysergic acid amide to prepare the compound according to formula (I).

[0097] In one or more embodiments, the compound prepared according to method (C) is one of compounds 20 to 30 and / or any stereoisomer and / or diastereoisomer thereof.

[0098] In one or more embodiments, the lysergic acid amide from step (a) or step (c) of method (C) is selected from the group consisting of: and / or any stereoisomer thereof. In one or more embodiments, the lysergic acid amide is obtained from step (a) or step (c) of process (C).

[0099] The compounds of the present invention act as prodrugs which, after administration to a subject or patient, are converted in the body into the corresponding active compounds or metabolites.

[0100] The active metabolite can be LSD and / or any stereoisomer thereof, or a structural derivative of LSD and / or any stereoisomer thereof.

[0101] The active metabolite derived from LSD typically has the formula (I), where R1 and R2 are both hydrogen (H). The substituents R3, R4, and R5 are as described above.

[0102] Specific examples of active metabolites include compound 33 and / or any stereoisomers thereof, compound 34 and / or any stereoisomers thereof, compound 39 and / or compound 40. Examples

[0103] The following examples serve to demonstrate the underlying principles of the present invention. They are intended as illustrations and should in no way be interpreted as limiting.

[0104] The chemicals used were commercially sourced from Cymit Quimica SL in Barcelona, ​​Spain, and Syntho-Life-Lab UG in Berlin, Germany. Example 1: Conversion of selected prodrugs into their active metabolites

[0105] The prodrugs according to the present invention are converted in the body into active metabolites, as shown below. Example 2: Evaluation of active metabolites in silico

[0106] LSD and its active metabolites, compound 39 and compound 40, were studied in in silico docking studies.

[0107] LSD, Compound 39 and Compound 40 were docked into the binding pockets of three different crystal structures of the serotonin receptors, namely the 5-HT 1A -Subtype (Protein Data Bank (PDB) access code: 7E2Y), the 5-HT 2A -Subtype (PDB access code: 6A93) and the 5-HT 2C -Subtype (PDB access code: 8DPF). Method:

[0108] A proprietary in silico platform, based on the AlphaFold protein database developed by Google DeepMind, was used to evaluate and rank potential agonists for serotonin receptors relevant to depression treatment. The system integrates automated docking, receptor selectivity profiling, and molecular dynamics simulations into a unified workflow.

[0109] High-resolution receptor structures were obtained from the Protein Data Bank and included 5-HT. 2A (PDB access code: 6A93), 5-HT 1A (PDB access code: 7E2Y) and 5-HT 2C (PDB access code: 8DPF). All structures were preprocessed according to standard protocols. Protonation was performed in an aqueous medium at pH 7.4 and a temperature of 310.15 K, side chains were added, and restrictive energy minimization was carried out.

[0110] Candidate ligands were docked using a flexible ligand and a semi-flexible receptor approach. Each docking generated multiple poses per ligand, which were evaluated using a composite function that considered the predicted bond-free energy (ΔG), hydrogen bonds, π-interactions, and spatial complementarity. Five different ligand conformations were calculated for each measurement. These included various positions within the receptor and rotations at sigma bonds. Molecular vibrations, polarization of the molecule, and water as a binding partner were not considered. Selectivity for receptor subtypes was determined by comparing docking scores and residual-level interaction fingerprints between 5-HT and 5-HT. 2A , 5-HT 1A and 5-HT 2C evaluated. A selectivity index was calculated based on ΔG values ​​and Tanimoto similarity of the interaction profiles.

[0111] The highest-ranked ligand-receptor complexes underwent 100 ns molecular dynamics (MD) simulations under NPT conditions (temperature 310 K, pressure 1 atm, 5 molecules), periodic boundary conditions, Nose-Hoover thermostat, Parrinello-Rahman barostat, TIP3P water model, and a 2 fs time interval to assess conformational stability and binding persistence. Simulations were performed without restrictions after equilibrium was reached. Key measurements included mean squared deviation (RMSD), mean squared fluctuation (RMSF), and occupancy of critical binding interactions. All results were automatically summarized in structured reports, enabling ranking of compounds by potency, receptor selectivity, and dynamic stability. This computational pipeline allows for efficient screening of serotonin agonists in early development for further experimental validation. Results:

[0112] The ΔG values ​​obtained using the method described above are summarized in Table 2. G corresponds to the Gibbs free energy. The change in G, denoted as ΔG, represents the difference in Gibbs free energy between the compounds in their unbound state and their bound state after binding to the receptor. Therefore, the ΔG values ​​provide an estimate of the probability of the compounds interacting with the receptor. A low, negative ΔG value generally indicates a strong affinity for the receptor, meaning the compounds are likely to interact favorably with it.

[0113] The ΔG values ​​were then used to calculate the inhibitor constant, i.e., the Ki values ​​for LSD, compound 39, and compound 40, using the following formula: Ki=eΔGRT where K i the inhibitor constant is, ΔG is Gibbs free energy, R is the ideal gas constant with a value of 8.314 J / mol·K, T is the temperature in Kelvin (K).

[0114] The inhibitor constant provides an estimate of the binding affinity of the compounds to the receptor. The lower the Ki, the greater the affinity. i The higher the value, the higher the binding affinity of the compounds to the receptor. The K i The values ​​of the compounds are shown in Table 2.

[0115] Table 2: ΔG and K i -Values ​​for LSD, Compound 39 and Compound 40, as obtained from the docking studies Connection AT 5-HT1A AT 5-HT2A AT 5-HT2C To (5-HT1A) To (5-HT2A) To (5-HT2C) LSD -10.82 -10.56 -9.89 11.7 18.1 55.8 Connection 39 -10.55 -9.56 -9.74 18.4 97.6 72.3 Connection40 -9.98 -9.47 -10.73 49.4 113.9 13.7

[0116] From the ΔG and K values ​​shown above i Based on the values, it can be concluded that connection 39 and connection 40 each have high K values. i -Values ​​at 5-HT 2A-receptor expression suggests that they likely have a low binding affinity for this particular receptor subtype. These results suggest that compound 39 and compound 40 may have a lower tendency to produce the hallucinogenic effects associated with LSD. Example 3: Determining the subtype selectivity profile of LSD, compound 39 and compound 40

[0117] The above determined K i Values ​​were used to evaluate the subtype selectivity profile of compound 39 and compound 40 compared to LSD. Accordingly, the Ki(5-HT) ratios were determined. 2A ):Ki(5-HT 1A ) and Ki(5-HT 2A ):Ki(5-HT 2C ) calculated. Results

[0118] Table 3 shows the calculated ratios for LSD, Compound 39 and Compound 40. Table 3: Calculated Ki(5-HT2A):Ki(5-HT1A) and Ki(5-HT2A):Ki(5-HT2C) ratios for LSD, Compound 39 and Compound 40 Connection K i (5-HT 2A ):K i (5-HT 1A ) K i (5-HT 2A ):K i (5-HT 2C ) LSD 1.55 0.32 39 5.30 1.35 40 2.31 8.31

[0119] Compared to compounds 39 and 40, LSD has the lowest K i (5-HT 2A ):K i (5-HT 1A )-ratio. Similar observations arise when comparing the K i (5-HT 2A ):K i (5-HT 2C )-ratio of the three compounds. This shows that LSD has the highest binding affinity to 5-HT. 2A Compounds 39 and 40 possess a 5-HT receptor subtype among the three compounds. In contrast, compounds 39 and 40 show a reduced affinity for 5-HT. 2A -Receptor subtype. Compound 39 exhibits an increased binding affinity to 5-HT. 1A -receptor subtype compared to LSD and Compound 40. On the other hand, Compound 40 shows an increased binding affinity to 5-HT. 2C-receptor subtype. Without being tied to any theory, it is assumed that the reduced affinity for 5-HT 2A The effects shown by compounds 39 and 40 could lead to a reduced tendency to produce the hallucinogenic effects associated with LSD. These results suggest that compounds 39 and 40, as derivatives of LSD with improved safety and tolerability, could find useful therapeutic applications in clinical settings. Example 4: Synthesis of the compounds Scheme 1: Preparation of 6-substituted lysergic acid amide Method 1: Preparation of 6-substituted lysergic acid amide

[0120] Lysergic acid amide can be obtained by known methods, such as those described in David E. Nichols: “Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)” in ACS Chemical Neuroscience 2018, Volume 9, Issue 10; and in Aaron P. Monte, Danuta Marona-Lewicka, Arthi Kanthasamy, Elaine Sanders-Bush, David E. Nichols: “Stereoselective LSD-like Activity in a Series of d-Lysergic Acid Amides of (R)- and (S)-2-Aminoalkanes” in Journal of Medicinal Chemistry 1995, Volume 38, Issue 6. Scheme 1: Preparation of 6-substituted lysergic acid amide Step a: Production of lysergic acid from 9-substituted lysergic acid amides

[0121] Methyl lysergic acid ester (1.00 g, 3.5 mmol, 1.00 equiv) was suspended in 20 mL of 1 N NaOH and heated to 75 °C for 2 hours. The reaction mixture was cooled in an ice bath, acidified to pH 5–6, and the resulting precipitate filtered off. The filtrate was dried over magnesium sulfate, filtered, and concentrated under vacuum to obtain lysergic acid in 99% yield. The product was used without further purification. MP: > 240 °C (decomposition)

[0122] δ(DMSO-d6, 400 MHz) = 10.74 (s, br, 1H), 7.12 (dd, J = 6.9 Hz, J = 1.6 Hz, 1H), 7.01-7.06 (m, 3H), 6.42 (dd, J = 5.5 Hz, J = 1.8 Hz, 1H), 3.39 (m, 1H), 3.23 (m, 1H), 3.19 (dd, J = 12.0 Hz, J = 2.8 Hz, 1H), 3.01 (m, 1H), 2.66 (dd, J = 12.0 Hz, J = 4.6 Hz, 1H), 2.46 (m, 1H), 2.44 (s, 3H). Step b: General procedure - Production of lysergic acid amide

[0123] Lysergic acid (1.00 mmol, 1.00 eq.) and the corresponding alkylamine (1.00 mmol, 1.00 eq.) were suspended in 10 mL of DCM. Phosphoryl chloride (2.00 mmol, 2.00 eq.) was added dropwise over 2 minutes. The resulting mixture was heated under reflux for 20 minutes. After cooling to room temperature, the mixture was suspended in 20 mL of 1 N ammonium hydroxide solution. The phases were separated, dried over magnesium sulfate, and the solvent was removed under vacuum. The crude product was purified by flash column chromatography over aluminum oxide using hexane / DCM (3:1) to obtain the desired lysergic acid alkylamide or lysergic acid dialkylamide. Step c: General procedure - Preparation of 6-cyano-lyserquiamides

[0124] The lysergic acid alkylamide or lysergic acid dialkylamide obtained from step (b) (1.00 mmol, 1.00 eq.) was dissolved in 10 mL of CHCl3, diluted with 70 mL of CCl4, and added to a refluxed solution of cyanogen bromide (4.00 mmol, 4.00 eq.) in 30 mL of CCl4 under a nitrogen atmosphere for 1 hour. The resulting mixture was heated under reflux for a further 6 hours, then cooled to room temperature. The solvents were removed under vacuum, the residue was dissolved in 50 mL of DCM, and washed with 40 mL of a 5% tartaric acid solution. The phases were separated, washed with 20 mL of salt solution, and dried over Na2SO4. After removal of the solvent under vacuum, the crude product was purified by flash column chromatography over neutral aluminium oxide using DCM / MeOH (9:1) as eluent to obtain the desired 6-cyano-lysergic acid amide. Step d: General procedure - Production of nor-lysergic acid amides

[0125] Powdered zinc (9.00 mmol, 9.00 eq.) was added to a solution of 6-cyano-lysergamide from step (c) (1.00 mmol, 1.00 eq.) in 3.5 mL of 83% ethanol-water solution under a nitrogen atmosphere. The mixture was heated at 130 °C with stirring for 4 hours. After cooling in an ice bath, 4 mL of water were added and the pH was adjusted to 10⁻¹² with ammonium chloride (aq). The suspension was extracted with DCM (5 × 10⁻¹⁰ mL), the combined organic phases were washed with salt solution, and the mixture was dried over sodium hydroxide. The solvent was removed under vacuum. The crude product was purified by flash column chromatography over neutral aluminum oxide using DCM / MeOH (8:1) as the eluent to obtain the desired nor-lysergamide. Nor-lyserquic acid diethylamide MP: 195-198 °C (decomposition) δ(CDCl3, 400 MHz) = 7.88 (s, br, 1H), 7.13-7.23 (m, 3H), 6.90 (t, J = 2.0 Hz, 1H), 6.60 (s, br, 1H), 3.76 (s, 3H), 3.73 (m, 1H), 3.50 (dd, J = 14.0 Hz, J = 6.0 Hz, 1H), 3.27 (dd, J = 11.0 Hz, J = 5.0 Hz, 1H), 3.20 (m, 1H), 2.70 (ddd, J = 14.0 Hz, J = 12.0 Hz, J = 2.0 Hz, 1H), 2.68 (t, J = 11.0 Hz, 1H), 2.62 (s, 3H). Step e: General procedure - Preparation of 9-substituted lysergic acid amides

[0126] The nor-lysergamide obtained from step (d) (1.00 mmol, 1.00 eq.) was dissolved in 10 mL of DMF under a nitrogen atmosphere. Finely powdered anhydrous K₂CO₃ (3.50 mmol, 3.50 eq.) was added, followed by the corresponding alkyl or alkenyl tosylate (1.05 mmol, 1.05 eq.) with vigorous stirring. After TLC showed complete conversion of the nor-lysergamide, all volatile components were removed under high vacuum. The crude product was purified by flash column chromatography over neutral aluminum oxide using DCM / MeOH (9:1) as the eluent. Method A: Preparation of 14-Dialkylborate lysergic acid amides Scheme 2: Preparation of 14-Dialkylborate lysergic acid amides Step a: General procedure for the preparation of 14-BPin lysergic acid amides

[0127] The reaction can be carried out analogously to the method described in Andrew S. Eastabrook, Jonathan Sperry: “Synthetic Access to 3,5,7-Trisubstituted Indoles Enabled by Iridium-Catalyzed CH Borylation” in Synthesis 2017, 49, AG, (DOI: 10.1055 / s-0036-1589018). Me4Phen can be replaced by 4,4'-di-tert-butyl-2,2'-dipyridyl (dtbpy) for improved selectivity and yield.

[0128] 2.5 mol% [Ir(cod)(OMe)]₂ and 5 mol% dtbpy ligand were dissolved in 2 mL of absolute THF under a nitrogen atmosphere and stirred for 10 minutes. The corresponding lysergic acid amide (0.10 mmol, 1.00 eq.) and B₂pin₂ (0.20 mmol, 2.00 eq.) were added simultaneously, and the mixture was stirred for 20 hours at 75 °C. After cooling to room temperature, 5 mL of water and 5 mL of EtOAc were added. The phases were separated, dried over magnesium sulfate, and the solvent was removed under vacuum. The crude product was purified by basified flash column chromatography over silica using hexane / EtOAc (7:3) with 0.5% triethylamine to obtain the desired 14-BPin lysergic acid amide. Step b: General procedure for the preparation of 14-boric acid lysergic acid amides

[0129] The reaction can be carried out according to the method described in Stephan PA Hinkes, Christian DP Klein: “Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids” in Organic Letters 2019, Volume 21, Issue 9 (DOI: 10.1021 / acs.orglett.9b00584). The 14-BPin-lysergic acid amide (0.10 mmol, 1.00 eq.) and methylboronic acid (1.00 mmol, 10.00 eq.) obtained in step (a) were dissolved in 1 mL of acetone under a nitrogen atmosphere. After adding 1 mL of 0.1 N NaOH(aq), the reaction mixture was stirred for 20 hours under a nitrogen atmosphere. The solution was carefully neutralized with 0.1 N HCl. 5 mL of DCM were added, the phases were separated, and dried over MgSO4. The solvent was removed under vacuum, yielding the raw product which was used without further purification. Step c: General procedure for the preparation of 14-dialkylborate lysergic acid amides

[0130] The 14-boric acid lysergic acid amide (0.1 mmol, 1.00 eq.) and the corresponding trialkyl orthoformate (1.00 mmol, 10.00 eq.) obtained in step (b) were dissolved in 2 mL of CHCl3. Anhydrous 3 Å molecular sieves (50 mg) were added, and the mixture was heated for 2 hours at 70 °C under a nitrogen atmosphere. After completion of the reaction, the solvent was removed under vacuum. The crude product was purified by basified flash column chromatography over silica using hexane / EtOAc (7:3) with 0.5% triethylamine. Methods B and C: Preparation of N1-substituted lysergic acid amides Scheme 3: Preparation of N1-substituted lysergic acid amides Method B: Method B1: Preparation of acyl-N1-substituted lysergic acid amides

[0131] The corresponding lysergic acid amide (1.05 mmol, 1.05 eq.) was dissolved in 40 mL of absolute DCM under a nitrogen atmosphere. Dry tetrabutylammonium hydrogen sulfate (1.25 mmol, 0.6 eq.) and finely powdered, dry NaOH (102.5 mmol, 50.0 eq.) were added while stirring. The two-phase mixture was cooled to -10 °C, and the appropriately substituted alkylacyl chloride (1.00 mmol, 1.0 eq.) was added dropwise, taking care that the temperature did not exceed -5 °C. After stirring for 4 hours at -10 °C, the reaction mixture was filtered through Celite and washed with DCM (2 × 50 mL). The solution was washed with water (2 × 40 mL) and then with salt solution (30 mL) and dried over MgSO₄. After removal of the solvent under vacuum, the crude product was purified by flash column chromatography over silica using DCM / MeOH gradients. Method B2: Preparation of alkyl-N1-substituted lysergic acid amides

[0132] A solution of the appropriately substituted alkyl bromide (1.00 mmol, 1.00 eq.) was dissolved in 50 mL of acetone. Potassium iodide (3.5 mmol, 3.50 eq.) was added while stirring. The appropriate lysergic acid amide (1.05 mmol, 1.05 eq.) and DMAP (0.25 mmol, 0.25 eq.) were dissolved in 40 mL of acetone. After stirring for 4 hours at room temperature, the solution of the appropriately substituted alkyl halide was added dropwise over 1 hour at 0 °C. After the addition, the reaction mixture was stirred for another hour at room temperature. The solution was washed with water (2 × 40 mL), then with salt solution (30 mL), and dried over MgSO₄. After removal of the solvent under vacuum, the crude product was purified by flash column chromatography over silica using DCM / MeOH gradients. Method C: Preparation of dimeric N1-substituted lysergic acid amides

[0133] The corresponding lysergic acid amide (2.05 mmol, 2.05 eq.) was dissolved in 40 mL of absolute DCM under a nitrogen atmosphere. Dry tetrabutylammonium hydrogen sulfate (1.25 mmol, 0.6 eq.) and finely powdered, dry NaOH (102.5 mmol, 50.0 eq.) were added while stirring. The two-phase mixture was cooled to -10 °C, and the appropriately substituted acyl chloride linker (1.00 mmol, 1.0 eq.) was added dropwise, taking care that the temperature did not exceed -5 °C. After stirring for 4 hours at -10 °C, the reaction mixture was filtered through Celite and washed with DCM (2 × 50 mL). The solution was washed with water (2 × 40 mL), then with salt solution (30 mL), and dried over MgSO₄. After removal of the solvent under vacuum, the crude product was purified by flash column chromatography over silica using DCM / MeOH gradients. QUOTES INCLUDED IN THE DESCRIPTION

[0000] This list of documents cited by the applicant was automatically generated and is included solely for the reader's convenience. The list is not part of the German patent or utility model application. The DPMA accepts no liability for any errors or omissions. Cited non-patent literature

[0000] David E. Nichols: “Dark Classics in Chemical Neuroscience: Lysergic Acid Diethylamide (LSD)” in ACS Chemical Neuroscience 2018, Volume 9, Issue 10 [0086, 0120] Aaron P. Monte, Danuta Marona-Lewicka, Arthi Kanthasamy, Elaine Sanders-Bush, David E. Nichols: “Stereoselective LSD-like Activity in a Series of d-Lysergic Acid Amides of (R)- and (S)-2-Aminoalkanes” in Journal of Medicinal Chemistry 1995, Volume 38, Issue 6 [0086, 0120] Andrew S. Eastabrook, Jonathan Sperry: „Synthetic Access to 3,5,7-Trisubstituted Indoles Enabled by Iridium-Catalyzed C-H Borylation“ in Synthesis 2017, 49, A-G, (DOI: 10.1055 / s-0036-1589018 [0088, 0127] Stephan P. A. Hinkes, Christian D. P. Klein: „Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids“ in Organic Letters 2019, Band 21, Ausgabe 9 (DOI: 10.1021 / acs.orglett.9b00584

[0089] Stephan P. A. Hinkes, Christian D. P. Klein: „Virtues of Volatility: A Facile Transesterification Approach to Boronic Acids“ in Organic Letters 2019, Band 21, Ausgabe 9 (DOI: 10.1021 / acs.orglett.9b00584)

[0129]

Claims

[1] A compound of formula (I), a stereoisomer, a pharmaceutically acceptable salt, a solvate and / or hydrate thereof: where R1 is H, XYZ or where L is a leftist; X is selected from the group consisting of C=O, C=S, C=NH, C=N-Me, C=N-OH, C=NO-Me, S=O, SO2 and CH2; Y is selected from the group consisting of O, S, NH, Aryl, Heteroaryl, Selenophenyl, linear or branched C 1-12 -Alkyl, optionally substituted with one or more R 10 , linear or branched C 1-12 -Alkyl ether, optionally substituted with one or more R 10 , linear or branched C 1-12 -Alkylamine, optionally substituted with one or several R 10 , linear or branched C 1-12 -Thioalkyl, optionally substituted with one or more R 10 , linear or branched C 1-12-Alkyl selenoethers, optionally substituted with one or more R 10 , linear or branched C 1-12 -Alkylcarbonyl, optionally substituted with one or more R 10 , OP(=O)(ORa)2, OP(=O)(ORa)(ORb), OP(=O)(ORa)(Ra), OP(=O)(ORa)(Rb), OP(=O)(Ra)2, OP(=O)(Ra)(Rb), P(=O)(ORa)2, P(=O)(ORa)(ORb), P(=O)(ORa)(Ra), P(=O)(ORa)(Rb), P(=O)(Ra)2 and P(=O)(Ra)(Rb), where Ra and Rb each independently of each other C 3-10 -Cycloalkyl and / or linear or branched C 1-12 -Alkyl groups, optionally substituted with one or more R groups 10 , where R 10 selected from the group consisting of halogens, OH, NH2, SH, linear or branched C 1-6 -Perfluoroalkyl, linear or branched C 1-12 -Alkylthiol, linear or branched C 1-12 -Alkyl selenoethers, linear or branched C 1-12 -Alkylselenol, linear or branched C 1-12-Alkylether, linearem oder verzweigtem C 1-6 Alkylcarbonyl und linearem oder verzweigtem C 1-12 -Thioalkyl; Z abwesend oder ausgewählt ist aus der Gruppe bestehend aus H, O-P(=O)(OR a )2, O-P(=O)(OR a )(OR b ), O-P(=O)(OR a )(OR c ), O-P(=O)(OR c )2, O-P(=O)(OR a )(R a ), O-P(=O)(OR a )(R b ), O-P(=O)(OR a )(R c ), O-P(=O)(OR c )(R c ), O-P(=O)(R a )2, O-P(=O)(R c )2, O-P(=O)(R a )(R b ), O-P(=O)(R a )(R c ), P(=O)(OR a )2, P(=O)(OR a )(OR b ), P(=O)(OR c )2, P(=O)(OR a )(OR c ), P(=O)(OR a )(R a ), P(=O)(OR a )(R b ), P(=O)(OR a )(R c ), P(=O)(OR c )(R c ), P(=O)(R a )2, P(=O)(R a )(R b), P(=O)(R c )2, P(=O)(R a )(R c ), Si(R a )2(Ph), Si(R a )(R b )(Ph), Si(R a )2(CH2Ph), Si(R a )(R b )(CH2Ph), Si(R a )2(R d ), Si(R a )(R b )(R d ), Si(R a )2 (CH2R c ), Si(R a )(R b )(CH2R c ), Si(R c )3, Si(CH2R c )3, linear or branched C 1-12 -Alkyl selenoether, B(OR e )2, B(OCH(CH2)2)2, where R a and R b each linear or branched C 1-12 -Alkyl are; R c is C 3-10 -Cycloalkyl; R d is C 3-10 -Cycloalkenyl; R e is linear or branched C 1-6 -Alkyl and / or wherein C 1-12 -Alkyl selenoether is linear or branched; R2 and R6 are each independently selected from the group consisting of H, B(OH)2, B(OR 11)2 and B(OR 11 )(OR 12 ); where R 11 and R 12 Each is selected independently from the group consisting of linear or branched C 1-12 -Alkyl and linear or branched C 1-12 -Alkylcarbonyl; R3 and R7 are each independently selected from the group consisting of alkyl, alkenyl, alkynyl, cycloalkylmethyl, cycloalkyl, cycloalkylalkyl, carbocycle, heterocycle, methylazetidinyl and (1-methylazetidin-3-yl)methyl, where alkyl is linear or branched C 1-4 -Alkyl is optionally substituted with one or more OH and / or halogen atoms; alkenyl is linear or branched C 2-4 -Alkenyl, optionally substituted with one or more halogen atoms; alkynyl is linear or branched C 2-4 -Alkynyl, optionally substituted with one or more halogen atoms, cycloalkyl is C 3-6 -Cycloalkyl, optionally substituted with one or more halogen atoms; R4, R5, R8 and R9 are each independently selected from the group consisting of H, C 3-5 -Cycloalkyl, C 1-5 -Alkyl, where the C 1-5 -Alkyl is linear or branched, optionally substituted with one or more halogen atoms or trifluoromethyl groups; or R4 and R5 together form part of a C 3-6 -Carbocycle or one C 3-6 -Heterocycle; or R8 and R9 together form part of a C 3-6 -Carbocycle or one C 3-6 -Heterocycle; provided that if R1 and R2 are both H, R4 and R5 are not both ethyl groups, and R3 is not a methyl group. [2] A compound according to claim 1 wherein the compound has formula (II): and / or where R1 is. [3] The compound according to claim 1 or 2, wherein R1 is H and R2 is selected from the group consisting of B(OH)2, B(OR 11 )2 and B(OR 11 )(OR 12) consists of R 11 and R 12 linear or branched C 1-12 -Alkyl groups are, preferably linear or branched C 1-4 -Alkyl groups, especially preferably ethyl or isobutyl. [4] The compound according to any one of claims 1 to 3, wherein R4 and R5 are each independently selected from the group consisting of H, C 3-5 -Cycloalkyl, linear or branched C 1-5 -Alkyl consists of which is optionally substituted with one or more halogen atoms or trifluoromethyl groups, preferably unsubstituted linear C 1-5 -Alkyl. [5] The compound according to any one of claims 1 to 3, wherein R4 and R5 are part of a C 3-6 -Carbocycle or one C 3-6 -Heterocycles are, preferably of a C 3-6 -Heterocycle. [6] The compound according to any of the preceding claims, wherein the compound is selected from the group consisting of: and / or one of their stereoisomers. [7] The compound according to claim 1, wherein R2 is H and R1 is XYZ. [8] The compound according to claim 1 or 7, wherein R1 is XYZ, where X is CH2, Y is selected from the group consisting of OP(=O)(OR a )2, OP(=O)(OR a )(OR b ), OP(=O)(OR a )(R a ), OP(=O)(OR a )(R b ), OP(=O)(R a )2, OP(=O)(R a )(R b ), P(=O)(OR a )2, P(=O)(OR a )(OR b ), P(=O)(OR a )(R a ), P(=O)(OR a )(R b ), P(=O)(R a )2 and P(=O)(R a )(R b ), and where Z is absent, where R a and R b each independently linear or branched C 1-12 -Alkyl groups are preferably linear C 1-5 -Alkyl groups. [9] The compound according to claim 1 or 7, wherein R1 is XYZ, where XC=O, Y is a linear or branched C 1-12 -Alkyl group is, preferably a linear C 1-12 -Alkyl group, and Z is selected from the group consisting of OP(=O)(OR a )2, OP(=O)(OR a )(OR b ), OP(=O)(OR a )(R a ), OP(=O)(OR a )(R b ), OP(=O)(R a )2, OP(=O)(R a )(R b ), P(=O)(OR a )2, P(=O)(OR a )(OR b ), P(=O)(OR a )(R a ), P(=O)(OR a )(R b ), P(=O)(R a )2, P(=O)(R a )(R b ) and C 1-12 -Alkyl selenoethers, where R a and R b each independently linear or branched C 1-12 -Alkyl groups are preferably linear C 1-5 -Alkyl groups. [10] The compound according to one of claims 1 and 7 to 9, wherein R4 and R5 are each independently selected from the group consisting of H and linear or branched C 1-5 -Alkyl consists. [11] The compound according to any one of claims 7 to 10, wherein the compound is selected from the group consisting of: and / or one of their stereoisomers. [12] The compound according to claim 1 or 2 and / or one of its stereoisomers and / or diastereomers, wherein R2 is H and R1 is as follows: [13] The compound according to claim 12, wherein L is a linker selected from the group consisting of: where R 13 and R 14 each were selected independently from the group which consists of alkyl, alkenyl, alkynyl, cycloalkylmethyl, cycloalkyl, cycloalkylalkyl, carbocycle, heterocycle, methylazetidinyl and (1-methylazetidin-3-yl)methyl, wherein alkyl is a linear or branched C14 -Alkyl group, which may optionally be substituted with one or more OH and / or halogen atoms; alkenyl a linear or branched C 2-4 -Alkenyl residue, optionally with one or can be substituted with several halogen atoms; alkynyl a linear or branched C 2-4 -alkynyl group, which may optionally be substituted with one or more halogen atoms; cycloalkyl a C 3-6 -Cycloalkyl group, which may optionally be substituted with one or more halogen atoms. [14] The compound according to one of claims 12 or 13, wherein the compound is selected from the group consisting of: and / or one of their stereoisomers. [15] The compound according to any of the preceding claims for use as a medicinal product. [16] The compound according to any of the preceding claims for use in the treatment of mental disorders such as depression, anxiety disorder and / or post-traumatic stress disorder, addiction treatment, eating disorder, cluster headache and / or migraine. [17] Pharmaceutical composition comprising the compound according to any one of the preceding claims.