WO2015181337A1

WO2015181337A1 - Thiazolidinone compounds and their use in the treatment of psychiatric or neurological disorders and inflammation, in particular neuroinflammation

Info

Publication number: WO2015181337A1
Application number: PCT/EP2015/061915
Authority: WO
Inventors: Jean-Louis Reymond; Simon NICOLUSSI; Jürg Gertsch
Original assignee: Universität Bern
Priority date: 2014-05-28
Filing date: 2015-05-28
Publication date: 2015-12-03
Also published as: AU2015265865A1; US10392377B2; RU2016147230A3; DK3148990T3; US10774077B2; EP4011879A1; RS63107B1; EP3148990B1; PL3148990T3; US20190119265A1; MX2020013537A; BR112016027901A2; MX2016015627A; CA2950354C; US20190382397A1; CN106660976B; RU2734253C2; JP2017516795A; CN106660976A; CA2950354A1

Abstract

The invention relates to a compound comprising the following general formula (1) and said compound for use as a medicament, in particular for use in the treatment psychiatric or neurological disorders and inflammation, in particular neuroinflammation: (formula 1) wherein each of R¹, R² and R³ are selected independently from each other from alkyl, alkoxy, alkenyl, alkynyl, cycloalkyl, aryl, heterocycle, or heteroaryl.

Description

THIAZOLIDINONE COMPOUNDS AND THEIR USE IN THE TREATMENT OF PSYCHIATRIC OR NEUROLOGICAL DISORDERS AND INFLAMMATION, IN PARTICULAR NEUROINFLAMMATION

Field of the Invention

The present invention relates to a class of thiazolidinone derivatives as anandamide cellular uptake inhibitors and their use in the treatment of psychiatric or neurological disorders and inflammation, in particular neuroinflammation.

Background of the invention

The endocannabinoid system (ECS) is a lipid signaling system comprising endocannabinoids (ECs), which are lipids derived from arachidonic acid, the G-protein-coupled cannabinoid receptors CB1 and CB2, as well as several other actual and potential physiological targets involved in the synthesis, transport and degradation of ECs. The major ECs are 2- arachidonoylglycerol (2-AG) and /V-arachidonoyl ethanolamide (AEA; anandamide) which modulate synaptic transmission by retrograde signaling via CB1 receptors and exert potent immunomodulatory effects via both CB1 and CB2 receptors. The ECS has been implicated in physiological and pathophysiological conditions including inflammation, pain, psychiatric disorders and metabolic reprogramming. The ECS provides a primary on-demand protection system against acute excitotoxicity in the central nervous system (CNS) (Marsicano et al., 2003, Science, 302, 84-8.)

Therapeutic strategies within the ECS include the use of cannabinoid receptor agonists and antagonists, blockage of hydrolytic enzymes degrading ECs, such as fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), as well as inhibition of EC cell membrane trafficking. Although so far no membrane protein for EC transport has been identified, several lines of evidence suggest a facilitated membrane transport involving both membrane and cytoplasmic targets (Chicca et al., 2012, J Biol Chem. 287, 36944-67; Fowler CJ., 2013, FEBS J., 280:1895-904). The movement of AEA across the cell is affected by the concentration gradient enhanced by rapid intracellular hydrolysis of AEA catalyzed by FAAH. Therefore, FAAH plays a key role in AEA cellular uptake by generating an inward concentration gradient for AEA, which is the major driving force for its cellular uptake.

Using the commercially available AEA uptake inhibitors UCM707, OMDM-2 and LY2183240 evidence for bidirectional transport of both AEA and 2-AG across cell membranes, as well as a common mechanism of cellular membrane transport for all arachidonate-based ECs was recently provided (Chicca et al., 2012, J Biol Chem. 287, 36944-67). Since all of the available inhibitors are only moderately potent and show low selectivity towards AEA transport inhibition over FAAH inhibition or other cytoplasmic targets, investigations of the mechanisms of AEA and 2-AG cellular uptake are hampered by a lack of adequate tools. As indicated by a recent study (Nicolussi et al., Pharmacol Res., 2014,80:52-65), the CNS pharmacology of inhibitors of endocannabinoid breakdown and inhibitors of endocannabinoid membrane transport is distinctly different and that inhibition of FAAH and AEA cellular uptake, respectively, can be independent from each other. Prior art has shown the use of Dodeca- 2£,4£-diene amides as specific AEA cellular uptake inhibitors as anti-inflammatory agents in skin (WO 2010136221 A1 ). The potential therapeutic value of specific AEA cellular uptake inhibitors to treat CNS related diseases remains largely unknown. In a murine model of multiple sclerosis, the AEA cell membrane transport and FAAH inhibitor UCM707 showed beneficial effects by reducing microglial activation (Ortega-Gutierrez et al., 2005, FASEB J., 19, 1338-40). Using UCM707, it was shown that an increased AEA tone limits excitotoxicity in vitro and in a model of multiple sclerosis (Loria et al., 2010, Neurobiol Dis.,37, 166-76). The non-specific AEA cellular uptake and FAAH inhibitor AM404 was shown to reduce the rewarding effects of nicotine and nicotine-induced dopamine elevations in the nucleus accumbens shell in rats (Sherma et al., Br J Pharmacol., 2012, 165, 2539-48). The nonspecific AEA cell membrane transport inhibitor VDM-1 1 was shown to modulate sleep and c- Fos expression in the rat brain (Murillo-Rodriguez et al., Neuroscience, 2008, 157, 1 -1 1 ). The administration of AEA cell membrane transport inhibitors OMDM-2 or VDM-1 1 was shown to promote sleep and decreases extracellular levels of dopamine in rats (Murillo- Rodriguez et al., Physiol Behav. 2013, 109, 88-95). UCM707 was shown to behave as a symptom control agent in models of Huntington's disease and multiple sclerosis, but failed to delay/arrest the progression of different motor-related disorders (de Lago et al., Eur Neuropsychopharmacol., 2006, 16, 7-18). As shown by a study using UCM707 and AM404, AEA transport inhibitors may have potential in the treatment of painful diabetic neuropathy (Hasanein and Soltani, 2009, Clin Exp Pharmacol Physiol. 36, 1 127-31 ). Targeting fatty acid binding protein (FABP) intracellular AEA carriers has recently been suggested to be a strategy to generate anti-inflammatory and anti-nociceptive drugs (Berger et al., 2012, PLoS One., 7(12):e50968.). However, the pharmacology between the inhibition of AEA cell membrane transport and the inhibition of cytoplasmic carriers is expected to be different, as exemplified by the fact that FABP5 inhibitors do apparently not show the same degree of cannabimimetic effects observed with the potent AEA cell membrane transport inhibitor guineensine (Kaczocha et al., PLoS One. 2014, 9(4):e94200; Nicolussi et al., 2014, Pharmacol Res., 80, 52-65).

Overall, there is a need for novel inhibitors of AEA cell membrane transport with superior specificity and potency to address CNS and inflammation related diseases involving aberrant endocannabinoid tone or in which AEA cellular uptake inhibition can target pathophysiological conditions. Given the fact that AEA and other endocannabinoids are involved in both synaptic processes via retrograde signaling and immunomodulatory processes, specific inhibitors of AEA cell membrane transport are expected to exert therapeutic effects in neuropsychiatric diseases involving neuroinflammation. When the degradation of AEA and other endocannabinoids is blocked, for example by covalent inhibition of FAAH, the resulting intracellular accumulation of AEA (Chicca et al., 2012, J Biol Chem., 287, 36944-67) is expected to potentially also have proinflammatory effects via oxygenation of AEA and possibly other endocannabinoids by cyclooxygenase-2 (discussed in Chicca et al, 2014, ACS Chem Biol, http://pubs.acs.org/doi/abs/10.1021/cb500177c). Therefore, the inhibition of degradation of AEA and the inhibition of cell membrane transport are distinct pharmacological interventions. Moreover, specific inhibition of AEA cell membrane transport, unlike inhibition of FAAH or cytoplasmic carriers, is expected to differentially modulate the AEA tone without leading to activation of TRPV1 channels via intracellular AEA accumulation.

Our attention, therefore, is focused on the identification of new class of molecules able to specifically inhibit AEA cellular uptake that do not affect hydrolytic enzymes, such as the serine hydrolase FAAH. We show that these compounds trigger cannabimimetic behavioral effects and inhibit inflammation, in particular neuroinflammation.

The present invention relates to thiazolidinone derivatives and their use for the treatment of psychiatric or neurological disorders and inflammation, in particular neuroinflammation. The use of the compounds of the invention in a method for treatment of psychiatric or neurological disorders is related to attenuation of neuroinflammation and neuronal retrograde signaling mediated via AEA and other endocannabinoids. In example, such diseases include multiple sclerosis, epilepsy, Alzheimers disease, bipolar diseases, schizophrenia, sleeping disorders, and spinal cord injury (Ashton and Moore, Acta Psychiatr Scand. 201 1 , 124, 250- 61.; Aso and Ferrer I, Front Pharmacol., 2014, 5, 37; Correa et al. Vitam Horm. 2009, 81 , 207-30; Hofmann and Frazier, Exp Neurol. 2013, 244, 43-50; Pacher et al., Pharmacol Rev., 2006, 58, 389-462). Summary of the invention

A first aspect of the invention relates to a compound characterized by a general formula 1

(formula 1 )

wherein

1 is selected from

a substituted or unsubstituted heterocycle, in particular a substituted or unsubstituted C3-C1₀ heterocycle, or

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C₅-Ci₀ heteroaryl, and

each of R² and R³ are selected independently from each other from

a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted C1-C12 alkyl,

a substituted or unsubstituted alkoxy, in particular a substituted or unsubstituted C1-C12 alkoxy,

a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C2-C12 alkenyl,

a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C2-C12 alkynyl,

a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C3-C1₀ cycloalkyl,

a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Cio aryl,

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C1₀ heteroaryl. A second aspect of the invention relates to a compound characterized by a general formula 1

(formula 1 )

wherein

2 is selected from

a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C₃-C1₀ cycloalkyl,

a substituted or unsubstituted heterocycle, in particular a substituted or unsubstituted C₃-C1₀ heterocycle, or

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C1₀ heteroaryl, and

each of R¹ and R³ are selected independently from each other from

a substituted or unsubstituted alkoxy, in particular a substituted or unsubstituted C Ci₂ alkoxy,

a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C₂-Ci₂ alkenyl, a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C₂-Ci₂ alkynyl,

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C₅-Ci₀ heteroaryl.

A third aspect of the invention relates to a compound characterized by a general formula 1

(formula 1 )

wherein

3 is selected from

a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Cio aryl, a substituted or unsubstituted heterocycle, in particular a substituted or unsubstituted C3-C1₀ heterocycle, or

each of ¹ and R² are selected independently from each other from

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C1₀ heteroaryl.

A fourth aspect of the invention relates to a compound characterized by the following general formula (1 )

(formula 1 )

wherein

R¹ is selected from a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted C1-C12 alkyl,

- a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C2-C12 alkenyl,

a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C3-C10 cycloalkyl,

a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Cio aryl, and

each of R² and R³ are selected independently from each other from

a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C₂-Ci₂ alkenyl,

- a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C₂-Ci₂ alkynyl,

a substituted or unsubstituted heterocycle, in particular a substituted or unsubstituted C3-C10 heterocycle, or

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C10 heteroaryl.

A fifth aspect of the invention relates to a compound according to the first, second, third or fourth aspect of the invention for use as a medicament. A sixth aspect of the invention relates to a compound according to the first, second, third or fourth aspect of the invention for use in the treatment of psychiatric or neurological disorders and inflammation, in particular neuroinflammation.

A seventh aspect of the invention relates to a pharmaceutical preparation for use in the treatment of psychiatric or neurological disorders and inflammation, in particular neuroinflammation, comprising at least one compound according to the the first, second, third or fourth aspect of the invention.

A eight aspect of the invention relates to the compound of the first aspect, particularly the first, second and third sub aspect, of the invention for use as an endocannabinoid system modulator.

A ninth aspect of the invention relates to the compound of the first aspect, particularly the first, second and third sub aspect, of the invention for use as an AEA uptake Inhibitor.

The compounds of the invention may also be used as an analgesic. Reference is made to the figures and experimental section.

The term "substituted" refers to the addition of a substituent group to a parent moiety.

"Substituent groups" can be protected or unprotected and can be added to one available site or to many available sites in a parent moiety. Substituent groups may also be further substituted with other substituent groups and may be attached directly or by a linking group such as an alkyl, an amide or hydrocarbyl group to a parent moiety. "Substituent groups" amenable herein include, without limitation, halogen, oxygen, nitrogen, sulphur, hydroxyl, alkyl, alkenyl, alkynyl, acyl, carboxyl, aliphatic groups, alicyclic groups, alkoxy, substituted oxy, aryl, aralkyl, amino, imino, amido fluorinated compounds etc..

As used herein the term "alkyl," refers to a saturated straight or branched hydrocarbon moiety containing in particular up to 12 carbon atoms. Examples of alkyl groups include, without limitation, methyl, ethyl, propyl, butyl, isopropyl, n-hexyl, octyl, and the like. Alkyl groups typically include from 1 to about 12 carbon atoms (C1-C12 alkyl).

As used herein the term "cycloalkyl" refers to an interconnected alkyl group forming a saturated or unsaturated (or partially unsaturated) ring or polyring structure containing 3 to 10, particularly 5 to 10 carbon atoms. Examples of cycloalkyl groups include, without limitation, cyclopropane, cyclopentane, cyclohexane, norbornane, decaline or adamantan (Tricyclo[3.3.1 .1]decan), and the like. Cycloalkyl groups typically include from 5 to 10 carbon atoms (C5-C10 cycloalkyl).

Alkyl or cycloalkyl groups as used herein may optionally include further substituent groups. A substitution on the cycloalkyl group also encompasses an aryl, a hetreocylce or a heteroaryl substituent, which can be connected to the cycloalkyi group via one atom or two atoms of the cycloalkyi group.

As used herein the term "alkenyl," refers to a straight or branched hydrocarbon chain moiety containing in particular up to 12 carbon atoms and having at least one carbon-carbon double bond. Examples of alkenyl groups include, without limitation, ethenyl, propenyl, butenyl, 1 - methyl-2-buten-1 -yl, dienes such as 1 ,3-butadiene and the like. Alkenyl groups as used herein may optionally include further substituent groups.

As used herein the term "alkynyl," refers to a straight or branched hydrocarbon moiety containing in particular up to 12 carbon atoms and having at least one carbon-carbon triple bond. Examples of alkynyl groups include, without limitation, ethynyl, 1 -propynyl, 1 -butynyl, and the like. Alkynyl groups as used herein may optionally include further substituent groups.

As used herein the term "alkoxy," refers to an oxygen alkyl moiety containing in particular 1 to 12 carbon atoms comprising at least one oxygen moiety instead of a CH₂ moiety.

Examples of alkoxy groups include without limitation, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, n-pentoxy, neopentoxy, n-hexoxy and the like. Alkoxy groups as used herein may optionally include further substituent groups. Furthermore, "alkoxy" groups include straight or branched ether groups (e. g. -CH2-CH2-O-CH₃) or polyether groups, which comprise several interconnected momomere alkoxy groups (e. g. - 0-CH₂-CH₂-0-CH₃).

As used herein the term "heterocycle" refers to an interconnected alkyl group forming a saturated or unsaturated ring or polyring structure containing 3 to 10, particularly 5 to 10 carbon atoms in which at least one carbon atom is replaced with an oxygen, a nitrogen or a sulphur atom forming a nonaromatic structure. Heterocyclic groups as used herein may optionally include further substituent groups. A substitution on the heterocyclic group also encompasses an aryl, a cycloalkyi or a heteroaryl substituent, which can be connected to the heterocyclic group via one atom or two atoms of the heterocyclic group (comparable to indole).

As used herein the term "aryl" refers to a hydrocarbon with alternating double and single bonds between the carbon atoms forming an aromatic ring structure, in particular a six (C₆ to ten (C1₀) membered ring or polyring structure. The term "heteroaryl" refers to aromatic structures comprising a five to ten membered ring or polyring structure, comparable to aryl compounds, in which at least one member is an oxygen or a nitrogen or a sulphur atom. Due to simplicity reasons they are denominated C₅ to C1₀ heteroaryl, wherein at least one carbon atom is replaced with an oxygen, a nitrogen or a sulphur atom forming an aromatic structure. For example a C₅ heteroaryl comprises a five membered ring structure with at least one carbon atom being replaced with an oxygen, a nitrogen or a sulphur atom. Aryl or hetero aryl groups as used herein may optionally include further substituent groups. A substitution on the hetero aryl group also encompasses an aryl, a cycloalkyi or a heterocycle substituent, which can be connected to the hetero aryl via one atom or two atoms of the hetero aryl group (comparable to indole). The same applies to an aryl group.

As used herein "*" indicates a center of a E- or Z- isomer structure, which is located on the atom below the asterisk *.

Detailed description of the invention

According to a first aspect of the invention, the invention relates to a compound characterized by a general formula 1

(formula 1 )

wherein

1 is selected from

a substituted or unsubstituted heterocycle, in particular a substituted or unsubstituted C₃-Ci₀ heterocycle, or

each of R² and R³ are selected independently from each other from

a substituted or unsubstituted cycloalkyi, in particular a substituted or unsubstituted C3-C1₀ cycloalkyi, a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Cio aryl,

In some embodiments, R¹ comprises the general formula 2a' to 2j',

with D being a Ci to C₄ alkyl, with each T being selected independently from each other from -CH₂, -NH, -S, -O, - CHCH₃, -C(CH₃)₂ or -NR^c, in particular from NH, -S or -O, and

with T being selected from -CH₂, -NH, -S, -O, -CHCH₃, -C(CH₃)₂ or -NR^C, and with each T" being selected independently from each other from being selected from - CH or =N,

with R⁴ and R⁵ being selected independently from each other from -H, -F, -CH₃, - CH₂CH₃, -OCH₃, -CH₂CF₃, -CHFCF₃, -CF₂CF₃, -CHF₂, -CH₂F or -CF₃, in particular with R⁵ and R⁶ being selected independently from each other from H, -F or -CH₃, and

- with R⁶ being selected from -OH, -OCH₃, -OCH₂CH₃, -CH₃ or H,

- with R⁷ being selected from =NH, =S or =0, in particular from O, and

with n of Z¹ _n being 0, 1 , 2 or 3, in particular n of Z¹ _n being 0 or 1 , and with each Z¹ independently from any other Z¹ being selected from -F, -CI, -Br, -I, CN, -R^a, -OR^a, - (CH₂)_rOR^a, -SR^a, -(CH₂)_rSR^a or -NR^a ₂, with each R^a being selected independently from each other from H, a substituted or unsubstituted Ci-C₈ alkyi, in particular Ci-C₄ alkyi, a substituted or unsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 ,

- with R^c being -CH₂OH, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH(CH₃)₂, -CH₂CF₃, -CHFCF₃, - CF₂CF₃, -CHF₂, -CH₂F, -CF₃.

In some embodiments, R¹ comprises the general formula 2a to 2j,

- with each T being selected independently from each other from -CH₂, -NH, -S, -O, -

CHCH₃, -C(CH₃)₂ or -NR^c, in particular from NH, -S or -O, and

- with T being selected from -CH₂, -NH, -S, -O, -CHCH₃, -C(CH₃)₂ or -NR^c, and

- with each T" being selected independently from each other from being selected from -

CH or =N,

- with R⁴ and R⁵ being selected independently from each other from -H, -F, -CH₃, - CH₂CH₃, -OCH₃, -CH₂CF₃, -CHFCF₃, -CF₂CF₃, -CHF₂, -CH₂F or -CF₃, in particular with R⁵ and R⁶ being selected independently from each other from H, -F or -CH₃, and

- with R⁶ being selected from -OH, -OCH₃, -OCH₂CH₃, -CH₃ or H,

- with R⁷ being selected from =NH, =S or =0, in particular from O, and

- with n of Z¹ _n being 0, 1 , 2 or 3, in particular n of Z¹ _n being 0 or 1 , and with each Z¹ independently from any other Z¹ being selected from -F, -CI, -Br, -I, CN, -R^a, -OR^a, - (CH₂)_rOR^a, -SR^a, -(CH₂)_rSR^a or -NR^a ₂, with each R^a being selected independently from each other from H, a substituted or unsubstituted Ci-C₈ alkyl, in particular Ci-C₄ alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 ,

- with R^c being -CH₂OH, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH(CH₃)₂, -CH₂CF₃, -CHFCF₃, -CF₂CF₃, -CHF₂, -CH₂F, -CF₃.

In some embodiments, R¹ comprises the general formula 2b' to 2i' or 2b to 2i, in particular the general formula 2b to 2i, with R^c, n of Z_n ¹ and Z_n ¹ having the same meaning as defined previously, and

- with T of the compound according to formula 2a being selected from -NH, -S, -O or -NR^C, wherein in particular T is O, R⁴ and R⁵ being selected independently from each other from -H, -F, -CH₃, in particular with R⁵ and R⁶ being H, - with Τ' of the compound according to formula 2b or 2c being selected from -NH, -S, -O or -NR^C, wherein in particular T is S or -NH, and T" being selected from -CH or =N, and with R⁶ being selected from -CH₃ or H, in particular R⁶ is H,

- with each T of the compound according to formula 2d being selected independently from each other from -NH, -S, -O or -NR^c, in particular at least one T is selected from NH or -

NCH₃, more particularly the T in the position 4, with respect to the connection to the parent moiety, is -NH, and with R⁷ being selected from =NH, =S or =0, in particular from O, and

- with T of the compound according to formula 2e being selected from -CH₂, -NH, -S or -O, in particular T being -NH or -O,

- with each T" of the compound according to formula 2f being selected independently from each other from -CH or =N, in particular each T" is =N,

- with T of the compound according to formula 2g or 2h being selected from -NH, -S, -O or -NR^C, wherein in particular T is -NR^C or -NH, and T" being selected from -CH or =N, in particular T" is =N,

- with T of the compound according to formula 2i or 2j being selected from -NH or -NR^C, wherein in particular T is -NH, and T" is =N.

In some embodiments, R¹ comprises the general formula 2b to 2h,

with T, T, T", n of Z_n ¹, Z_n ¹, R⁶ and R⁷ having the same meaning as defined previously.

In some embodiments, R¹ comprises the general formula 2b' to 2h' or 2b to 2h, in particular the general formula 2b to 2h, with R^c, n of Z_n ¹ and Z_n ¹ having the same meaning as defined previously, and - with Τ' of the compound according to formula 2b or 2c being selected from -NH, -S, -O or -NR^C, wherein in particular T' is S or -NH, and T" being selected from -CH or =N, and with R⁶ being selected from -CH₃ or H, in particular R⁶ is H,

- with T' of the compound according to formula 2e being selected from -CH₂, -NH, -S or -O, in particular T' being -O,

- with T' of the compound according to formula 2g or 2h being selected from -NH, -S, -O or -NR^C, wherein in particular T' is -NR^C or -NH, and T" being selected from -CH or =N, in articular T" is =N.

I

R⁷ having the same meaning as defined previously.

In some embodiments, R¹ comprises the general formula 2b', 2c', 2e', 2g' or 2h' or 2b, 2c, 2e, 2g or 2h, in particular the general formula 2b, 2c, 2e, 2g or 2h, with R^c, n of Z_n ¹ and Z_n ¹ having the same meaning as defined previously and

- with T' of the compound according to formula 2b or 2c being selected from -NH, -S, -O or -NR^C, wherein in particular T' is S or -NH, and T" being selected from -CH or =N, and with R⁶ being selected from -CH₃ or H, in particular R⁶ is H,

- with T' of the compound according to formula 2e being selected from -CH₂, -NH, -S or -O, in particular T' being -O, - with Τ' of the compound according to formula 2g or 2h being selected from -NH, -S, -O or -NR^C, wherein in particular T' is -NR^C or -NH, and T" being selected from -CH or =N, in articular T" is =N.

In

as defined previously.

In some embodiments, R¹ comprises the general formula 2b', 2c', 2g' or 2h' or 2b, 2c, 2g or 2h, in particular the general formula 2b, 2c, 2g or 2h, with R^c, n of Z_n ¹ and Z_n ¹ having the same meaning as defined previously and

- with T' of the compound according to formula 2g or 2h being selected from -NH, -S, -O or -NR^C, wherein in particular T' is -NR^C or -NH, and T" being selected from -CH or =N, in particular T" is =N.

In some embodiments, R¹ comprises the general formula 2b or 2c

with T, T", n of Z_n ¹, Z_n ¹ and R⁶ having the same meaning as defined previously.

In some embodiments, R¹ comprises the general formula 2b' or 2c' or 2b or 2c, in particular the general formula 2b or 2c, with R^c, n of Z_n ¹ and Z_n ¹ having the same meaning as defined previously, - with Τ' of the compound according to formula 2b or 2c being selected from -NH, -S, -O or -NR^C, wherein in particular T is S or -NH, and T" being selected from -CH or =N, and with R⁶ being selected from -CH₃ or H, in particular R⁶ is H.

In some embodiments, R¹ comprises the general formula 2c

In some embodiments, R¹ comprises the general formula 2c' or 2c, in particular the general formula 2c, with R^c, n of Z_n ¹ and Z_n ¹ having the same meaning as defined previously,

- with T of the compound according to formula 2c being selected from -NH, -S, -O or -NR^C, wherein in particular T is -NH, and T" being selected from -CH or =N, in particular from

=N, and with R⁶ being selected from -CH₃ or H, in particular R⁶ is H.

In some embodiments, R^c is selected from -CH₂OH, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃ or - CH(CH₃)₂, in particular from -CH₃, -CH₂CH₃ or -CH(CH₃)₂, more particularly R^c is CH₃.

In some embodiments, n of Z¹ _n is 0, 1 or 2, in particular n is 0 or 1.

In some embodiments, n of Z¹ _n is 1.

In some embodiments, n of Z¹ _n is 0.

In some embodiments, each Z¹ independently from any other Z¹ is selected from -F, -CI, -Br, -I, CN, -R^a, -OR^a, CH₂OR^a, with each R^a being selected independently from each other from H, a substituted or unsubstituted Ci-C₈ alkyl, in particular Ci-C₄ alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂- C₈ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, each Z¹ independently from any other Z¹ is selected from -F, -CI, -Br, -I, CN, CH₂OR^a or -OR^a, with each R^a being selected independently from each other from H, a substituted or unsubstituted Ci-C₈ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂- C₈ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, each Z¹ independently from any other Z¹ is selected from -F, -CI, -Br, -I, CN, OH, CH₂OH, CH₂OR^a or -OR^a with R^a being selected from a C C₄ alkyl, C₂-C₄ alkenyl or C₂-C₄ alkenyl, in particular from a CrC₄ alkyl. In some embodiments, each Z¹ independently from any other Z¹ is selected from CN, OH, - OCH₃, -OCH₂CH₃, -0(CH₂)₂CH₃, -0(CH₂)CCH, -CH₂OCH₃, -CH₂OCH₂CH₃, -CH₂0(CH₂)₂CH₃ or -CH₂0(CH₂)CCH, in particular from CN, OH, -OCH₃ or -CH₂OCH₃, more particularly from - OCH₃ or -CH₂OCH₃.

In some embodiments, R¹ is selected from

or derivatives thereof.

In some embodiments, R¹ is selected from

or derivatives thereof.

some embodiments, R¹ is selected from

or derivatives thereof.

In some embodiments, R¹ is selected from

or or derivatives thereof.

In some embodiments R¹ comprises the general formula 3a to 3k

with each T being selected independently from each other from -CH₂, -NH, -S, -O, - CHCH₃, -C(CH₃)₂ or -NR^c, in particular from NH, -S or -O, and

with R⁴ and R⁵ being selected independently from each other from -H, -F, -CH₃, - CH₂CH₃, -OCH₃, -CH₂CF₃, -CHFCF₃, -CF₂CF₃, -CHF₂, -CH₂F or -CF₃, in particular with R⁵ and R⁶ being selected independently from each other from H, -F or -CH₃, and with R⁶ being selected from -OH, -OCH₃, -OCH₂CH₃, -CH₃ or H,

with R⁷ being selected from =NH, =S or =0, in particular from O, and - with R^c being -CH₂OH, -CH₃, -CH₂CH₃, -CH₂CH₂CH_3! -CH(CH₃)₂, -CH₂CF₃, -CHFCF₃, -CF₂CF₃, -CHF₂, -CH₂F, -CF₃.

In some embodiments R¹ comprises the general formula 3a to 3k

- with T of the compound according to formula 3a being selected from -NH, -S, -O or -NR^c, wherein in particular T is O, R⁴ and R⁵ being selected independently from each other from -H, -F, -CH₃, in particular with R⁵ and R⁶ being H,

- with T of the compound according to formula 3b or 3c being selected from -NH, - S, -O or -NR^c, wherein in particular T is -NH, and T" being selected from -CH or =N, and with R⁶ being selected from -CH₃ or H, in particular R⁶ is H,

- with each T of the compound according to formula 3d being selected

independently from each other from -NH, -S, -O or -NR^C, in particular at least one T is selected from NH or -NCH₃, more particularly the T in the position 4, with respect to the connection to the parent moiety, is -NH, and with R⁷ being selected from =NH , =S or =0, in particular from O, and

- with T of the compound according to formula 3e being selected from -CH₂, -NH, -S or -O, in particular T being -NH or -O,

- with each T" of the compound according to formula 3f being selected

independently from each other from -CH or =N, in particular each T" is =N,

- with T of the compound according to formula 3g or 3h being selected from -NH or -NR^C, wherein in particular T is -NCH₃ , and T" being selected from -CH or =N, in particular from =N,

- with T of the compound according to formula 3i or 3j being selected from -NH or - NR^C, wherein in particular T is -NH, and T" is =N.

In some embodiments R¹ is selected from a substituted or unsubstituted C₅ heterocycle or a substituted or unsubstituted C₅-C₆ heteroaryl, wherein in particular the substituted C₅ heterocycle or the substituted C₅-C₆ heteroaryl comprises at least one substituent Z¹

In some embodiments R¹ is selected from a substituted or unsubstituted pyran, furan, imidazole, thiophen, pyrrol, pyridine, pyrazine, thiazol, oxazol, cumarin, benzoimidazole, indol, Isoindol, benzodiazol, benzotriazol, benzoxazol, benzothiazol or pyrazin and derivatives thereof, wherein in particular the substituted compounds comprises at least one substituent Z

In some embodiments, R² is selected from - a substituted or unsubstituted alkyi, in particular a substituted or unsubstituted C1-C12 alkyi,

- a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C2-C12 alkynyl,

- a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C3-C1₀ cycloalkyl,

- a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Ci₀ aryl. In some embodiments, R² is selected from

- a substituted or unsubstituted alkyi, in particular a substituted or unsubstituted C Ci₂ alkyi,

- a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C₂-Ci₂ alkenyl,

- a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Ci₀ aryl, or

- a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C₅- C10 heteroaryl.

In some embodiments, R² is selected from

- a substituted or unsubstituted C1-C4 alkyi,

- a substituted or unsubstituted C₂-C₄ alkenyl,

- a substituted or unsubstituted C₂-C₄ alkynyl,

- a substituted or unsubstituted C₆ aryl, or

- a substituted or unsubstituted C₅-C₆- heteroaryl.

In some embodiments, R² is selected from

- a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula -L-Ar,

- with L being

an alkyi, in particular a C₁-C₁₂ alkyi, more particularly a C₁-C4 alkyi, an alkenyl, in particular a C₂-C₁₂ alkenyl, more particularly a C₂-C₄ alkenyl, an alkynyl, in particular a C₂-C₁₂ alkynyl, more particularly a C₂-C₄ alkynyl, and

- Ar being a substituted or unsubstituted C₅-C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, or

- a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z².

In some embodiments, R² is selected from

- a substituted alkyi, wherein the substituted alkyi comprises the formula -L-Ar,

- with L being

an alkyi, in particular a C Ci₂ alkyi, more particularly a C C₄ alkyi, and

- a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z².

In some embodiments, R² is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula -L-Ar, with L being an alkyi, in particular a C Ci₂ alkyi, more particularly a C C₄ alkyi, and Ar being a substituted or unsubstituted C₅-C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z².

In some embodiments, R² is selected from a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z².

In some embodiments, R² is selected from

- a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula 4a

(formula 4a) or

- a substituted or unsubstituted C₆- aryl, wherein the substituted C₆ aryl comprises the formula 4b

(formula 4b)

with L being

an alkyi, in particular a C₁-C₁₂ alkyi, more particularly a C₁-C4 alkyi, an alkenyl, in particular a C₂-Ci₂ alkenyl, more particularly a C₂-C₄ alkenyl, - an alkynyl, in particular a C₂-Ci₂ alkynyl, more particularly a C₂-C₄ alkynyl, and o of Z²o is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² independently from any other Z² is selected from -F, -CI, -Br, -I, CN, -R^b, - OR^b, -(CH₂)_rOR^b, -SR^b, -(CH₂)_rSR^b or -NR^b ₂, with each R^b being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C₁-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-

C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, R² is selected from

- a substituted alkyi wherein the substituted alkyi comprises the formula 4a

(formula 4a) or

a substituted or unsubstituted C₆- aryl, wherein the substituted C₆ aryl comprises the formula 4b

(formula 4b)

with L being an alkyi, in particular a C Ci₂ alkyi, more particularly a C₁-C4 alkyi, and o of Z²o is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² independently from any other Z² is selected from -F, -CI, -Br, -I, CN, -R^b, - OR^b, -(CH₂)_rOR^b, -SR^b, -(CH₂)_rSR^b or -NR^b ₂, with each R^b being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C₁-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 . In some embodiments, R² is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 4a, with L being an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi, and o of Z² ₀ is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² independently from any other Z² is selected from -F, -CI, -Br, -I, CN, -R^b, - OR^b, -(CH₂)_rOR^b or -NR^b ₂, with each R^b being selected independently from each other from

H, a substituted or unsubstituted C1-C12 alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂- Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

In some embodiments, R² is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 4a, with L being an alkyi, in particular a C Ci₂ alkyi, more particularly a C1-C4 alkyi, and o of Z² ₀ is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or

I , and each Z² independently from any other Z² is selected from -F, -CI, -Br, -I, CN, -R^b, - OR^b, -(CH₂)_rOR^b or -NR^b ₂, with each R^b being selected independently from each other from

H, a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-

Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

In some embodiments, R² is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 4a, with L being

an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi,

- an alkenyl, in particular a C₂-Ci₂ alkenyl, more particularly a C₂-C₄ alkenyl,

an alkynyl, in particular a C₂-Ci₂ alkynyl, more particularly a C₂-C₄ alkynyl,

and o of Z² ₀ is 1 and Z² is selected from -F, -CI, -Br, -I, CN, -R^b, -OR^b, -(CH₂)_rOR^b or -NR^b ₂, with each R^b being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

In some embodiments, R² is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 4a, with L being an alkyi, in particular a C Ci₂ alkyi, more particularly a C1-C4 alkyi, and o of Z² ₀ is 0.

In some embodiments, R² is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 4b, with o of Z² ₀ being 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² independently from any other Z² is selected from -F, -CI, -Br, -

I, CN, -R^b, -OR^b, -(CH₂)_rOR^b or -NR^b ₂, with each R^b being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C2-C12 alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, R² is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 4b, with o of Z² ₀ being 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² independently from any other Z² is selected from -F, -CI, -Br, - I, CN, -R^b, -OR^b, -(CH₂)_rOR^b or -NR^b ₂, with each R^b being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular d-C₄ alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, R² is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 4b, with o of Z² ₀ being 1 and Z² is selected from -F, -CI, -Br, -I, CN, - R^b, -OR^b, -(CH₂)_rOR^b or -NR^b ₂, with each R^b being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular d-C₄ alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂- Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

In some embodiments, R² is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 4b, with o of Z² ₀ being 0.

In some embodiments, o of Z² ₀ is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² is selected independently from any other Z² from -F, -CI, -Br, -I, CN, -R^b, - OR^b, CH₂OR^b or -NR^b ₂, in particular from -F, -CI, -R^b, -OR^b, CH₂OR^b or -NR^b ₂, more particularly from -F, -CI, -R^b, with each R^b being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C C₄ alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂- Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, o of Z² ₀ is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² is selected independently from any other Z² from -F, -CI, -Br, -I or -R^b, in particular from R^b, with R^b being selected from a substituted or unsubstituted C Ci₂ alkyi, in particular C C₄ alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, o of Z² ₀ is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² is selected independently from any other Z² from -F, -CI, -Br, -I or -R^b, in particular from R^b, with R^b being selected from a substituted or unsubstituted C Ci₂ alkyi, in particular C C₄ alkyi. In some embodiments, o of Z² ₀ is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² is selected independently from any other Z² is selected from -R^b, with R^b being selected from a substituted or unsubstituted C1-C12 alkyl, in particular C1-C4 alkyl.

In some embodiments, o of Z² ₀ is 0 or 1.

In some embodiments, o of Z² ₀ is 1 .

In some embodiments, o of Z² ₀ is 0.

In some embodiments, R² is selected from

In some embodiments, R² is selected from

, or er va ves ereo .

In some embodiments, R² is selected from

or , or derivatives thereof.

In some embodiments, R² is selected from

, or er va ves ereo .

In some embodiments, R² is selected from

or derivatives thereof.

In some embodiments, R² is selected from

or derivatives thereof.

In some embodiments, R³ is selected from

- a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted C1-C12 alkyl,

- a substituted or unsubstituted cycloalkyi, in particular a substituted or unsubstituted C3-C10 cycloalkyi,

- a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Ci₀ aryl. In some embodiments, R³ is selected from

- a substituted or unsubstituted alkyi, in particular a substituted or unsubstituted C1-C12 alkyi,

In some embodiments, R³ is selected from

- a substituted or unsubstituted C1-C4 alkyi,

- a substituted or unsubstituted C₂-C₄ alkenyl,

- a substituted or unsubstituted C₂-C₄ alkynyl,

- a substituted or unsubstituted C₆ aryl, or

- a substituted or unsubstituted C₅-C₆- heteroaryl.

In some embodiments, R³ is selected from

- a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula -D-Ar,

with D being

an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi, an alkenyl, in particular a C₂-Ci₂ alkenyl, more particularly a C₂-C₄ alkenyl, an alkynyl, in particular a C₂-Ci₂ alkynyl, more particularly a C₂-C₄ alkynyl, and - Ar being a substituted or unsubstituted C₅-C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, or

- a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z³.

In some embodiments, R³ is selected from

- a substituted alkyi, wherein the substituted alkyi comprises the formula -D-Ar, with D being

an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi, and

- a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z³.

In some embodiments, R³ is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula -D-Ar, with L being an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi, and Ar being a substituted or unsubstituted C₅-C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z³.

In some embodiments, R³ is selected from a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z³.

In some embodiments, R³ is selected from

- a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula 5a

(formula 5a) or

a substituted or unsubstituted C₆- aryl, wherein the substituted C₆ aryl comprises the formula 5b

(formula 5b)

with D being

an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi, an alkenyl, in particular a C2-C12 alkenyl, more particularly a C₂-C₄ alkenyl, an alkynyl, in particular a C2-C12 alkynyl, more particularly a C₂-C₄ alkynyl, and p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ independently from any other Z³ is selected from -F, -CI, -Br, -I, CN, -R^d, - OR^d, -(CH₂)_rOR^d, -SR^d, -(CH₂)_rSR^d or -NR^d ₂, with each R^d being selected independently from each other from H, a substituted or unsubstituted C1-C12 alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from

- a substituted alkyi wherein the substituted alkyi comprises the formula 5a

(formula 5a) or

- a substituted or unsubstituted C₆- aryl, wherein the substituted C₆ aryl comprises the formula 5b

(formula 5b)

with D being an alkyi, in particular a C Ci₂ alkyi, more particularly a C1-C4 alkyi, and p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ independently from any other Z³ is selected from -F, -CI, -Br, -I, CN, -R^d, - OR^d, -(CH₂)_rOR^d, -SR^d, -(CH₂)_rSR^d or -NR^d ₂, with each R^d being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 5a, with D being an alkyi, in particular a C Ci₂ alkyi, more particularly a C1-C4 alkyi, and p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ independently from any other Z³ is selected from -F, -CI, -Br, -I, CN, -R^d, - OR^d, -(CH₂)_rOR^d , -SR^d, -(CH₂)_rSR^d or -NR^d ₂, with each R^d being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 . In some embodiments, R³ is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 5a, with D being an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi, and p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ independently from any other Z³ is selected from -F, -CI, -Br, -I, CN, -R^d, - OR^d, -(CH₂)_rOR^d, -SR^d, -(CH₂)_rSR^d or -NR^d ₂, with each R^d being selected independently from each other from H, a substituted or unsubstituted C1-C12 alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, R³ is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 5a, with D being

an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi,

an alkenyl, in particular a C₂-Ci₂ alkenyl, more particularly a C₂-C₄ alkenyl,

and p of Z³ _P is 1 and Z³ is selected from -F, -CI, -Br, -I, CN, -R^d, -OR^d, -(CH₂)_rOR^d, -SR^d, - (CH₂)_rSR^d or -NR^d ₂, with each R^d being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂- Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, R³ is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 5a, with D being an alkyi, in particular a C Ci₂ alkyi, more particularly a C1-C4 alkyi, and p of Z³ _P is 0.

In some embodiments, R³ is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 5b, with p of Z³ _P being 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ independently from any other Z³ is selected from -F, -CI, -Br, - I, CN, -R^d, -OR^d, -(CH₂)_rOR^d , -SR^d, -(CH₂)_rSR^d or -NR^d ₂, with each R^d being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 5b, with p of Z³ _P being 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ independently from any other Z³ is selected from -F, -CI, -Br, - I, CN, -R^d, -OR^d, -(CH₂)_rOR^d, -SR^d, -(CH₂)_rSR^d or -NR^d ₂, with each R^d being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C2-C12 alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

In some embodiments, R³ is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 5b, with p of Z³ _P being 1 and Z³ is selected from -F, -CI, -Br, -I, CN, - R^d, -OR^d, -(CH₂)_rOR^d, -SR^d, -(CH₂)_rSR^d or -NR^d ₂, with each R^d being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular d-C₄ alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, R³ is selected from a substituted alkyi, wherein the substituted alkyi comprises the formula 5b, p of Z³ _P being 0.

In some embodiments, p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I, CN, -R^d, - OR^d, CH₂OR^d or -NR^d ₂, in particular from -F, -CI, -R^d, -OR^d, CH₂OR^d or -NR^d ₂, more particularly from -F, -CI, -R^d, with each R^d being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C C₄ alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂- Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I or -R^d, in particular from R^d, with R^d being selected from a substituted or unsubstituted C Ci₂ alkyi, in particular C C₄ alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I or -R^d, in particular from R^d, with R^d being selected from a substituted or unsubstituted C Ci₂ alkyi, in particular C C₄ alkyi.

In some embodiments, p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ is selected from -R^d, with R^d being selected from a substituted or unsubstituted C Ci₂ alkyi, in particular d-C₄ alkyi.

In some embodiments, p of Z³ _P is 0 or 1.

In some embodiments, p of Z³ _P is 1 .

In some embodiments, p of Z³ _P is 0.

In some embodiments, R³ is selected from

or , or derivatives thereof.

In some embodiments, R³ is selected from

In some embodiments, R³ is selected from

In some embodiments, R³ is selected from

or derivatives thereof.

Any embodiment described for R² or R³ according to the first aspect of the invention may be combined with any embodiment described for R¹ according to the first aspect of the invention. In some embodiments of a first sub aspect of the first aspect, R¹ comprises the general formula 2a' or 2e',

- with D being a Ci to C₄ alkyl,

or the general formula 2a or 2e,

- with each T being selected independently from each other from -CH₂, -NH, -S, -O, - CHCHs, -C(CH₃)₂ or -NR^c, in particular from NH, -S or -O, with R^c being -CH₂OH, - CH₃, -CH2CH₃, -CH2CH2CH₃, -CH(CH₃)2, -CH2CF₃, -CHFCF₃, -CF2CF₃, -CHF2, -CH2F, -CF₃ and

- with T being selected from -CH₂, -NH, -S, -O, -CHCH₃, or -C(CH₃)₂ and

- with R⁴ and R⁵ being selected independently from each other from -H, -F, -CH₃, - CH2CH3, -OCH3, -CH2CF3, -CHFCF3, -CF2CF3, -CHF₂, -CH₂F or -CF₃, in particular with R⁵ and R⁶ being selected independently from each other from H, -F or -CH₃, and

- with n of Z¹ _n being 0, 1 , 2 or 3, , in particular n of Z¹ _n being 0 or 1 , and with each Z¹ independently from any other Z¹ being selected from -F, -CI, -Br, -I, CN, -R^a, -OR^a, - (CH₂)_rOR^a, -SR^a, -(CH₂)_rSR^a or -NR^a ₂, with each R^a being selected independently from each other from H, a substituted or unsubstituted Ci-C₈ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 ,

R² is selected from

a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Cio aryl, a substituted or unsubstituted saturated heterocycle, in particular a substituted or unsubstituted C3-C10 heterocycle, or

and R³ is selected from

- a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C1-C12 alkenyl,

a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C1-C12 alkynyl,

a substituted or unsubstituted saturated heterocycle, in particular a substituted or unsubstituted C3-C10 heterocycle, or

- a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C10 heteroaryl.

In some embodiments, particularly of the first sub aspect, R¹ comprises the general formula 2a or 2e,

(2e), in particular 2e, with D, T, T, n of Z_n ¹, Z_n ¹, R⁴ and R⁵ having the same meaning as defined previously.

In some embodiments, particularly of the first sub aspect, T of the compound according to formula 2a is selected from -NH, -S, -O or -NR^c, wherein in particular T is O, R⁴ and R⁵ being selected independently from each other from -H, -F, -CH₃, in particular with R⁵ and R¹ being H, and T of the compound according to formula 2e is selected from -CH₂, -NH, -S or - O, in particular T is -NH or -O, more particularly O.

In some embodiments, particularly of the first sub aspect, n of Z¹ _n is 0, 1 or 2, in particular n is 0 or 1. In some embodiments, n of Z¹ _n is 1. In some embodiments, n of Z¹ _n is 0.

In some embodiments, particularly of the first sub aspect, each Z¹ independently from any other Z¹ is selected from -F, -CI, -Br, -I, CN, -R^a, -OR^a, CH₂OR^a, with each R^a being selected independently from each other from H, a substituted or unsubstituted Ci-C₈ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl

In some embodiments, particularly of the first sub aspect, each Z¹ independently from any other Z¹ is selected from -F, -CI, -Br, -I, CN, CH₂OR^a or -OR^a, with each R^a being selected independently from each other from H, a substituted or unsubstituted Ci-C₈ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, particularly of the first sub aspect, each Z¹ independently from any other Z¹ is selected from -F, -CI, -Br, -I, CN, OH, CH₂OH, CH₂OR^a or -OR^a with R^a being selected from a C1-C4 alkyl, C₂-C₄ alkenyl or C₂-C₄ alkenyl, in particular from a C1-C4 alkyl.

In some embodiments, particularly of the first sub aspect, each Z¹ independently from any other Z¹ is selected from CN, OH, -OCH₃, -OCH₂CH₃, -0(CH₂)₂CH₃, -0(CH₂)CCH, - CH₂OCH₃, -CH₂OCH₂CH₃, -CH₂0(CH₂)₂CH₃ or -CH₂0(CH₂)CCH, in particular from CN, OH, - OCH₃ or -CH₂OCH₃, more particularly from -OCH₃ or -CH₂OCH₃.

In some embodiments, particularly of the first sub aspect, R² is selected from a substituted or unsubstituted C₃-C₆ cycloalkyi, a substituted or unsubstituted C₆ aryl, or a substituted or unsubstituted C₅-C₆- heteroaryl.

In some embodiments, particularly of the first sub aspect, R² is selected from

- a substituted alkyl, alkenyl or alkynyl, wherein the substituted alkyl, alkenyl or alkynyl comprises the formula -L-Ar,

with L being

an alkyl, in particular a C1-C12 alkyl, more particularly a C1-C4 alkyl, - an alkenyl, in particular a C Ci₂ alkenyl, more particularly a C1-C4 alkenyl,

an alkynyl, in particular a C Ci₂ alkynyl, more particularly a C1-C4 alkynyl, and - Ar being a substituted or unsubstituted C₅-C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, or

a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z².

embodiments, particularly of the first sub aspect, R² is selected from

a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula 4a

(formula 4a) or

(formula 4b)

with L being

an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi, an alkenyl, in particular a C1-C12 alkenyl, more particularly a C1-C4 alkenyl,

an alkynyl, in particular a C1-C12 alkynyl, more particularly a C1-C4 alkynyl, and

o of Z²o is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and

each Z² independently from any other Z² is selected from -F, -CI, -Br, -I, CN, -R^b, -OR^b, - (CH₂)_rOR^b, -SR^b, -(CH₂)_rSR^b or -NR^b ₂, with each R^b being selected independently from each other from H, a substituted or unsubstituted C1-C12 alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, particularly of the first sub aspect, o of Z² ₀ is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² is selected independently from any other Z² from -F, -CI, -Br, -I, CN, -R^b, -OR^b, CH₂OR^b or -NR^b ₂, in particular from -F, -CI, - R^b, -OR^b, CH₂OR^b or -NR^b ₂, more particularly from -F, -CI, -R^b, with each R^b being selected independently from each other from H, a substituted or unsubstituted C1-C12 alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl,

In some embodiments, particularly of the first sub aspect, o of Z² ₀ is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² is selected independently from any other Z² from -F, -CI, -Br, -I or -R^b, in particular from R^b, with R^b being selected from a substituted or unsubstituted C Ci₂ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂- Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, particularly of the first sub aspect, o of Z² ₀ is 0

In some embodiments, particularly of the first sub aspect, R³ is selected from a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted C1-C10 alkyl, a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C1-C10 alkenyl, a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C1-C10 alkynyl, a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C3-C10 cycloalkyl, a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆- C10 aryl, a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C10 heteroaryl.

In some embodiments, particularly of the first sub aspect, R³ is selected from a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted C1-C10 alkyl, a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C1-C10 alkenyl, a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C1-C10 alkynyl, a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Ci₀ aryl, or a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C10 heteroaryl.

In some embodiments, particularly of the first sub aspect, R³ is selected from a substituted or unsubstituted Ci-C₄ alkyl, a substituted or unsubstituted Ci-C₄ alkenyl, a substituted or unsubstituted Ci-C₄ alkynyl, a substituted or unsubstituted C₆ aryl, a substituted or unsubstituted C₆-cycloalkyl; or a substituted or unsubstituted C₅-C₆- heteroaryl, in particular a substituted or unsubstituted C₆-cycloalkyl or a substituted or unsubstituted C₅-C₆- heteroaryl.

In some embodiments, particularly of the first sub aspect, R³ is selected from

- a substituted alkyl, alkenyl or alkynyl, wherein the substituted alkyl, alkenyl or alkynyl comprises the formula -D-Ar,

- with D being an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi, an alkenyl, in particular a C1-C12 alkenyl, more particularly a C1-C4 alkenyl,

a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z³.

embodiments, particularly of the first sub aspect, R³ is selected from

a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula 5a

(formula 5a) or

(formula 5b), in particular the formula 5b,

with D being

Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and

each Z³ independently from any other Z³ is selected from -F, -CI, -Br, -I, CN, -R^d, -OR^d, -(CH₂)_rOR^d -SR^d, -(CH₂)_rSR^d or -NR^d ₂, with each R^d being selected independently from each other from H, a substituted or unsubstituted C1-C12 alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C2-C12 alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, particularly of the first sub aspect, p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I, CN, -R^d, -OR^d, CH₂OR^d or -NR^d ₂, in particular from -F, -CI, - R^d, -OR^d, CH₂OR^d or -NR^d ₂, more particularly from -F, -CI, -R^d, with each R^d being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, particularly of the first sub aspect, p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I or -R^d, in particular from R^d, with R^d being selected from a substituted or unsubstituted C Ci₂ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂- Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, particularly of the first sub aspect, p of Z³ _P is 0.

In some embodiments, particularly of the first sub aspect, R¹ comprises the general formula 2e,

with T being O and n of Z_n ¹ being 0, and

R³ is selected from a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C₃-C1₀ cycloalkyl, more particularly cyclohexane Z_n ¹, R⁴ and R⁵ having the same meaning as defined previously, and

R² is selected from

a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Cio aryl, a substituted or unsubstituted saturated heterocycle, in particular a substituted or unsubstituted C3-C₁₀ heterocycle, or

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C₅-Ci₀ heteroaryl, or

R² is selected from

a substituted or unsubstituted C₃-C₆ cycloalkyi, a substituted or unsubstituted C₆ aryl, or a substituted or unsubstituted C₅-C₆- heteroaryl, or

R² is selected from

with L being

an alkyi, in particular a C₁-C₁₂ alkyi, more particularly a C₁-C4 alkyi, an alkenyl, in particular a C₁-C₁₂ alkenyl, more particularly a C₁-C4 alkenyl,

an alkynyl, in particular a C₁-C₁₂ alkynyl, more particularly a C₁-C4 alkynyl, and

a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z², or

R² is selected from

(formula 4a) or

(formula 4b) with L being

an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a CrC₄ alkyl, an alkenyl, in particular a C₁-C₁₂ alkenyl, more particularly a C C₄ alkenyl,

an alkynyl, in particular a C₁-C₁₂ alkynyl, more particularly a C C₄ alkynyl, and

each Z² independently from any other Z² is selected from -F, -CI, -Br, - I, CN, -R^b, -OR^b, -(CH₂)_rOR^b, -SR^b, -(CH₂)_rSR^b or -NR^b ₂, with each R^b being selected independently from each other from H, a substituted or unsubstituted C₁-C₁₂ alkyl, in particular d-C₄ alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 , or

o of Z²o is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² is selected independently from any other Z² from -F, - CI, -Br, -I, CN, -R^b, -OR^b, CH₂OR^b or -NR^b ₂, in particular from -F, -CI, - R^b, -OR^b, CH₂OR^b or -NR^b ₂, more particularly from -F, -CI, -R^b, with each R^b being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular C C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, or

o of Z²o is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² is selected independently from any other Z² from -F, - CI, -Br, -I or -R^b, in particular from R^b, with R^b being selected from a substituted or unsubstituted C Ci₂ alkyl, in particular C C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl,

o of Z² ₀ is O, or

R² is selected from

, wherein the structure is exploratory and OH is in ortho, para or meta position to the attachment position to the parent moiety.,

wherein the structure is exploratory and OCH₃ is in ortho, para or meta position to the attachment position to the parent moiety,

wherein the structure is exploratory and N is in ortho, para or meta position to the attachment position to the parent moiety,

Particular embodiments of the first sub aspect are:





The lUPAC name is given below:

_Q_I (2Z,5Z)-2-(4-methoxybenzylimino)-3-cyclohexyl-5-((2,3- di hydro benzo[b] [l,4]dioxin-6-yl)methylene)thiazolidin-4-one _P_L (2Z,5Z)-2-(4-fluorobenzylimino)-3-(4-chlorophenyl)-5-((2,3- di hydro benzo[b] [l,4]dioxin-6-yl)methylene)thiazolidin-4-one _Q_L (2Z,5Z)-2-(4-methoxybenzylimino)-3-(4-chlorophenyl)-5-((2,3- di hydro benzo[b] [l,4]dioxin-6-yl)methylene)thiazolidin-4-one _P_I (2Z,5Z)-2-(4-fluorobenzylimino)-3-cyclohexyl-5-((2,3- di hydro benzo[b] [l,4]dioxin-6-yl)methylene)thiazolidin-4-one _Q_X (2Z,5Z)-2-(4-methoxybenzylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6- yl)methylene)-3-isobutylthiazolidin-4-one _A_B (2Z,5Z)-5-(2,3-di hydro- l,4-benzodioxin-6-ylmethylene)-3-(4- fluorophenyl)-2-(p-tolylimino)thiazolidin-4-one _B_I (2Z,5Z)-2-(4-fluorophenylimino)-3-cyclohexyl-5-((2,3- di hydro benzo[b] [l,4]dioxin-6-yl)methylene)thiazolidin-4-one _B_X (2Z,5Z)-2-(4-fluorophenylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6- yl)methylene)-3-isobutylthiazolidin-4-one _Q_A (2Z,5Z)-2-(4-methoxybenzylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6- yl)methylene)-3-p-tolylthiazolidin-4-one _B_B (2Z,5Z)-2-(4-fluorophenylimino)-3-(4-fluorophenyl)-5-((2,3- di hydro benzo[b] [l,4]dioxin-6-yl)methylene)thiazolidin-4-one _C_N (2Z,5Z)-2-(benzylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6- yl)methylene)-3-phenylthiazolidin-4-one _N_X (2Z,5Z)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6-yl)methylene)-3-isobutyl-2- (phenylimino)thiazolidin-4-one _B_A (2Z,5Z)-2-(4-fluorophenylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6- yl)methylene)-3-p-tolylthiazolidin-4-one _P_A (2Z,5Z)-2-(4-fluorobenzylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6- yl)methylene)-3-p-tolylthiazolidin-4-one _A_A (2Z,5Z)-2-(p-tolylimino)-5-((2,3-dihydrobenzo[b] [l,4]dioxin-6- yl)methylene)-3-p-tolylthiazolidin-4-one _A_I (2Z,5Z)-3-cyclohexyl-5-(2,3-dihydro-l,4-benzodioxin-6-ylmethylene)-2-(p- tolylimino)thiazolidin-4-one _N_A (2Z,5Z)-5-((2,3-dihydrobenzo[b] [ l,4]dioxin-6-yl)methylene)-2- (phenylimino)-3-p-tolylthiazolidin-4-one _Q_N (2Z,5Z)-2-(4-methoxybenzylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-7- yl)methylene)-3-phenylthiazolidin-4-one _B_N (2Z,5Z)-2-(4-fluorophenylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6- yl)methylene)-3-phenylthiazolidin-4-one _N_I (2Z,5Z)-3-cyclohexyl-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6-yl)methylene)- 2-(phenylimino)thiazolidin-4-one _P_X (2Z,5Z)-2-(4-fluorobenzylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6- yl)methylene)-3-isobutylthiazolidin-4-one _P_N (2Z,5Z)-2-(4-fluorobenzylimino)-5-((2,3-dihydrobenzo[b] [l,4]dioxin-6- yl)methylene)-3-phenylthiazolidin-4-one _A_L (2Z,5Z)-2-(p-tolylimino)-3-(4-chlorophenyl)-5-((2,3- di hydro benzo[b] [ l,4]dioxin-6-yl)methylene)thiazolidin-4-one _B_L (2Z,5Z)-2-(4-fluorophenylimino)-3-(4-chlorophenyl)-5-((2,3- dihydrobenzo[b] [ l,4]dioxin-6-yl)methylene)thiazolidin-4-one _N_B (2Z,5Z)-3-(4-fluorophenyl)-5-((2,3-dihydrobenzo[b] [ l,4]dioxin-6- yl)methylene)-2-(phenylimino)thiazolidin-4-one _A_X (2Z,5Z)-2-(p-tolylimino)-5-((2,3-dihydrobenzo[b] [ l,4]dioxin-6- yl)methylene)-3-isobutylthiazolidin-4-one

(2Z,5Z)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6-yl)methylene)-3-phenyl-2- (phenylimino)thiazolidin-4-one _F_N (2Z,5Z)-2-(4-methoxyphenylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6- yl)methylene)-3-phenylthiazolidin-4-one _P_B (2Z,5Z)-2-(4-fluorobenzylimino)-3-(4-fluorophenyl)-5-((2,3- di hydro benzo[b] [ l,4]dioxin-6-yl)methylene)thiazolidin-4-one _S_N (2Z,5Z)-2-((pyridin-3-yl)methylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin- 7-yl)methylene)-3-phenylthiazolidin-4-one _A_N (2Z,5Z)-2-(p-tolylimino)-5-((2,3-dihydrobenzo[b] [ l,4]dioxin-6- yl)methylene)-3-phenylthiazolidin-4-one 24_K_N (2Z,5Z)-2-(3-phenylpropylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-7- yl)methylene)-3-phenylthiazolidin-4-one

24_C_G (2Z,5Z)-2-(benzylimino)-3-butyl-5-((2,3-di hydro benzo[b] [ l,4]dioxin-7- yl)methylene)thiazolidin-4-one

24_C_0 (2Z,5Z)-2-(benzylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-7- yl)methylene)-3-phenethylthiazolidin-4-one

25 (2Z,5Z)-5-((benzo[d] [ l,3]dioxol-5-yl)methylene)-3-phenyl-2- (phenylimino)thiazolidin-4-one

24_C_B (2Z,5Z)-2-(benzylimino)-3-(4-fluorophenyl)-5-((2,3- di hydro benzo[b] [ l,4]dioxin-7-yl)methylene)thiazolidin-4-one

24_A_V (2Z,5Z)-2-(p-tolylimino)-3-dodecyl-5-((2,3-di hydro benzo[b] [ l,4]dioxin-6- yl)methylene)thiazolidin-4-one

24_C_K (2Z,5Z)-2-(benzylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-7- yl)methylene)-3-(3-phenylpropyl)thiazolidin-4-one

24_B_V (2Z,5Z)-2-(4-fluorophenylimino)-3-dodecyl-5-((2,3- di hydro benzo[b] [ l,4]dioxin-6-yl)methylene)thiazolidin-4-one

24_C_C (2Z,5Z)-3-benzyl-2-(benzylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-7- yl)methylene)thiazolidin-4-one

24_C_F (2Z,5Z)-2-(benzylimino)-5-((2,3-di hydro benzo[b] [ l,4]dioxin-7- yl)methylene)-3-(4-methoxyphenyl)thiazolidin-4-one

24_U_N (2Z,5Z)-5-((2,3-dihydrobenzo[b] [ l,4]dioxin-7-yl)methylene)-2- (phenethylimino)-3-phenylthiazolidin-4-one

Any embodiment described for R² or R³ according to the first aspect of the invention may be combined with any embodiment described for R¹ according to the first sub aspect of first aspect of the invention.

some embodiments of a second sub aspect of the first aspect, R¹ is selected from

- - a substituted alkyl, in particular a substituted alky, alkenyl or alkynyl, wherein substituted alkyl, alkenyl or alkynyl comprises the formula 6a

(formula 6a) or - a substituted or unsubstituted heterocycle, in particular a substituted or unsubstituted C3-C₁₀ heterocycle, or

- a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C₅-Ci₀ heteroaryl,

- a substituted or unsubstituted C₆- aryl, wherein the substituted C₆ aryl comprises the formula 6b

(formula 6b)

with M being

an alkyl, in particular a Ci-Ci₂ alkyl, more particularly a CrC₄ alkyl, an alkenyl, in particular a CrCi₂ alkenyl, more particularly a CrC₄ alkenyl, an alkynyl, in particular a CrCi₂ alkynyl, more particularly a CrC₄ alkynyl, and

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I, CN, -R^e, - OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular C C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

and

R² is selected from

a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted Ci-Ci₂ alkyl,

a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C Ci₂ alkenyl,

a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C Ci₂ alkynyl,

a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C₃-Ci₀ cycloalkyl, a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Cio aryl,

R³ is selected from a substituted or unsubstituted cycloalkyi, in particular a substituted or unsubstituted C₃-C10 cycloalkyi, more particularly cyclohexane

Concerning embodiments of Ri with respect to a substituted or unsubstituted heterocycle, in particular a substituted or unsubstituted C₃-C10 heterocycle, or a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C₅-Ci₀ heteroaryl, reference is made to the specific embodiments of the first aspect and the first and third sub aspect of the invention.

In some embodiments, particularly of the second sub aspect, R¹ is selected from

- a substituted or unsubstituted C₆- aryl, wherein the C₆ aryl comprises the formula 6b

(formula 6b)

with M being an alkyl, in particular a C1-C12 alkyl, more particularly a CrC₄ alkyl, and I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I, CN, -R^e, -OR^e, - (CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected independently from each other from H, a substituted or unsubstituted C1-C12 alkyl, in particular d-C₄ alkyl, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, particularly of the second sub aspect, I of Z¹° is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ is selected independently from any other Z¹⁰ from -F, -CI, -Br, -I, CN, -R^e, -SR^e, -CH₂SR^e, -OR^e, CH₂OR^e or -NR^e ₂, in particular from -F, -CI, CN, -R^e, -OR^e, -CH₂OR^e or -NR^e ₂, more particularly from CN, -OR^e or CH₂OR^e, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular C C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₁₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, particularly of the second sub aspect, I of Z¹° is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I, CN, -OR^e or -CH₂OR^e, in particular from R^e, with R^e being selected from a substituted or unsubstituted C Ci₂ alkyl, in particular d-C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, particularly of the second sub aspect, I of Z¹° is 0, 1 or 2, in particular 0 or 1 .

In some embodiments, particularly of the second sub aspect, R¹ is selected from.

In some embodiments, particularly of the second sub aspect, R² is selected from a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted C-i-C-io alkyl, a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C-I-C-IO alkenyl, a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C Cio alkynyl, a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C₃-Ci₀ cycloalkyl, a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Ci₀ aryl, a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C₅-Ci₀ heteroaryl.

In some embodiments, particularly of the second sub aspect, R² is selected from a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted C₁-C₁₀ alkyl, a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C-I-C-IO alkenyl, a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C Cio alkynyl, a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆- Cio aryl, or a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C₅-Ci₀ heteroaryl. In some embodiments, particularly of the second sub aspect, R² is selected from a substituted or unsubstituted C1-C4 alkyl, a substituted or unsubstituted C1-C4 alkenyl, a substituted or unsubstituted C1-C4 alkynyl, a substituted or unsubstituted C₆ aryl, or a substituted or unsubstituted C₅-C₆- heteroaryl.

In some embodiments, particularly of the second sub aspect, R¹ comprises the general formula 2e,

with T being O and n of Z_n ¹ being 0, and

R³ is selected from a substituted or unsubstituted cycloalkyi, in particular a substituted or unsubstituted C3-C1₀ cycloalkyi, more particularly cyclohexane Z_n ¹ , R⁴ and R⁵ having the same meaning as defined previously, and

R² is selected from

a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C1-C12 alkenyl,

a substituted or unsubstituted cycloalkyi, in particular a substituted or unsubstituted C3-C1₀ cycloalkyi,

a substituted or unsubstituted saturated heterocycle, in particular a substituted or unsubstituted C3-C1₀ heterocycle, or

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C10 heteroaryl, or

R² is selected from a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C3-C₁₀ cycloalkyl,

a substituted or unsubstituted saturated heterocycle, in particular a substituted or unsubstituted C3-C₁₀ heterocycle, or

R² is selected from

a substituted or unsubstituted C₃-C₆ cycloalkyl, a substituted or unsubstituted C₆ aryl, or a substituted or unsubstituted C₅-C₆- heteroaryl, or

R² is selected from

with L being

R² is selected from

(formula 4a) or - a substituted or unsubstituted C₆- aryl, wherein the substituted C₆ aryl comprises the formula 4b

(formula 4b)

with L being

an alkyl, in particular a Ci-Ci₂ alkyl, more particularly a CrC₄ alkyl, an alkenyl, in particular a C₁-C₁₂ alkenyl, more particularly a C C₄ alkenyl,

each Z² independently from any other Z² is selected from -F, -CI, -Br, - I, CN, -R^b, -OR^b, -(CH₂)_rOR^b, -SR^b, -(CH₂)_rSR^b or -NR^b ₂, with each R^b being selected independently from each other from H, a substituted or unsubstituted C₁-C₁₂ alkyl, in particular C C₄ alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 , or

R² is selected from

with A being -(CH)(CH₃)₃, -(CH₂)CN, -(CH₂)C(=0)ONH₂., -(CH₂)N(CH₂CH₃)₂, , -(CH₂)CH₂OH, -(CH₂)C(=0)NH_2..

Particular embodiment is given below:

Concerning further embodiments of R² reference is made to the first aspect of the invention, particularly to the first sub aspect of first aspect of the invention.

Concerning further embodiments of o of Z² ₀ and Z² reference is made to the first aspect of the invention, particularly to the first sub aspect of first aspect of the invention.

In some embodiments of a third sub aspect of the first aspect,

each of R² and R³ are selected independently from each other from

- a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C Ci₂ alkenyl,

R¹ comprises

a. the general formula 2b' to 2d' and 2f to 2j',

being a Ci to C₄ alkyl, or R¹ comprises the general formula 2b to 2d and

CHCH₃, -C(CH₃)₂ or -NR^c, in particular from NH, -S or -O, and

CH or =N,

- with R⁴ and R⁵ being selected independently from each other from -H, -F, -CH₃, -

CH₂CH₃, -OCH₃, -CH₂CF₃, -CHFCF₃, -CF₂CF₃, -CHF₂, -CH₂F or -CF₃, in particular with R⁵ and R⁶ being selected independently from each other from H, -F or -CH₃, and

- with R⁶ being selected from -OH, -OCH₃, -OCH₂CH₃, -CH₃ or H,

- with R⁷ being selected from =NH, =S or =0, in particular from O, and

- with n of Z¹ _n being 0, 1 , 2 or 3, , in particular n of Z¹ _n being 0 or 1 , and with each Z¹ independently from any other Z¹ being selected from -F, -CI, -Br, -I, CN, -R^a, -OR^a, - (CH₂)_rOR^a, -SR^a, -(CH₂)_rSR^a or -NR^a ₂, with each R^a being selected independently from each other from H, a substituted or unsubstituted Ci-C₈ alkyi, in particular Ci-C₄ alkyi, a substituted or unsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 ,

with R^c being -CH₂OH, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃, -CH(CH₃)₂, -CH₂CF₃, -CHFCF₃, - CF₂CF₃, -CHF₂, -CH₂F, -CF₃. In some embodiments, particularly of the third sub aspect, R¹ comprises the general formula 2b to 2h, in particular the formula 2b, 2c, 2g or 2h, more particularly the formula 2b, 2c, 2g or 2h.

In some embodiments, particularly of the third sub aspect, R¹ comprises the general formula 2b or 2c, in particular 2c. In some embodiments, particularly of the third sub aspect,

- T of the compound according to formula 2b or 2c is selected from -NH, -S, -O or - NR^C, wherein in particular T is S or -NH, and T" being selected from -CH or =N, and with R⁶ being selected from -CH₃ or H, in particular R⁶ is H,

each T of the compound according to formula 2d being selected independently from each other from -NH, -S, -O or -NR^C, in particular at least one T is selected from NH or -NCH₃, more particularly the T in the position 4, with respect to the connection to the parent moiety, is -NH, and with R⁷ being selected from =NH, =S or =0, in particular from O, and

- each T" of the compound according to formula 2f is selected independently from each other from -CH or =N, in particular each T" is =N,

- T of the compound according to formula 2g or 2h is selected from -NH, -S, -O or - NR^C, wherein in particular T is -NR^C or -NH, and T" being selected from -CH or =N, in particular T" is =N,

- T of the compound according to formula 2i or 2j is selected from -NH or -NR^C, wherein in particular T is -NH, and T" is =N.

In some embodiments, particularly of the third sub aspect, R^c is selected from -CH₂OH, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃ or -CH(CH₃)₂, in particular from -CH₃, -CH₂CH₃ or -CH(CH₃)₂, more particularly R^c is CH₃.

Concerning further embodiments of n of Z¹ _n and Z¹ _n reference is made to the first aspect of the invention, particularly to the first sub aspect of first aspect of the invention.

Concerning further embodiments of R² reference is made to the first aspect of the invention, particularly to the second sub aspect of first aspect of the invention. Concerning further embodiments of o of Z² ₀ and Z² ₀ reference is made to the first aspect of the invention, particularly to the first sub aspect of first aspect of the invention.

Concerning further embodiments of R³ reference is made to the first aspect of the invention, particularly to the second sub aspect of first aspect of the invention. In some embodiments, particularly of the third sub aspect, R³ is selected from

- a substituted or unsubstituted CrC₄ alkyl,

- a substituted or unsubstituted C C₄ alkenyl,

- a substituted or unsubstituted C C₄ alkynyl,

- a substituted or unsubstituted C₆ aryl,

- a substituted or unsubstituted C₆-cycloalkyl or

a substituted or unsubstituted C₅-C₆- heteroaryl, in particular a substituted or unsubstituted C₆-cycloalkyl or a substituted or unsubstituted C₅-C₆- heteroaryl.

Concerning further more specific embodiments of R³ reference is made to the first aspect of the invention, particularly to the second sub aspect of first aspect of the invention. Concerning further embodiments of p of Z³ _P and Z³ _P reference is made to the first aspect of the invention, particularly to the first sub aspect of first aspect of the invention.

Particular embodiments of this sub aspect are given below:

phenylthiazolidin-4-one

(2Z,5Z)-5-((benzo[d]thiazol-6-yl)methylene)-3-phenyl-2- (phenylimino)thiazolidin-4-one _A_A (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(p-tolylimino)-3-p-tolylthiazolidin- 4-one _A_X (2Z,5Z)-2-(p-tolylimino)-5-((benzo[d]thiazol-6-yl)methylene)-3- isobutylthiazolidin-4-one _A_I (2Z,5Z)-2-(p-tolylimino)-5-((benzo[d]thiazol-6-yl)methylene)-3- cyclohexylthiazolidin-4-one _A_X (2Z,5Z)-2-(p-tolylimino)-3-isobutyl-5-((l-methyl-lH-indazol-5- yl)methylene)thiazolidin-4-one _A_I (2Z,5Z)-2-(p-tolylimino)-3-cyclohexyl-5-((l-methyl-lH-indazol-5- yl)methylene)thiazolidin-4-one _A_A (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(p-tolylimino)-3-p- tolylthiazolidin-4-one _P_N (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(4-fluorobenzylimino)-3- phenylthiazolidin-4-one _B_X (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(4-fluorophenylimino)-3- isobutylthiazolidin-4-one _C_F (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3-(4- methoxyphenyl)thiazolidin-4-one _U_N (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(phenethylimino)-3- phenylthiazolidin-4-one

(2Z,5Z)-5-((l-methyl-lH-indazol-5-yl)methylene)-3-phenyl-2- (phenylimino)thiazolidin-4-one _B_A (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(4- fluorophenylimino)-3-p-tolylthiazolidin-4-one _N_G (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-3-butyl-2- (phenylimino)thiazolidin-4-one _C_K (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(benzylimino)-3-(3- phenylpropyl)thiazolidin-4-one _N_K (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(phenylimino)-3-(3- phenylpropyl)thiazolidin-4-one _B_X (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(4- fluorophenylimino)-3-isobutylthiazolidin-4-one _N_C (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-3-benzyl-2- (phenylimino)thiazolidin-4-one _B_A (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(4- fluorophenylimino)-3-p-tolylthiazolidin-4-one _N_G (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-3-butyl-2- (phenylimino)thiazolidin-4- _C_O (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(benzylimino)-3- phenethylthiazolidin-4-one _N_K (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(phenylimino)-3-(3- phenylpropyl)thiazolidin-4-one

(2Z,5Z)-5-((lH-indol-5-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin- 4-one _B_A (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(4-fluorophenylimino)-3-p- tolylthiazolidin-4-one _C_B (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3-(4- fluorophenyl)thiazolidin-4-one _S_N (2Z,5Z)-2-((pyridin-3-yl)methylimino)-5-((lH-benzo[d]imidazol-5- yl)methylene)-3-phenylthiazolidin-4-one _N_M (2Z,5Z)-5-((lH-indol-5-yl)methylene)-3-((furan-2-yl)methyl)-2- (phenylimino)thiazolidin-4-one _B_X (2Z,5Z)-2-(4-fluorophenylimino)-5-((benzo[d]thiazol-6-yl)methylene)-3- isobutylthiazolidin-4-one _P_N (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(4- fluorobenzylimino)-3-phenylthiazolidin-4-one _C_G (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3- butylthiazolidin-4-one _F_N (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(4-methoxyphenylimino)-3- phenylthiazolidin-4-one _C_O (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3- phenethylthiazolidin-4-one _C_K (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3-(3- phenylpropyl)thiazolidin-4-one _U_N (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(phenethylimino)-3- phenylthiazolidin-4-one _D_N (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(5-methylpyridin-2- ylimino)-3-phenylthiazolidin-4-one _B_I (2Z,5Z)-2-(4-fluorophenylimino)-3-cyclohexyl-5-((l-methyl-lH-indazol-5- yl)methylene)thiazolidin-4-one _N_M (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-3-((fu ran-2-yl)methyl)- 2-(phenylimino)thiazolidin-4-one _C_N (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3- phenylthiazolidin-4-one _C_C (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-3-benzyl-2- (benzylimino)thiazolidin-4-one _N_C (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-3-benzyl-2- (phenylimino)thiazolidin-4-one

(2Z,5Z)-5-((lH-indol-6-yl)methylene)-3-phenyl-2-(phenylimino)thiazolidin- 4-one _C_B (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(benzylimino)-3-(4- fluorophenyl)thiazolidin-4-one _D_N (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(5-methylpyridin-2-ylimino)-3- phenylthiazolidin-4-one _C_N (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(benzylimino)-3- phenylthiazolidin-4-one _B_A (2Z,5Z)-2-(4-fluorophenylimino)-5-((l-methyl-lH-indazol-5- yl)methylene)-3-p-tolylthiazolidin-4-one

(2Z,5Z)-5-((benzofu ran-5-yl)methylene)-3-phenyl-2- (phenylimino)thiazolidin-4-one _A_A (2Z,5Z)-2-(4-fluorophenylimino)-5-((l-methyl-lH-indazol-5- yl)methylene)-3-p-tolylthiazolidin-4-one

(2Z,5Z)-5-((benzo[b]thiophen-5-yl)methylene)-3-phenyl-2- (phenylimino)thiazolidin-4-one _C_G (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(benzylimino)-3-butylthiazolidin- 4-one

6-((13Z)-((Z)-4-oxo-3-phenyl-2-(phenylimino)thiazolidin-5- ylidene)methyl)benzo[d]oxazol-2(3H)-one

(2Z,5Z)-3-phenyl-2-(phenylimino)-5-((quinoxalin-6- yl)methylene)thiazolidin-4-one _R_N (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(4-tert- butylbenzylimino)-3-phenylthiazolidin-4-one

(2Z,5Z)-5-((benzo[d]thiazol-5-yl)methylene)-3-phenyl-2- (phenylimino)thiazolidin-4-one _E_N (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(methylimino)-3- phenylthiazolidin-4-one _A_V (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(p-tolylimino)-3- dodecylthiazolidin-4-one

(2Z,5Z)-5-((2-methylbenzo[d]thiazol-6-yl)methylene)-3-phenyl-2- (phenylimino)thiazolidin-4-one

3-methyl-6-((18Z)-((Z)-4-oxo-3-phenyl-2-(phenylimino)thiazolidin-5- ylidene)methyl)benzo[d]thiazol-2(3H)-one

5-((18Z)-((Z)-4-oxo-3-phenyl-2-(phenylimino)thiazolidin-5- ylidene)methyl)-lH-benzo[d]imidazol-2(3H)-one _N_F (2Z,5Z)-5-((lH-indol-5-yl)methylene)-3-(4-methoxyphenyl)-2- (phenylimino)thiazolidin-4-one _Q_N (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(4-methoxybenzylimino)-3- phenylthiazolidin-4-one _R_N (2Z,5Z)-5-((lH-indol-5-yl)methylene)-2-(4-tert-butylbenzylimino)-3- phenylthiazolidin-4- _E_N (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(methylimino)-3- phenylthiazolidin-4-one

04_N_F (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-3-(4-methoxyphenyl)-2- (phenylimino)thiazolidin-4-one

04_T_N (2Z,5Z)-5-((lH-benzo[d]imidazol-5-yl)methylene)-2-(2- chlorobenzylimino)-3-phenylthiazolidin-4-one

According to the second aspect the invention relates to a compound characterized by a general formula 1

(formula 1 )

wherein

R² is selected from

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C1₀ heteroaryl, and each of R¹ and R³ are selected independently from each other from

In some embodiments, R² is selected from a moiety described in the embodiments of the first aspect of the invention concerning the substituent R². Reference made to the detailed description above, in order to avoid repetition.

In some embodiments, R¹ is selected from a moiety described in the embodiments of the first aspect of the invention concerning the substituent R¹. Reference made to the detailed description above, in order to avoid repetition.

In some embodiments, R³ is selected from a moiety described in the embodiments of the first aspect of the invention concerning the substituent R³. Reference made to the detailed description above, in order to avoid repetition.

Any embodiment described for R¹ or R³ according to the second aspect of the invention may be combined with any embodiment described for R² according to the second aspect of the invention.

According to the third aspect the invention relates to a compound characterized by a general formula 1

(formula 1 )

wherein

3 is selected from

each of R¹ and R² are selected independently from each other from

- a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C₂-Ci₂ alkenyl, a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C₂-Ci₂ alkynyl,

a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C3-C₁₀ cycloalkyl,

a substituted or unsubstituted heterocycle, in particular a substituted or unsubstituted C3-C₁₀ heterocycle, or

Any embodiment described for R¹ or R² according to the third aspect of the invention may be combined with any embodiment described for R³ according to the third aspect of the invention.

According to the fourth aspect the invention relates to a compound comprising the following general formula (1 )

(formula 1 )

wherein R¹ is selected from

each of R² and R³ are selected independently from each other from

a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C₂-Ci₂ alkynyl,

some embodiments, R¹ is selected from - a substituted or unsubstituted alkyi, in particular a substituted or unsubstituted C Ci2 alkyi,

- a substituted or unsubstituted alkoxy, in particular a substituted or unsubstituted C1-C12 alkoxy,

- a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C12-C12 alkenyl,

- a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆- C10 aryl.

n some embodiments, R¹ is selected from

- a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula -M-Ar,

with M being

an alkyi, in particular a C1-C12 alkyi, more particularly a C C₄ alkyi, an alkenyl, in particular a C2-C12 alkenyl, more particularly alkenyl,

an alkynyl, in particular a C2-C12 alkynyl, more particularly a C₂-C₄ alkynyl, and

- a substituted or unsubstituted C₆- aryl, wherein in particular the substituted C₆- aryl comprises at least one substituent Z¹⁰.

n some embodiments, R¹ is selected from

- a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula 6a

(formula 6a) or

(formula 6b)

with M being

an alkyi, in particular a C₁-C₁₂ alkyi, more particularly a C₁-C4 alkyi, an alkenyl, in particular a C₂-Ci₂ alkenyl, more particularly a C₂-C₄ alkenyl, an alkynyl, in particular a C₂-Ci₂ alkynyl, more particularly a C₂-C₄ alkynyl, and

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I, CN, -R^e, - OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C₁-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

some embodiments, R¹ is selected from

- a substituted alkyi, wherein the substituted alkyi comprises the formula 6a

(formula 6a) or

(formula 6b)

with M being

an alkyi, in particular a C Ci₂ alkyi, more particularly a C₁-C4 alkyi, and

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I, CN, -R^e, - OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C₁-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, R¹ is selected from

(formula 6b)

with I of Z¹⁰i being 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and

each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I, CN, -R^e, - OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular C C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, R¹ is selected from

(formula 6b)

I of Z¹⁰i is 1 , 2, 3, 4 or 5, in particular 1 , 2 or 3, more particularly 1 , and

- each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I , CN, -R^e, -

OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular d-C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 , wherein at least one Z¹⁰ is -

(CH₂)_rOR^e, in particular in position 3.

In some embodiments, I of Z¹° is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ is selected independently from any other Z¹⁰ from -F, -CI, -Br, -I , CN, - R^e, -SR^e, -CH₂SR^e, -OR^e, CH₂OR^e or -NR^e ₂, in particular from -F, -CI, CN, -R^e, -OR^e, - CH₂OR^e or -NR^e ₂, more particularly from CN, -OR^e or CH₂OR^e, with each R^e being selected independently from each other from H, a substituted or unsubstituted C1-C12 alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C2-C12 alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, I of Z¹° is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I, CN, -OR^e or -CH₂OR^e, in particular from R^e, with R^e being selected from a substituted or unsubstituted Ci-Ci₂ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, I of Z¹° is 1 , 2, 3, 4 or 5, in particular 1 , 2 or 3, more particularly 1 , and each Z¹⁰ is selected independently from any other Z¹⁰ from -F, -CI, -Br, -I, CN, -R^e, -SR^e, -CH₂SR^e, -OR^e, CH₂OR^e or -NR^e ₂, in particular from -F, -CI, CN, -R^e, -OR^e, -CH₂OR^e or - NR^e ₂, more particularly from CN, -OR^e or CH₂OR^e, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, I of Z¹° is 1 , 2, 3, 4 or 5, in particular 1 , 2 or 3, more particularly 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I, CN, -OR^e or - CH₂OR^e, in particular from R^e, with R^e being selected from a substituted or unsubstituted C Ci₂ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl.

In some embodiments, I of Z¹° is 1 or 2, in particular 1 .

In some embodiments, I of Z¹° the at least one Z¹⁰ is -(CH₂)_rOR^e, in particular in position 3, with R^e being H or CH₃, with r being selected from 1 , 2, 3, in particular with r being 1.

In some embodiments, I of Z¹° is 0, 1 or 2, in particular 0 or 1.

In some embodiments, R¹ is selected from.

thereof.

In some embodiments, R¹ is selected from.

, or , or derivatives thereof.

In some embodiments, R¹ is selected from

Any embodiment described for R² or R³ according to the fourth aspect of the invention may be combined with any embodiment described for R¹ according to the fourth aspect of the invention.

Particular embodiments are given below:

_A_N (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(p-tolylimino)-3- phenylthiazolidin-4-one _B_X (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-fluorophenylimino)-3- isobutylthiazolidin-4-one _F_N (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-methoxyphenylimino)-3- phenylthiazolidin-4-one _A_X (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(p-tolylimino)-3- isobutylthiazolidin-4- _A_A (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(p-tolylimino)-3-p- tolylthiazolidin-4-one _Q_N (2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-2-(4-methoxybenzylimino)-3- phenylthiazolidin-4-one _B_A (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-fluorophenylimino)-3-p- tolylthiazolidin-4-one _P_N (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-fluorobenzylimino)-3- phenylthiazolidin-4-one _C_F (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3-(4- methoxyphenyl)thiazolidin-4-one _N_C (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-benzyl-2- (phenylimino)thiazolidin-4-one _C_K (2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-2-(benzylimino)-3-(3- phenylpropyl)thiazolidin-4-one _Q_N (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-methoxybenzylimino)-3- phenylthiazolidin-4-one

(2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-phenyl-2- (phenylimino)thiazolidin-4-one _U_N (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(phenethylimino)-3- phenylthiazolidin-4-one _N_K (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(phenylimino)-3-(3- phenylpropyl)thiazolidin-4-

(2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-3-phenyl-2- (phenylimino)thiazolidin-4-one _N_G (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-butyl-2- (phenylimino)thiazolidin-4-one _C_0 (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3- phenethylthiazolidin-4- _C_G (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3- butylthiazolidin-4-one _N_M (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-((fu ran-2-yl)methyl)-2- (phenylimino)thiazolidin-4-one _C_K (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3-(3- phenylpropyl)thiazolidin-4- _D_N (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(5-methylpyridin-2-ylimino)- 3-phenylthiazolidin-4-one _C_0 (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3- phenethylthiazolidin-4-one _C_N (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3- phenylthiazolidin-4-one _C_N (2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-2-(benzylimino)-3- phenylthiazolidin-4- _C_B (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(benzylimino)-3-(4- fluorophenyl)thiazolidin-4-one _T_N (2Z,5Z)-2-(2-chlorobenzylimino)-5-(3-(methoxymethyl)benzylidene)-3- phenylthiazolidin-4-one _R_N (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-tert-butylbenzylimino)-3- phenylthiazolidin-4-one _C_C (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-benzyl-2- (benzylimino)thiazolidin-4-one _A_V (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-fluorophenylimino)-3- dodecylthiazolidin-4-one _B_V (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(4-fluorophenylimino)-3- dodecylthiazolidin-4-one 15_U_N (2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-2-(phenethylimino)-3- phenylthiazolidin-4-one

34 (2Z,5Z)-5-(4-(methoxymethyl)benzylidene)-3-phenyl-2- (phenylimino)thiazolidin-4-one

04_A_V (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(p-tolylimino)-3- dodecylthiazolidin-4-one

15_R_N (2Z,5Z)-5-(3-(methoxymethyl)benzylidene)-2-(4-tert-butylbenzylimino)-3- phenylthiazolidin-4-one

22_A_V (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(p-tolylimino)-3- dodecylthiazolidin-4-one

22_E_N (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-2-(methylimino)-3- phenylthiazolidin-4-one

22_N_F (2Z,5Z)-5-(4-(hydroxymethyl)benzylidene)-3-(4-methoxyphenyl)-2- (phenylimino)thiazolidin-4-one

22_T_N (2Z,5Z)-2-(2-chlorobenzylimino)-5-(4-(hydroxymethyl)benzylidene)-3- phenylthiazolidin-4-one

In some embodiments of a first sub aspect of the fourth aspect of the invention

R¹ is selected from

- a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C1-C12 alkynyl,

a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Cio aryl, and each of R² and R³ are selected independently from each other from

a substituted or unsubstituted alkyi, in particular a substituted or unsubstituted C1-C12 alkyi,

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C10 heteroaryl,

wherein at least one of R-i, R₂ and R₃ is selected form,

from

with M being

an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi, - an alkenyl, in particular a C1-C12 alkenyl, more particularly a C1-C4 alkenyl,

Ar being a C₆- aryl, wherein in particular the substituted C₆- aryl comprises at least one substituent Z¹⁰,

in case of R₂ from - a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula -L-Ar,

with L being

an alkyi, in particular a C₁-C₁₂ alkyi, more particularly a C₁-C4 alkyi, - an alkenyl, in particular a C₁-C₁₂ alkenyl, more particularly a C₁-C4 alkenyl,

- a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z², and

in case of R₃ from

with D being

- a substituted or unsubstituted C₆- aryl or a substituted or unsubstituted

C₅-C₆- heteroaryl, wherein in particular the substituted C₆- aryl or the substituted C₅-C₆- heteroaryl comprises at least one substituent Z³

In some embodiments, particularly of the first aspect of the fourth invention, R¹ is selected from

(formula 6a) or

with M being

an alkyl, in particular a Ci-Ci₂ alkyl, more particularly a CrC₄ alkyl, an alkenyl, in particular a Ci-Ci₂ alkenyl, more particularly a CrC₄ alkenyl, an alkynyl, in particular a Ci-Ci₂ alkynyl, more particularly a CrC₄ alkynyl, and

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I, CN, -R^e, -OR^e, - (CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular d-C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 .

In some embodiments, particularly of the first aspect of the fourth invention, R¹ is selected from wherein R¹ is selected from

- a substituted alkyl, wherein the substituted alkyl comprises the formula 6a

(formula 6a)

with M being

an alkyl, in particular a C Ci₂ alkyl, more particularly a C C₄ alkyl, and

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I, CN, -R^e, - OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular C C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1

Concerning further embodiments of I of Z¹° and Z¹° reference is made to the first aspect of the invention, particularly to the first sub aspect of first aspect of the invention. Concerning further embodiments of R² reference is made to the first aspect of the invention, particularly to the second sub aspect of first aspect of the invention.

Concerning further embodiments of o of Z² ₀ and Z² ₀ reference is made to the first aspect of the invention, particularly to the first sub aspect of first aspect of the invention.

Concerning further embodiments of R³ reference is made to the first aspect of the invention, particularly to the second sub aspect of first aspect of the invention.

In some embodiments, particularly of the third sub aspect, R³ is selected from

- a substituted or unsubstituted CrC₄ alkyl,

- a substituted or unsubstituted C C₄ alkenyl,

- a substituted or unsubstituted C C₄ alkynyl,

- a substituted or unsubstituted C₆ aryl,

- a substituted or unsubstituted C₆-cycloalkyl or

- a substituted or unsubstituted C₅-C₆- heteroaryl, in particular a substituted or unsubstituted C₆-cycloalkyl or a substituted or unsubstituted C₅-C₆- heteroaryl.

Concerning further more specific embodiments of R³ reference is made to the first aspect of the invention, particularly to the second sub aspect of first aspect of the invention.

Concerning further embodiments of p of Z³ _p and Z³ _P reference is made to the first aspect of the invention, particularly to the first sub aspect of first aspect of the invention.

Particular embodiments are given below:

23_C_0 (2Z,5Z)-5-benzylidene-2-(benzylimino)-3-phenethylthiazolidin-4-one

23_N_M (2Z,5Z)-5-benzylidene-3-((fu ran-2-yl)methyl)-2-(phenylimino)thiazolidin- 4-one

23_F_N (2Z,5Z)-2-(4-methoxyphenylimino)-5-benzylidene-3-phenylthiazolidin-4- one

23_A_A (2Z,5Z)-2-(p-tolylimino)-5-benzylidene-3-p-tolylthiazolidin-4-one

23 (2Z,5Z)-5-benzylidene-3-phenyl-2-(phenylimino)thiazolidin-4-one

23_K_N (2Z,5Z)-2-(3-phenylpropylimino)-5-benzylidene-3-phenylthiazolidin-4-one

23_A_N (2Z,5Z)-2-(p-tolylimino)-5-benzylidene-3-phenylthiazolidin-4-one

23_N_G (2Z,5Z)-5-benzylidene-3-butyl-2-(phenylimino)thiazolidin-4-one

23_N_C (2Z,5Z)-3-benzyl-5-benzylidene-2-(phenylimino)thiazolidin-4-one

23_P_N (2Z,5Z)-2-(4-fluorobenzylimino)-5-benzylidene-3-phenylthiazolidin-4-one

23_C_B (2Z,5Z)-5-benzylidene-2-(benzylimino)-3-(4-fluorophenyl)thiazolidin-4-one

23_E_N (2Z,5Z)-5-benzylidene-2-(methylimino)-3-phenylthiazolidin-4-one

23_C_K (2Z,5Z)-5-benzylidene-2-(benzylimino)-3-(3-phenylpropyl)thiazolidin-4- one

23_B_V (2Z,5Z)-2-(4-fluorophenylimino)-5-benzylidene-3-dodecylthiazolidin-4-one

23_D_N (2Z,5Z)-2-(5-methylpyridin-2-ylimino)-5-benzylidene-3-phenylthiazolidin- 4-one

23_N_L (2Z,5Z)-5-benzylidene-3-(4-chlorophenyl)-2-(phenylimino)thiazolidin-4- one

In some embodiments the compound of the invention according to the first, second, third or fourth aspect of the invention comprises a (2Z,5Z), (2Z,5E), (2E,5Z) or (2E,5E) isomer form, in particular a (2Z,5Z) or (2Z,5E), more particularly a (2Z,5Z) isomer form, characterized by formula 1 a

(formula 1 a) with the isomer center being indicated by the asterix (^*),with R¹, R² and R³ having the same meaning as defined previously, wherein the compound of the invention comprises the before mentioned isomers in an essentially pure form, with R¹, R² and R³ having the same meaning as defined previously.

As used herein the term "essentially pure" refers to a purity of≥ 90 %, in particular of≥ 95 %.

In some embodiments the compound of the invention comprises a mixture of the (2Z,5Z), (2Z,5E), (2E,5Z) or (2E,5E) isomer forms, in particular a mixture of (2Z,5Z) and (2Z,5E). characterized by formula 1 a as depicted above.

The following formulas show the respective configuration:

withR¹, R² and R³ having the same meaning as defined previously.

Particular embodiments of the invention are:

87

A fifth aspect of the invention relates to a compound according to the first, second, third or fourth aspect of the invention for use as a medicament.

A sixth aspect of the invention relates to a compound according to the first, second, third or fourth aspect of the invention for use in the treatment of psychiatric or neurological disorders and inflammation, in particular neuroinflammation.

The compounds of the invention are potent inhibitors of AEA cell membrane transport and do not inhibit the AEA metabolic enzyme FAAH. The compounds of the invention show both cannabimimetic behavioral effects and antiinflammatory effects, in particular an anti- neuroinflammatory effect, as exemplified in the experimental section.

By inhibiting AEA uptake the ECS can be modulated in a unique way, leading to diverse pharmacological actions like analgesia, anti-inflammatory and CNS effects exemplified by the tetrad effect (Nicolussi & Gertsch, 2015, Vitam Horm. 98:441 -85.).

The use of the compounds of the invention in a method for treatment of psychiatric or neurological disorders is related to attenuation of neuroinflammation and neuronal retrograde signaling mediated via endocannabinoids including AEA. Such diseases include bipolar diseases, schizophrenia, sleeping disorders, multiple sclerosis and Alzheimers disease (Ashton and Moore Acta Psychiatr Scand. 201 1 , 124, 250-61 .; Aso and Ferrer I, Front Pharmacol. 2014, 5:37.; Correa et al. Vitam Horm. 2009, 81 , 207-30.)

In some embodiments, the compounds of the general formula (1 ) may be isolated in form of salts, in particular in form of pharmaceutically acceptable salts. The same applies to all of the before mentioned embodiments. In some embodiments, the compounds of the general formula (1 ) may be isolated in form of a tautomer, a hydrate or a solvate.

Such salts are formed, for example, as acid addition salts, preferably with organic or inorganic acids, from compounds of the general formula (1 ) with a basic nitrogen atom, in particular the pharmaceutically acceptable salts are formed in such a way. Suitable inorganic acids are, without being limited to, halogen acids, such as hydrochloric acid, sulfuric acid, or phosphoric acid and the like. Suitable organic acids are, without being limited to, carboxylic, phosphonic, sulfonic or sulfamic acids and the like. Such organic acids may be, without being limited to, acetic acid, glycolic acid, lactic acid, malic acid, tartaric acid, or citric acid. Salts may also be formed, for example, as salts with organic or inorganic bases, from compounds of the general formula (1 ) with a nitrogen atom bearing an acidic hydrogen. Examples of suitable cations are - without being limited to - sodium, potassium, calcium or magnesium cations, or cations of organic nitrogen bases, e.g. protonated mono-, di- or tri-(2- hydroxethyl)amine.

In view of the close relationship between the novel compounds in their free form and those in the form of their salts, any reference to the free compounds hereinbefore and hereinafter is to be understood as referring also to the corresponding salts, as appropriate and expedient. Likewise, in view of the close relationship between the novel compounds of the general formula (1 ) and their tautomers, any reference to the compounds of the general formula (1 ) is to be understood as referring also to the corresponding tautomers. The same applies to a hydrate or a solvate.

In some embodiments, the pharmaceutical preparation comprises at least one compound according to the invention as an active ingredient and at least one pharmaceutically acceptable carrier. In some embodiments, the pharmaceutical preparation comprises at least one compound according to the invention in its free form as an active ingredient. In some embodiments, the pharmaceutical preparation comprises at least one compound according to the invention in its free form as an active ingredient and at least one pharmaceutically acceptable carrier.

In some embodiments, the pharmaceutical preparation comprises at least one compound according to the invention in form of a salt, a tautomer, a pharmaceutically acceptable salt, a hydrate or a solvate. In some embodiments, the pharmaceutical preparation comprises at least one compound according to the invention in form of a salt, a tautomer, a pharmaceutically acceptable salt, a hydrate or a solvate and at least one pharmaceutically acceptable carrier.

Furthermore the invention relates to pharmaceutical preparations comprising at least one compound mentioned herein before as active ingredient, which can be used especially in the treatment of the diseases mentioned. The pharmaceutical preparations may be used in particular for a method for treatment of psychiatric disorders.

In some embodiments, the pharmaceutical preparations is for enteral administration, such as nasal, buccal, rectal, local or, especially, oral administration, and for parenteral administration, such as intravenous, intramuscular or subcutaneous administration, are especially preferred. The preparations comprise the active ingredient alone or, in particular, together with a pharmaceutically acceptable carrier. The dosage of the active ingredient depends upon the disease to be treated and upon the species, its age, weight, and individual condition, the individual pharmacokinetic data, and the mode of administration. In particular, the oral application of the active ingredient is preferred. In some embodiments, the pharmaceutical preparations comprise from approximately 1 % to approximately 95% active ingredient. Unit dose forms are, for example, coated and uncoated tablets, ampoules, vials, suppositories, or capsules. Further dosage forms are, for example, ointments, creams, pastes, foams, tinctures, lip-sticks, drops, sprays, dispersions, etc. Examples are capsules containing from about 0.005 g to about 1.0 g active ingredient.

In some embodiments, the pharmaceutical preparations of the present invention are prepared in a manner known per se, for example by means of conventional mixing, granulating, coating, dissolving or lyophilizing processes.

In some embodiments, the pharmaceutical preparations is in form of solutions of the active ingredient, and also suspensions or dispersions, especially isotonic aqueous solutions, dispersions or suspensions which, for example in the case of lyophilized preparations comprising the active ingredient alone or together with a carrier, for example mannitol, can be made up before use.

In some embodiments, the pharmaceutical preparations may be sterilized and/or may comprise excipients, for example preservatives, stabilizers, wetting agents and/or emulsifiers, solubilizers, salts for regulating osmotic pressure and/or buffers and are prepared in a manner known per se, for example by means of conventional dissolving and lyophilizing processes. The said solutions or suspensions may comprise viscosity-increasing agents, typically sodium carboxymethylcellulose, carboxymethylcellulose, dextran, polyvinylpyrrolidone, or gelatins, or also solubilizers, e.g. Tween 80® (polyoxyethylene(20)sorbitan mono-oleate).

In some embodiments, the pharmaceutical preparation comprises suspensions in oil, which comprise as the oil component a vegetable, synthetic, or semi-synthetic oils customary for injection purposes. In some embodiments, the pharmaceutical preparation comprises a mixtures of fatty acid esters, vegetable oils such as, without being limited to, cottonseed oil, almond oil, olive oil, castor oil, sesame oil, soybean oil and groundnut oil. The manufacture of injectable preparations is usually carried out under sterile conditions, as is the filling, for example, into ampoules or vials, and the sealing of the containers.

Suitable carriers are especially fillers, such as sugars, for example lactose, saccharose, mannitol or sorbitol, cellulose preparations, and/or calcium phosphates, for example tricalcium phosphate or calcium hydrogen phosphate, and also binders, such as starches, for example corn, wheat, rice or potato starch, methylcellulose, hydroxypropyl methylcellulose, sodium carboxymethylcellulose, and/or polyvinylpyrrolidone, and/or, if desired, disintegrators, such as the above-mentioned starches, also carboxymethyl starch, crosslinked polyvinyl pyrrolidone, alginic acid or a salt thereof, such as sodium alginate. Additional excipients are especially flow conditioners and lubricants, for example silicic acid, talc, stearic acid or salts thereof, such as magnesium or calcium stearate, and/or polyethylene glycol, or derivatives thereof.

Tablet cores can be provided with suitable, optionally enteric, coatings through the use of, inter alia, concentrated sugar solutions which may comprise gum arabic, talc, polyvinyl- pyrrolidone, polyethylene glycol and/or titanium dioxide, or coating solutions in suitable organic solvents or solvent mixtures, or, for the preparation of enteric coatings, solutions of suitable cellulose preparations, such as acetylcellulose phthalate or hydroxypropyl- methylcellulose phthalate. Dyes or pigments may be added to the tablets or tablet coatings, for example for identification purposes or to indicate different doses of active ingredient. In some embodiments, the pharmaceutical preparation is suitable for oral administration also include hard capsules consisting of gelatin, and also soft, sealed capsules consisting of gelatin and a plasticizer, such as glycerol or sorbitol. The hard capsules may contain the active ingredient in the form of granules, for example in admixture with fillers, such as corn starch, binders, and/or glidants, such as talc or magnesium stearate, and optionally stabilizers. In soft capsules, the active ingredient is preferably dissolved or suspended in suitable liquid excipients, such as fatty oils, paraffin oil or liquid polyethylene glycols or fatty acid esters of ethylene or propylene glycol, to which stabilizers and detergents, for example of the polyoxy ethylene sorbitan fatty acid ester type, may also be added.

In some embodiments, the pharmaceutical preparation is suitable for rectal administration are, for example, suppositories that consist of a combination of the active ingredient and a suppository base. Suitable suppository bases are, for example, natural or synthetic triglycerides, paraffin hydrocarbons, polyethylene glycols or higher alkanols.

In some embodiments, the pharmaceutical preparation is suitable for parenteral administration, aqueous solutions of an active ingredient in water-soluble form or aqueous injection suspensions that contain viscosity-increasing substances, for example sodium carboxymethylcellulose, sorbitol and/or dextran, and, if desired, stabilizers, are especially suitable. The active ingredient, optionally together with excipients, can also be in the form of a lyophilizate and can be made into a solution before parenteral administration by the addition of suitable solvents. Solutions such as are used, for example, for parenteral administration can also be employed as infusion solutions. Preferred preservatives are, for example, antioxidants, such as ascorbic acid, or microbicides, such as sorbic acid or benzoic acid.

General Methods and Materials

Compounds and chemicals were of purest possible grade. Anandamide (AEA), (R)-N-(1 -(4- hydroxyphenyl)-2-hydroxyethyl)oleamide (OMDM-2), N-(3-furanylmethyl)-(5Z,8Z,1 1Z,14Z)- eicosatetraenamide (UCM707), [ethanolamine-1 -3H]-AEA (60 Ci/mmol) was purchased from American Radiolabeled Chemicals. Albumin from bovine serum essentially fatty acid free (BSA) (A7030), fetal bovine serum (F7524), RPMI-1640 were purchased from Sigma-Aldrich, Germany. AquaSilTM siliconizing fluid was purchased from Thermo Scientific.

r³Hl-AEA cellular uptake

Screening for AEA cellular uptake inhibition was performed in a semi-automated procedure: Pipetting and washing steps were performed by a Biomek3000 laboratory workstation. First, required amounts of U937 cells were centrifuged at 100 x g for 5 min and resuspended in RPMI (37°C) to a final concentration of 2 x 10⁶ cells/mL. Then, 250 μΙ_ of cell suspension (0.5 x 10⁶ cells per sample) were transferred into AquaSil™ silanized glass vials (Chromacol 1.1 - MTV) in 96-well format. After addition of 5 μΙ_ vehicle (DMSO) or compounds the cells were incubated at 37°C for 15 min. As positive controls OMDM-2 and UCM707 were used at 10 μΜ in each run. The ETI-T compounds were measured at up to 7 concentrations in triplicates from 100 pM - 100 μΜ. After pre-incubation, a mixture of 0.5 nM[ei/?ano/am/^'ne-1 -³H]-AEA, (60 Ci/mmol) and 99.5 nM of cold AEA (final 100 nM) was added and samples were incubated at 37°C for another 15 min. The reaction was stopped by rapid filtration over UniFilter-96 GF/C filters (PerkinElmer) pre-soaked with PBS 0.25 % BSA. Cells were washed three times with 100 μΙ_ ice-cold PBS buffer containing 1 % fatty acid free BSA. After drying, 45 μΙ_ MicroScint 20 scintillation cocktail (PerkinElmer, Waltham, MA, US) was added to the wells and the plate was sealed. Radioactivity was measured by liquid scintillation counting on a PerkinElmer Wallac Trilux MicroBeta 1450 during 2 min. Non-specific binding of [³H]AEA (100 nM) to the glass vials was never higher than 10 %. IC₅₀ values were calculated by GraphPad^® by non-linear regression using the built-in log(inhibitor) vs. response -variable slope (four parameters) function.

FAAH activity

Hydrolysis of [³H]-AEA by FAAH was determined as previously described in cell homogenates of U937 cells (0.18 mg protein) (Omeir et al., 1999, Biochem Biophys Res Commun, 264, 316-20; Mor et al., 2004, J Med Chem, 47, 4998-5008). Protein amounts of cell homogenates corresponded to 0.5 x 10⁶ cells (U937), to assure best possible comparability of IC₅₀ values as used for the AEA cellular uptake assays. URB597 was used as positive control. Protein quantification was performed using a BCA assay (Thermo Scientific). Enzyme activity was assessed by addition of vehicle or compounds in 10 μΙ_ DMSO to 490 μΙ_ homogenate in 10 mM Tris HCI, 1 mM EDTA, 0.1 % (w/v) BSA fatty acid free, pH = 8 and incubation for 15 min at 37°C. After, a mixture of AEA plus [ethanolamine^ - ³H]-AEA (0.5 nM) at final 100 nM was added to the homogenates and incubated for 15 min at 37°C. The reaction was stopped by addition of 1 mL ice-cold CHCI₃:MeOH (1 :1 ) followed by vigorous vortexing. Phase separation was achieved by centrifugation at 10Ό00 x g at 4°C for 10 min. Radioactivity of the separated aqueous phase (upper phase) containing [³H- ethanolamine] or [³H-glycerol] was measured by liquid scintillation counting on a Tri-Carb 2100 TR liquid scintillation analyzer after addition of 3.5 mL Ultima Gold scintillation cocktail (PerkinElmer Life Sciences). Results are expressed as hydrolysis of tritium substrate in percent of vehicle treated control. IC₅₀ values were calculated by GraphPad^®. Data are reported as means of n = 3 independent experiments performed in triplicates.

Radioligand CB receptor binding

Binding properties of ETI-T compounds to hCB1 or hCB2 receptors were performed as previously reported in a [³H]-CP55,940 displacement assay (Gertsch et al., 2008, Proc Natl Acad Sci 105, 9099-104). WIN 55,212-2 was used as positive control. In brief, 20 μg protein of CHO-K1 frCB-i or hC ₂ membrane preparations were thawed on ice and resuspended in a final volume of 500 μΙ_ binding buffer (50 mM Tris-HCI, 2.5 mM EDTA, 5 mM MgCI2, 0.5 % fatty acid free BSA, pH 7.4) in silanized glass vials. [³H]-CP55,940 (168 Ci/mmol) (PerkinElmer, Waltham, MA, US) was added to a final concentration of 0.5 nM followed by the addition of competitors or vehicle in 5 μΙ_ DMSO. Membrane binding was equilibrated for 2 h at room temperature (25°C). Samples were filter through a 0.1 % polyethylenimine pre- soaked UniFilter^®-96 GF/B plate (PerkinElmer) and washed twelve times with 167 μΙ_ ice-cold assay-buffer. The plate was dried, bottom sealed and 45 μΙ_ MicroScint 20 scintillation cocktail (PerkinElmer) were added before measured on a PerkinElmer 1450 Microbeta TRILUX liquid scintillation counter. Unspecific binding was determined by WIN 55,212-2, 10 μΜ and subtracted from all values. IC₅₀ values.

General synthesis

The compounds of the invention may be produced according to one of the pathways depicted in scheme 1 or scheme 2. The starting materials may be purchased or produced accordin to literature procedures.

Scheme 1 : a) solvent, optional a base; b) R¹-CH=0, piperidine, EtOH, 18 h or 2 eq. NaOH, AcOH, 60 - 1 10 °C, 3-24 h (analogue to J.Med.Chem.;20W; 53 (10), 4198 or J.Med.Chem.;200S; 51, 1242), with R being H, methyl or ethyl and LG being a leaving group such as CI or Br.

Scheme 2: a) solvent, base; b) R¹-CH=0, piperidine, EtOH, 18 h or 2 eq. NaOH, AcOH, 60 - 1 10 °C, 3-24 h (analogue to J.Med.Chem.;20 0; 53 (10), 4198 or J.Med.Chem.;200S; 51, 1242).

Evaluation:

Table 1 - AEA uptake inhibition

97

98

102

Table 2 - AEA uptake inhibition of further compounds

Table 3 - FAAH inhibition of further compounds

Table 4 - CB1 receptor binding of further compounds

Table 5 - AEA uptake inhibition of further compounds

Table 6 - FAAH inhibition of further compounds

Table 7 - CB1 receptor binding of further compounds

Table 8 - AEA uptake inhibition of further compounds

Table 9 and 10 - FAAH inhibition andCBI receptor binding of further compounds

Table 1 1 - AEA uptake inhibition ,FAAH inhibition andCBI receptor binding of further compounds

Claims

Claims:

1 . A compound comprising the following general formula

(formula 1 )

wherein R¹ comprises the general formula 2a' or 2e\

- with D being a Ci to C₄ alkyl,

or the general formula 2a or 2e, wherein R¹ comprises particularly the general formula 2a or 2e,

- with each T being selected independently from each otherfrom -CH₂, -NH , -S, -O, - CHCHs, -C(CH₃)₂ or -NR^c, in particular from NH, -S or -O, with R^c being -CH₂OH, - CH₃, -CH2CH₃, -CH2CH2CH₃, -CH(CH₃)2, -CH2CF₃, -CHFCF₃, -CF2CF₃, -CHF2, -CH2F, -CF₃ and

- with T being selected from -CH₂, -NH , -S, -O, -CHCH₃, or -C(CH₃)₂ and

R² is selected from

a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C10 heteroaryl, and

and R³ is selected from

The compound according to claim 1 , - with T of the compound according to formula 2a' or 2a, particularly formula

2abeing selected from -NH, -S, -O or -N ^c, wherein in particular T is O, R⁴ and R⁵ being selected independently from each other from -H, -F, -CH₃, in particular with R⁵ and R⁶ being H,

- with T of the compound according to formula 2e' or 2e, particularly formula 2e being selected from -CH₂, -NH, -S or -O, in particular T being -NH or -O, more particularly O.

3. A compound comprising the following general formula (1 )

(formula 1 )

wherein

R¹ is selected from

- - a substituted alkyl, in particular a substituted alky, alkenyl or alkynyl, wherein the substituted alkyl, alkenyl or alkynyl comprises the formula 6a

(formula 6a) or

- a substituted or unsubstituted heterocycle, in particular a substituted or unsubstituted C₃-Ci₀ heterocycle, or

- a substituted or unsubstituted C¾- aryl, wherein the substituted C₆ aryl comprises the formula 6b

(formula 6b) with M being

an alkyl, in particular a C1-C12 alkyl, more particularly a CrC₄ alkyl, an alkenyl, in particular a Ci-Ci₂ alkenyl, more particularly a CrC₄ alkenyl, an alkynyl, in particular a Ci-Ci₂ alkynyl, more particularly a CrC₄ alkynyl, and

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I, CN, -R^e, - OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular d-C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

and

R² is selected from

a substituted or unsubstituted cycloalkyi, in particular a substituted or unsubstituted C₃-C1₀ cycloalkyi,

a substituted or unsubstituted saturated heterocycle, in particular a substituted or unsubstituted C₃-C1₀ heterocycle, or

R³ is selected from a substituted or unsubstituted cycloalkyi, in particular a substituted or unsubstituted C₃-C1₀ cycloalkyi, more particularly cyclohexane.

4. The compound according to claim 3, wherein R¹ is selected from - a substituted or unsubstituted C¾- aryl, wherein the C₆ aryl comprises the formula

6b

(formula 6b)

with M being an alkyl, in particular a C₁-C₁₂ alkyl, more particularly a CrC₄ alkyl, and

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I, CN, - ^e, - OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected

independently from each other from H, a substituted or unsubstituted C₁-C₁₂ alkyl, in particular C₁-C4 alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

5. A compound comprising the following general formula (1 )

(formula 1 )

wherein

each of R² and R³ are selected independently from each other from

a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C Ci₂ alkynyl, a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C3-C1₀ cycloalkyl,

R¹ comprises

a. the general formula 2b' to 2d' and 2f to 2j',

being a Ci to C₄ alkyl, or R¹ comprises the general formula 2b to 2d and

CHCH₃, -C(CH₃)₂ or -NR^c, in particular from NH, -S or -O, and

CH or =N,

- with R⁶ being selected from -OH, -OCH₃, -OCH₂CH₃, -CH₃ or H,

- with R⁷ being selected from =NH, =S or =0, in particular from O, and

6. The compound according to claim 5, wherein

a. R¹ comprises the general formula 2b to 2h, in particular the formula 2b, 2c, 2g or 2h, more particularly the formula 2b, 2c, 2g or 2h, particularly

b. R¹ comprises the general formula 2b or 2c, in particular 2c.

7. The compound according to any one of claims 5 to 6,

- with T of the compound according to formula 2b or 2c being selected from -NH, -

S, -O or -NR^c, wherein in particular T is S or -NH, and T" being selected from - CH or =N, and with R⁶ being selected from -CH₃ or H, in particular R⁶ is H,

- with each T of the compound according to formula 2d being selected

independently from each other from -NH, -S, -O or -NR^C, in particular at least one T is selected from NH or -NCH₃, more particularly the T in the position 4, with respect to the connection to the parent moiety, is -NH, and with R⁷ being selected from =NH, =S or =0, in particular from O, and

- with each T" of the compound according to formula 2f being selected

independently from each other from -CH or =N, in particular each T" is =N, - with T of the compound according to formula 2g or 2h being selected from -NH, -

S, -O or -NR^C, wherein in particular T is -NR^C or -NH, and T" being selected from -CH or =N, in particular T" is =N,

- with T of the compound according to formula 2i or 2j being selected from -NH or - NR^C, wherein in particular T is -NH, and T" is =N.

8. The compound according to any one of the claims 5 to 7, wherein R^c is selected from -CH₂OH, -CH₃, -CH₂CH₃, -CH₂CH₂CH₃ or -CH(CH₃)₂, in particular from -CH₃, - CH₂CH₃ or -CH(CH₃)₂, more particularly R^c is CH₃.

9. A compound comprising the following general formula (1 )

(formula 1 )

wherein

1 is selected from

- a substituted or unsubstituted C_¾- aryl, wherein the substituted C₆ aryl comprises the formula 6b

(formula 6b)

each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I , CN , -R^e, - OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -NR^e ₂, with each R^e being selected independently from each other from H, a substituted or unsubstituted C1-C12 alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1 , wherein at least one Z¹⁰ is - (CH₂)_rOR^e, in particular in position 3,

each of R² and R³ are selected independently from each other from

10. A compound comprising the following general formula (1 )

wherein

1 is selected from

each of R² and R³ are selected independently from each other from a substituted or unsubstituted alkyi, in particular a substituted or unsubstituted C1-C12 alkyi,

wherein at least one of R-i , R₂ and R₃ is selected form,

from

with M being

in case of R₂ from

- a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula -L-Ar, with L being

in case of R₃ from

with D being

1 1 . The compound according to claim 10, wherein R¹ is selected from

(formula 6a) or

with M being an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi,

an alkenyl, in particular a CrCi₂ alkenyl, more particularly a CrC₄ alkenyl, an alkynyl, in particular a CrCi₂ alkynyl, more particularly a CrC₄ alkynyl, and

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I , CN , -R^e, - OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -N R^e ₂, with each R^e being selected independently from each other from H , a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂- C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

12. The compound according any one of the claims 10 to 1 1 , wherein R¹ is selected from

- a substituted alkyi, wherein the substituted alkyi comprises the formula 6a

(formula 6a)

with M being

an alkyi, in particular a C Ci₂ alkyi, more particularly a C1-C4 alkyi, and

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ independently from any other Z¹⁰ is selected from -F, -CI, -Br, -I , CN , -R^e, - OR^e, -(CH₂)_rOR^e, -SR^e, -(CH₂)_rSR^e or -N R^e ₂, with each R^e being selected

independently from each other from H , a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

13. The compound according to any one of the claims 1 , 2 or 5 to 8, wherein n of Z¹ _n is 0, 1 or 2, in particular n is 0 or 1 .

14. The compound according to any one of the claims 1 , 2, 5 to 8 or 13 wherein

a. each Z¹ independently from any other Z¹ is selected from -F, -CI, -Br, -I , CN , - R^a, -OR^a, CH₂OR^a, with each R^a being selected independently from each other from H , a substituted or unsubstituted Ci-C₈ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl, in particular b. each Z¹ independently from any other Z¹ is selected from -F, -CI, -Br, -I , CN , CH₂OR^a or -OR^a, with each R^a being selected independently from each other from H, a substituted or unsubstituted Ci-C₈ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-C₈ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-C₈ alkynyl, in particular C₂-C₄ alkynyl, more particularly

c. each Z¹ independently from any other Z¹ is selected from -F, -CI, -Br, -I, CN , OH, CH₂OH, CH₂OR^a or -OR^a with R^a being selected from a C C₄ alkyl, C₂-C₄ alkenyl or C₂-C₄ alkenyl, in particular from a C1-C4 alkyl.

15. The compound according to any one of the claims 1 , 2, 5 to 8 or 13 to 14, wherein each Z¹ independently from any other Z¹ is selected from CN, OH, -OCH₃, -OCH₂CH₃, -0(CH₂)₂CH₃, -0(CH₂)CCH, -CH₂OCH₃, -CH₂OCH₂CH₃, -CH₂0(CH₂)₂CH₃ or - CH₂0(CH₂)CCH, in particular from CN, OH, -OCH₃ or -CH₂OCH₃, more particularly from -OCH₃ or -CH₂OCH₃.

16. The compound according to any one of the claims 3, 9 or 10 to 12, wherein

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z¹⁰ is selected independently from any other Z¹⁰ from -F, -CI, -Br, -I , CN, -R^e, - SR^e, -CH₂SR^e, -OR^e, CH₂OR^e or -NR^e ₂, in particular from -F, -CI, CN, -R^e, -OR^e, - CH₂OR^e or -NR^e ₂, more particularly from CN, -OR^e or CH₂OR^e, with each R^e being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, particularly

I of Z¹⁰i is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I , CN, -OR^e or -CH₂OR^e, in particular from R^e, with R^e being selected from a substituted or unsubstituted C Ci₂ alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, more particularly

I of Z¹⁰i is 0, 1 or 2, in particular 0 or 1.

17. The compound according to claim 9, wherein the at least one Z¹⁰ is -(CH₂)_rOR^e, in particular in position 3, with R^e being H or CH₃, with r being selected from 1 , 2, 3, in particular with r being 1

18. The compound according to claim 3, wherein R¹ is selected from.

19. The compound according to claim 9, wherein R¹ is selected from

20. The compound according to any one of the claims 1 , 2, 13 to 15, wherein R² is selected from a substituted or unsubstituted C₃-C₆ cycloalkyi, a substituted or unsubstituted C₆ aryl, or a substituted or unsubstituted C₅-C₆- heteroaryl.

21 . The compound according to any one of claim 3, 5, 9 or 10, wherein

R² is selected from

- a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted C Cio alkyl,

- a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C1-C10 alkenyl,

- a substituted or unsubstituted alkynyl, in particular a substituted or unsubstituted C1-C10 alkynyl,

- a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆- C10 aryl,

- a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C10 heteroaryl, particularly

R² is selected from

- a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted C C10 alkyl, - a substituted or unsubstituted alkenyl, in particular a substituted or unsubstituted C1-C10 alkenyl,

- a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-

C10 aryl, or

- a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C10 heteroaryl, more particualrly

R² is selected from

- a substituted or unsubstituted C1-C4 alkyi,

- a substituted or unsubstituted C1-C4 alkenyl,

- a substituted or unsubstituted C1-C4 alkynyl,

- a substituted or unsubstituted C₆ aryl, or

- a substituted or unsubstituted C₅-C₆- heteroaryl.

22. The compound according to any one of the claims 1 , 3, 5, 9 or 10, wherein R² is selected from

with L being

- an alkyi, in particular a C1-C12 alkyi, more particularly a C1-C4 alkyi, an alkenyl, in particular a C1-C12 alkenyl, more particularly a C1-C4 alkenyl,

23. The compound according to any one of the claims 1 , 3, 5, 9 or 10, wherein R² is selected from - a substituted alkyi, alkenyl or alkynyl, wherein the substituted alkyi, alkenyl or alkynyl comprises the formula 4a

(formula 4a) or

(formula 4b)

with L being

each Z² independently from any other Z² is selected from -F, -CI, -Br, -I, CN, -R^b, -OR^b, -(CH₂)_rOR^b, -SR^b, -(CH₂)_rSR^b or -NR^b ₂, with each R^b being selected independently from each other from H, a substituted or unsubstituted C1-C12 alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

24. The compound according to claim 23, wherein

- o of Z²o is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² is selected independently from any other Z² from -F, -CI, -Br, -I , CN, -R^b, - OR^b, CH₂OR^b or -NR^b ₂, in particular from -F, -CI, -R^b, -OR^b, CH₂OR^b or -NR^b ₂, more particularly from -F, -CI, -R^b, with each R^b being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyi, in particular C1-C4 alkyi, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl; in particular - o of Z²o is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z² is selected independently from any other Z² from -F, -CI, -Br, -I or -R^b, in particular from R^b, with R^b being selected from a substituted or unsubstituted C Ci2 alkyl, in particular CrC₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, more particularly

25. The compound according any one of the claims 1 , 5, 9 or 10, wherein

- R³ is selected from

- a substituted or unsubstituted alkyl, in particular a substituted or unsubstituted C1-C10 alkyl,

- a substituted or unsubstituted cycloalkyl, in particular a substituted or unsubstituted C3-C10 cycloalkyl,

- a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Cio aryl,

- a substituted or unsubstituted heteroaryl, in particular a substituted or unsubstituted C5-C10 heteroaryl, in particular

- R³ is selected from

- a substituted or unsubstituted aryl, in particular a substituted or unsubstituted C₆-Cio aryl, or

26. The compound according any one of the claims 1 or 9, wherein R³ is selected from a substituted or unsubstituted Ci-C₄ alkyl, a substituted or unsubstituted C C₄ alkenyl, a substituted or unsubstituted C C₄ alkynyl, a substituted or unsubstituted C₆ aryl, a substituted or unsubstituted C₆-cycloalkyl; or a substituted or unsubstituted C₅-C₆- heteroaryl, in particular a substituted or unsubstituted C₆-cycloalkyl or a substituted or unsubstituted C₅-C₆- heteroaryl.

27. The compound according to any one of the claims 5 or 10, wherein R³ is selected from a substituted or unsubstituted C C₄ alkyl, a substituted or unsubstituted C C₄ alkenyl, a substituted or unsubstituted C C₄ alkynyl, a substituted or unsubstituted C₆ aryl, a substituted or unsubstituted C₆-cycloalkyl or a substituted or unsubstituted C₅-C₆- heteroaryl, in particular a substituted or unsubstituted C₆-cycloalkyl or a substituted or unsubstituted C₅-C₆- heteroaryl.

28. The compound according to any one of the claims 1 , 5, 9, 10, wherein R³ is selected a substituted or unsubstituted C₃-Ci₀-cycloalkyl, particularly a substituted or unsubstituted C₆-cycloalkyl, more particularly cyclohexane.

29. The compound according to any one of the claims 1 , 5, 9, or 10, wherein R³ is selected from

with D being

an alkyl, in particular a C1-C12 alkyl, more particularly a C C₄ alkyl, an alkenyl, in particular a C1-C12 alkenyl, more particularly a C C₄ alkenyl,

an alkynyl, in particular a C1-C12 alkynyl, more particularly a C C₄ alkynyl, and

30. The compound according to any one of the claims 1 , 5, 9, or 10, wherein R³ is selected from

- a substituted alkyl, alkenyl or alkynyl, wherein the substituted alkyl, alkenyl or alkynyl comprises the formula 5a

(formula 5a) or

(formula 5b), in particular the formula 5b,

with D being

p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and

each Z³ independently from any other Z³ is selected from -F, -CI, -Br, -I, CN, -R^d, -OR^d, -(CH₂)_rOR^d -SR^d, -(CH₂)_rSR^d or -NR^d ₂, with each R^d being selected independently from each other from H, a substituted or unsubstituted C₁-C₁₂ alkyl, in particular C C₄ alkyl, a substituted or unsubstituted C₂-C₁₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, with r being 1 , 2, 3 or 4, in particular r is 1.

e compound according to 30, wherein

- p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I, CN, -R^d, - OR^d, CH₂OR^d or -NR^d ₂, in particular from -F, -CI, -R^d, -OR^d, CH₂OR^d or -NR^d ₂, more particularly from -F, -CI, -R^d, with each R^d being selected independently from each other from H, a substituted or unsubstituted C Ci₂ alkyl, in particular d-C₄ alkyl, a substituted or unsubstituted C₂-Ci₂ alkenyl, in particular C₂-C₄ alkenyl, or a substituted or unsubstituted C₂-Ci₂ alkynyl, in particular C₂-C₄ alkynyl, in particular

- p of Z³ _P is 0, 1 , 2, 3, 4 or 5, in particular 0, 1 , 2 or 3, more particularly 0 or 1 , and each Z³ is selected independently from any other Z³ from -F, -CI, -Br, -I or -R^d, in particular from R^d, with R^d being selected from a substituted or unsubstituted C Ci2 alkyl, in particular C1-C4 alkyl, a substituted or unsubstituted C2-C12 alkenyl, in particular C₂-C₄ alkenyl or a substituted or unsubstituted C2-C12 alkynyl, in particular C₂-C₄ alkynyl, more particularly

32. The compound according to any of the previous claims, wherein the compound comprises a (2Z,5Z), (2Z,5E), (2E,5Z) or (2E,5E) isomer form, in particular a (2Z,5Z) or (2Z,5E), more particularly a (2Z,5Z) isomer form, or mixtures of the before mentioned isomer forms, characterized by formula 1 a

(formula 1 a)

with the isomer center being indicated by the asterix (^*), with R¹, R² and R³ having the same meaning as defined previously.

33. The compound according to any of the previous claims for use as a medicament.

34. The compound according to any of the previous claims for use for use in the treatment of psychiatric or neurological disorders and inflammation, in particular neuroinflammation.

35. The compound according to any of the previous claims for use as an endocannabinoid system modulator, in particular for use as an AEA uptake Inhibitor.

36. The compound according to any of the previous claims for use for use as an AEA uptake Inhibitor.