Phenoxy(hetero)aryl ethers with antiproliferative activity

Abstract

To provide a composition comprising novel aromatic molecules that can be used in the treatment of pathological conditions such as cancer, skin diseases, muscle disorders, and immune system-related disorders, including disorders of the hematopoietic system involving the vascular system, in human and veterinary medicine.SOLUTION: Provided is a pharmaceutical composition comprising a compound represented by general formula (I), or a salt or solvate thereof. Specific examples of the compound represented by general formula (I) include, for example, the following compound.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to novel compounds and their use as therapeutic agents in human and veterinary medicine. The compounds of the present invention can be used for the treatment of pathological conditions including cancer, skin disorders, muscle disorders, lung disorders, hematopoietic disorders including blood systems, and immune system-related disorders.

Background Art

[0002] The present invention targets novel molecules that exhibit significant biological activity against cells derived from humans and animals. These compounds have been found to affect the growth and survival of cancer cells and primary non-cancer cells. In particular, molecules have been identified that can completely or partially inhibit cell proliferation or cause cell death.

[0003] That is, the present invention relates to compounds defined herein that are characterized by anti-proliferative activity and can be used for the treatment of benign and malignant hyperproliferative disorders in human and veterinary medicine. In particular, the present invention relates to immune system-related disorders, skin and mucosal malignant and non-malignant disorders in human and veterinary medicine, such as keratinization disorders, muscle hyperplasia and muscle hypertrophy, muscle malignant and non-malignant disorders including muscle hyperproliferative disorders, neuroendocrine system disorders, non-melanoma skin cancers including squamous cell carcinoma and basal cell carcinoma, skin and mucosal hyperproliferative disorders such as actinic keratosis, cancer and precancerous lesions, oral and tongue hyperproliferative disorders and cancer, neuroendocrine system hyperproliferative disorders and cancer such as medullary thyroid cancer, hematopoietic system hyperproliferative disorders and cancer including blood systems such as leukemia and lymphoma, and the treatment of hyperproliferative disorders and cancer of the urogenital system including the lung, breast, stomach, such as cervical cancer and ovarian cancer. The present invention relates to the compounds defined herein.

Summary of the Invention

[0004] The compounds of the present invention relate to bisallyl ethers composed of two six-membered aromatic rings, where one of the aromatic rings is an unsubstituted or substituted benzyl ring and the other aromatic ring is an unsubstituted or substituted aryl ring, which optionally contains an N-atom, i.e., optionally a six-membered heteroaromatic ring. All such bisallyl ether structures share the common feature of containing substituents at both para positions of the ether bond, where such substituents on the benzene ring, which cannot be a heteroaromatic ring, are preferably non-polar residues and / or sterically undemanding groups. and wherein such substituents on the aryl ring, which may optionally be a heteroaromatic ring, are preferably selected from structural units containing a large amount of heteroatoms.

[0005] A first aspect of the present invention relates to compounds of general formula (I) and salts and solvates thereof:

[0006] [ka]

[0007] (In the formula, R 1 is C1-C 12 Preferably C4-C 12 Alkyl, C2-C 12 Preferably C4-C 12 Alkenyl, C2-C 12 Preferably C4-C 12 Alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, C5-C 12 Bicycloalkyl, C7 -C 12 Bicycloalkenyl, C8-C 14 Tricycloalkyl, -OC1-C 12 Preferably -OC3-C 12 Alkyl, -OC2-C 12 Preferably -OC3-C 12 Alkenyl, -OC2-C 12 Preferably -OC3-C 12 Alkynyl, -OC3-C8 cycloalkyl, -OC5-C8 cycloalkenyl, -OC5-C12 Bicycloalkyl, -OC7-C 12 Bicycloalkenyl, -OC8-C 14 Tricycloalkyl, -SC1-C 12 Preferably -SC3-C 12 Alkyl, -SC2-C 12 Preferably -SC3-C 12 Alkenyl, -SC2-C 12 Preferably -SC3-C 12 Alkynyl, -SC3-C8 cycloalkyl, -SC5-C8 cycloalkenyl, -SC5-C 12 Bicycloalkyl, -SC7-C 12 Bicycloalkenyl, -SC8-C 14 Tricycloalkyl, -NHR 9 Or -NR 9 R 10 (Wherein R 9 And R 10 Are each independently C1-C 12 Preferably C3-C 12 Alkyl, C2-C 12 Preferably C3-C 12 Alkenyl, C2-C 12 Preferably C3-C 12 Alkynyl, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, C5-C 12 Bicycloalkyl, C7-C 12 Bicycloalkenyl, C8-C 14 Selected from tricycloalkyl, or R 9 Is R 10 And can form a ring structure together; wherein the ring structure containing an N atom is selected from a 3- to 8-membered cyclic structure or a 5- to 12-membered bicyclic structure, and wherein all said ring structures can further contain one or more heteroatoms independently selected from O, S and N in place of the carbon atoms contained in the ring structure, in particular here such substitution results in a residue containing at least twice as many C atoms as a heteroatom independently selected from O, S and N); Here, R 1 、R 9 And R 10All alkyl, alkenyl, and alkynyl residues included in the definition are linear or branched and unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH2, -NO2, =O, C3-C8 cycloalkyl, C5-C8 cycloalkenyl, C5-C 12 bicycloalkyl, C7-C 12 bicycloalkenyl, C8-C 14 tricycloalkyl, -OC1-C5 alkyl such as linear or branched -OCH3, -OC3-C5 cycloalkyl such as -O(cyclopropyl), linear or branched -NH(C1-C5 alkyl), linear or branched -N(C1-C5 alkyl)(C1-C5 alkyl), -NH(C3-C5 cycloalkyl) such as -NH(cyclopropyl), -N(C3-C5 cycloalkyl)(C3-C5 cycloalkyl), linear or branched -N(C1-C5 alkyl)(C3-C5 cycloalkyl); wherein, R 1 , R 9 and R 10 If one or more substituents in which the alkyl, alkenyl, and alkynyl residues included in the definition of are =O, such substitution with =O cannot be one of the groups selected from C=O, S=O, and N=O directly bonded to the aromatic ring; wherein, R 1 , R 9 and R 10All cyclic, bicyclic, and tricyclic structures containing cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, and tricycloalkyl residues included in the definition of are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH2, -NO2, =O, C1-C5 alkyl such as linear or branched -CH3, -OC1-C5 alkyl such as linear or branched -OCH3, linear or branched -NH(C1-C5 alkyl), linear or branched -N(C1-C5 alkyl)(C1-C5 alkyl), -NH(C3-C5 cycloalkyl) such as -NH(cyclopropyl), -N(C3-C5 cycloalkyl)(C3-C5 cycloalkyl), linear or branched -N(C1-C5 alkyl)(C3-C5 cycloalkyl); where R 1 、R 9 and R 10 All alkyl, alkenyl, and alkynyl residues included in the definition of may contain one or more heteroatoms independently selected from O, S, and N in place of carbon atoms, and where such substitution results in a residue containing at least twice the number of C atoms as heteroatoms independently selected from O, S, and N, and where such substitution cannot be one of the groups selected from C=O, S=O, and N=O directly bonded to an aromatic ring; selected from; where R 1 、R 9 and R 10 All cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, and tricycloalkyl residues included in the definition of may contain one or more heteroatoms independently selected from O, S, and N in place of carbon atoms, and where such substitution results in a residue containing at least the same number of C atoms as heteroatoms independently selected from O, S, and N; where R 1 、R 9 and R 10All alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues included in the definition may be partially or fully halogenated, in particular fluorinated, more particularly perfluorinated; wherein the bicyclic and tricyclic residues include fused, bridged and spiro systems; and wherein R 1is preferably methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, iso-propyl, sec-butyl, tert-butyl, tert-pentyl, tert-octyl, 3-pentyl, -CF3, -CF2CF3, -(CF2)2CF3, -CH(CF3)2, -CH2SCH3, -CH2CH2SCH3, -CH2SCH2CH3, -CH2CH2SCH2CH3, methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, propoxymethyl, dimethyl-aminomethyl, dimethyl-aminoethyl, diethyl-aminomethyl, ethyl-methyl-aminomethyl, cyclopropyl, methyl-cyclopropyl, ethyl-cyclopropyl, trifluoromethyl-cyclopropyl, perfluoroethyl-cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl, bicycloheptyl preferably norbornyl, bicyclooctyl, bicyclooctenyl, bicyclononyl, methylbicyclononyl, adamantyl, tricyclodecyl, oxiranyl, oxetanyl, tetrahydrofuranyl, methyltetrahydrofuranyl, trimethyltetrahydrofuranyl, tetrahydropyranyl, aziridinyl, N-methylaziridinyl, azetidinyl, N-methylazetidinyl, difluoroazetidinyl, pyrrolidinyl, N-methylpyrrolidinyl, piperidinyl, N-methylpiperidinyl, difluoropiperidinyl, thianyl, thietanyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, dioxanyl, piperazinyl, dimethylpiperazinyl, dithianly, morpholinyl, N-methylmorpholinyl, thiomorpholinyl, N-methylthiomorpholinyl, oxa-azaspiroheptyl, N-methyloxo-azaspiroheptyl, azaspiroheptyl, N-methylazaspiroheptyl, thia-azaspiroheptyl, N-methylthia-azaspiroheptyl, difluorothia-azaspiroheptyl, azaspirooctyl, N-methylazaspirooctyl, oxa-azaspirooctyl, N-methyloxo-azaspirooctyl, oxa-azaspirononyl, N-methyloxo-azaspirononyl, azaspirononyl, N-methylazaspirononyl, oxa-azaspirodecyl,N-Methyloxo-azaspirodecyl, azaspirodecyl, N-methylazaspirodecyl, dihydro-oxazinyl, N-methyldihydro-oxazinyl, oxazolidinyl, N-methyloxazolidinyl, dioxolanyl, imidazolidinyl, N-methylimidazolidinyl, N,N-dimethylimidazolidinyl, azepanyl, N-methylazepanyl, azaspirohexyl, N-methylazaspirohexyl, oxa-azaspirodecyl, N-methyloxa-azaspirodecyl, azaspirodecyl, N-methylazaspirodecyl, oxa-azabicyclooctyl, N-methyloxa-azabicyclooctyl, azabicyclooctyl, N-methylazabicyclooctyl, azabicycloheptyl, N-methylazabicycloheptyl, azabicyclononyl, N-methylazabicyclononyl, azadamantyl, -O(adamantyl), oxa-azabicyclononyl, N-methyloxa-azabicyclononyl, oxa-azabicycloheptyl, N-methyloxa-azabicycloheptyl, diazabicyclooctyl, N-methyldiazabicyclooctyl, N,N-dimethyldiazabicyclooctyl, diazabicycloheptyl, N-methyldiazabicycloheptyl, N,N-dimethyldiazabicycloheptyl; 4-oxocyclohexyl; 3-oxocyclo, pentyl; 2-oxocyclobutyl, 4-oxobicyclo[4.1.0]heptan-1-yl selected from; and wherein R 1 is more preferably C4-C 12 alkyl, C4-C 12 alkenyl, C4-C 12 alkynyl, cyclic, bicyclic and tricyclic residues selected from, wherein the alkyl, alkenyl and alkynyl residues are preferably branched and include the following;

[0008]

Chemical formula

[0009] R 2 -R 5are each independently selected from -H, -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH2, -NO2, linear or branched C1-C4 alkyl, linear or branched C2-C4 alkenyl, linear or branched C2-C4 alkynyl, C3-C6 cycloalkyl, -CH2(C3-C6 cycloalkyl), linear or branched -OC1-C3 alkyl, -O(cyclopropyl), linear or branched -NH(C1-C3 alkyl), linear or branched -N(C1-C3 alkyl)(C1-C3 alkyl), -NH(cyclopropyl), -N(cyclopropyl)2, linear or branched -N(C1-C3 alkyl)(cyclopropyl); wherein R 2 -R 5 all alkyl, alkenyl, alkynyl and cycloalkyl residues included in the definition of are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CH3, -CF3, -OH and -OCH3, -OCF3, -NH2, -NHCH3, -N(CH3)2; wherein R 2 -R 5 all alkyl, alkenyl, alkynyl and cycloalkyl residues included in the definition of may contain one or more heteroatoms independently selected from O, S and N in place of carbon atoms, and wherein such substitution cannot be one of the groups selected from C=O and S=O directly bonded to the aromatic ring; wherein R 2 -R 3 are each preferably -H, R 4 is preferably -H or -F, R 5 is preferably -H, -F, -Cl, -Br, -CH3, -CF3, -CH=CH2, -C≡CH, -CH2OH, -CH2NHCH3, -OH, -OCH3, -OCF3, cyclopropyl, oxiranyl, -CH2-N-morpholinyl, -C(CH3)3, -CH2OCH3, -NO2, -CN, -NH2, -N(CH3)2, -OCH(CH3)2, -CH2NH2, -CH2N(CH3)2; Here, the substituent R as defined by the general formula (I) 1 from R 5 to which the 6-membered aromatic ring to which it is attached is preferably selected from the following;

[0010] [Chemical formula]

[0011] X 1 -X 4 are each independently N, CR 11 , CR 12 , CR 13 , CR 14 selected from; R 11 -R 14 are each independently -H, -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH2, -NO2, linear or branched C1-C4 alkyl, linear or branched C2-C4 alkenyl, linear or branched C2-C4 alkynyl, C3-C6 cycloalkyl, -CH2(C3-C6 cycloalkyl), linear or branched -OC1-C3 alkyl, -O(cyclopropyl), linear or branched -NH(C1-C3 alkyl), linear or branched -N(C1-C3 alkyl)(C1-C3 alkyl), -NH(cyclopropyl), -N(cyclopropyl)2, linear or branched -N(C1-C3 alkyl)(cyclopropyl) selected from; Here, all alkyl, alkenyl, alkynyl and cycloalkyl residues included in the definition of R 11 -R 14 are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CH3, -CF3, -OH and -OCH3, -OCF3, -NH2, -NHCH3, -N(CH3)2; Here, R 11 -R 14All alkyl, alkenyl, alkynyl and cycloalkyl residues included in the definition may contain one or more heteroatoms independently selected from O, S and N in place of carbon atoms, and here, such substitution cannot be one of the groups selected from C=O and S=O directly bonded to the aromatic ring; where R 11 -R 14 is preferably selected from -H, -F, -Cl, -Br, -CH3, -CF3, -OH, -OCH3, -OCF3, cyclopropyl, oxiranyl, -C(CH3)3, -N(CH3)2, -NH2, -CN, -CH2OCH3, -OCH(CH3)2, -CH2NH2, -CH2N(CH3)2, -CH2OH, -NO2, -CH2-N-morpholinyl; where X defined by the general formula (I) 1 -X 4 The 6-membered aromatic ring containing is preferably selected from the following;

[0012]

Chemical formula

[0013] R 6 and R 7 are independently selected from -H, -F, -CH3; or R 6 and R 7 together form a cyclic residue containing the carbon atom to which they are attached, and here, the cyclic residue is C3 cycloalkyl; R 8 is selected from -H, C1-C3 alkyl preferably -CH3, C2-C3 alkenyl, C2-C alkynyl, -F, -CF3 and aromatic and heteroaromatic residues preferably 6-membered aromatic rings and 5- to 6-membered heteroaromatic rings; where 8 The said aromatic and heteroaromatic residues included in the definition of R 8 can optionally be bonded to the carbon atom to which R where R 8All aromatic and heteroaromatic residues included in the definition of are substituted with one or more substituents independently selected from unsubstituted or -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH2, linear or branched C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, cyclopropyl, linear or branched -OC1-C3 alkyl such as -OCH3, -O(cyclopropyl), linear or branched -NH(C1-C3 alkyl), linear or branched -N(C1-C3 alkyl)(C1-C3 alkyl), -NH(cyclopropyl), -N(cyclopropyl)2, linear or branched -N(C1-C3 alkyl)(cyclopropyl); Here, R 8 All heteroaromatic residues included in the definition of can contain one or more heteroatoms independently selected from O, S and N instead of carbon atoms; Here, R 8 All alkyl, alkenyl, alkynyl residues included in the definition of are linear or branched and are substituted with one or more substituents independently selected from unsubstituted or -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH and -NH2; Here, R 8 is preferably -H, -F, -CH3, -CH2CH3 -CF3, -C6H5; Here, R 2 -R 8 and R 11 -R 14 All alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl, aromatic and heteroaromatic residues included in the definition of can be partially or completely halogenated, particularly fluorinated, more particularly perfluorinated; Z 1 and Z 2 are selected from the following groups:

[0014]

Chemical formula

[0015] Here, Z 1 is selected from -H, linear or branched C1-C3 alkyl, preferably -CH3, cyclopropyl, oxiranyl, N-methyl-aziridinyl, thiiranyl, -N3, -CF3, -CF2CF3, and here, Z 2 is independently selected from linear or branched C1-C3 alkyl, preferably -CH3, -CF3, -CF2CF3, -OS(O)2CH3, -OS(O)2CF3, -OS(O)2C6H4CH3, -CN, and -OR 15 (general formula Ia), where R 15 is -H, C1-C8, preferably C1-C4 alkyl, C2-C8, preferably C2-C4 alkenyl, C2-C8, preferably C2-C4 alkynyl, C3-C6 cycloalkyl, C5-C6 cycloalkenyl, C5-C 12 bicycloalkyl, C7-C 12 bicycloalkenyl, C8-C 14 tricycloalkyl, and aromatic and heteroaromatic residues, preferably selected from 5- to 6-membered aromatic rings and 5- to 6-membered heteroaromatic rings; Here, the bicyclic and tricyclic residues include fused, bridged, and spiro systems; Here, R 15 The cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl, aromatic, and heteroaromatic residues included in the definition of can be optionally bonded to the O to which R 15 is bonded via a C1 alkylene or C2 alkylene or C3 alkylene linker; Here, R 15All aromatic and heteroaromatic residues included in the definition of are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH2, -NO2, linear or branched C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, cyclopropyl, linear or branched -OC1-C3 alkyl such as -OCH3, -O(cyclopropyl), linear or branched -NH(C1-C3 alkyl), linear or branched -N(C1-C3 alkyl)(C1-C3 alkyl), -NH(cyclopropyl), -N(cyclopropyl)2, linear or branched -N(C1-C3 alkyl)(cyclopropyl); where R 15 All alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues, as well as alkylene linkers, included in the definition of are linear or branched and are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH2, -NO2, linear or branched C1-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, cyclopropyl, linear or branched -OC1-C3 alkyl such as -OCH3, -O(cyclopropyl), linear or branched -NH(C1-C3 alkyl), linear or branched -N(C1-C3 alkyl)(C1-C3 alkyl), -NH(cyclopropyl), -N(cyclopropyl)2, linear or branched -N(C1-C3 alkyl)(cyclopropyl); where R 15 All alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl and heteroaromatic residues, as well as alkylene linkers, included in the definition of can contain one or more heteroatoms independently selected from O, S and N in place of carbon atoms; where R 15All alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl and heteroaromatic residues, as well as alkylene linkers, included in the definition of may be partially or fully halogenated, in particular fluorinated, more in particular perfluorinated; where R 15 is preferably —H, —CH3, —CH2CH3, n-propyl, isopropyl, cyclopropyl, benzyl; where Z 1 is preferably —H, —CH 3 , —CF 3 and cyclopropyl; and / or where Z 2 is preferably —OH, —OS(O)2CH3, —OS(O)2CF3, —OS(O)2-C6H4-Me and —CN; for example:

[0016] [ka]

[0017] Or here, Z 1 and Z 2 Together, =O, =S, =NR 16 or zwitterionic = N [+] R 17 O [-] (general formula Ib); where R 16 -H, -O H, —OCH3, —CN, —S(O)CH3, —S(O)CF3, —S(O)C(CH3)3, —S(O)2CH3, —S(O)2CF3, linear or branched C1-C3 alkyl preferably selected from —CH3, cyclopropyl, —CF3, —CF2CF3, —CH2CF3, —C6H5 and —CH2C6H5; where R 17 is selected from linear or branched C1-C3 alkyl, preferably —CH3, cyclopropyl, —C6H5 and —CH2C6H5; where Z 1 and Z 2 are preferably =O, =NR 16 or zwitterionic = N[+] R 17 O [-] is; where R 16 is preferably -H, -OH, -O CH3, -CH3, cyclopropyl and -CH2C6H5; where R 17 is preferably -CH3, -C(CH3)3 and -CH2C6H5;

[0018]

Chemical formula

[0019] or where Z 1 and Z 2 together form a cyclic residue containing the carbon atom to which they are attached (general formula Ic); where the cyclic residue is selected from 3-membered, 4-membered, 5-membered and 6-membered rings, where all rings can optionally contain one or more heteroatoms independently selected from O, S and N in place of carbon atoms; where all rings are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, =O, -CH3 and -CF3; where Z 1 and Z 2 together preferably form a 3-membered or 4-membered or 5-membered cyclic residue containing the carbon atom to which they are attached; where the cyclic residue is preferably selected from cyclopropyl, cyclobutyl, oxiranyl, oxetanyl, aziridinyl, azetidinyl, thietanyl, thiazolidinyl, methylthiazolidinyl, thiazolidine-dionyl, methylthiazolidine-dionyl and oxazolidinyl, methyloxazolidinyl, oxazolidine-dionyl and methyloxazolidine-dionyl; and where the cyclic residue is optionally preferably substituted with -F, -OH, -OCH3, -NH2, -NHCH3, -N(CH3)2, =O, -CH3 and -CF3;

[0020] [Chemistry]

[0021] Here, Z 1 and Z 2 All alkyl and cyclic residues included in the definitions of may be partially or fully halogenated, particularly fluorinated, more particularly perfluorinated)

Mode for Carrying Out the Invention

[0022] R 1 -R 17 、X 1 -X 4 、Z 1 and Z 2 The following preferred definitions of, and, may optionally be applied independently and / or in combination to all aspects including the preferred and a certain aspect, all embodiments including the preferred and a certain embodiment, and all sub-genera as defined in the present invention. 1) R 1 preferably contains 4 or more, preferably 6 or more, even more preferably 7 or more carbon atoms; 2) R 1 is preferably selected from branched alkyl, alkenyl and alkynyl residues; 3) R 1 is preferably selected from cyclic, bicyclic and tricyclic structures, where bicyclic and tricyclic residues include fused, bridged and spiro systems; 4) R 1 preferably contains no heteroatoms; 5) R 1 is preferably selected from cyclohexyl, norbornyl, bicyclooctyl, bicyclononyl, methylbicyclononyl, tricyclodecyl, most preferably adamantyl, such as 1-adamantyl and 2-adamantyl; 6) R 1 preferably contains one or more heteroatoms independently selected from O, S and N, preferably 1, 2 or 3 heteroatoms, instead of the carbon atoms contained in R 1 7) R 1is preferably selected from tetrahydropyranyl, N - methylpiperidinyl, morpholinyl, 4 - oxocyclohexyl, azabicycloheptyl, N - methylazabicycloheptyl, oxa - azabicycloheptyl, N - methyldiazabicycloheptyl, azabicyclooctyl, diazabicyclooctyl, N - methyldiazabicyclooctyl, oxa - azabicyclooctyl, azabicyclononyl, azadamantyl and - O(adamantyl); 8)R 2 -R 5 Preferably two, more preferably three substituents independently selected from are - H, i.e., R 2 -R 5 Preferably two, more preferably one substituent independently selected from is different from - H; 9)R 2 -R 5 When two of the substituents independently selected from are different from - H and are in the ortho position to the ether bond, these two substituents are preferably different from - F, - Cl, - Br, - I and - NO2 and more preferably different from each other; 10)X 1 -X 4 The ring - atom composition defined by is preferably that all of X 1 -X 4 are selected independently from CR 11 、CR 12 、CR 13 、CR 14 or one of X 1 -X 4 is N and the other three are selected independently from CR 11 、CR 12 、CR 13 、CR 14 or two of X 1 -X 4 are N and the other two are selected independently from CR 11 、CR 12 、CR 13 、CR 14 selected from the cases where; that is, the aromatic ring or hetero - aromatic ring is selected from benzene, pyridine, pyrimidine, pyridazine and pyrazine; 11) R 11 -R 14 Two, preferably, or more preferably three substituents independently selected from are -H, i.e., R 11 -R 14 One, preferably, and more preferably one substituent independently selected from is different from -H; 12) R 11 -R 14 When two of the substituents independently selected from are different from -H and are in the ortho position to the ether bond, these two substituents are preferably different from -F, -Cl, -Br, -I, and -NO2, and more preferably different from each other; 13) R 6 , R 7 and R 8 are preferably each -F; 14) R 6 and R 7 preferably form a cyclic residue containing the carbon atom to which they are attached, where the cyclic residue is cyclopropyl.

[0023] A preferred aspect of the present invention relates to compounds of general formula (I) and their salts and solvates, where R 6 , R 7 and R 8 are each -F, and R 1 -R 5 , R 9 -R 17 , X 1 -X 4 , Z 1 and Z 2 are as defined in general formula (I), including substituents and preferred definitions.

[0024] An even more preferred aspect of the present invention relates to compounds of general formula (Ia) and their salts and solvates, where R 6 , R 7 and R 8 are each -F or each is -H, and where Z 2 is -OH or -OS(O)2CH3, and R 1 -R 5 、R 9 -R 14 、X 1 -X 4 and Z 1 are as defined in general formula (I), including substituents and preferred definitions.

[0025] A further preferred aspect of the present invention relates to compounds of general formula (Ia) and their salts and solvates, wherein R 6 and R 7 together form a cyclic residue containing the carbon atom to which they are attached, and wherein the cyclic residue is cyclopropyl, and wherein R 8 is -H, and wherein Z 1 is selected from -H, -CH3 and -CF3, and wherein Z 2 is -OH or -OS(O)2CH3, and R 1 -R 5 、R 9 -R 14 and X 1 -X 4 are as defined in general formula (I), including substituents and preferred definitions.

[0026] A further preferred aspect of the present invention relates to compounds of general formula (I) and their salts and solvates, wherein R 1 is selected from residues containing 4 or more, preferably 6 or more, more preferably 7 or more carbon atoms as included in the general definition of R 1 、 and wherein R 1 contains no heteroatoms, and wherein R 1 is more preferably selected from cyclic, bicyclic and tricyclic structures, and wherein R 1is more preferably selected from cyclohexyl, norbornyl, bicyclooctyl, bicyclononyl, methylbicyclononyl, tricyclodecyl and adamantyl, and wherein R 1 is most preferably adamantyl, and R 2 -R 8 、R 11 -R 17 、X 1 -X 4 、Z 1 and Z 2 are as defined in general formula (I), including substituents and preferred definitions.

[0027] A more preferred aspect of the present invention relates to compounds of general formula (I) and their salts and solvates, wherein R 1 is selected from residues containing four or more, preferably six or more, more preferably seven or more carbon atoms, which are included in the general definition of R 1 , and wherein R 1 is selected from one or more, preferably one to two heteroatoms independently selected from O, S and N in place of the carbon atoms contained in R 1 , and wherein R 1 is more preferably selected from cyclic, bicyclic and tricyclic structures, or wherein R 1 is selected from residues having cyclic, bicyclic and tricyclic structures, and wherein R 1 is more preferably selected from tetrahydropyranyl, N-methylpiperidinyl, morpholinyl, 4-oxocyclohexyl, azabicycloheptyl, N-methylazabicycloheptyl, oxa-azabicycloheptyl, N-methyldiazabicycloheptyl, azabicyclooctyl, diazabicyclooctyl, N-methyldiazabicyclooctyl, oxa-azabicyclooctyl, azabicyclononyl, aza-adamantyl and O-(adamantyl), and wherein R 1is most preferably tetrahydropyranyl, N-methylpiperidinyl, morpholinyl, 4-oxocyclohexyl, azabicyclooctyl, azaadamantyl, and O-(adamantyl), and and R 2 -R 17 and X 1 -X 4 and Z 1 and Z 2 are as defined in general formula (I), including substituents and preferred definitions.

[0028] In one aspect, the present invention relates to compounds of general formula (I) and salts and solvates thereof, wherein R 1 is adamantyl, and where Z 1 and Z 2 are as defined in general formula (I) including general formulas (Ia), (Ib), and (Ic), including substituents and preferred definitions, and where R 15 is as defined in general formula (Ia), including substituents and preferred definitions, and where R 16 and R 17 are as defined in general formula (Ib), including substituents and preferred definitions, and where R 2 -R 8 and R[[ID=4_{3}]] 11 -R 14 and X 1 -X 4 are as defined in general formula (I), including substituents and preferred definitions, and where the compound shares the following structure (I-1)

[0029]

Chemical formula

[0030] And here, the compounds of structure (I-1) are for use in human and veterinary medicine, in particular the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapies and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and cancers of the hematopoietic and blood systems such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovary, and cancers of the neuroendocrine system. Examples include compounds XPF-0014, XPF-0042, XPF-0070, XPF-0182, XPF-0210, XPF-0266, XPF-0434, XPF-0476, XPF-0504, XPF-0518, XPF-0630, XPF-1162, XPF-1190, XPF-1330, XPF-1554, XPF-1596, XPF-1624, XPF-2242, XPF-2244, XPF-2245, XPF-2247, XPF-2251, XPF-2252, XPF-2253 and XPF-2254.

[0031] In a further aspect, the present invention relates to compounds of general formula (I) and their salts and solvates, and here, R 1 is as defined in general formula (I), including substituents and preferred definitions, where R 1 is selected from cyclic, bicyclic and tricyclic structures, and here, R 1 optionally contains six or more carbon atoms and is independently substituted with heteroatoms selected from O, S and N as defined in general formula (I). Here, R 6 is as defined in general formula (I), including substituents and preferred definitions, where R 6 is different from -H, and further provided that optionally R 6 is different from -CH3. And here, Z 1 and Z 2 are as defined in general formula (I) including general formula (Ia), general formula (Ib) and general formula (Ic), including substituents and preferred definitions. and here, R 15 is as defined in general formula (Ia), including substituents and preferred definitions, and here, R 16 and R 17 are as defined in general formula (Ib), including substituents and preferred definitions, and here, R 2 -R 5 、R 7 -R 14 and X 1 -X 4 are as defined in general formula (I), including substituents and preferred definitions, and here, the compound shares the following structure (I-2)

[0032]

Chemical formula

[0033] and here, the compound of structure (I-2) is preferably used in human and veterinary medicine, particularly in the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapy and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and cancers of the hematopoietic and blood systems such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovary, and neuroendocrine system, without further provisos in particular. Examples include the compounds XPF-0042, XPF-0062, XPF-0063, XPF-0064, XPF-0065, XPF-0070, XPF-0202, XPF-0205, XPF-0210, XPF-0230, XPF-0426, XPF-0429, XPF-0434, XPF-0454, XPF-0469, XPF-0476, XPF-0496, XPF-0504, XPF-0518, XPF-0630, XPF-1162, XPF-1182, XPF-1185, XPF-1190, XPF-1196, XPF-1322, XPF-1325, XPF-1330, XPF-1546, XPF-1549, XPF-1554, XPF-1588, XPF-1596, XPF-1602, XPF-1616, XPF-1624, XPF-2241, XPF-2242, XPF-2243, XPF-2244, XPF-2245, XPF-2246, XPF-2247, XPF-2248, XPF-2249, XPF-2250, XPF-2251, XPF-2252, XPF-2253 and XPF-2254.

[0034] In a further aspect, the present invention relates to compounds of general formula (I) and salts and solvates thereof, and wherein R 1 is as defined in general formula (I), including substituents and preferred definitions, wherein R 1 is selected from cyclic, bicyclic and tricyclic structures, and wherein R 1 optionally contains six or more carbon atoms and is independently substituted with heteroatoms selected from O, S and N as defined in general formula (I). Here, R 8 is as defined in general formula (I), including substituents and preferred definitions, wherein R 8 is different from -H, and further provided that optionally R 8 is different from -CH3. And here, Z 1 and Z 2 are as defined in general formula (I) including general formulas (Ia), (Ib) and (Ic), including substituents and preferred definitions. and here, R 15 is as defined in general formula (Ia), including substituents and preferred definitions, and here, R 16 and R 17 is as defined in general formula (Ib), including substituents and preferred definitions, and here, R 2 -R 7 , R 9 -R 14 and X 1 -X 4 is as defined in general formula (I), including substituents and preferred definitions, and here, the compound shares the following structure (I-3)

[0035]

Chemical formula

[0036] and here, the compound of structure (I-3) is preferably used - especially without further provisos - in human and veterinary medicine, especially in the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapy and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and hematopoietic and blood cancers such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovary, and neuroendocrine system. Examples include compounds XPF-0062, XPF-0063, XPF-0064, XPF-0065, XPF-0070, XPF-0202, XPF-0205, XPF-0210, XPF-0230, XPF-0426, XPF-0429, XPF-0434, XPF-0454, XPF-0469, XPF-0476, XPF-0496, XPF-0504, XPF-0518, XPF-0630, XPF-1182, XPF-1185, XPF-1190, XPF-1196, XPF-1322, XPF-1325, XPF-1330, XPF-1546, XPF-1549, XPF-1554, XPF-1588, XPF-1596, XPF-1602, XPF-1616, XPF-1624, XPF-2241, XPF-2242, XPF-2243, XPF-2244, XPF-2245, XPF-2246, XPF-2247, XPF-2248, XPF-2249, XPF-2250, XPF-2251, XPF-2252, XPF-2253 and XPF-2254.

[0037] In a further aspect, the present invention relates to compounds of general formula (I) and salts and solvates thereof, wherein R 6 , R 7 and R 8 are each -H, and wherein X 1 is CR 11 , X 2 is CR 12 , X 3 is CR 13 , X 4 is CR 14 , and wherein R 1 is as defined in general formula (I) including substituents and preferred definitions, wherein R 1 is selected from cyclic, bicyclic and tricyclic structures, and wherein R 1 is optionally independently substituted with heteroatoms selected from O, S and N as defined in general formula (I) and contains six or more carbon atoms, provided that R 1 containing any substituentscontains no heteroatom selected from O, S, N or contains one heteroatom, and here, Z 1 and Z 2 is as defined in general formula (I) including general formula (Ia), general formula (Ib) and general formula (Ic), including substituents and preferred definitions, and here, R 15 is as defined in general formula (Ia), including substituents and preferred definitions, and here, R 16 and R 17 is as defined in general formula (Ib), including substituents and preferred definitions, and here, R 2 -R 5 and R 9 -R 14 is as defined in general formula (I), including substituents and preferred definitions, and here, the compound shares the following structure (I-4)

[0038]

Chemical formula

[0039] and here, the compound of structure (I-4) is preferred for use in human and veterinary medicine, particularly in the medical uses described in the present invention, preferably in immune system-related applications including immunotherapy and other immunotherapies as defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, proliferative disorders, and cancers of the hematopoietic and blood systems such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, and cancers of the neuroendocrine system. Examples include compounds XPF-0006, XPF-0014, XPF-0174 and XPF-0182, XPF-0258, XPF-0266.

[0040] In a further aspect, the present invention relates to compounds of general formula (Ia) and their salts and solvates, where Z 2 is -OR 15 and R15 is -H, and here, R 6 , R 7 and R 8 are each -F, and here, Z 1 is as defined in general formula (Ia), including substituents and preferred definitions, provided that optionally Z 1 is different from -CF3, and here, R 1 -R 5 , R 9 -R 14 and X 1 -X 4 are as defined in general formula (I), including substituents and preferred definitions, and here, the compound shares the following structure (Ia-1)

[0041]

Chemical formula

[0042] and here, the compound of structure (Ia-1) is preferably used in human and veterinary medicine, especially - in the absence of special provisos - in immune system-related applications including the medical uses described in the present invention, preferably the immunotherapy and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and cancers of the hematopoietic and blood systems such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovary, and cancers of the neuroendocrine system. Examples include compounds XPF-0057, XPF-0058, XPF-0062, XPF-0063, XPF-0064, XPF-0065, XPF-0070, XPF-0169, XPF-0170, XPF-0174, XPF-0182, XPF-0202, XPF-0205, XPF-0210, XPF-0230, XPF-0630, XPF-1178, XPF-1182, XPF-1185, XPF-1190, XPF-1322, XPF-1325, XPF-1330, XPF-2241, XPF-2242, XPF-2243, XPF-2244, XPF-2248, XPF-2251 and XPF-2252.

[0043] In a further aspect, the present invention relates to compounds of general formula (Ia) and their salts and solvates, where Z 1 is cyclopropyl, and where R 1 is as defined in general formula (I), including substituents and preferred definitions, provided that optionally R 1 is different from -CF3 and -CHF2, and where Z 2 and R 15 are as defined in general formula (Ia), including substituents and preferred definitions, and where R 2 -R 14 and X 1 -X 4 are as defined in general formula (I), including substituents and preferred definitions, and where the compound shares the following structure (Ia-2)

[0044]

Chemical formula

[0045] And here, the compounds of structure (Ia-2) are, - unless otherwise specified - for human and veterinary use, in particular for the medical uses described in the present invention, preferably for immune system-related applications including the immunotherapies and other immunotherapies defined in the present invention, and for the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and cancers of the hematopoietic and blood systems such as leukemia and lymphoma, cancers including skin, oral mucosa, tongue, lung, stomach, breast, ovarian cancers, and cancers of the neuroendocrine system. Examples include XPF-0202, XPF-0205, XPF-0210, XPF-1322, XPF-1325 and XPF-1330.

[0046] In a further aspect, the present invention relates to compounds of general formula (Ia) and their salts and solvates, where R 6 and R 7 together form a cyclic residue containing the carbon atom to which they are attached, and where the cyclic residue is C3 cycloalkyl, i.e. cyclopropyl, and here, Z 1 , Z 2 and R 15 are as defined in general formula (Ia), including substituents and preferred definitions, and here, R 1 -R 5 , R 8 -R 14 and X 1 -X 4 are as defined in general formula (I), including substituents and preferred definitions, and here, the compound shares the following structure (Ia-3)

[0047]

Chemical formula

[0048] And here, the compounds of structure (Ia-3) are useful in human and veterinary medicine, particularly in the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapies and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and cancers of the hematopoietic and blood systems such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, ovary, and cancers of the neuroendocrine system. Examples include XPF-0042, XPF-0202, XPF-0205, XPF-02 10, XPF-1162, XPF-1322, XPF-1325 and XPF-1330.

[0049] In a further aspect, the present invention relates to compounds of general formula (Ia) and their salts and solvates, where R 6 , R 7 and R 8 are each -F, and here, Z 1 is as defined in general formula (Ia) including substituents and preferred definitions, provided that optionally Z 1 is different from -CF3, and here, Z 2 and R 15 are as defined in general formula (Ia) including substituents and preferred definitions, and here, R 1 -R 5 , R 9 -R 14 and X 1 -X 4 are as defined in general formula (I) including substituents and preferred definitions, and here, the compound shares the following structure (Ia-4)

[0050]

Chemical formula

[0051] And here, the compounds of structure (Ia-4) are, - unless otherwise specified - for use in human and veterinary medicine, in particular the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapies and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and cancers of the hematopoietic and blood systems such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovary, and cancers of the neuroendocrine system. Examples include XPF-0057, XPF-0058, XPF-0062, XPF-0063, XPF-0064, XPF-0065, XPF-0070, XPF-0169, XPF-0170, XPF-0174, XPF-0182, XPF-0202, XPF-0205, XPF-0210, XPF-0230, XPF-0630, XPF-1178, XPF-1182, XPF-1185, XPF-1190, XPF-1196, XPF-1322, XPF-1325, XPF-1330, XPF-2241, XPF-2242, XPF-2243, XPF-2244, XPF-2248, XPF-2251 and XPF-2252.

[0052] In a further aspect, the present invention relates to compounds of general formula (Ib) and their salts and solvates, where Z 1 and Z 2 together are =NR 16 and where R 6 , R 7 and R 8 are each -F, and where R 1 is as defined in general formula (I) including substituents and preferred definitions, provided that optionally R 1 is different from -CF3, and where R 16 is as defined in general formula (Ib) including substituents and preferred definitions, and where R 2 -R 5 , R 9 -R 14 and X1 -X 4 is as defined in general formula (I), including substituents and preferred definitions, and where the compound shares the following structure (Ib-1)

[0053]

Chemical formula

[0054] and where the compound of structure (Ib-1) is preferably used in human and veterinary medicine, in particular the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapy and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, proliferative disorders, and hematopoietic and blood cancers such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovary, and cancers of the neuroendocrine system, provided there is no specific proviso. Examples include XPF-0454, XPF-0469, XPF-0476, XPF-1588, XPF-1596, XPF-1602, and XPF-2249.

[0055] In a further aspect, the present invention relates to compounds of general formula (Ib) and their salts and solvates, where Z 1 and Z 2 together form a zwitterionic =N [+] R 17 O [-] and and where R 17 is as defined in general formula (Ib), including substituents and preferred definitions, and where R 1 -R 14 and X 1 -X 4 are as defined in general formula (I), including substituents and preferred definitions, and where the compound shares the following structure (Ib-2)

[0056] [Chemical formula]

[0057] and herein, the compound of structure (Ib-2) is for use in human and veterinary medicine, particularly the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapy and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and hematopoietic and blood cancers such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, and neuroendocrine system. Examples include XPF-0496, XPF-0504, XPF-1616, and XPF-1624.

[0058] In a further aspect, the present invention relates to a compound of general formula (Ib) and its salts and solvates, wherein Z 1 and Z 2 together form a zwitterionic =N [+] R 17 O [-] and herein, R and herein, R 6 , R 7 and R 8 are each -F, and herein, R 17 is as defined in general formula (Ib), including substituents and preferred definitions, and herein, R 1 -R 5 , R 9 -R 14 and X 1 -X 4 are as defined in general formula (I), including substituents and preferred definitions, and herein, the compound shares the following structure (Ib-3)

[0059] [Chemical formula]

[0060] And here, the compounds of structure (Ib-3) are useful in human and veterinary medicine, particularly in the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapies and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and cancers of the hematopoietic and blood systems such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, and neuroendocrine system. Examples include XPF-0496, XPF-0504, XPF-1616 and XPF-1624.

[0061] In a further aspect, the present invention relates to compounds of general formula (Ib) and their salts and solvates, wherein Z 1 and Z 2 together are =O, and wherein R 6 , R 7 and R 8 are each -F, and wherein R 1 is as defined in general formula (Ib) including substituents and preferred definitions, provided that optionally R 1 is different from -CH3 and -OCH3, and wherein R 2 -R 5 , R 9 -R 14 and X 1 -X 4 are as defined in general formula (I) including substituents and preferred definitions, and wherein the compound shares the following structure (Ib-4)

[0062]

Chemical formula

[0063] And here, the compounds of structure (Ib-4) are, unless otherwise specified, for human and veterinary use, in particular the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapies and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and cancers of the hematopoietic and blood systems such as leukemia and lymphoma, cancers including skin, oral mucosa, tongue, lung, stomach, breast, cervical cancers, and cancers of the neuroendocrine system. Examples include XPF-0421, XPF-0422, XPF-0426, XPF-0429, XPF-0434, XPF-1541, XPF-1542, XPF-1546, XPF-1549, XPF-1554, XPF-2245, XPF-2246, XPF-2247, XPF-2250, XPF-2253 and XPF-2254.

[0064] In a further aspect, the present invention relates to compounds of general formula (Ic) and their salts and solvates, where Z 1 and Z 2 together form a cyclic residue containing the carbon atom to which they are attached, and where Z 1 and Z 2 are as defined in general formula (Ic), including substituents and preferred definitions, and where R 6 , R 7 and R 8 are each -F, and where R 1 -R 5 , R 9 -R 14 and X 1 -X 4 are as defined in general formula (I), including substituents and preferred definitions, and where the compound shares the following structure (Ic-1)

[0065]

Chemical formula

[0066] And herein, the compounds of structure (Ic-1) are useful in human and veterinary medicine, particularly in the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapies and other immunotherapies defined in the present invention, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and hematopoietic and blood cancers such as leukemia and lymphoma, cancers including skin, oral mucosa, tongue, lung, stomach, breast, cervical, ovarian cancers, and cancers of the neuroendocrine system. An example is XPF-0518.

[0067] In a further aspect, the present invention relates to compounds of general formula (Ic) and their salts and solvates, wherein Z 1 and Z 2 together form a cyclic residue containing the carbon atom to which they are attached, and wherein Z 1 and Z 2 are as defined in general formula (Ic) including substituents and preferred definitions, and wherein said cyclic residue is selected from 3-membered and 4-membered rings, and wherein R 8 is as defined in general formula (I) including substituents and preferred definitions, provided that optionally R 8 is different from -H, and wherein R 1 -R 7 , R 9 -R 14 and X 1 -X 4 are as defined in general formula (I) including substituents and preferred definitions, and wherein the compound shares the following structure (Ic-2)

[0068]

Chemical formula

[0069] And here, the compound of structure (Ic-2) is, unless otherwise specified, for use in human and veterinary medicine, in particular the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapies and other immunotherapies defined in the present invention, and in immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and hematopoietic and blood cancers such as leukemia and lymphoma, cancers of the skin, oral mucosa, tongue, lung, stomach, breast, cervix, ovary, and neuroendocrine system Preferably for use in the treatment of cancer. An example is XPF-0518.

[0070] In a further aspect, the present invention relates to a compound of general formula (Ic) and its salts and solvates, where Z 1 and Z 2 together form a cyclic residue containing the carbon atom to which they are attached, and where Z 1 and Z 2 are as defined in general formula (Ic) including substituents and preferred definitions, and where the cyclic residue is selected from 3-membered and 4-membered rings, provided that optionally the cyclic residue is different from oxiranyl, and where R 1 -R 14 and X 1 -X 4 are as defined in general formula (I) including substituents and preferred definitions, and where the compound shares the following structure (Ic-3)

[0071]

Chemical formula

[0072] And here, the compounds of structure (Ic-3) are, - unless otherwise specified - for use in human and veterinary medicine, particularly for the medical uses described in the present invention, preferably in immune system-related applications including the immunotherapies defined in the present invention and other immunotherapies, and in the treatment of immune system-related disorders, skin diseases, muscle diseases, hyperproliferative disorders, and hematopoietic and blood cancers such as leukemia and lymphoma, cancers including skin, oral mucosa, tongue, lung, stomach, breast, cervical, ovarian cancer, and cancers of the neuroendocrine system. An example is XPF-0518.

[0073] In some embodiments, the following compounds shown in Tables 1 to 3 are expressly excluded from the scope of the invention.

[0074] The compounds of Table 1 specifically indicated by their CAS Registry Numbers were identified by the inventors, who are persons skilled in the art. In embodiments where these compounds are included in general formula (I) or any of the sub-general formulas defined herein, they are expressly excluded from the scope of the invention with respect to compound protection. As far as the inventors are aware, these compounds are not known for any medical use. That is, the present invention encompasses any medical use of the compounds of Table 1.

[0075]

Table 1-1

[0076]

Table 1-2

[0077] The compounds in Table 2 specifically indicated by CAS registration numbers were identified by the inventors who are persons skilled in the art. In embodiments where these compounds are included in general formula (I) or any of the sub-general formulas defined herein, they are explicitly excluded from the scope of the present invention with respect to compound protection. As far as the inventors know, these compounds are not known for any medical use defined in the present invention. That is, the compounds in Table 2 are explicitly included in the scope of the present invention with respect to the medical use defined in the present invention, particularly in the treatment of non-malignant or malignant proliferative diseases.

[0078]

Table 2

[0079] The compounds in Table 3 specifically indicated by CAS registration numbers were identified by the inventors who are persons skilled in the art. In embodiments where these compounds are included in general formula (I) or any of the sub-general formulas defined herein, they are explicitly excluded from the scope of the present invention with respect to compound protection. Furthermore, as far as the inventors know, these compounds are known for medical use, and such use may be included in the medical use defined herein in some embodiments. That is, the compounds in Table 3 may be explicitly excluded from the scope of the present invention with respect to compound protection and with respect to a certain medical use in some embodiments defined herein.

[0080]

Table 3

[0081] Specific examples of compounds falling within the scope of formula (I) are shown in Tables 4 to 28. The intermediates are shown as "XPF-I".

[0082]

Table 4

[0083] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0084] [Table 5]

[0085] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0086] [Table 6]

[0087] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0088] [Table 7]

[0089] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0090] [Table 8]

[0091] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0092] [Table 9]

[0093] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0094]

Table 10

[0095] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0096]

Table 11

[0097] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvate adducts.

[0098]

Table 12

[0099] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvate adducts.

[0100]

Table 13

[0101] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvate adducts.

[0102]

Table 14

[0103] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvate adducts.

[0104]

Table 15

[0105] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0106]

Table 16

[0107] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0108]

Table 17

[0109] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0110]

Table 18

[0111] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0112]

Table 19

[0113] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0114]

Table 20

[0115] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0116] [Table 21]

[0117] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0118] [Table 22]

[0119] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0120] [Table 23]

[0121] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates.

[0122] [Table 24]

[0123] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates, and also of the intermediates used in the synthesis of the specifically shown compounds and their salts and solvates. Such intermediates and their salts and solvates are also part of the present invention and are within the framework of the process for generating the final compounds.

[0124] [Table 25]

[0125] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates, and of the intermediates used in the synthesis of the specifically shown compounds, as well as their salts and solvates. Such intermediates, as well as their salts and solvates, are also part of the present invention and are within the framework of the process for generating the final compounds.

[0126] [Table 26]

[0127] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates, and of the intermediates used in the synthesis of the specifically shown compounds, as well as their salts and solvates. Such intermediates, as well as their salts and solvates, are also part of the present invention and are within the framework of the process for generating the final compounds.

[0128] [Table 27]

[0129] The above table constitutes individual descriptions of each of the compounds specifically shown therein, as well as their salts and solvates, and of the intermediates used in the synthesis of the specifically shown compounds, as well as their salts and solvates. Such intermediates, as well as their salts and solvates, are also part of the present invention and are within the framework of the process for generating the final compounds.

[0130] [Table 28]

[0131] The above table constitutes an individual description of each of the compounds specifically shown therein, as well as their salts and solvates, and of the intermediates used in the synthesis of the specifically shown compounds, as well as their salts and solvates. Such intermediates, as well as their salts and solvates, are also part of the present invention and are also within the framework of the process for generating the final compounds.

[0132] Also included are isomers of the above-described compounds, such as enantiomers or diastereomers or mixtures of isomers, salts, particularly pharmaceutically acceptable salts, and solvates.

[0133] [Further Definitions] The term "C1-C 12 "alkyl" includes all isomers of the corresponding saturated aliphatic hydrocarbon groups containing from 1 to 12 carbon atoms; this includes methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl, tert-butyl, n-pentyl, sec-pentyl, 3-pentyl, 2-methylbutyl, iso-pentyl, 2-methylbutan-2-yl, 3-methylbutan-2-yl, all hexyl isomers, all heptyl isomers, all octyl isomers, all nonyl isomers, all decyl isomers, all undecyl isomers, and all dodecyl isomers. The term "C2-C 12 "alkenyl" includes all isomers of the corresponding unsaturated olefinic hydrocarbon groups containing from 2 to 12 carbon atoms linked by (i.e., containing) one or more double bonds; this includes vinyl, all propenyl isomers, all butenyl isomers, all pentenyl isomers, all hexenyl isomers, all heptenyl isomers, all octenyl isomers, all nonenyl isomers, all decenyl isomers, all undecenyl isomers, and all dodecenyl isomers. The term "C2-C 12The term "alkynyl" includes all isomers of the corresponding unsaturated acetylenic hydrocarbon group containing from 2 to 12 carbon atoms linked (i.e., containing) by one or more triple bonds; this includes ethynyl, all propynyl isomers, all butynyl isomers, all pentynyl isomers, all hexynyl isomers, all heptynyl isomers, all octynyl isomers, all nonynyl isomers, all decynyl isomers, all undecynyl isomers and all dodecynyl isomers. The term "alkynyl" also includes compounds having one or more triple bonds and one or more double bonds. The term "C3-C8 cycloalkyl" includes the corresponding saturated hydrocarbon groups containing from 3 to 8 carbon atoms arranged in a monocyclic ring structure; this includes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl. The term "C5-C8 cycloalkenyl" has at least one of which is sp 3 hybridized, arranged in a monocyclic ring structure, and includes the corresponding unsaturated non-aromatic and non-heteroaromatic hydrocarbon groups containing from 5 to 8 carbon atoms linked (i.e., containing) by one or more double bonds; this includes all cyclopentenyl isomers, all cyclohexenyl isomers, all cycloheptenyl isomers, all cyclooctenyl isomers. The term "C5-C 12 The term "C5-C12 bicycloalkyl" includes the corresponding saturated hydrocarbon groups containing from 5 to 12 carbon atoms arranged in a bicyclic ring structure; where these bicyclic ring structures include fused, bridged and spiro systems. The term "C7-C 12 The term "C7-C12 bicycloalkenyl" includes the corresponding unsaturated non-aromatic and non-heteroaromatic hydrocarbon groups containing from 7 to 12 carbon atoms arranged in a bicyclic ring structure and linked (i.e., containing) by one or more double bonds; where these bicyclic ring structures include fused, bridged and spiro systems. The term "C8-C 14The term "tricycloalkyl" includes the corresponding saturated hydrocarbon group containing 8 to 14 carbon atoms arranged in a tricyclic ring structure; where these tricyclic ring structures include fused, bridged and spiro systems. R 1 The terms "cyclic", "bicyclic", "tricyclic", "cycloalkyl", "cycloalkenyl", "bicycloalkyl", "bicycloalkenyl" and "tricycloalkyl" for R 1 mean that such cyclic, bicyclic or tricyclic residues are directly bonded to the aromatic ring to which R1 is bonded by a chemical bond, and the terms "cyclic", "bicyclic", "tricyclic", "cycloalkyl", "cycloalkenyl", "bicycloalkyl", "bicycloalkenyl" and "tricycloalkyl" for the substituents of R 1 mean that such cyclic, bicyclic or tricyclic residues are directly bonded to one of the C atoms or N atoms or O atoms or S atoms contained in R 1 ; for example, "R 1 is cyclohexyl" means that the cyclohexyl residue is bonded to the aromatic ring to which R 1 is bonded; "R 1 is methyl and R 1 is substituted with cyclohexyl" means that the resulting -CH2(cyclohexyl) residue is bonded to the aromatic ring to which R . When a carbon atom is substituted with a heteroatom selected from O, N or S, the number of substituents on each heteroatom is adjusted according to its valence. For example, a -CR2- group may be substituted with a -NR-, -NR2 + -, -O- or -S- group. The term "perhalogenated" relates to the thorough halogenation of a carbon scaffold; the corresponding residues include the corresponding perfluorinated, perchlorinated, perbrominated and periodinated groups. Preferably, the term "perhalogenated" relates to perfluorinated or perchlorinated groups, more preferably perfluorinated groups.

[0134] The following includes definitions of terms used in this specification. The first definition provided for a group or term in this specification applies to that group or term throughout this specification, individually or as part of another group, unless otherwise indicated. The compounds of the present invention may form salts, which are also within the scope of the present invention. References to the compounds of the present invention in this specification are understood to include references to their salts, unless otherwise indicated. The term "salt" as used herein refers to acidic and / or basic salts formed with inorganic and / or organic acids and bases. Zwitterions (internal or inner salts) are included within the term "salt" as used herein (and can be formed, for example, when a substituent contains an acid moiety such as a carboxyl group and an amino group). Quaternary ammonium salts such as alkylammonium salts are also included herein. The salts of the compounds may be formed, for example, by reacting the compound with an acid or base in an amount, such as an equivalent amount, in a medium such as a medium in which the salt precipitates or in an aqueous medium followed by lyophilization. Exemplary salts resulting from the addition of an acid include acetates (formed with acetic acid or trihaloacetic acid, such as those formed with trifluoroacetic acid), adipates, alginates, ascorbates, aspartates, benzoates, benzenesulfonates, bisulfates, borates, butyrates, citrates, camphorates, camphorsulfonates, cyclopentanepropionates, digluconates, dodecyl sulfates, ethanesulfonates, fumarates, glucoheptanoates, glycerophosphates, hemisulfates, heptanoates, hexanoates, hydrochlorides, hydrobromides, hydroiodides, chlorates, bromates, iodates, 2-hydroxyethanesulfonates, lactates, maleates, methanesulfonates, 2-naphthalenesulfonates, nicotinates, nitrates, oxalates, pectates, persulfates, 3-phenylpropionates, phosphates, picrates, pivalates, propionates, salicylates, succinates, sulfates (such as those formed with sulfuric acid), sulfonates (such as those described herein), tartrates, thiocyanates, toluenesulfonates such as tosylates, undecanoates, and the like. Exemplary salts resulting from the addition of a base (e.g., formed when the substituent contains an acidic moiety such as a carboxyl group) include ammonium salts, alkali metal salts such as sodium, lithium, and potassium salts, alkaline earth metal salts such as calcium and magnesium salts, organic salts with organic bases (e.g., organic amines) such as benzathine, dicyclohexylamine, hydrabamine, N-methyl-D-glucamine, N-methyl-D-glucamide, tert-butylamine, and salts with amino acids such as arginine and lysine. The basic nitrogen-containing group may be quaternized with reagents such as lower alkyl halides (e.g., methyl, ethyl, propyl, and butyl chlorides, bromides, and iodides), dialkyl sulfates (e.g., dimethyl, diethyl, dibutyl, and diamyl sulfates), long-chain halides (e.g., decyl, lauryl, myristyl, and stearyl chlorides, bromides, and iodides), aralkyl halides (e.g., benzyl and phenethyl bromide). The present invention also includes pharmaceutically acceptable salts of the compounds described herein. As used herein, "pharmaceutically acceptable salts" refers to derivatives of the disclosed compounds in which the parent compound is modified by converting an existing acidic or basic moiety to its salt form. Pharmaceutically Examples of acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines, and alkali or organic salts of acidic residues such as carboxylic acids. The pharmaceutically acceptable salts of the present invention include conventional non-toxic salts of the parent compounds formed from non-toxic inorganic or organic acids, for example. The pharmaceutically acceptable salts of the present invention can be synthesized from the parent compounds containing basic or acidic moieties by conventional chemical methods. Generally, such salts can be prepared by reacting these compounds in the form of the free acid or base with a stoichiometric amount of the appropriate base or acid in water or an organic solvent or a mixture of the two; generally, non-aqueous media such as ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are preferred. A list of suitable salts is provided in Remington’s Pharmaceutical Sciences, 17 thFound in ed., Mack Publishing Company, Easton, PA., 1985, p. 1418 and Journal of Pharmaceutical Science 1977, 66(2), each of which is hereby incorporated by reference in its entirety. As used herein, the term "pharmaceutically acceptable" refers to compounds, materials, compositions and / or dosage forms that are suitable for use in contact with the tissues of humans and animals within the scope of sound medical judgment, without undue toxicity, irritation, allergic response, or other problems or complications, and commensurate with a reasonable benefit / risk ratio. Furthermore, in the case of the compounds of the present invention containing an asymmetric carbon atom or an atropisomeric bond, the present invention relates to the D-form, L-form and D, L-mixtures, and also to the diastereomeric forms when one or more asymmetric carbon atoms or atropisomeric bonds are present. Those compounds of the present invention that contain an asymmetric carbon atom or an atropisomeric bond and which in principle occur as racemates can be separated into the optically active isomers by known methods, for example using an optically active acid. However, it is also possible to use optically active starting materials from the beginning, in which case the corresponding optically active or diastereomeric compounds are obtained as the final product. The compounds of the present invention also include tautomers. Tautomers result from the exchange of a single bond adjacent to a double bond with the concomitant transfer of a proton. Tautomers include prototropic tautomers which are protonation states of isomers having the same empirical formula and total charge. Examples of prototropic tautomers include the keto-enol pair, the amide-imidic acid pair, the lactam-lactim pair, the amide-imidic acid pair, the enamine-imine pair, and cyclic forms in which a proton can occupy two or more positions in a heterocyclic system, such as 1H- and 3H-imidazole, 1H-, 2H- and 4H-1,2,4-triazole, 1H- and 2H-isoindole, and 1H- and 2H-pyrazole. Tautomers can be in equilibrium or can be stereochemically fixed in one form by appropriate substitution. The compounds described herein may be asymmetric (e.g., having one or more stereocenters). All stereoisomers such as enantiomers and diastereomers are intended unless otherwise indicated. Compounds of the invention containing an asymmetrically substituted carbon atom can be isolated in optically active or racemic form. Methods for preparing the optically active form from optically active starting materials are known in the art, such as by resolution of a racemic mixture or by stereoselective synthesis. Many geometric isomers such as olefins, C=N double bonds, etc. may also be present in the compounds described herein, and all such stable isomers are contemplated in the present invention. The cis and trans geometric isomers of the compounds of the invention are described and may be isolated as mixtures of isomers or as the separated isomers. The compounds of the invention may also include all isotopes of atoms that occur in the intermediates or final compounds. Isotopes include atoms having the same atomic number but different mass numbers. For example, isotopes of hydrogen include tritium and deuterium. Also included are solvates and hydrates of the compounds of the invention, and solvates and hydrates of their pharmaceutically acceptable salts. As used herein, the term "compound" is intended to include, unless otherwise indicated, all stereoisomers, geometric isomers, tautomers, rotational isomers and isotopes of the indicated structure is contemplated. In some embodiments, the compound may be provided as a prodrug. As used herein, the term "prodrug" refers to a compound that undergoes a chemical conversion by a metabolic or chemical process upon administration to a subject to produce a compound of the invention or a salt and / or solvate thereof. In some embodiments, the compounds of the invention and their salts are substantially isolated. "Substantially isolated" means that the compound is at least partially or substantially separated from the environment in which it is formed or detected. Partial separation can mean, for example, that the composition may contain a composition rich in the compounds of the invention. Substantial separation can include compositions containing at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, at least about 97% or at least about 99% by weight of the compound of the invention or its salt.

[0135] [Pharmaceutical method] The compounds of the invention have been found to have pharmacologically important properties that can be used therapeutically. The compounds of the invention can be used alone, in combination with each other, or in combination with other active compounds. In some embodiments, the compounds of the invention may exhibit growth inhibitory properties in hyperproliferative processes. The anti-proliferative activities of the compounds entering into formulae (1a), (1b) and (1c) were investigated in hematopoietic systems including the bone marrow cell compartment and lymphoid cell compartments (T cells and B cells), neuroendocrine systems, cervical, breast, ovarian, lung, gastrointestinal tract, and mucosal epithelial disorders, and cells or cell lines derived from skin epithelium and muscle. For this purpose, HL-60 cells, NB-4 cells, HH cells, RPMI-8402 cells, TANOUE cells, TT cells, HeLa cells, MDA-MB-231 cells, FU-OV-1 cells, LOU-NH91 cells, 23132 / 87 cells, CAL-27 cells, BHY cells, SCC-25 cells, A-431 cells, human primary epidermal keratinocytes (HPEK), and C2C12 cells were seeded at the following initial cell numbers in 96-well plates suitable for fluorescence assays (CORNING #3598). For HL-60, 1000 cells per well; for NB-4, 1000 cells per well; for HH, 5000 cells per well; for RPMI-8402, 5000 cells per well; for TANOUE, 1500 cells per well; for TT, 9000 cells per well; for HeLa, 2000 cells per well; for MDA-MB-231, 3000 cells per well; for FU-OV-1, 3000 cells per well; for L0U-NH91, 4000 cells per well; for 23132 / 87, 2000 cells per well; for CAL-27, 2000 cells per well; for BHY, 1500 cells per well; for SCC-25, 1500 cells per well; for A-431, 700 cells per well; for HPEK, 1000 cells per well; for C2C1, 500 cells per well. The cells were treated for 5 days with the compounds at the indicated final concentrations (diluted from a 1000x stock solution in DMSO to a final DMSO concentration of 0.1% v / v in H2O (Water for Injection, WFI, Fisherscientific #10378939)) or with an empty carrier as a control, 0.1% v / v DMSO. On the 5th day after the start of the treatment, the cells were subjected to an alamarBlue® proliferation assay (Bio-Rad Serotec GmbH, BUF012B) according to the manufacturer's protocol.Reading was performed using a fluorescence mode multi-well plate reader with a filter for excitation at 560 nm (bandwidth 10 nm) and emission at 590 nm (bandwidth 10 nm). Control treatments for growth inhibition with commercially available compounds such as methotrexate (MTREX) and resveratrol (RES) were included in all plates. The assay was performed in two or more replicates of an independent single experiment, each containing six replicates for all conditions. For each individual plate, the measured fluorescence intensity values for the conditions with compound treatment were normalized to the corresponding equally weighted arithmetic mean of the fluorescence intensity values of six DMSO-treated control wells in order to obtain relative values with respect to a baseline level of 1.0. Two independent outlier analyses were performed according to the method of Peirce and Chauvenet (Ross, Journal of Engineering Technology 2003, 1 - 12). Outliers identified by at least one method were excluded from the calculation, but were one or fewer out of six values per compound within a single experiment. The weighted arithmetic mean (here abbreviated as AVE) of each compound was calculated from the normalized values of all independent replicates of a single experiment, each containing six replicates. The standard deviation corresponding to the weighted arithmetic mean was calculated according to the method described by Bronstein et al. (Bronstein, Semendjajew, Musiol, Muehlig, Taschenbuch der Mathematik, 5th Edition 2001 (German), Publisher: Verlag Harri Deutsch, Frankfurt am Main and Thun) and combined with the Gaussian error propagation associated with the calculations performed for normalization. The resulting standard deviation is referred to herein as the "combined standard deviation". W If there was significant variation in the normalized equally weighted arithmetic means obtained from two independent replicates, the number of independent replicates was increased to three or more. For four or more independent replicates, a second outlier analysis was applied to all normalized equally weighted arithmetic means according to the above method of Peirce and Chauvenet. ​ In some embodiments, the compounds of the present invention can be growth inhibitors in proliferative processes, including malignant and non-malignant proliferative processes. In one embodiment, several compounds of the present invention were found to inhibit the growth of HL-60 cells (human acute myeloid leukemia cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC3. The HL-60 cells were cultured in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37 °C and 5% CO2. A compound is considered a growth inhibitor of HL-60 cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less with respect to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from DMSO control measurements, in the same way as the calculations performed for the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the scope of the compounds defined by formulas (1a), (1b), and (1c) herein were identified as growth inhibitors of HL-60 cells. The HL-60 growth inhibitors identified so far relate to the compounds listed in Table 29. The entries in Table 29 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range, without considering the respective standard deviations.

[0136]

Table 29-1

[0137]

Table 29-2

[0138] In one embodiment, several compounds of the invention inhibit the growth of NB-4 cells (human acute promyelocytic leukemia cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 207. The NB-4 cells were cultured in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37 °C and 5% CO2. A compound is considered a growth inhibitor of NB-4 cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less relative to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements, in the same way as the calculations performed on the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the scope of the compounds defined by formulas (1a) and (1b) herein were identified as growth inhibitors of NB-4 cells. The NB-4 growth inhibitors identified so far relate to the compounds listed in Table 30. The entries in Table 30 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range without considering their respective standard deviations.

[0139]

Table 30

[0140] In one embodiment, several compounds of the present invention were found to inhibit the growth of HH cells (human cutaneous T cell lymphoma cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 707. The HH cells were cultured in RPMI 1640 medium (Fisher scientific, #11554526) containing 10% fetal bovine serum (Fisher scientific, #15517589) at 37°C and 5% CO2. A compound is considered a growth inhibitor of HH cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less with respect to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from DMSO control measurements, in the same way as the calculations performed for the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. Following the above method, several molecules falling within the scope of the compounds defined by formulas (1a) and (1b) herein were identified as growth inhibitors of HH cells. The HH growth inhibitors identified so far relate to the compounds listed in Table 31. The entries in Table 31 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range, without considering the respective standard deviations.

[0141]

Table 31

[0142] In one embodiment, several compounds of the invention were found to inhibit the growth of RPMI-8402 cells (human T-cell acute lymphoblastic leukemia cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 290. The RPMI-8402 cells were cultured in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37 °C and 5% CO2. The compound is considered to be a growth inhibitor of RPMI-8402 cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less and 0.2 or less with respect to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements, in the same way as the calculations performed for the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the scope of the compounds defined by formulas (1a), (1b) and (1c) herein were identified as growth inhibitors of RPMI-8402 cells. The RPMI-8402 growth inhibitors identified so far relate to the compounds listed in Table 32. The entries in Table 32 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range without considering the respective standard deviations.

[0143]

Table 32-1

[0144]

Table 32-2

[0145] In one embodiment, several compounds of the present invention were found to inhibit the growth of TANOUE cells (human B-cell leukemia cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 399. The TANOUE cells were cultured in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37 °C and 5% CO2. A compound is considered a growth inhibitor of TANOUE cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less with respect to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from DMSO control measurements, in the same way as the calculations performed on the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the ranges of the compounds defined by formulas (1a), (1b), and (1c) herein were identified as growth inhibitors of TANOUE cells. The TANOUE growth inhibitors identified so far relate to the compounds listed in Table 33. The entries in Table 33 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range, without considering the respective standard deviations.

[0146]

Table 33-1

[0147]

Table 33-2

[0148] In one embodiment, several compounds of the present invention were found to inhibit the growth of TT cells (human medullary thyroid carcinoma cells) available from the American Type Culture Collection (ATCC) under accession number ATCC-CRL-1803. The TT cells were cultured at 37 °C and 5% CO2 in F-12K medium (Fisher scientific, #11580556, or ATCC, #ATCC-30-2004) containing 10% fetal bovine serum (Fisher scientific, #15517589). A compound is considered a growth inhibitor of TT cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less relative to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements, in the same way as the calculations performed on the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the ranges of the compounds defined by formulas (1a) and (1b) herein were identified as growth inhibitors of TT cells. The TT growth inhibitors identified so far relate to the compounds listed in Table 34. The entries in Table 34 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range, without considering the respective standard deviations.

[0149]

Table 34

[0150] In one embodiment, several compounds of the present invention were found to inhibit the growth of HeLa cells (human cervical adenocarcinoma cells) available from the American Type Culture Collection (ATCC) under accession number ATCC-CCL-2. The HeLa cells were cultured in DMEM medium (Fisher scientific, #11584456) containing 10% fetal bovine serum (Fisher scientific, #15517589) at 37°C and 5% CO2. A compound is considered a growth inhibitor of HeLa cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less with respect to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from DMSO control measurements, in the same manner as the calculations performed on the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the scope of the compounds defined by formulas (1a) and (1b) herein were identified as growth inhibitors of HeLa cells. The HeLa growth inhibitors identified so far relate to the compounds listed in Table 35. The entries in Table 35 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range, without considering the respective standard deviations.

[0151] [Table 35]

[0152] ​In one embodiment, several compounds of the present invention were found to inhibit the growth of MDA-MB-231 cells (human breast cancer cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 732. The MDA-MB-231 cells were cultured in Leibovitz's L-15 (without phenol red) medium (Fisherscientific, #11540556) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37 °C and 0% CO2. A compound is considered a growth inhibitor of MDA-MB-231 cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less with respect to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from DMSO control measurements, in the same way as the calculations performed on the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the ranges of the compounds defined by formulas (1a), (1b), and (1c) herein were identified as growth inhibitors of MDA-MB-231 cells. The MDA-MB-231 growth inhibitors identified so far relate to the compounds listed in Table 36. The entries in Table 36 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range without considering their respective standard deviations.

[0153] [Table 36-1]

[0154] [Table 36-2]

[0155] In one embodiment, several compounds of the present invention were found to inhibit the growth of FU-OV-1 cells (human ovarian cancer cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 444. The FU-OV-1 cells were cultured at 37 °C and 5% CO2 in Ham's F-12 / DMEM (1:1) medium (Fisherscientific, #11514436) containing 10% fetal bovine serum (Fisherscientific, #15517589) and 1 mM sodium pyruvate (Fisherscientific, #11501871). A compound is considered a growth inhibitor of FU-OV-1 cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less with respect to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from DMSO control measurements, in the same way as the calculations performed for the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the scope of the compounds defined by formula (1a) herein were identified as growth inhibitors of FU-OV-1 cells. The FU-OV-1 growth inhibitors identified so far relate to the compounds listed in Table 37. The entries in Table 37 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range, without considering their respective standard deviations.

[0156]

Table 37

[0157] In one embodiment, several compounds of the invention were found to inhibit the growth of LOU-NH91 cells (human lung squamous carcinoma cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 393. The LOU-NH91 cells were cultured in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37 °C and 5% CO2. A compound is considered to be a growth inhibitor of LOU-NH91 cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less and 0.2 or less relative to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements, in the same way as the calculations performed for the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the scope of the compounds defined by formulae (1a) and (1b) herein were identified as growth inhibitors of LOU-NH91 cells. The LOU-NH91 growth inhibitors identified so far relate to the compounds listed in Table 38. The entries in Table 38 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range, without considering the respective standard deviations.

[0158] [Table 38]

[0159] In one embodiment, several compounds of the invention were found to inhibit the growth of the 23132 / 87 cells (human gastric adenocarcinoma cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 201. The 23132 / 87 cells were cultured at 37 °C and 5% CO2 in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589). and cultured at 37 °C and 5% CO2 in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589). A compound is considered to be a growth inhibitor of 23132 / 87 cells if, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, in particular 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less and 0.2 or less relative to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements, in the same way as the calculations performed for the test compounds. The corresponding binding standard deviation for the DMSO values is less than 1·10 -2 less than. According to the above method, several molecules falling within the scope of the compounds defined by formulas (1a) and (1b) herein were identified as growth inhibitors of 23132 / 87 cells. The 23132 / 87 growth inhibitors identified so far relate to the compounds listed in Table 39. The entries in Table 39 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range, without taking into account the respective standard deviations.

[0160]

Table 39

[0161] In one embodiment, several compounds of the invention are Deutsche Sammlu It has been found that it inhibits the growth of CAL-27 cells (human tongue squamous cell carcinoma cells) available from DSMZ (Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH) under accession number ACC 446. The CAL-27 cells were cultured in DMEM medium (Fisherscientific, #11584456) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37 °C and 5% CO2. The compound is considered a growth inhibitor of CAL-27 cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less with respect to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements, in the same way as the calculations performed on the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the scope of the compounds defined by formulas (1a), (1b), and (1c) herein were identified as growth inhibitors of CAL-27 cells. The CAL-27 growth inhibitors identified so far relate to the compounds listed in Table 40. The entries in Table 40 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range, without considering the respective standard deviations.

[0162] [Table 40]

[0163] In one embodiment, several compounds of the present invention have been found to inhibit the growth of BHY cells (human oral squamous cell carcinoma cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 404. The BHY cells were cultured in DMEM medium (Fisherscientific, #11584456) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37 °C and 5% CO2. A compound is considered a growth inhibitor of BHY cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less with respect to an overall reference level of 1.0. The overall reference level is calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements, similarly to the calculations performed for the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the ranges of the compounds defined by formulas (1a) and (1b) herein have been identified as growth inhibitors of BHY cells. The BHY growth inhibitors identified so far relate to the compounds listed in Table 41. The entries in Table 41 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range without considering the respective standard deviations.

[0164]

Table 41

[0165] In one embodiment, several compounds of the invention were found to inhibit the growth of SCC-25 cells (human tongue squamous cell carcinoma cells) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 617. The SCC-25 cells were cultured in Ham's F-12 / DMEM (1:1) medium (Fisherscientific, #11514436) containing 10% fetal bovine serum (Fisherscientific, #15517589) and 1 mM sodium pyruvate (Fisherscientific, #11501871) at 37 °C and 5% CO2. The compound, at a reference concentration of 20 μM, has a normalized fluorescence intensity value weighted arithmetic mean, after addition of the corresponding binding standard deviation, of 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less and 0.2 or less relative to an overall reference level of 1.0, is considered a growth inhibitor of SCC-25 cells. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from DMSO control measurements, in the same way as the calculations performed on the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the scope of the compounds defined by formulas (1a) and (1b) herein were identified as growth inhibitors of SCC-25 cells. The SCC-25 growth inhibitors identified so far relate to the compounds listed in Table 42. The entries in Table 42 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range without considering the respective standard deviations.

[0166]

Table 42

[0167] In one embodiment, several compounds of the present invention were found to inhibit the growth of A-431 cells (human epidermoid carcinoma cells) available from Cell Lines Service GmbH (CLS) under accession number 300112. The A-431 cells were cultured in DMEM medium (Fisherscientific, #11584456) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37 °C and 5% CO2. The compound is considered a growth inhibitor of A-431 cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less with respect to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements, in the same way as the calculations performed on the test compounds. The corresponding binding standard deviation for the DMSO values is less than 1·10 less. -2 According to the above method, several molecules falling within the ranges of the compounds defined by formulas (1a) and (1b) herein were identified as growth inhibitors of A-431 cells. The A-431 growth inhibitors identified so far relate to the compounds listed in Table 43. The entries in Table 43 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range without considering their respective standard deviations.

[0168]

Table 43

[0169] In one embodiment, several compounds of the present invention are available from CELLnTEC Advanced Cell Systems AG under accession number HPEKp ​It has been found that the growth of human epidermal keratinocyte progenitor cells (HPEKp, pooled) is inhibited. HPEKp cells were cultured at 37 °C and 5% CO2 in CnT-Prime epithelial culture medium (CELLnTEC, #CnT-PR, a well-defined low calcium formulation that does not contain any animal or human-derived components) without adding additional components. When the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less, and 0.2 or less with respect to the overall reference level of 1.0 at a reference concentration of 10 μM for the compound, the compound is considered a growth inhibitor of HPEKp cells. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from DMSO control measurements, similar to the calculations performed for the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. According to the above method, several molecules falling within the ranges of the compounds defined by formulas (1a), (1b), and (1c) herein were identified as growth inhibitors of HPEKp cells. The HPEKp growth inhibitors identified so far relate to the compounds listed in Table 44. The entries in Table 44 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range without considering their respective standard deviations.

[0170]

Table 44-1

[0171]

Table 44-2

[0172] In one embodiment, several compounds of the invention were found to inhibit the growth of C2C12 cells (mouse myoblasts) available from Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH (DSMZ) under accession number ACC 565. The C2C12 cells were cultured in RPMI 1640 medium (Fisherscientific, #11554526) containing 10% fetal bovine serum (Fisherscientific, #15517589) at 37 °C and 5% CO2. A compound is considered a growth inhibitor of C2C12 cells when, at a reference concentration of 20 μM, the weighted arithmetic mean of the normalized fluorescence intensity values after addition of the corresponding binding standard deviation is 0.9 or less, particularly 0.8 or less, 0.7 or less, 0.6 or less, 0.4 or less and 0.2 or less relative to an overall reference level of 1.0. The overall reference level was calculated as the weighted arithmetic mean of all normalized values from the DMSO control measurements, in the same way as the calculations performed on the test compounds. The corresponding binding standard deviation for the DMSO values is 1·10 -2 less than. Following the above method, several molecules falling within the ranges of the compounds defined by formulas (1a) and (1b) herein were identified as growth inhibitors of C2C12 cells. The C2C12 growth inhibitors identified so far relate to the compounds listed in Table 45. The entries in Table 45 are classified by the corresponding weighted arithmetic mean of the compounds falling within the indicated activity range, without considering the respective standard deviations.

[0173]

Table 45

[0174] In one aspect, the present invention relates to the treatment of skin, skin appendages, mucous membranes, mucous membrane appendages, cornea, and all types of epithelial tissues. The term "skin" relates to tissues including the epidermis and dermis. The term "mucous membrane" relates to mucous membranes and submucosal tissues including oral mucosa, nasal mucosa, ocular mucosa, ear mucosa, respiratory mucosa, genital mucosa, urinary tract mucosa, anal mucosa, and rectal mucosa. The term "appendage" relates to tissues including hair follicles, hair, fingernails, toenails, and glands including sebaceous glands, sweat glands such as apocrine or eccrine sweat glands, and mammary glands. In one embodiment, the present invention relates to the treatment of non-melanoma skin cancers and precancerous lesions such as basal cell carcinoma (BCC), squamous cell carcinoma (SCC), adenocarcinoma, Merkel cell carcinoma, angiosarcoma, cutaneous B-cell lymphoma, cutaneous T-cell lymphoma, dermatofibrosarcoma, actinic keratosis (AK) or Bowen's disease (BD), and other squamous cell carcinomas and precancerous lesions, such as cutaneous SCC, lung SCC, head and neck SCC, oral SCC, tongue SCC, esophageal SCC, cervical SCC, periocular SCC, thyroid SCC, penile SCC, vaginal SCC, prostate SCC, and bladder SCC. In a further embodiment, the present invention relates to the treatment of skin and mucous membrane disorders associated with keratinization defects (keratoses) and / or abnormal keratinocyte proliferation, such as psoriasis, Darier's disease, lichen planus, erythema multiforme, ichthyosis, or verruca vulgaris (senile). In a further embodiment, the present invention relates to warts and warts associated with HPV (human papillomavirus), papillomas, HPV-related papillomas, papillomatosis, and HPV-related papillomatosis, such as Verruca (plantar wart), Verruca plana (flat wart), Ve Verruca filiformis, mosaic verruca, periungual verruca, subungual verruca, oral verruca, genital verruca, fibroepithelial papilloma, intraductal papilloma, papilloma in duct, inverted papilloma, basal cell papilloma, flat papilloma, cutaneous papilloma, fibro-vascular papilloma, plexiform papilloma, nasal papilloma, pharyngeal papilloma, papillomatosis cutis carcinoid, papillomatosis cutis lymphangioperitonealis, confluent and reticulated papillomatosis or laryngeal papillomatosis (respiratory papillomatosis), herpes-related diseases, such as herpes labialis, genital herpes, herpes zoster, herpes keratitis or Kaposi's sarcoma, and skin and mucosal diseases respectively related to and / or caused by viral infections such as HPV-related cancers of the cervix, vulva, penis, vagina, anus, oropharynx, tongue and oral cavity, and for the treatment of skin and mucosal cancers. In a further embodiment, the invention relates to the treatment of atopic dermatitis. In a further embodiment, the invention relates to the treatment of acne. In a further embodiment, the invention relates to the treatment of skin wounds, where the process of wound healing is accelerated. In a further embodiment, the invention relates to the treatment of cancers related to and / or caused by viral infections, i.e., tumor viral infections, such as cancers related to HBV and HCV (hepatitis B and C viruses) such as liver cancer, cancers related to EBV (Epstein-Barr virus) such as Burkitt lymphoma, Hodgkin and non-Hodgkin lymphoma and gastric cancer, cancers related to HPV (human papillomavirus) such as cervical cancer, cancers related to HHV (human herpesvirus) such as Kaposi's sarcoma, and cancers related to HTLV (human T-lymphotropic virus) such as T-cell leukemia and T-cell lymphoma. A further aspect of the invention relates to the treatment of immune system-related disorders. As used herein, the term "immune system-related disorders" applies to pathological conditions of the hematopoietic system including the vascular system, particularly to pathological conditions of immune cells belonging to the congenital or acquired immune system. Examples include myeloid malignancies, including acute and chronic forms of leukemia, such as chronic myelomonocytic leukemia (CMML), acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL); or lymphoid malignancies, including acute and chronic forms of leukemia and lymphoma, such as T-cell acute lymphoblastic leukemia (T-ALL), T-cell pre-acute lymphoblastic leukemia (pre-T-ALL), cutaneous T-cell lymphoma, chronic lymphocytic leukemia (CLL) including T-cell CLL (T-CLL) and B-cell - CLL (B-CLL), prolymphocytic leukemia (PLL) including T-cell PLL (T-PLL) and B-cell - PLL (B-PLL), B-cell acute lymphoblastic leukemia (B-ALL), B-cell pre-acute lymphoblastic leukemia (pre-B-ALL), cutaneous B-cell lymphoma, Hodgkin lymphoma, non-Hodgkin lymphoma, mantle cell lymphoma, myeloma or multiple myeloma; or hematopoietic diseases including the blood system such as acute lymphoblastic and acute myeloid mixed lineage leukemia with MLL gene translocation. A further aspect of the invention relates to therapeutic use in immune system-related applications. As used herein, the term "immune system-related application" applies to interventions into the proliferation, differentiation and / or activation of cell lineages of the hematopoietic system, including the vasculature, for the regulation (immunomodulation) of the immune response. As used herein, the term "immune system-related application" also applies to interventions into the cellular and acellular microenvironment at the site of action of immune cells to support and / or enable the performance of immune cells. In particular, the interventions defined herein by the term "immune system-related application" relate to immune cells belonging to the innate or adaptive immune system. That is, the compounds of the invention may be used in immunotherapy, alone or together with other methods or compounds of immunotherapy, as immunological adjuvants, such as vaccine adjuvants, or as adjuvants for immunotherapy. As used herein, the term "immunotherapy" applies to activated immunotherapy in patients without immunodeficiency or with acquired or congenital immunodeficiency, as immune restoration that enhances the function of the immune system in response to pathogens such as cancer cells or pathologically transformed endogenous cells. As used herein, the term "other immunotherapies" applies to vaccination, antibody therapy, cytokine therapy, the use of immune checkpoint inhibitors and immune response stimulants, and the autologous transplantation of genetically modified or unmodified immune cells, which may be stimulated by intercellular signals, or signaling molecules, or antigens, or antibodies, i.e., adoptive immune cell transfer. The methods of use of the present invention in immune system-related applications and other immunotherapies relate to in vivo, in vitro, and ex vivo use, respectively. Specific examples include the stimulation of immune responses, particularly the proliferation and / or production and / or secretion of cytokines, and / or the amplification of cytotoxic agents upon antigen recognition to amplify immune responses, and the activation and / or enhanced activation of peripheral T lymphocytes, including T helper cells and cytotoxic T cells; the activation and / or enhanced activation of B lymphocytes to amplify immune responses, particularly the stimulation of proliferation and / or antibody production and / or secretion; and the enhancement of immune responses through the regulation of cell fate determination during differentiation and / or immune cell development, for example, to regulate, particularly to increase the number of specific immune cell subtypes belonging to the T and B cell lineages, including marginal zone B cells, cytotoxic T cells, or T helper (Th) subsets, particularly Th1, Th2, Th17, and regulatory T cells; or use as an immune adjuvant, such as a vaccine adjuvant. Yet another aspect of the present invention relates to the treatment of muscle diseases, including diseases of skeletal muscle, cardiac muscle, and smooth muscle. In one embodiment, the present invention relates to the treatment of muscular dystrophy (MD). Specific examples include Duchenne MD, Becker MD, congenital MD, limb-girdle MD, facioscapulohumeral MD, Emery-Dreifuss MD, distal MD, myotonic MD, or oculopharyngeal MD. In a further embodiment, the present invention relates to the treatment of muscle hyperproliferative disorders, including myoblastoma, rhabdomyosarcoma, and rhabdomyosarcoma, as well as muscle hyperplasia and muscle hypertrophy. In a further embodiment, the compounds of the present invention can be used for the regeneration of diseased muscle degeneration or atrophy caused by trauma, muscle ischemia or inflammation in muscle atrophy associated with aging, for example, or in muscle atrophy associated with diseases such as myositis and fibromyositis or polio. Yet another aspect relates to the treatment of disorders of the neuroendocrine system, such as cancers of the neuroendocrine system including neuroendocrine small cell carcinoma, neuroendocrine large cell carcinoma and carcinoid tumors, such as pituitary neuroendocrine tumors, adrenal neuroendocrine tumors, medullary thyroid carcinoma (MTC), C cell hyperplasia, anaplastic thyroid carcinoma (ATC), parathyroid adenoma, intrathyroidal nodules, insular carcinoma, hyalinizing trabecular neoplasm, paraganglioma, pulmonary carcinoid tumor, neuroblastoma, gastrointestinal carcinoid, goblet cell carcinoid, pancreatic carcinoid, gastrinoma, glucagonoma, somatostatinoma, VIPoma, insulinoma, non-functional pancreatic islet cell tumor, multiple endocrine neoplasia type 1, or pulmonary carcinoid, for example, in the brain, thyroid, pancreas, gastrointestinal tract, liver, esophagus and lung. Yet another aspect relates to the treatment of disorders of the lung, such as cancers of the lung including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) including squamous cell lung cancer, adenocarcinoma of the lung and large cell carcinoma of the lung. Yet another aspect relates to the treatment of hyperproliferative diseases, cancers or pre-cancerous lesions of the brain, pancreas, breast, ovary, liver, thyroid, urogenital tract, gastrointestinal tract and endothelial tissue, including glioma, mixed glioma, glioblastoma multiforme, astrocytoma, undifferentiated astrocytoma, glioblastoma, oligodendroglioma, undifferentiated oligodendroglioma, undifferentiated oligoastrocytoma, ependymoma, undifferentiated ependymoma, myxopapillary ependymoma, subependymoma, brainstem glioma, optic nerve glioma, as well as forebrain tumors, pancreatic adenocarcinoma, pancreatic ductal adenocarcinoma, pancreatic acinar cell carcinoma, pancreatic solid pseudopapillary neoplasm, intraductal papillary mucinous neoplasm, pancreatic mucinous cystadenocarcinoma, pancreatoblastoma and pancreatic intraepithelial neoplasm, hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, papillary thyroid carcinoma and follicular thyroid carcinoma, cervical cancer, hormone receptor positive breast cancer and hormone receptor negative breast cancer, ovarian cancer, gastric cancer and angiosarcoma. The methods of use of the present invention relate to in vivo, in vitro and ex vivo use, respectively. As used herein, the terms "treating" or "treatment" refer to: (1) inhibiting a disease; e.g., inhibiting a disease, condition or disorder in an individual who is experiencing or displaying the morbidity or symptoms of the disease, condition or disorder (i.e., preventing further progression of the morbidity and / or symptoms); and (2) alleviating a disease; e.g., alleviating a disease, condition or disorder in an individual who is experiencing or displaying the morbidity or symptoms of the disease, condition or disorder, such as reducing the severity of the disease (i.e., reversing the morbidity and / or symptoms); and (3) referring to one or more of slowing the progression of a disease. The term "treating" includes post-treatment care. In some embodiments, administration of a compound of the invention or a pharmaceutically acceptable salt thereof is effective to prevent a disease, e.g., in an individual who may be predisposed to a disease, condition or disorder but who has not yet experienced or displayed the morbidity or symptoms of the disease. In some embodiments, administration of a compound of the invention or a pharmaceutically acceptable salt thereof is effective to prevent a disease, e.g., in an individual who may be predisposed to a disease, condition or disorder but who has not yet experienced or displayed the morbidity or symptoms of the disease. The compounds of the invention may be used in human and veterinary medicine, including the treatment of companion animals such as horses, dogs, cats, rabbits, guinea pigs, fish such as carp, birds such as falcons; and livestock such as cows, poultry, pigs, sheep, goats, camels, yaks and llamas.

[0175] [Pharmaceutical Composition] The present invention further provides a pharmaceutical composition comprising a compound described herein or a pharmaceutically acceptable salt thereof for use in medicine, e.g., in human or veterinary medicine. In some embodiments, the composition further comprises a pharmaceutically acceptable carrier. The effective dosage of the compounds of the present invention, or salts, solvates or prodrugs thereof, is used in addition to physiologically acceptable carriers, diluents and / or adjuvants for manufacturing pharmaceutical compositions. The dosage of the active compound may vary depending on the route of administration, the age and weight of the patient, the nature and severity of the disease to be treated, and similar factors. The daily dosage can be given as a single dose administered once, or can be divided into two or more daily dosages, and is usually 0.001 - 2000 mg. It is particularly preferred to administer a daily dosage of 0.1 - 500 mg, for example 0.1 - 100 mg. Suitable dosage forms are local or systemic, including enteral, oral, rectal, and parenteral, such as infusion and injection, intravenous, intraarterial, intraperitoneal, intramuscular, intracardiac, epidural, intracerebral, intraventricular, intraosseous, intraarticular, intravitreal, intravitreous, intrathecal, intravaginal, intracavitary, intravesical, subcutaneous, intradermal, transdermal, transmucosal, inhalation, intranasal, oral, sublingual, and intralesional formulations. It is particularly preferred to use oral, parenteral, such as intravenous or intramuscular, intranasal formulations, such as dry powder or sublingual, of the compounds of the present invention. Conventional herbal medicine dosage forms, such as tablets, sugar-coated tablets, capsules, dispersible powders, granules, aqueous solutions, alcohol-containing aqueous solutions, aqueous or oily suspensions, gels, hydrogels, ointments, creams, lotions, shampoos, lip balms, mouthwashes, foams, pastes, tinctures, skin patches and tapes, time-release drug delivery systems, and electrophoretic skin delivery systems including implants and devices, and jet injectors, liposomes and transferosome vesicles, vapors, sprays, syrups, juices or drops and eye drops, in occluded or combined forms can be used. Solid pharmaceutical forms can contain inert ingredients and carrier substances such as calcium carbonate, calcium phosphate, sodium phosphate, lactose, starch, mannitol, alginic acid, gelatin, guar gum, magnesium stearate, aluminum stearate, methylcellulose, talc, highly disperse silicic acid, silicone oil, higher molecular weight fatty acids (such as stearic acid), gelatin, agar-agar or vegetable or animal fats and oils, or solid high molecular weight polymers (such as polyethylene glycol); formulations suitable for oral administration can additionally contain flavorings and / or sweeteners, if necessary. Liquid pharmaceutical forms can be sterilized and / or, where appropriate, can contain auxiliary substances such as preservatives, stabilizers, wetting agents, penetration agents, emulsifying agents, spreading agents, solubilizing agents, salts, saccharides or sugar alcohols, and / or viscosity regulators for adjusting the osmotic pressure or for buffering. Examples of such additives are tartaric and citric acid buffers, ethanol and sequestering agents (such as ethylenediaminetetraacetic acid and its non-toxic salts). Liquid polyethylene Oxides, high molecular weight polymers such as microcrystalline cellulose, carboxymethylcellulose, polyvinylpyrrolidone, dextran or gelatin are suitable for adjusting the viscosity. Examples of solid carrier substances are starch, lactose, mannitol, methylcellulose, talc, highly disperse silicic acid, higher molecular weight fatty acids (such as stearic acid), gelatin, agar-agar, calcium phosphate, magnesium stearate, animal and vegetable fats, and solid high molecular weight polymers such as polyethylene glycol. Oily suspensions for parenteral or topical application can be vegetable, synthetic or semi-synthetic oils, such as liquid fatty acid esters having from 8 to 22 C atoms in the fatty acid chain in each case, for example palmitic acid, lauric acid, tridecanoic acid, margaric acid, stearic acid, arachidic acid, myristic acid, behenic acid, pentadecanoic acid, linoleic acid, elaidic acid, brassidic acid, erucic acid or oleic acid, esterified with monohydric to trihydric alcohols having from 1 to 6 C atoms, such as methanol, ethanol, propanol, butanol, pentanol or their isomers, glycols or glycerol. Examples of such fatty acid esters are commercially available Miglyol, isopropyl myristate, isopropyl palmitate, isopropyl stearate, PEG6-capric acid, caprylic / capric acid esters of saturated aliphatic alcohols, polyoxyethylene glycerol trioleate, ethyl oleate, especially artificial duck tail gland fat, coconut fatty acid isopropyl ester, oleyl oleate, decyl oleate, ethyl lactate, dibutyl phthalate, diisopropyl adipate, waxy fatty acid esters such as polyol fatty acid esters. Silicon oils of different viscosities, or aliphatic alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol or oleyl alcohol, or fatty acids such as oleic acid are also suitable. It is also further possible to use vegetable oils such as castor oil, almond oil, olive oil, sesame oil, cottonseed oil, peanut oil or soybean oil. Suitable solvents, gelatinizing agents and solubilizing agents are water or water-miscible solvents. Examples of suitable substances are alcohols such as ethanol or isopropyl alcohol, benzyl alcohol, 2-octyldodecanol, polyethylene glycol, phthalic acid esters, adipic acid esters, propylene glycol, glycerol, di- or tripropylene glycol, waxes, methyl cellosolve, cellosolve, esters, morpholines, dioxane, dimethyl sulfoxide, dimethylformamide, tetrahydrofuran, cyclohexanone and the like. Cellulose ethers such as hydroxypropyl methylcellulose, methylcellulose or ethylcellulose, or soluble starch, which can be dissolved or swollen in both water and organic solvents, can be used as film-forming agents. A mixture of a gelatinizing agent and a film-forming agent is also entirely possible. In this case, in particular, ionic polymers such as sodium carboxymethylcellulose, polyacrylic acid, polymethacrylic acid and their salts, sodium amylopectin semiglycolate, alginic acid or propylene glycol alginate as the sodium salt, gum arabic, xanthan gum, guar gum or carrageenan are used. The following can be used as further pharmaceutical adjuvants: glycerol, paraffins of different viscosities, triethanolamine, collagen, allantoin and novanthisol acid. The use of surfactants, emulsifiers or wetting agents, for example, Na lauryl sulfate, aliphatic alcohol ether sulfate, di-Na-N-lauryl-beta-iminodipropionate, polyethoxylated castor oil or sorbitan monooleate, sorbitan monostearate, polysorbate (for example Tween), cetyl alcohol, lecithin, glycerol monostearate, polyoxyethylene stearate, alkylphenol polyglycol ether, cetyltrimethylammonium chloride or mono / dialkyl polyglycol ether monoethanolamine salt of orthophosphoric acid may also be required for the preparation of the formulation. Stabilizers such as montmorillonite or colloidal silica, for example tocopherol or butylhydroxyanisole, or p- Preservatives such as p-hydroxybenzoic acid esters can also be used to prepare the desired formulation. Formulations for parenteral administration may exist in individual dosage unit forms such as ampoules or vials. Preferably, solutions of the active compound, preferably aqueous solutions, and especially isotonic solutions and suspensions are also used. These injection forms may be available as ready-to-use formulations, or, where appropriate, the active compound, for example a lyophilisate, containing other solid carrier substances, may be prepared directly before use by mixing with the desired solvent or suspending agent. Intranasal formulations may exist as aqueous or oily solutions or aqueous or oily suspensions. They may also exist as lyophilisates which are prepared before use with a suitable solvent or suspending agent. Inhalable formulations may exist as powders, solutions or suspensions. Preferably, inhalable formulations are in the form of powders as a mixture of the active ingredient with a suitable formulation adjuvant such as lactose, for example. The formulations are manufactured, aliquoted and sealed under customary antibacterial and aseptic conditions. As described above, the compounds of the present invention may be administered, as a combination therapy, as a continuous therapy or as a simultaneous combination therapy, together with a further active agent, for example a therapeutically active compound useful in the treatment of the above-mentioned disorders. These therapeutically active compounds are nucleosides and nucleobase analogs such as cytarabine, gemcitabine, azathioprine, mercaptopurine, fluorouracil, thioguanine, azacitidine, capecitabine, doxifluridine, etc.; platinum-based drugs such as cisplatin, oxaliplatin, carboplatin and nedaplatin, etc.; anthracyclines such as doxorubicin, epirubicin, valrubicin, idarubicin, daunorubicin, sabarubicin, pixantrone and mitoxantrone, etc.; peptide antibiotics such as actinomycin and bleomycin, etc.; alkylating agents such as mechlorethamine, chlorambucil, melphalan, nitrosourea, dacarbazine, temozolomide and cyclophosphamide, etc.; mitotic inhibitors including taxanes and vinca alkaloids such as docetaxel, paclitaxel, abraxane, cabazitaxel, vinblastine, vindesine, vinorelbine and vincristine, etc.; topoisomerase inhibitors such as irinotecan, topotecan, teniposide and etoposide, etc.; other cytostatic agents such as hydroxyurea and methotrexate, etc.; proteasome inhibitors such as bortezomib, ixazomib, etc. chemotherapeutic agents;and kinase inhibitors, other targeted therapeutic agents such as cell cycle inhibitors, regulators, i.e., inhibitors and activators of signaling pathways including growth factor signaling, cytokine signaling, NF-kappa B signaling, AP1 signaling, JAK / STAT signaling, EGFR signaling, TGF-beta signaling, Notch signaling, Wnt signaling, Hedgehog signaling, hormone and nuclear receptor signaling, e.g., erlotinib, lapatinib, dasatinib, imatinib, afatinib, vemurafenib, dabrafenib, nilotinib, cetuximab, trametinib, palbociclib, cobimetinib, cabozantinib, pegaptanib, crizotinib, olaparib, panitumumab, cabozantinib, ponatinib, regorafenib, entrectinib, ranibizumab, ibrutinib, trastuzumab, rituximab, alemtuzumab, gefitinib, bevacizumab, lenvatinib, bosutinib, axitinib, pazopanib, everolimus, temsirolimus, luxolitinib, tofacitinib, sorafenib, sunitinib, aflibercept, vandetanib; vismodegib and sonidegib; retinoids such as retinol, tretinoin, isotretinoin, alitretinoin, bexarotene, tazarotene, acitretin, adapalene and etretinate; hormone signaling modulators including estrogen receptor modulators, androgen receptor modulators and aromatase inhibitors, e.g., raloxifene, tamoxifen, fulvestrant, lasofoxifene, toremifene, bicalutamide, flutamide, anastrozole, letrozole and exemestane; histone deacetylase inhibitors; , for example, vorinostat, romidepsin, panobinostat, belinostat and tidamide; and ingenol mebutate; valproic acid, resveratrol, hesperetin, chrysin, phenethyl isothiocyanate, thiocolchicine; N-methylhematecine chloride; and immune response modifiers including immune checkpoint inhibitors, for example imiquimod, ipilimumab, atezolizumab, ofatumumab, rituximab, nivolumab and pembrolizumab; and anti-inflammatory agents including glucocorticoids, and non-steroidal anti-inflammatory drugs, for example corticosteroid preparations, dexamethasone, betamethasone, prednisone, prednisolone, methylprednisolone, triamcinolone-hexacetonide, mometasone furoate, clobetasol propionate, acetylsalicylic acid, salicylic acid and other salicylic acid esters, diflunisal, ibuprofen, dexibuprofen, naproxen, fenoprofen, ketoprofen, dexketoprofen, loxoprofen, flurbiprofen, oxaprozin, indomethacin, ketorolac, tolmetin, diclofenac, etodolac, aceclofenac, nabumetone, sulindac, mefenamic acid, meclofenamic acid, flufenamic acid, tolfenamic acid, celecoxib, parecoxib, etoricoxib and firocoxib; and ACE inhibitors; and beta-blockers; and myostatin inhibitors; and PDE-5 inhibitors; and antihistamines may be included but are not limited thereto. For combination therapy, the active ingredients may be formulated as a composition containing several active ingredients in a single dosage form and / or as a kit containing the individual active ingredients in separate dosage forms. The active ingredients used in combination therapy may be co-administered or administered individually. The compounds of the invention may be administered as antibody-drug conjugates. The compounds of the invention may be administered in combination with surgery, cryotherapy, electrodessication, radiation therapy, photodynamic therapy, laser therapy, chemotherapy, targeted therapy, immunotherapy, gene therapy, antisense therapy, cell-based transplantation therapy, stem cell therapy, physical therapy and occupational therapy.

[0176] [Chemical Synthesis] Abbreviations

[0177]

Table 46

[0178] [General Considerations] The compounds listed in Tables 46 and 47 were identified using pre-coated silica TLC sheets and common organic solvents such as petroleum ether, ethyl acetate, dichloromethane, methanol, toluene, triethylamine or acetic acid as eluents, preferably as binary or ternary solvent mixtures thereof. UV light with a wavelength of 254 or 366 nm, and / or common staining solutions such as phosphomolybdic acid, potassium permanganate, or ninhydrin were used to visualize the compounds. The reactions were also monitored by this method for completion. Unless otherwise specified, the reactions were carried out under an inert atmosphere. If necessary, dry solvents were used. All reactions were stirred using a stirring plate and a magnetic stir bar. The compounds listed in Table 46 were further identified by mass spectrometry using formic acid in the mobile phase for cation detection, while no additives were used for anions. When the molecule was difficult to ionize in the negative mode, ammonium carbonate was used. Representative compounds and compounds showing insufficient ionization by mass spectrometry were also identified by nuclear magnetic resonance spectroscopy (Table 47). Chemical shifts (δ) were reported in parts per million (ppm) relative to the residual solvent peak rounded to the nearest 0.01 ppm for protons and 0.1 ppm for carbon (Reference: CHCI3 1 H: 7.26 ppm, 13 C: 77.2 ppm], DMSO 1 H: 2.50 ppm, 13C: 39.5 ppm]). The coupling constant (J) was reported in Hz to the nearest 0.1 Hz. The peak multiplicities were indicated as follows: s (singlet), d (doublet), t (triplet), q (quartet), hept (heptet), m (multiplet), and br (broad).

[0179] [Synthesis of the Described Compounds] The aforementioned compounds of the present invention falling within the scope of Formula I can be synthesized and purified by those skilled in the art, and are preferably synthesized according to the general procedures (A to I) described herein, as shown in Scheme 1.

[0180]

Chemical Formula

[0181] Scheme 1: General synthesis scheme A) Under argon, with stirring, to a solution of the corresponding mono- or disubstituted phenol (1.0 - 1.5 equiv) dissolved in DMSO (0.5 M) and 4-alkyl ester halo(hetero)aryl (1 equiv), K2CO3 (1.5 equiv) was added, and the mixture was stirred at room temperature until completely converted or heated between 40 °C and 160 °C. The mixture was returned to room temperature and partitioned between an organic solvent, preferably petroleum ether, and water. The aqueous layer was extracted two more times, then the combined organic phases were washed with NaOH (aq, 2 M) and then brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was then purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt, DCM / MeOH or petroleum ether / AcOEt / NEt3) to obtain the desired bi(hetero)aryl ether ethyl ester.

[0182] B) The corresponding bis(hetero)aryl ether alkyl ester (1 equiv) was dissolved in dry THF (0.2 M) with stirring under argon, and the resulting solution was cooled to 0 °C in an ice bath. Then DIBAL-H (2.5 equiv, 1.2 M in toluene) was added dropwise, and the mixture was stirred at that temperature until complete conversion. The reaction was quenched by the Feiser method, filtered, concentrated under vacuum, and the residue was then purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to give the desired alcohol.

[0183] C) Depending on the scale and substrate, one of these procedures was used. MnO2 (2 - 4 equiv) was added to the corresponding alcohol (1 equiv) dissolved in DCM (0.2 M) with vigorous stirring. The resulting suspension was stirred at room temperature or 40 °C until complete conversion. The reaction was then diluted with AcOEt, filtered through celite, and concentrated under vacuum. The residue was then purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to give the desired aldehyde.

[0184] Dess-Martin periodinane (1.2 equiv) was added to the corresponding alcohol (1 equiv) dissolved in DCM or DMSO (0.2 M) with vigorous stirring. The resulting suspension was stirred at room temperature until complete conversion. The solution was diluted with AcOEt, quenched with aq. sat. NaHCO3, and the phases were separated. The aqueous layer was extracted two more times, and the combined organic phases were then washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was then purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to give the desired aldehyde.

[0185] To a solution of oxalyl chloride (2 equiv) in DCM (0.2 M) at -78 °C, dry DMSO (4 equiv) was added and the mixture was stirred for 30 minutes. Then a solution of the corresponding alcohol (1 equiv) in DCM (0.2 M) was added, followed by freshly distilled NEt3 (8 equiv). The resulting solution was stirred for 1 hour and then slowly returned to room temperature. The solution was diluted with AcOEt, quenched with 1 M aq HCl, and the phases were separated. The aqueous layer was extracted two more times, and then the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was then purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to afford the desired aldehyde.

[0186] In some cases, the desired aldehyde was found to be unstable and was used directly in the subsequent step without characterization after rapid purification using the indicated method.

[0187] D) To the corresponding aldehyde (1 equiv) dissolved in dry THF (0.2 M) under stirring at 0 °C under argon, either TMSCF3 (2 equiv) followed by TBAF (1 mol%) to obtain the secondary alcohol having the corresponding CF3 or a Grignard reagent (2 equiv) to obtain the corresponding secondary alkyl alcohol was added. In either case, the resulting solution was kept stirred at that temperature until complete conversion. Then, aq HCl (2.5 M) was added and the reaction was kept stirred for an additional 1 hour. Then the reaction was partitioned between AcOEt and water. The aqueous layer was extracted two more times, and then the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was then purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to afford the desired secondary alcohol.

[0188] E) To a stirred solution of the corresponding secondary alcohol (1 equiv) in chloroform (0.2 M) at 0 °C, Dess-Martin periodinane (1.5 equiv) was added. After completion of the reaction, it was partitioned between AcOEt and sat. NaHCO3 aq. The aqueous layer was extracted two more times, and then the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was then purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to afford the desired ketone.

[0189] F) To a stirred solution of the corresponding ketone (1 equiv) in ethanol or methanol (0.2 M), either (hydroxyl)amine (1.2 - 40 equiv), followed by a catalytic amount of PTSA in the case of aliphatic amines or a base (2.5 - 40 equiv) in the case of hydroxylamine, was added. The reaction was then refluxed for 24 - 72 h. After this, celite was added and the volatiles were evaporated under vacuum, or the reaction was then partitioned between AcOEt and HCl a q (1 M), the aqueous layer was extracted two more times, the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. In either case, the residue was purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to afford the desired imine.

[0190] G) To a stirred solution of the corresponding alcohol (1 equiv) in DMF (0.2 M), trimethylamine (2 equiv) was added at 0 °C under stirring under argon, followed by methanesulfonyl chloride (1.2 equiv). The reaction was then stirred for 24 h and then partitioned between AcOEt and H2O. The aqueous layer was extracted two more times, and then the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was then purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to afford the desired mesylate. [[ID=1']]

[0191] H) The corresponding ketone (1 equiv) dissolved in dry THF (0.2 M) under stirring at 0 °C under argon was added with either TMSCF3 (1.3 equiv) to obtain the corresponding di-CF3 alcohol and then TBAF (1 mol%), or a Grignard reagent (2 equiv) to obtain the corresponding tertiary alcohol. In either case, the resulting solution was kept stirred at that temperature until it was completely converted. In the first case, after completion of the conversion, further TBAF (10 mol%) and then water (5.6 equiv) were added, and the reaction mixture was kept stirred for an additional 1 hour. In either case, the reaction mixture was then partitioned between AcOEt and HCl aq (1 M). The aqueous layer was extracted two more times, and then the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to obtain the desired tertiary alcohol.

[0192] I) To the corresponding 4-substituted phenol (1 - 2 equiv) and 4-substituted bromoaryl (1 - 2.5 equiv) dissolved in DMF (0.2 M) were added Cs2CO3 (2 equiv), CuI (10 mol%), and tBuXPos (20 mol%). The mixture was degassed using the freeze-pump-thaw method, placed under argon, stirred vigorously, and refluxed (165 °C) for 72 hours. The mixture was allowed to return to room temperature and partitioned between petroleum ether and NaOH aq (2 M). The aqueous layer was extracted two more times, and then the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to obtain the desired bisaryl ether.

Example

[0193] [Analysis Data] The following compounds were synthesized according to the aforementioned protocol and characterized by mass spectrometry (Table 46) or NMR (Table 47).

[0194]

Table 47-1

[0195]

Table 47-2

[0196]

Table 47-3

[0197]

Table 48

[0198] For the sake of explanation, the synthesis and properties of the following examples will be described in detail.

[0199] XPF-0062: 1-(4-(4-Cyclohexylphenoxy)phenyl)-2,2,2-trifluoroethan-1-ol

[0200]

Chemical formula

[0201] 4-(4-Cyclohexylphenoxy)benzaldehyde (1.84 g, 6.55 mmol, 1 equiv) dissolved in dry THF (26.2 mL, 0.2 M) under stirring at 0 °C under argon was added with TMSCF3 (1.93 mL, 13.1 mmol, 2 equiv) and then TBAF (65 μL, 66 μmol, 1 mol%). The resulting solution was kept stirring at that temperature until it was completely converted. Then, HCl aq (2.5 M) was added and the reaction mixture was kept stirring for an additional 1 hour. Then, the reaction mixture was partitioned between AcOEt and water It was partitioned. The aqueous layer was extracted two more times, and then the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to give 2.13 g of 1-(4-(4-cyclohexylphenoxy)phenyl)-2,2,2-trifluoroethan-1-ol (93%).

[0202] MS: m / z[M-OH] + , calc for [C 20 H 20 F3O] + = 333.14; found 333.19 1 1H-NMR(300MHz,CDCl3) δ 7.41(dt,J=9.0,0.6Hz,2H), 7.23-7.16(m,2H), 7.04-6.91(m,4H), 5.00(qd,J=6.7,4.4Hz,1H), 2.61-2.37(m,2H), 1.99-1.67(m,5H), 1.50-1.19(m,5H). 13 13C-NMR(75MHz,CDCl3) δ 159.1, 154.2, 143.9, 128.9, 128.1, 128.0, 124.3(q,J=282.0 Hz), 119.4, 118.1, 72.47(q,J=32.2Hz), 43.9, 34.6, 26.9, 26.1.

[0203] XPF-0434: 1-(4-(4-(adamantan-1-yl)phenoxy)phenyl)-2,2,2-trifluoroethan-1-one

[0204]

Chemical Structure

[0205] To a stirred solution of 1-(4-(4-(adamantan-1-yl)phenoxy)phenyl)-2,2,2-trifluoroethan-1-ol (750 mg, 1.86 mmol, 1 equiv) in chloroform (9.3 mL, 0.2 M) at 0 °C was added Dess-Martin periodinane (1.03 g, 2.42 mmol, 1.5 equiv). After completion of the reaction, it was partitioned between AcOEt and sat. NaHCO3aq. The aqueous layer was extracted twice more, then the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to afford 647 mg of 1-(4-(4-(adamantan-1-yl)phenoxy)phenyl)-2,2,2-trifluoroethan-1-one (87%).

[0206] MS: m / z[M+H] + , calc for [C 24 H 21 F3O2] + = 399.16; found 399.16 1 1H-NMR(300MHz,CDCl3) δ 8.10-7.89(m,2H), 7.44-7.25(m,2H), 7.02-6.86(m,4H), 2.05(p,J=3.1Hz,3H), 1.86(d,J=2.9Hz,6H), 1.80-1.60(m,6H). 13 13C-NMR(75MHz,CDCl3) δ 179.1(q,J=31Hz), 164.6, 152.0, 148.7, 132.7(q,J=2.3Hz), 126.7, 123.9(q,J=291Hz), 120.2, 117.1, 43.3, 36.7, 36.1, 28.9.

[0207] XPF-1330: 1-(6-(4-(adamantan-1-yl)phenoxy)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethan-1-ol

[0208]

Chemical Structure

[0209] 1-(6-(4-(Adamantan-1-yl)phenoxy)pyridin-3-yl)-2,2,2-trifluoroethan-1-one (52 mg, 0.13 mmol, 1 equiv), which was dissolved in dry THF (0.8 mL, 0.16 M) under stirring at 0 °C under argon, was added with cyclopropylmagnesium bromide (0.6 mL, 0.26 mmol, 2 equiv, 0.4 M solution in THF). The resulting solution was stirred at that temperature until it was completely converted. After completion of the conversion, the reaction mixture was partitioned between AcOEt and HCl aq (1 M). The aqueous layer was extracted twice more, then the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to give 43 mg of 1-(6-(4-(Adamantan-1-yl)phenoxy)pyridin-3-yl)-1-cyclopropyl-2,2,2-trifluoroethan-1-ol (75%).

[0210] MS: m / z[M+H] + , calc for [C 26 H 29 F3NO2] + = 444.21; found 444.30 1 1H-NMR (300 MHz, CDCl3) δ 8.38 (d, J = 2.5 Hz, 1H), 8.05 (dd, J = 8.7, 2.6 Hz, 1H), 7.45 - 7.31 (m, 2H), 7.17 - 6.96 (m, 3H), 6.23 (s, 1H), 2.08 (q, J = 3.1 Hz, 3H), 1.89 (d, J = 3.0 Hz, 6H), 1.79 - 1.62 (m, 7H), 0.87 - 0.72 (m, 1H), 0.64 - 0.48 (m, 1H), 0.40 (tdd, J = 9.1, 5.9, 4.1 Hz, 1H), 0.27 (dtd, J = 9.5, 5.9, 4.2 Hz, 1H). 1313C-NMR (300 MHz, CDCl3) δ 163.6, 151.7, 147.7, 146.5, 139.3, 130.4, 126.3, 121.3, 110.7, 73.68 (d, J = 27.6 Hz), 43.1, 36.5, 35.9, 28.7, 14.8, 1.6. (One of the remaining CF3 groups was not observed due to relaxation time)

[0211] XPF-2249: 1-(4-(4-Cyclohexyl-2-methylphenoxy)phenyl)-2,2,2-trifluoroethan-1-one oxime

[0212]

Chemical Structure

[0213] To a stirred solution of 1-(4-(4-cyclohexyl-2-methylphenoxy)phenyl)-2,2,2-trifluoroethan-1-one (50 mg, 0.14 mmol, 1 equiv) in methanol (0.7 mL, 0.2 M), hydroxylamine hydrochloride (11.5 mg, 0.17 mmol, 1.2 equiv) and then sodium acetate (34 mg, 0.41 mmol, 3 equiv) were added. The reaction mixture was then refluxed for 24 h and partitioned between AcOEt and HCl aq (1 M). The aqueous layer was extracted twice more, and the combined organic phases were washed with brine, dried over Na2SO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to afford 38 mg of 1-(4-(4-cyclohexyl-2-methylphenoxy)phenyl)-2,2,2-trifluoroethan-1-one oxime (73%).

[0214] MS: m / z [M-H] - , calc for [C 21 H 21 F3NO2] - = 376.15; found 376.58 11H-NMR (400 MHz, CDCl3) δ 8.56 (brs, 0.3H), 8.54 (s, 0.7H), 7.56 - 7.47 (m, 1.5H), 7.45 - 7.38 (m, 0.5H), 7.15 - 7.06 (m, 1H), 7.07 - 7.01 (m, 1H), 6.98 - 6.85 (m, 3H), 2.49 (tt, J = 11.5, 3.8 Hz, 1H), 2.18 (s, 2H), 2.17 (s, 1H), 1.96 - 1.80 (m, 4H), 1.80 - 1.72 (m, 1H), 1.49 - 1.33 (m, 4H), 1.33 - 1.19 (m, 1H). 13 13C NMR (101 MHz, CDCl3) δ 160.33, 160.22, 151.08, 150.93, 145.01, 144.93, 130.59, 130.07, 130.01, 125.62, 120.71, 120.58, 118.96, 116.36, 116.22, 44.02, 34.63, 26.92, 26.16, 16.22.

[0215] XPF - 0518: 1-(4-(4-(1-(Trifluoromethyl)cyclopropyl)-phenoxy)phenyl)adamantane

[0216]

Chem.

[0217] 4-(Adamantan-1-yl)phenol (137 mg, 0.6 mmol, 1.5 equiv) and 1-bromo-4-(1-(trifluoromethyl)cyclopropyl)benzene (106 mg, 0.4 mmol, 1 equiv) dissolved in DMF (1.6 mL, 0.2 M) were added with Cs2CO3 (260 mg, 0.8 mmol, 2 equiv), CuI (7.6 mg, 40 μmol, 10 mol%) and tBuXPos (34 mg, 80 μmol, 20 mol%). The mixture was degassed using the freeze, pump, thaw method, placed under argon, stirred vigorously and refluxed (165 °C) for 72 h. The mixture was allowed to return to room temperature and partitioned between petroleum ether and NaOH aq. 2M. The aqueous layer was extracted two more times, then the combined organic phases were washed with brine, dried over Na2SO4, filtered and concentrated under vacuum. The residue was purified by flash chromatography (SiO2, gradient petroleum ether / AcOEt) to give 120 mg of 1-(4-(4-(1-(trifluoromethyl)cyclopropyl)-phenoxy)phenyl)adamantane (72%).

[0218] MS: calc for [C 26 H 26 F3O] + = 411.19; found 411.20 1 1H-NMR (300 MHz, CDCl3) δ 7.43 - 7.36 (m, 2H), 7.36 - 7.30 (m, 2H), 7.03 - 6.91 (m, 4H), 2.18 - 2.04 (m, 3H), 1.95 - 1.88 (m, 6H), 1.86 - 1.68 (m, 6H), 1.38 - 1.30 (m, 2H), 1.05 - 0.97 (m, 2H). 13 13C-NMR (300 MHz, CDCl3) δ 157.9, 154.2, 146.9, 132.6, 130.3, 126.2, 126.42 (q, J = 273.5 Hz) 118.9, 118.0, 43.3, 36.8, 35.9, 27.5 (q, J = 33.3 Hz), 9.81 (q, J = 2.3 Hz).

Claims

1. A compound according to general formula (I) as defined herein, or a salt or solvate thereof. 【Chemical 1】 (wherein, R １ is C １ -C １２ preferably C ４ -C １２ alkyl, C ２ -C １２ preferably C ４ -C １２ alkenyl, C ２ -C １２ preferably C ４ -C １２ alkynyl, C ３ -C ８ cycloalkyl, C ５ -C ８ cycloalkenyl, C ５ -C １２ bicycloalkyl, C ７ -C １２ bicycloalkenyl, C ８ -C １４ tricycloalkyl, -OC １ -C １２ preferably -OC ３ -C １２ alkyl, -OC ２ -C １２ preferably -OC ３ -C １２ alkenyl, -OC ２ -C １２ preferably -OC ３ -C １２ alkynyl, -OC ３ -C ８ cycloalkyl, -OC ５ -C ８ cycloalkenyl, -OC ５ -C １２ bicycloalkyl, -OC ７ -C １２ bicycloalkenyl, -OC ８ -C １４ tricycloalkyl, -SC １ -C １２ preferably -SC ３ -C １２ alkyl, -SC ２ -C １２ preferably -SC ３ -C １２ alkenyl, -SC ２ -C １２ Preferably -SC ３ -C １２ Alkynyl, -SC ３ -C ８ Cycloalkyl, -SC ５ -C ８ Cycloalkenyl, -SC ５ -C １２ Bicycloalkyl, -SC ７ -C １２ Bicycloalkenyl, -SC ８ -C １４ Tricycloalkyl, -NHR ９ Or -NR ９ R １０ (Wherein, R ９ And R １０ Are each independently C １ -C １２ Preferably C ３ -C １２ Alkyl, C ２ -C １２ Preferably C ３ -C １２ Alkenyl, C ２ -C １２ Preferably C ３ -C １２ Alkynyl, C ３ -C ８ Cycloalkyl, C ５ -C ８ Cycloalkenyl, C ５ -C １２ Bicycloalkyl, C ７ -C １２ Bicycloalkenyl, C ８ -C １４ Selected from tricycloalkyl, or R ９ Can form a ring structure together with R １０ ; Wherein, the ring structure containing an N atom is selected from a 3- to 8-membered cyclic structure or a 5- to 12-membered bicyclic structure, and here, all of the above ring structures can further contain one or more heteroatoms independently selected from O, S, and N instead of the carbon atoms contained in the ring structure, in particular here, such substitution results in a residue containing at least twice the number of C atoms as the heteroatom independently selected from O, S, and N). Here, R １ and R ９ and all alkyl, alkenyl, and alkynyl residues included in the definition of R １０ are linear or branched and unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH ２ , -NO ２ , =O, C ３ -C ８ cycloalkyl, C ５ -C ８ cycloalkenyl, C ５ -C １２ bicycloalkyl, C ７ -C １２ bicycloalkenyl, C ８ -C １４ tricycloalkyl, linear or branched -OCH ３ such as -OC １ -C ５ alkyl, -O(cyclopropyl) such as -OC ３ -C ５ cycloalkyl, linear or branched -NH(C １ -C ５ alkyl), linear or branched -N(C １ -C ５ alkyl)(C １ -C ５ alkyl), -NH(cyclopropyl) such as -NH(C ３ -C ５ cycloalkyl), -N(C ３ -C ５ cycloalkyl)(C ３ -C ５ cycloalkyl), linear or branched -N(C １ -C ５ alkyl)(C ３ -C ５ cycloalkyl); Here, R １ , R ９ and R １０ When one or more substituents in which the alkyl, alkenyl and alkynyl residues included in the definitions of are ═O are substituted, such substitution with ═O cannot be one of the groups selected from C═O, S═O and N═O directly bonded to the aromatic ring; Here, R １ , R ９ and R １０ cycloalkyl, cycloalkenyl included in the definitions of All cyclic, bicyclic, and tricyclic structures containing bicycloalkyl, bicycloalkenyl, and tricycloalkyl residues are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH ２ , -NO ２ , =O, linear or branched -CH ３ such as C １ -C ５ alkyl, linear or branched -OCH ３ such as -OC １ -C ５ alkyl, linear or branched -NH(C １ -C ５ alkyl), linear or branched -N(C １ -C ５ alkyl)(C １ -C ５ alkyl), -NH(cyclopropyl) such as -NH(C ３ -C ５ cycloalkyl), -N(C ３ -C ５ cycloalkyl)(C ３ -C ５ cycloalkyl), linear or branched -N(C １ -C ５ alkyl)(C ３ -C ５ cycloalkyl); provided that all alkyl, alkenyl, and alkynyl residues included in the definitions of R １ , R ９ and R １０ may contain one or more heteroatoms independently selected from O, S, and N in place of carbon atoms, and provided that such substitution results in a residue containing at least twice as many C atoms as heteroatoms independently selected from O, S, and N, and provided that such substitution cannot be one of the groups selected from C=O, S=O, and N=O directly bonded to the aromatic ring; Here, R １ , R ９ and R １０ All cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues included in the definitions of may contain one or more heteroatoms independently selected from O, S and N instead of carbon atoms, and here such substitution results in a residue containing at least the same number of C atoms as the heteroatoms independently selected from O, S and N; Here, R １ , R ９ and R １０ all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl and tricycloalkyl residues included in the definitions of may be partially or fully halogenated, in particular fluorinated, more particularly perfluorinated; Herein, the bicyclic and tricyclic residues include fused, bridged and spiro systems; R ２ -R ５ are each independently -H, -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH ２ , -NO ２ , linear or branched C １ -C ４ alkyl, linear or branched C ２ -C ４ alkenyl, linear or branched C ２ -C ４ alkynyl, C ３ -C ６ cycloalkyl, -CH ２ (C ３ -C ６ cycloalkyl), linear or branched -OC １ -C ３ alkyl, -O(cyclopropyl), linear or branched -NH(C １ -C ３ alkyl), linear or branched -N(C １ -C ３ alkyl)(C １ -C ３ alkyl), -NH(cyclopropyl), -N(cyclopropyl) ２ , linear or branched -N(C １ -C ３ alkyl)(cyclopropyl) and are selected from; Here, R ２ -R ５ All alkyl, alkenyl, alkynyl, and cycloalkyl residues included in the definition of are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CH ３ , -CF ３ , -OH, and -OCH ３ , -OCF ３ , -NH ２ , -NHCH ３ , -N(CH ３ ) ２ and are substituted with; Here, R ２ -R ５ All alkyl, alkenyl, alkynyl and cycloalkyl residues included in the definition of may contain one or more heteroatoms independently selected from O, S and N in place of carbon atoms, and here such substitution cannot be one of the groups selected from C=O and S=O directly bonded to the aromatic ring; X １ -X ４ are each independently N, CR １１ , CR １２ , CR １３ , CR １４ and are selected from; R １１ -R １４ are, independently of each other, -H, -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH ２ , -NO ２ , linear or branched C １ -C ４ alkyl, linear or branched C ２ -C ４ alkenyl, linear or branched C ２ -C ４ alkynyl, C ３ -C ６ cycloalkyl, -CH ２ (C ３ -C ６ cycloalkyl), linear or branched -OC １ -C ３ alkyl, -O(cyclopropyl), linear or branched -NH(C １ -C ３ alkyl), linear or branched -N(C １ -C ３ alkyl)(C １ -C ３ alkyl), -NH(cyclopropyl), -N(cyclopropyl) ２ , linear or is selected from branched -N(C １ -C ３ alkyl)(cyclopropyl); Here, R １１ -R １４ All alkyl, alkenyl, alkynyl, and cycloalkyl residues included in the definition of are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CH ３ , -CF ３ , -OH, and -OCH ３ , -OCF ３ , -NH ２ , -NHCH ３ , -N(CH ３ ) ２ and are substituted with; Here, R １１ -R １４ All alkyl, alkenyl, alkynyl, and cycloalkyl residues included in the definition of may contain one or more heteroatoms independently selected from O, S, and N in place of carbon atoms, and here, such substitution cannot be one of the groups selected from C=O and S=O directly bonded to the aromatic ring; Here, R １１ -R １４ is preferably -H, -F, -Cl, -Br, -CH ３ , -CF ３ , -OH, -OCH ３ , -OCF ３ , cyclopropyl, oxiranyl, -C(CH ３ ) ３ , -N(CH ３ ) ２ , -NH ２ , -CN, -CH ２ OCH ３ , -OCH(CH ３ ) ２ , -CH ２ NH ２ , -CH ２ N(CH ３ ) ２ , -CH ２ OH, -NO ２ , -CH ２ -N-morpholinyl; and is selected from R ６ and R ７ are each independently selected from -H, -F, -CH ３ ; or R ６ and R ７ together form a cyclic residue containing the carbon atom to which they are attached, and wherein the cyclic residue is C[[ID=#]] ３ cycloalkyl; R ８ is -H, C １ -C ３ alkyl, preferably -CH ３ , C ２ -C ３ alkenyl, C ２ -C ３ alkynyl, -F, -CF ３ and aromatic and heteroaromatic residues, preferably selected from 6-membered aromatic rings and 5- to 6-membered heteroaromatic rings; Here, R ８ The aromatic and heteroaromatic residues included in the definition of １ C alkylene or C ２ alkylene linker can be bonded to the carbon atom to which R ８ is bonded; Here, all aromatic and heteroaromatic residues included in the definition of R ８ are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH ２ , -NO ２ , linear or branched C １ -C ３ alkyl, C ２ -C ３ alkenyl, C ２ -C ３ alkynyl, cyclopropyl, linear or branched -OCH ３ such as -OC １ -C ３ alkyl, -O(cyclopropyl), linear or branched -NH(C １ -C ３ alkyl), linear or branched -N(C １ -C ３ alkyl)(C １ -C ３ alkyl), -NH(cyclopropyl), -N(cyclopropyl) ２ , linear or branched -N(C １ -C ３ alkyl)(cyclopropyl); Here, R ８ all heteroaromatic residues included in the definition of can contain one or more heteroatoms independently selected from O, S and N instead of carbon atoms; Here, R ８ All alkyl, alkenyl, and alkynyl residues included in the definition of are linear or branched and unsubstituted or substituted with one or more substituents independently selected from ２ -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, and -NH Here, R ８ is preferably -H, -F, -CH ３ , -CH ２ CH ３ -CF ３ , -C ６ H ５ ; Here, R ２ -R ８ and all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl, aromatic and heteroaromatic residues included in the definition of R １１ -R １４ may be partially or fully halogenated, in particular fluorinated, more particularly perfluorinated; Z １ and Z ２ are selected from the following groups: 【Chemical 2】 Here, Z １ is selected from -H, linear or branched C １ -C ３ alkyl, preferably -CH ３ , cyclopropyl, oxiranyl, N-methyl-aziridinyl, thietanyl, -N ３ , -CF ３ , -CF ２ CF ３ and here, Z ２ is selected from linear or branched C １ -C ３ alkyl, preferably -CH ３ , -CF ３ , -CF ２ CF ３ , -OS(O) ２ CH ３ , -OS(O) ２ CF ３ , -OS(O) ２ C ６ H ４ CH ３ , -CN and -OR １５ independently (general formula Ia), where R １５ is -H, C １ -C ８ preferably C １ -C ４ alkyl, C ２ -C ８ preferably C ２ -C ４ alkenyl, C ２ -C ８ preferably C ２ -C ４ alkynyl, C ３ -C ６ cycloalkyl, C ５ -C ６ cycloalkenyl, C ５ -C １２ bicycloalkyl, C ７ -C １２ bicycloalkenyl, C ８ -C １４ tricycloalkyl as well as aromatic and heteroaromatic residues, preferably selected from 5- to 6-membered aromatic rings and 5- to 6-membered heteroaromatic rings; Herein, the bicyclic and tricyclic residues include fused, bridged and spiro systems; Here, R １５ The cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl, aromatic and heteroaromatic residues included in the definition of １ C alkylene or C ２ C alkylene or C ３ C alkylene can be bonded to the O to which R １５ is bonded via a linker; Here, all aromatic and heteroaromatic residues included in the definition of R １５ are unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH ２ , -NO ２ , linear or branched C １ -C ３ alkyl, C ２ -C ３ alkenyl, C ２ -C ３ alkynyl, cyclopropyl, linear or branched -OCH ３ such as -OC １ -C ３ alkyl, -O(cyclopropyl), linear or branched -NH(C １ -C ３ alkyl), linear or branched -N(C １ -C ３ alkyl)(C １ -C ３ alkyl), -NH(cyclopropyl), -N(cyclopropyl) ２ , linear or branched -N(C １ -C ３ alkyl)(cyclopropyl); Here, all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, and tricycloalkyl residues, as well as alkylene linkers, included in the definition of R １５ are linear or branched and unsubstituted or substituted with one or more substituents independently selected from -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -NH ２ , -NO ２ , linear or branched C １ -C ３ alkyl, C ２ -C ３ alkenyl, C ２ -C ３ alkynyl, cyclopropyl, linear or branched -OCH ３ such as -OC １ -C ３ alkyl, -O(cyclopropyl), linear or branched -NH(C １ -C ３ alkyl), linear or branched -N(C １ -C ３ alkyl)(C １ -C ３ alkyl), -NH(cyclopropyl), -N(cyclopropyl) ２ , linear or branched -N(C １ -C ３ alkyl)(cyclopropyl); Here, R １５ all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl and heteroaromatic residues, and alkylene linkers included in the definition of may contain one or more heteroatoms independently selected from O, S and N instead of carbon atoms; Here, all alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkenyl, bicycloalkyl, bicycloalkenyl, tricycloalkyl and heteroaromatic residues, and alkylene linkers included in the definition of R １５ may be partially or fully halogenated, in particular fluorinated, more particularly perfluorinated; Here, R １５ is preferably -H, -CH ３ , -CH ２ CH ３ , n-propyl, isopropyl, cyclopropyl, benzyl; Or here, Z １ and Z ２ together are =O, =S, =NR １６ or zwitterionic =N ［＋］ R １７ O ［-］ and is (general formula Ib); where R １６ is -H, -O H, -OCH ３ , -CN, -S(O)CH ３ , -S(O)CF ３ , -S(O)C(CH ３ ) ３ , -S(O) ２ CH ３ , -S(O) ２ CF ３ , a linear or branched C １ -C ３ alkyl, preferably -CH ３ , cyclopropyl, -CF ３ , -CF ２ CF ３ , -CH ２ CF ３ , -C ６ H ５ and -CH ２ C ６ H ５ selected from; where R １７ is a linear or branched C １ -C ３ alkyl, preferably -CH ３ , cyclopropyl, -C ６ H ５ and -CH ２ C ６ H ５ selected from; Or here, Z １ and Z ２ together form a cyclic residue containing the carbon atoms to which they are attached (general formula Ic); where the cyclic residue is selected from 3-membered, 4-membered, 5-membered and 6-membered rings, where all rings can optionally contain one or more heteroatoms independently selected from O, S and N in place of carbon atoms; where all rings are unsubstituted or -F, -Cl, -Br, -I, -CN, -NCO, -NCS, -OH, -OCH ３ , -NH ２ , -NHCH ３ , -N(CH ３ ) ２ , =O, -CH ３ and -CF ３ and are substituted with one or more substituents independently selected from; Here, Z １ and all alkyl and cyclic residues included in the definition of Z ２ can be partially or fully halogenated, especially fluorinated, more particularly perfluorinated)

2. The compound of claim 1 according to general formula (Ia), or a salt or solvate thereof.

3. The compound of claim 1 according to general formula (Ib), or a salt or solvate thereof.

4. The compound of claim 1 according to general formula (Ic), or a salt or solvate thereof.

5. The compound of any one of claims 1 to 4 under the following conditions. (i) The compounds shown in Table 1 are excluded, (ii) The compounds shown in Table 2 are excluded, and / or (iii) The compounds shown in Table 3 are excluded

6. R １ is methyl, ethyl, n-propyl, n-butyl, n-pentyl, n-hexyl, iso-propyl, sec-butyl, tert-butyl, tert-pentyl, tert-octyl, 3-pentyl, -CF ３ , -CF ２ CF ３ , -(CF ２ ) ２ CF ３ , -CH(CF ３ ) ２ , -CH ２ SCH ３ , -CH ２ CH ２ SCH ３ , -CH ２ SCH ２ CH ３ , -CH ２ CH ２ SCH ２ CH ３ , methoxymethyl, methoxyethyl, methoxypropyl, ethoxymethyl, ethoxyethyl, propoxymethyl, dimethyl-aminomethyl, dimethyl-aminoethyl, diethyl-aminomethyl, ethyl-methyl-aminomethyl, cyclopropyl, methyl-cyclopropyl, ethyl-cyclopropyl, trifluoromethyl-cyclopropyl, perfluoroethyl-cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclopentyl, bicyclohexyl, bicycloheptyl preferably norbornyl, bicyclooctyl, bicyclooctenyl, bicyclononyl, methylbicyclononyl, adamantyl, tricyclodecyl, oxiranyl, oxetanyl, tetrahydrofuranyl, methyltetrahydrofuranyl, trimethyltetrahydrofuranyl, tetrahydropyranyl, aziridinyl, N-methylaziridinyl, azetidinyl, N-methylazetidinyl, difluoroazetidinyl, pyrrolidinyl, N-methylpyrrolidinyl , piperidinyl, N - methylpiperidinyl, difluoropiperidinyl, thiiranyl, thietanyl, tetrahydrothiophenyl, tetrahydrothiopyranyl, dioxanyl, piperazinyl, dimethylpiperazinyl, dithianly, morpholinyl, N - methylmorpholinyl, thiomorpholinyl, N - methylthiomorpholinyl, oxa - azaspiroheptyl, N - methyloxa - azaspiroheptyl, azaspiroheptyl, N - methylazaspiroheptyl, thia - azaspiroheptyl, N - methylthia - azaspiroheptyl, difluorothia - azaspiroheptyl, azaspirooctyl, N - methylazaspirooctyl, oxa - azaspirooctyl, N - methyloxa - azaspirooctyl, oxa - azaspirononyl, N - methyloxa - azaspirononyl, azaspirononyl, N - methylazaspirononyl, oxa - azaspirodecyl, N - methyloxa - azaspirodecyl, azaspirodecyl, N - methylazaspirodecyl, dihydro - oxazinyl, N - methyldihydro - oxazinyl, oxazolidinyl, N - methyloxazolidinyl, dioxolanyl, imidazolidinyl, N - methylimidazolidinyl, N,N - dimethylimidazolidinyl, azepanyl, N - methylazepanyl, azaspirohexyl, N - methylazaspirohexyl, oxa - azadispirodecy, N - methyloxa - azadispirodecy, azadispirodecy, N - methylazadispirodecy, oxa - azabicyclooctyl, N - methyloxa - azabicyclooctyl, azabicyclooctyl, N - methylazabicyclooctyl, azabicycloheptyl, N - methylazabicycloheptyl, azabicyclononyl, N - methylazabicyclononyl, azadamantyl, - O(adamantyl), oxa - azabicyclononyl, N - methyloxa - azabicyclononyl, oxa - azabicycloheptyl, N - methyloxa - azabicycloheptyl, diazabicyclooctyl, N - methyldiazabicyclooctyl, N,N - dimethyldiazabicyclooctyl, diazabicycloheptyl, N - methyldiazabicycloheptyl, N,N - dimethyldiazabicycloheptyl; 4 - oxocyclohexyl; 3 - oxocyclopentyl;The compound according to any one of claims 1 to 5, selected from 2-oxocyclobutyl and 4-oxobicyclo[4.1.0]heptan-1-yl;

7. R １ is preferably C ４ -C １２ alkyl, C ４ -C １２ alkenyl, C ４ -C １２ alkynyl, cyclic, bicyclic and tricyclic residues, a compound according to any one of claims 1 to 6, wherein the alkyl, alkenyl and alkynyl residues are preferably branched and include the following). 【Chemical Formula 3】

8. R ２ -R ３ is each -H, and R ４ is preferably -H or -F, and / or R ５ is -H, -F, -Cl, -Br, -CH ３ , -CF ３ , -CH=CH ２ , -C≡CH, -CH ２ OH, -CH ２ NHCH ３ , -OH, -OCH ３ , -OCF ３ , cyclopropyl, oxiranyl, -CH ２ -N-morpholinyl, -C(CH ３ ) ３ , -CH ２ OCH ３ , -NO ２ , -CN, -NH ２ , -N(CH ３ ) ２ , -OCH(CH ３ ) ２ , -CH ２ NH ２ , -CH ２ N(CH ３ ) ２ The compound according to any one of claims 1 to 7.

9. Substituent R as defined by general formula (I) １ from R ５ The compound according to any one of claims 1 to 8, wherein the 6-membered aromatic ring to which is attached is selected from the following 【Chemical Formula 4】

10. X defined by the general formula (I) １ -X ４ The compound according to any one of claims 1 to 9, wherein the 6-membered aromatic ring containing is selected from the following. 【Chemical Formula 5】

11. Z １ is -H, -CH ３ , -CF ３ or cyclopropyl; and / or, Z ２ is -OH, -OS(O) ２ CH ３ and -CN; for example, a compound according to any one of claims 1 to 10 below. 【Chemical Formula 6】

12. Z １ and Z ２ are combined to form =O, =NR １６ or zwitterionic =N ［＋］ R １７ O ［-］ wherein; here, R １６ is preferably -H, -OH, -OCH ３ , -CH ３ , Cyclopropyl and -CH ２ C ６ H ５ selected from; and wherein R １７ is preferably -CH ３ , -C(CH ３ ) ３ and -CH ２ C ６ H ５ and is a compound according to any one of claims 1 to 10. 【Chemical Formula 7】

13. Z １ and Z ２ together form a 3-, 4- or 5-membered cyclic residue containing the carbon atoms to which they are attached; where this cyclic residue is preferably selected from cyclopropyl, cyclobutyl, oxiranyl, oxetanyl, aziridinyl, azetidinyl, thietanyl, thiazolidinyl, methylthiazolidinyl, thiazolidine-dionyl, methylthiazolidine-dionyl and oxazolidinyl, methyloxazolidinyl, oxazolidine-dionyl and methyloxazolidine-dionyl; and where this cyclic residue is optionally preferably substituted with -F, -OH, -OCH ３ , -NH ２ , -NHCH ３ , -N(CH ３ ), =O, -CH ２ and -CF ３ ３ ３ and is substituted with; And herein, this cyclic residue is more preferably further [Chemical 8] The compound of any one of claims 1 to 10 selected from.

14. R ６ , R ７ and R ８ is -F, respectively, of the compound according to any one of claims 1 to 13.

15. R ６ and R ７ together form a cyclic residue containing a carbon atom to which they are attached, wherein the cyclic residue is cyclopropyl, a compound according to any one of claims 1 to 14.

16. R １ The compound according to any one of claims 1 to 15, wherein R does not contain a heteroatom.

17. R １ The compound of claim 16, wherein R is selected from cyclic, bicyclic and tricyclic structures.

18. R １ The compound according to claim 16 or 17, wherein R is selected from cyclohexyl, norbornyl, bicyclooctyl, bicyclononyl, methylbicyclononyl, tricyclodecyl and adamantyl.

19. R １ The compound of claim 18, wherein R is adamantyl.

20. R １ The compound according to any one of claims 1 to 18, wherein R is selected from residues containing 4 or more, preferably 6 or more, and even more preferably 7 or more carbon atoms.

21. R １ wherein one or more, preferably one or two, of the R １ contain a heteroatom independently selected from O, S and N in place of a carbon atom contained therein, a compound according to any one of claims 1 to 15 or 20.

22. R １ is selected from cyclic, bicyclic and tricyclic structures, or R １ is a compound according to claim 21 selected from residues containing cyclic, bicyclic and tricyclic structures.

23. R １ is a compound according to claim 21 or 22 selected from tetrahydropyranyl, N-methylpiperidinyl, morpholinyl, 4-oxocyclohexyl, azabicycloheptyl, N-methylazabicycloheptyl, oxa-azabicycloheptyl, N-methyldiazabicycloheptyl, azabicyclooctyl, diazabicyclooctyl, N-methyldiazabicyclooctyl, oxa-azabicyclooctyl, azabicyclononyl, aza-adamantyl and -O(adamantyl).

24. R １ The compound of claim 23 wherein R is azabicyclo[3.2.1]octyl and -O(adamantyl).

25. The compound of any one of claims 1 to 24 having structure I-1. 【Chemical Formula 9】 (wherein Z １ and Z ２ are as defined in general formula (I) including general formulas (Ia), (Ib) and (Ic), including substituents and preferred definitions, R １５ is as defined in general formula (Ia), including substituents and preferred definitions, R １６ and R １７ are as defined in general formula (Ib), including substituents and preferred definitions, R ２ -R ８ 、R １１ -R １４ and X １ -X ４ include substituents and preferred definitions, and one As defined in general formula (I))

26. The compound of any one of claims 1 to 25 having structure I-2. 【Chemical 10】 (wherein R １ is as defined in general formula (I) including substituents and preferred definitions, where R １ is selected from cyclic, bicyclic and tricyclic structures, and where R １ contains six or more carbon atoms, optionally independently substituted with heteroatoms selected from O, S and N as defined in general formula (I) R ６ is as defined in general formula (I), including substituents and preferred definitions, where R ６ is different from -H, and furthermore provided that optionally R ６ is different from -CH ３ ​ Z １ and Z ２ are as defined in general formula (I) including general formula (Ia), general formula (Ib) and general formula (Ic), including substituents and preferred definitions, R １５ is as defined in general formula (Ia), including substituents and preferred definitions, R １６ and R １７ are as defined in general formula (Ib), including substituents and preferred definitions, R ２ -R ５ 、R ７ -R １４ and X １ -X ４ include substituents and preferred definitions, and generally As defined in formula (I))

27. The compound of any one of claims 1 to 26 having structure I-3. 【Chemical Formula 11】 (wherein R １ is selected from cyclic, bicyclic and tricyclic structures, and wherein R １ is optionally independently substituted with a heteroatom selected from O, S and N as defined in general formula (I) and contains six or more carbon atoms, R ８ is as defined in general formula (I), including substituents and preferred definitions, where R ８ is different from -H, and furthermore provided that optionally R ８ is different from -CH ３ and is different from Z １ and Z ２ are as defined in general formula (I) including general formula (Ia), general formula (Ib) and general formula (Ic), including substituents and preferred definitions, R １５ is as defined in general formula (Ia), including substituents and preferred definitions, R １６ and R １７ are as defined in general formula (Ib), including substituents and preferred definitions)

28. The compound shown in any one of Tables 4 to 28, or a salt or solvate thereof.

29. The compound of any one of claims 1 to 28 for use in medicine, such as human or veterinary medicine.

30. The compound of any one of claims 1 to 28 for use in the treatment of proliferative disorders, including malignant and non-malignant proliferative disorders.

31. Compounds according to any one of claims 1 to 28 for use in the treatment of non-melanoma skin cancers including squamous cell carcinoma and basal cell carcinoma, precancerous lesions including solar keratosis, cancers such as skin and / or mucosal disorders associated with keratinization defects and / or abnormal keratinocyte proliferation, skin and / or mucosal diseases associated with, attendant to and / or caused by viral infections, skin, mucosal, skin and mucosal appendage, corneal and epithelial tissue diseases including atopic dermatitis and acne, and malignant, non-malignant and hyperproliferative disorders, and for promoting wound healing of the skin and mucosa.

32. Compounds according to any one of claims 1 to 28 for use in the treatment of hyperproliferative disorders, cancers or precancerous lesions of the skin, oral mucosa, tongue, lung, stomach, breast, neuroendocrine cancers such as medullary thyroid cancer, and genitourinary cancers including cancers of the brain, pancreas, liver, thyroid, and cervical and ovarian cancers.

33. Compounds according to any one of claims 1 to 28 for use in the treatment of malignant and non-malignant muscle diseases including muscular dystrophy, or for muscle regeneration, or for hyperproliferative disorders of muscle such as muscle overgrowth and muscle hypertrophy.

34. Compounds according to any one of claims 1 to 28 for use in the treatment of immune system-related disorders including hematopoietic and vascular system disorders such as leukemia and lymphoma, including hematopoietic system cancers such as myeloid malignancies, for example acute and chronic myeloid leukemia and acute and chronic promyelocytic leukemia, and lymphoid malignancies, for example acute and chronic T-cell leukemia and acute and chronic B-cell leukemia and cutaneous T-cell lymphoma.

35. Compounds according to any one of claims 1 to 28 for use in therapeutic immune system-related applications including other immunotherapies such as for use as immunotherapy and immunological adjuvants or vaccine adjuvants.

36. A method of treating a hyperproliferative disorder comprising administering to a subject in need thereof, particularly a human subject, a therapeutically effective amount of a compound according to any one of claims 1 to 28.

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