Repellent compounds comprising a thienopyridine structure

Abstract

The present invention relates to novel anthelmintic compounds. These compounds can be used, for example, for the treatment of the class of helminthiases caused by helminths such as Dirofilaria, in particular Dirofilaria immitis.

Description

Technical Field

[0001] This invention relates to novel anthelmintic compounds. These compounds can be used, for example, to treat helminthiasis caused by worms, such as Dirofilaria, particularly Dirofilaria immitis. Background Technology

[0002] Several serious animal diseases are caused by worms, which can be classified into the following categories: a) tapeworms: for example, *Anaplocephala* spp.; *Dipylidium* spp.; *Diphyllobothrium* spp.; *Echinococcus* spp.; *Moniezias* spp.; *Taenia* spp.; b) trematodes: for example, *Dicrocoelium* spp.; *Fasciola* spp.; *Paramphistomum* spp.; *Schistosoma* spp.; or c) nematodes: for example, *Acanthocheilonema*. spp.); Ancylostomas spp.; Anecator spp.; Ascaridia spp.; Ascaris spp.; Brugia spp.; Bunostomum spp.; Capillaria spp.; Chabertia spp.; Cooperia spp.; Cyathostomum spp.; Cylicocyclus spp.; Cylicodontophorus spp.; Cylicostephanus spp.; Craterostomum spp.; Dictyocaulus spp.); Dipetalonema spp.; Dirofilaria spp.; Dracunculus spp.; Enterobius spp.; Filaroides spp.; Habronema spp.; Haemonchus spp.; Heterakis spp.; Hyostrongylus spp.; Metastrongylus spp.; Meullerius spp.; Necator spp.; Nematodirus spp.; Nippostrongylus spp.); *Oesophagostomum* spp.; *Onchocerca* spp.; *Onchocercidae* spp.; *Ostertagia* spp.; *Oxyuris* spp.; *Parascaris* spp.; *Stephanurus* spp.; *Strongylus* spp.; *Syngamus* spp.; *Toxocara* spp.; *Strongyloides* spp.; *Teladorsagia* spp.; *Toxascaris* spp.; *Trichinella* spp.; *Trichuris* *Trichostrongylus* spp.; *Triodontophorous* spp.; *Uncinaria* spp.; and / or *Wuchereria* spp.

[0003] The helminthiasis caused by the aforementioned worms is also known as helminth infection. These worms typically live in the host's gastrointestinal tract, but can also burrow into other organs, where they can cause physiological damage. For example, the genus *Ascaridia* has been reported to cause partial or even complete gastrointestinal obstruction in affected animals, particularly feathered animals such as birds. Furthermore, another genus of worms, *Haemonchus*, is known to affect animals such as sheep and goats, where this infection typically results in the worm attaching to the gastric mucosa to suck blood from the host. Consequently, affected animals develop anemia and shortness of breath. Further still, the genus *Oesophagostomum* is known to form nodules in the intestines of its infected hosts, which can lead to dysentery.

[0004] Furthermore, heartworm disease, also known as cardiovascular fibrillation, is a serious and often fatal disease that can affect internal organs such as the lungs and heart in pets and some other mammals. This disease is caused by the parasitic nematode *Dirofilaria immitis*, which can reach approximately 30 cm in length and 1 mm in thickness in its adult form. These nematodes live in the heart, lungs, and related blood vessels, causing severe lung disease, heart failure, and damage to other internal organs such as the liver and kidneys. Therefore, heartworm infection can lead to complications in the host, often ultimately resulting in death.

[0005] Heartworm disease is known to affect pets, especially dogs, which are considered the definitive host. However, cats, ferrets, wolves, coyotes, jackals, foxes, bears, sea lions, and in rare cases even humans (a zoonotic disease) can also be affected by heartworm.

[0006] Heartworms must go through different stages before becoming adults and infecting host animals. Mosquitoes play a crucial role in the heartworm's life cycle as they are needed as intermediate hosts. Adult female heartworms living in an infected host produce larvae called microfilariae, which can circulate in the bloodstream for up to two years and are ingested by mosquitoes. When a mosquito bites and draws blood from this infected host, it takes the microfilariae with it. These microfilariae begin to develop inside the mosquito, thus the first and second larval stages (L1) and (L2) of heartworm development occur within the mosquito. Once the larvae mature to the third larval stage (L3), the infective larval stage, the mosquito lands and bites a host. These infective larvae are deposited on the host's skin surface through the mosquito bite and enter the new host, thus entering the subcutaneous tissue at the bite site. After a short period of further growth of about two weeks, they develop into the fourth larval stage (L4) and migrate to the thorax and abdominal muscles. 45 to 60 days after infection, the larvae develop into immature adults (fifth larval stage; L5). Between 75 and 120 days after infection (mosquito bite), these immature heartworms enter the bloodstream and are carried to the heart and lung system, where they grow significantly in size over the next three months. Seven months after infection (mosquito bite), the adults mate, and the females begin to lay the aforementioned microfilariae. Mature heartworms can survive for up to 7 years in dogs and up to 3 years in cats. Due to the long lifespan of these worms, the number of heartworms in infected pets increases every mosquito season.

[0007] Due to the widespread use of anthelmintic compounds, highly resistant worm populations have been reported. This resistance to known anthelmintics is considered to be posing an increasing challenge to the successful treatment of these diseases.

[0008] Both WO2018 / 087036A1 and WO2019 / 025341A1 disclose a compound believed to be an insect repellent, namely a quinoline 3-formamide derivative having the following structure.

[0009]

[0010] Among them, residue R 1 R 2 R 3 R 4 R 5 R 6A and Q are defined accordingly.

[0011] In addition, WO 2017 / 178416 discloses a compound that is considered an insect repellent, namely a pyrazolopyrimidine derivative having the following structure.

[0012]

[0013] Among them, residue R 0 R 1 R 2 R 3 R 4 Q, X, Y, and variable n are defined accordingly.

[0014] These molecules are believed to be regulators of the nematode calcium-activated potassium channel slo-1, which can be considered a nematode ortholog of the human KCa1.1 channel (the Mα1 subfamily of potassium-calcium activated channels), encoded by the KCNMA1 gene (KCa1.1 and KCNMA1 are often used interchangeably). Slo-1 exhibits both calcium-activated potassium channel activity and voltage-gated potassium channel activity. The Slo-1 channel plays an important role in the neuromuscular system and secretory cells. Therefore, slo-1 regulators have been reported to be involved in several processes, including behavioral responses to ethanol, movement, and pharyngeal suction. More specifically, it disrupts neuromuscular transmission, leading to flaccid paralysis, and also affects feeding and oviposition. Furthermore, it slows down the development of larvae and adults in the corresponding worms.

[0015] However, especially given the emergence of resistance to known anthelmintic compounds, there remains an urgent need for novel active pharmaceutical ingredients capable of addressing worm infections.

[0016] Therefore, one object of the present invention is to overcome one or more defects of the prior art.

[0017] One objective is to provide novel anthelmintic compounds that can be used to treat infections in mammals, particularly pets such as cats and dogs, especially dogs. Specifically, one objective is to provide novel anthelmintic compounds that can be used to treat infections in mammals caused by parasites such as *Ostertagia ostertagi*, *Cooperia oncophora*, *Cooperia punctata*, *Trichostrongylus axei*, *Haemonchus placei*, *Haemonchus contortus*, *Nematodirus helvetianus*, *Nematodirus spathiger*, *Trichostrongylus colubriformis*, *Trichostrongylus circumcincta*, *Oesophagostomumvenulosum*, and *Chabertia sheep*. a) worms: * Dictyocaulus viviparous, * Dictyocaulus filaria*, *Dirofilaria immitis*, *Dirofilaria repens*; b) flukes: *Fasciola hepatica*, *Fascioloides magna*, *Dicrocoelium dentriticum*, *Paramphistomum cervi*; c) tapeworms: *Monezia expansa*, especially through infection with *Dirofilaria immitis* (heartworm).

[0018] Another objective is to provide novel anthelmintic compounds that can be used to treat infections in mammals, wherein these compounds are compatible with standard antiparasitic treatments for pets, particularly cats and dogs, especially dogs. Specifically, one objective is to provide novel anthelmintic compounds that can be used to treat infections in pets such as cats and dogs and can be administered orally or topically.

[0019] More specifically, one objective is to provide novel anthelmintic compounds that can be used to treat parasitic infections in mammals, particularly those caused by Dirofilaria immitis (heartworm), without negatively impacting the host due to undesirable side effects.

[0020] In addition, one objective is that the novel anthelmintic compound can be used in different treatment regimens, particularly monthly or longer-term treatment regimens. Summary of the Invention

[0021] Surprisingly, at least one objective can be achieved by providing a compound according to formula (I) or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof:

[0022]

[0023]

[0024] in

[0025] R 1 Selected independently from the following

[0026] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 Aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy group, C 1-6 -alkyl mercapto, halogen, cyano, nitro, hydroxyl, mercapto, NR 2 R 3 COOH, C(=O)OR 4 SR 4 SOR 4 SO2R 4 SO2NR 5 R 6 and C(=O)NR 5 R 6 ,

[0027] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 Aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy or C 1-6The alkyl mercapto groups are each optionally replaced independently by one or more substituents selected from the following groups.

[0028] C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy group, C 1-6 -alkyl mercapto, halogen, cyano, nitro, hydroxyl, mercapto, NR 2’ R 3’ C(=O)OR 4’ SR 4’ SOR 4’ SO2R 4’ SO2NR 5’ R 6’ and C(=O)NR 5’ R 6’ ,

[0029] R 2 and R 3 Selected independently from the following

[0030] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy-C 1-6 -alkyl, C 3-10 -Cycloalkyl-substituted C 1-6 -alkyl group, C substituted with a 5- to 10-membered heterocyclic group 1-6 -alkyl, C 6-10 -Aryl-substituted C 1-6 -alkyl groups and C groups substituted with 5- to 10-heteroaryl groups 1-6 -alkyl, or

[0031] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2, or 3 other ring atoms are selected from N, S, and O.

[0032] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy-C 1-6- Alkyl, C 3-10 -Cycloalkyl-substituted C 1-6 -alkyl group, C substituted with a 5- to 10-membered heterocyclic group 1-6 -alkyl, C 6-10 -Aryl-substituted C 1-6 -alkyl or C-substituted with 5- to 10-heteroaryl groups 1-6 -alkyl or derived from R 2 and R 3 The heterocycle formed together with the N atom to which it is attached is optionally substituted independently by one or more substituents selected from the following.

[0033] C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxyl, mercapto, NR 2” R 3” C(=O)OR 4” SR 4” SOR 4 SO2R 4” SO2NR 5” R 6” and C(=O)NR 5” R 6” ,

[0034] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl,

[0035] R 2’ R 3’ R 4’ R 5’ and R 6’ Independently selected from hydrogen and C 1-6 -alkyl,

[0036] R 2” R 3” R 4” R 5” and R 6” Independently selected from hydrogen and C 1-6 -alkyl,

[0037] R 7Selected independently from the following

[0038] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 4- to 10-membered heterocyclic, C 6-10 Aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy group, C 1-6 -alkyl mercapto, halogen, cyano, nitro, hydroxyl, mercapto, NR 8 R 9 COOH, C(=O)OR 10 SR 10 SOR 10 SO2R 10 SO2NR 11 R 12 and C(=O)NR 11 R 12 ,

[0039] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 4- to 10-membered heterocyclic, C 6-10 Aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy or C 1-6 The alkyl mercapto groups are each optionally replaced independently by one or more substituents selected from the following groups.

[0040] C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy group, C 1-6 -alkyl mercapto, halogen, cyano, nitro, hydroxyl, mercapto, oxo, NR 8’ R 9’ C(=O)OR 10’ SR 10’ SOR 10’ SO2R 10’ SO2NR 11’ R 12’ and C(=O)NR 11’ R 12’ ,

[0041] R 8 and R 9Selected independently from the following

[0042] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy-C1-6-alkyl, with C 3-10 -Cycloalkyl-substituted C 1-6 -alkyl group, C substituted with a 5- to 10-membered heterocyclic group 1-6 -alkyl, C 6-10 -Fragrant substitutes for C 1-6 -alkyl groups and C groups substituted with 5- to 10-heteroaryl groups 1-6 -alkyl, or

[0043] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2, or 3 other ring atoms are selected from N, S, and O.

[0044] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy-C1-6-alkyl, with C 3-10 -Cycloalkyl-substituted C 1-6 -alkyl group, C substituted with a 5- to 10-membered heterocyclic group 1-6 -alkyl, C 6-10 -Aryl-substituted C 1-6 -alkyl or C-substituted with 5- to 10-heteroaryl groups 1-6 -alkyl or derived from R 8 and R 9 The heterocycle formed together with the N atom to which it is attached is each optionally substituted independently by one or more substituents selected from the following.

[0045] C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxyl, mercapto, NR 8” R9” C(=O)OR 10” SR 10” SOR 10” SO2R 10” SO2NR 11” R 12” and C(=O)NR 11” R 12” ,

[0046] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[0047] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[0048] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl,

[0049] R 13 Is it hydrogen or C? 1-3 alkyl,

[0050] R 14 It is hydrogen, C 1-3 Alkyl, C 1-3 Alkoxy, NR 14’ R 14” , where R 14’ and R 14” C is independent 1-3 -alkyl or

[0051] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-, or

[0052] R 13 and R 14 Together with the atoms to which it is attached, it forms an unsaturated ring containing five or six carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms.1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[0053] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0054] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[0055] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0056] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl,

[0057] R 19 Select independently from the following C 6-10 -aryl and 5- to 10-membered heteroaryl,

[0058] Where C 6-10 -Aryl or 5- to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following.

[0059] C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy group, C 1-6 -alkyl mercapto, halogen, cyano, nitro, hydroxyl, mercapto, NR 20 R 21 C(=O)OR 22 SR 22 SOR 22 SO2R 22 SO2NR 23 R 24 and C(=O)NR 23 R 24 ,

[0060] R 20 and R 21 Selected independently from the following

[0061] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy-C 1-6- Alkyl, C 6-10 -aryl-substituted C1-C6-alkyl, C1- to C6-substituted heteroaryl groups 1-6 -alkyl, or

[0062] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2, or 3 other ring atoms are selected from N, S, and O.

[0063] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy or C 1-6 -alkyl mercapto group or R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0064] C 1-6 -alkyl, C 2-6 -Alkenyl, C 2-6 -Alynyl group, C3-10 -cycloalkyl, 5- to 10-membered heterocyclic, C 6-10 -Aryl, 5-to-10-membered heteroaryl, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxyl, mercapto, NR 20’ R 21’ C(=O)OR 22’ SR 22’ SOR 22’ SO2R 22’ SO2NR 23’ R 24’ and C(=O)NR 23’ R 24’ ,

[0065] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[0066] R 20’ R 21’ R 22’ ,R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl,

[0067] R 25 Independently selected from hydrogen and C 1-6 -alkyl.

[0068] In one embodiment of the present invention and / or its embodiments, R 1 Selected independently from the following

[0069] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0070] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0071] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3Selected independently from the following

[0072] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[0073] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O.

[0074] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5- to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0075] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[0076] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl,

[0077] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl.

[0078] In one embodiment of the present invention and / or its embodiments, R 1 Selected independently from the following

[0079] Hydrogen, C 1-6- Alkyl, C 1-6- Alkoxy and halogen,

[0080] Where C 1-6- Alkyl or C 1-6- Each alkoxy group may optionally be substituted by one or more substituents selected independently from the following groups.

[0081] C 1-6- Alkyl, C 1-6- Alkoxy, halogen, cyano, hydroxyl and NR 2’ R 3’ ,

[0082] Where R2’ and R 3’ Independently selected from hydrogen and C 1-3- alkyl.

[0083] In one embodiment of the present invention and / or its embodiments, R 1 Selected independently from the following

[0084] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine, especially hydrogen and methyl.

[0085] In one embodiment of the present invention and / or its embodiments,

[0086] R 7 Selected independently from the following

[0087] Hydrogen, C 1-6- Alkyl, C 2-6- alkenyl, C 3-10- Cycloalkyl, 4- to 10-membered heterocyclic groups, C 1-6- Alkyl, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[0088] Where C 1-6- Alkyl, C 2-6- alkenyl, C 3-10- Cycloalkyl, 4- to 10-membered heterocyclic or C 1-6- Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0089] C 1-6- Alkyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic, C 1-6- Alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0090] R 8 and R 9 Selected independently from the following

[0091] Hydrogen, C 1-6- Alkyl, C 3-10- cycloalkyl, C 6-10-aryl, 5- to 10-membered heterocyclic and 5- to 10-membered heteroaryl, or

[0092] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0093] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5-to-10-membered heterocyclic and 5-to-10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0094] C 1-6- Alkyl, C 1-6- Alkyl, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)-OR 10” and C(=O)NR 11” R 12” ;

[0095] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6- alkyl,

[0096] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6- alkyl,

[0097] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6- alkyl.

[0098] In one embodiment of the present invention and / or its embodiments,

[0099] R 7 Selected independently from the following

[0100] Hydrogen, C 1-6- Alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic groups, C 1-6-Alkoxy, hydroxy, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[0101] Where C 1-6- Alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic or C 1-6- Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0102] C 1-6- Alkyl, 5- to 10-membered heterocyclic, C 1-6- Alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0103] R 8 and R 9 Selected independently from the following

[0104] Hydrogen, C 1-6- Alkyl, C 3-10- cycloalkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[0105] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0106] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 The heterocycle formed together with the N atom attached thereto is optionally substituted by one or more independent substituents selected from the following.

[0107] C 1-6- Alkyl, C 1-6- Alkoxy, hydroxyl and NR 8” R 9” ,

[0108] R 10 R11 and R 12 Independently selected from hydrogen or C 1-6- alkyl,

[0109] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-6- alkyl.

[0110] R 8” and R 9” Independently selected from hydrogen or C 1-6- alkyl.

[0111] In one embodiment of the present invention and / or its embodiments, R 7 Selected independently from the following

[0112] Hydrogen, C 1-6- Alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic groups, C 1-6- Alkoxy, NR 8 R 9 ,

[0113] Where C 1-6- Alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic or C 1-6- Each alkoxy group may optionally be substituted by one or more substituents selected independently from the following groups.

[0114] C 1-6- Alkyl, C 1-6- Alkoxy and halogen,

[0115] R 8 and R 9 Selected independently from the following

[0116] Hydrogen, C 1-6- Alkyl, C 3-6- cycloalkyl,

[0117] Where C 1-6- Alkyl or C 3-6- The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[0118] C 1-6- Alkyl, C 1-6- Alkyl and hydroxyl groups.

[0119] In one embodiment of the present invention and / or its embodiments, R 7 Selected independently from the following

[0120] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[0121] In one embodiment of the present invention and / or its embodiments,

[0122] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3- Alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-, or

[0123] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3- Alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[0124] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3- alkyl,

[0125] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3- alkyl,

[0126] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3- alkyl,

[0127] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3- alkyl.

[0128] In one embodiment of the present invention and / or its embodiments,

[0129] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, or -S-, or

[0130] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[0131] A1 is CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3- alkyl,

[0132] A2 is CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R16” C is independent 1-3- alkyl,

[0133] A3 is CR 17 , where R 17 It's hydrogen.

[0134] A4 is CR 18 , where R 18 It is hydrogen.

[0135] In one embodiment of the present invention and / or its embodiments, 0, 1, or 2 of residues A1, A2, A3, and A4 are N.

[0136] In one embodiment of the present invention and / or its embodiments, R 19 Selected independently from the following

[0137] C 6-10- Aryl and 5- to 10-membered heteroaryl,

[0138] Where C 6-10- The aryl or 5- to 10-membered heteroaryl groups are each optionally substituted by one or more substituents selected independently from the following groups.

[0139] C 1-6- Alkyl, C 3-10- Cycloalkyl, 5- to 10-membered heterocyclic, C 6-10- Aryl, 5- to 10-membered heteroaryl, C 1-6- Alkoxy, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0140] R 20 and R 21 Selected independently from the following

[0141] Hydrogen, C 1-6- Alkyl, C 3-10- cycloalkyl and C 6-10- aryl or

[0142] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0143] Where C 1-6 -alkyl, C 1-6- Alkoxy, C 3-10 -cycloalkyl or C 6-10-Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0144] C 1-6- Alkyl, C 3-10- Cycloalkyl, 5- to 10-membered heterocyclic, C 6-10- Aryl, 5- to 10-membered heteroaryl, C 1-6- Alkyl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’

[0145] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6- alkyl,

[0146] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6- alkyl.

[0147] In one embodiment of the present invention and / or its embodiments, R 19 Selected independently from the following

[0148] C 6-10- Aryl and 5- to 10-membered heteroaryl

[0149] Where C 6-10- The aryl or 5- to 10-membered heteroaryl groups are each optionally substituted by one or more substituents independently selected from the following.

[0150] C 1-6- Alkyl, C 1-6- Alkyl, halogen, cyano, nitro, and hydroxyl groups

[0151] Where C 1-6- Alkyl, C 1-6- Each alkoxy group is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6- Alkyl, C 1-6- Each alkoxy group may optionally be replaced by one or more halogens.

[0152] In one embodiment of the present invention and / or its embodiments, R 19 It is C 6-10-Aryl,

[0153] Where C 6-10- The aryl group is optionally substituted by one or more substituents selected independently from the following groups.

[0154] C 1-6- Alkyl, halogen, cyano, and nitro groups, where C 1-6- Each alkyl group may optionally be replaced by one or more halogens.

[0155] In one embodiment of the present invention and / or its embodiments, R 19 It is C 6-10- Aryl,

[0156] Where C 6-10- The aryl group is a phenyl group that is substituted by one, two, or three independent substituents selected from the following groups.

[0157] Fluorine, chlorine, bromine, trifluoromethoxy, and trifluoromethyl.

[0158] In one embodiment of the present invention and / or its embodiments, R 25 It is hydrogen.

[0159] In one embodiment of the present invention and / or its embodiments, the compound according to formula (I) exists as an (S)-enantiomer.

[0160] Furthermore, the present invention provides a method for preparing a compound according to formula (I), comprising the following steps:

[0161] Compound of formula (A)

[0162]

[0163] Reaction with compound of formula (B)

[0164]

[0165] Where R 1 R 7 R 13 R 14 A1, A2, A3, A4, R 19 and R 25 It is as defined in any of the embodiments described above.

[0166] To obtain the compound according to formula (I).

[0167] Furthermore, the present invention provides a veterinary composition comprising...

[0168] - The compound according to formula (I) as defined in any of the embodiments described herein, and

[0169] - One or more physiologically acceptable excipients.

[0170] In one embodiment of the present invention and / or its embodiments, the one or more physiologically acceptable excipients are selected from carriers, fillers, flavoring agents, binders, antioxidants, buffers, sugar components, lubricants, surfactants, stabilizers, flow agents, disintegrants, and preservatives and mixtures thereof.

[0171] Furthermore, the present invention provides compounds according to formula (I) as defined in any of the embodiments described herein, or veterinary compositions according to the present invention, which are used as pharmaceuticals.

[0172] Furthermore, the present invention provides compounds according to formula (I) or veterinary compositions according to the present invention for treating symptoms / diseases caused by worms.

[0173] In one embodiment of the present invention and / or its embodiments, the disease is heartworm disease.

[0174] In one embodiment of the present invention and / or its embodiments, the worm is *Filaria canis*. Detailed Implementation

[0175] Compounds according to formula (I) or their stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof have been found to be useful for treating helmintic diseases, such as those caused by worms like *Ascaridia galli*, *Haemonchus contortus*, *Oesophagostomum dentatum*, and *Dirofilaria immitis*. In particular, compounds according to the invention and / or any embodiment thereof can be used to treat heartworm disease. Optionally, compounds according to the invention and / or any embodiment thereof can be used to treat diseases caused by nematodes, particularly *Dirofilaria immitis*, wherein the disease caused by *Dirofilaria immitis* is heartworm disease.

[0176] Advantageously, compounds according to the present invention and / or any embodiment thereof are effective against worms such as *Filaria canis*, but are ineffective against bacteria particularly relevant to the health of mammals, especially dogs, such as *Acinetobacter baumannii*, *Staphylococcus* spp., or *Streptococcus* spp.

[0177] The inventors have found that the compounds of the present invention meet these requirements and are therefore very useful in the treatment (and prevention) of diseases caused by worms, such as heartworm disease.

[0178] The following abbreviations and definitions are used throughout this application.

[0179] Generally, referring to an element means including all isotopes of that element. For example, if a group is defined as including hydrogen or having hydrogen residues, it also includes deuterium and tritium.

[0180] Term "C" 1-6 "-alkyl" refers to an alkyl group having 1 to 6 carbon atoms and containing no heteroatoms. Therefore, this term includes straight-chain alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, and hexyl. This term also includes branched isomers of straight-chain alkyl groups, including, but not limited to, the following provided as examples: -CH(CH3)2, -CH(CH3)(CH2CH3), -CH(CH2CH3)2, -C(CH3)3, -CH2CH(CH3)2, -CH2CH(CH2CH3)2, -CH2C(CH3)3, -CH(CH3)CH(CH3)(CH2CH3), -CH2CH2CH(CH3)2, -CH2CH2CH(CH3)(CH2CH3), -CH2CH2C(CH3)3, etc. Therefore, the term "C"... 1-6 "-alkyl" includes primary alkyl groups having 1 to 6 carbon atoms, secondary alkyl groups having 3 to 6 carbon atoms, and tertiary alkyl groups having 4 to 6 carbon atoms.

[0181] Accordingly, the term "C" 1-3 "-alkyl" refers to an alkyl group having 1 to 3 carbon atoms and containing no heteroatoms. Therefore, this term includes straight-chain alkyl groups such as methyl, ethyl, and propyl. The term also includes branched isomers of straight-chain alkyl groups, namely CH(CH3)2. Therefore, the term "C 1-3 "-alkyl" includes primary alkyl groups having 1 to 3 carbon atoms and secondary alkyl groups having 3 carbon atoms.

[0182] Term "C" 2-6 "-Alkenyl" refers to both straight-chain and branched alkenyl groups, such as the "C" defined above. 2-6The terms "-alkyl" refer to those that, except for those with at least one double bond between two carbon atoms, include, but are not limited to, -CH=CH2, -C(CH3)=CH2, -CH=CH(CH3), -CH=C(CH3)2, -CH=CH(CH3), -C(CH3)=CH(CH3), -C(CH2CH3)H=CH2, -CH2=CH(CH2CH3), -CH2CH2-CH=CH2, CH2CH2-C(CH3)=CH2, CH2CH2-CH=C(CH3)H, -CH=CH-(CH2)2CH3, -CH=C(CH3)-CH2CH3, -(CH2)3-CH=CH2, -(CH2)4-CH=CH2, -(CH2)2-CH=C(CH3)2, butadienyl, pentadienyl, and hexadienyl, etc.

[0183] Term "C" 2-6 "-Alynyl" refers to both straight-chain and branched alynyl groups, such as the "C" group defined above. 2-6 The terms "-alkyl" refer to those that, except for the presence of at least one triple bond between two carbon atoms. Examples include, but are not limited to, -C≡CH, -C≡CCH3, -C≡C-CH2CH3, -CH2-C≡CH, -CH(CH3)-C≡CH, -C(CH3)2-C≡CH, -CH2-C≡CCH3, -CH(CH3)-C≡CCH3, -C(CH3)2-C≡CCH3, -CH2-C≡C-CH2CH3, -CH(CH3)-C≡C-CH2CH3, -C(CH3)2-C≡C-CH2CH3, -(CH2)2-C≡C-CH2CH3, -(CH2)3-C≡C-CH3, etc.

[0184] Term "C" 3-10 "-Cycloalkyl" refers to a non-aromatic monocycloalkyl group having 3 to 10 carbon atoms or a non-aromatic polycycloalkyl group having 3 to 10 carbon atoms, wherein the group consists only of carbon and hydrogen atoms. Cycloalkyl groups may contain fused ring or bridged ring systems having 3 to 10 carbon atoms. Non-aromatic monocycloalkyl groups having 3 to 10 carbon atoms include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc. Non-aromatic polycycloalkyl groups having 3 to 10 carbon atoms include, but are not limited to, adamantane, norbornene, decahydronaphthyl, 7,7-dimethyl-bicyclo[2.2.1]heptyl, etc.

[0185] The term "5- to 10-membered heterocyclic group" refers to a cyclic group in which 5 to 10 members (atoms) form a backbone, wherein the backbone of the cyclic compound comprises at least one carbon atom and at least one heteroatom. Examples of heteroatoms include, but are not limited to, N, O, and S. Unless otherwise specified in the specification, a "5- to 10-membered heterocyclic group" can be a monocyclic, bicyclic, or polycyclic group, which may comprise a fused ring or bridged ring system, wherein a portion of the fused ring system may be aromatic; the nitrogen, carbon, or sulfur atom in the "5- to 10-membered heterocyclic group" may optionally be oxidized; the nitrogen atom may optionally be quaternized; and the heterocyclic group residues may be partially saturated.

[0186] Examples of heterocyclic groups include, but are not limited to, pyrrolinyl, 3H-pyrazolyl, 4H-pyrazolyl, dihydropyridinyl, pyrrolylalkyl, imidazoalkyl, piperidinyl, piperazinyl, homopiperazinyl, indolinyl, quininyl, morpholinyl, thiomorpholinyl, thiazoalkyl, dihydrodithiopheneyl, dihydrodithionyl, tetrahydrothiophene, tetrahydrothiaran, benzothiazinyl such as 2H-1,4-benzothiazinyl, dihydrobenzothiazinyl such as 2H-3,4-dihydrobenzothiazinyl, benzodioxoyl such as 1,3-benzodioxoyl, dihydrooxothiopheneyl, and 1,4-oxothiopheneyl. Other examples of heterocyclic groups include, but are not limited to, those described above, in which one or more S atoms in the ring are double-bonded to one or two oxygen atoms (sulfoxide and sulfone), such as tetrahydrothiophene, tetrahydrothiophene oxide and tetrahydrothiophene-1,1-dioxide, as well as thiomorpholine, thiomorpholine oxide and thiomorpholine-1,1-dioxide.

[0187] Term "C" 6-10 "Aryl" refers to a group with an aromatic skeleton structure, where the ring atom of the aromatic skeleton structure is a carbon atom. In other words, "C 6-10 Aryl groups do not contain heteroatoms such as N, S, or O in their aromatic skeleton structures.

[0188] Examples of aryl groups include, but are not limited to, phenyl, biphenyl, and naphthyl groups.

[0189] The term "5- to 10-membered heteroaryl" refers to an aromatic group in which 5 to 10 members (atoms) form the backbone, wherein the backbone of the cyclic compound comprises at least one carbon atom and at least one heteroatom. Examples of heteroatoms include, but are not limited to, N, O, and S. Unless otherwise specified in the specification, "5- to 10-membered heterocyclic group" can be a monocyclic, bicyclic, or polycyclic group, which may include fused ring systems.

[0190] Examples of 5- to 10-membered heteroaryl groups include, but are not limited to, pyrroloyl, imidazolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrazinyl, triazolyl such as 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl and 4H-1,2,4-triazolyl, tetrazolyl such as 1H-tetrazolyl, 2H-tetrazolyl and 5H-tetrazolyl, indole, isoindole, indolinyl, indololinyl, indolazinyl, benzimidazolyl, quinolinyl, isoquinolinyl, indazole, naphridinyl, benzotriazolyl, oxazolyl, isoxazolyl, oxadiazolyl such as 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl , 1,2,5-oxadiazolyl, benzoxadiazolyl, benzoxadiazolyl, benzoxazinyl such as 2H-1,4-benzoxazinyl, thiazolyl, isothiazolyl, thiadiazolyl such as 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl and 1,2,5-thiadiazolyl, thienyl, benzothiazolyl, benzothiadiazolyl, benzothiazinyl, benzofuranyl, quinolinyl, isoquinolinyl, cinnamyl, quinazolinyl, quinoxolinyl, triazinyl, tetraazinyl, purinyl, pteridineyl, furanyl, benzodioxinyl such as 1,3-benzodioxinyl, benzothiophene, benzodithiophene and benzothiazinyl.

[0191] Term "C" 1-6 "-alkoxy" refers to a group based on an alkyl group having 1-6 carbon atoms bonded to an oxygen atom. Alkyl groups having 1-6 carbon atoms can be straight-chain or branched, as defined above regarding "C". 1-6 Those described by "-alkyl".

[0192] Accordingly, the term "C" 1-3 "-alkoxy" refers to a group based on an alkyl group having 1-3 carbon atoms bonded to an oxygen atom. Alkyl groups having 1-3 carbon atoms can be straight-chain or branched, as defined above regarding "C". 1-3 Those described by "-alkyl".

[0193] Term "C" 1-6 "-alkylthiol" refers to a group based on an alkyl group having 1-6 carbon atoms bonded to sulfur. Alkyl groups having 1-6 carbon atoms can be straight-chain or branched, as defined above regarding "C". 1-6 Those described by "-alkyl".

[0194] "Optionally substituted" refers to one or more hydrogen atoms of a substituent group that is optionally substituted by one or more defined substituents.

[0195] Other amines, hydroxyl groups, and thiol groups can be protected. The term "protected" refers to the presence of protecting groups in the functional forms to prevent undesirable reactions. These protecting groups are known to those skilled in the art, for example, from the protecting groups described in Organic Synthesis; Wuts, PGM, John Wiley & Sons, New York, NY (53rd edition, 2014). Protecting groups can be added or removed using the procedures described herein.

[0196] Examples of protected hydroxyl groups include, but are not limited to, silyl ethers, such as those obtained by reacting the hydroxyl group with reagents such as, but not limited to, tert-butyldimethylchlorosilane, trimethylchlorosilane, triisopropylchlorosilane, and triethylchlorosilane; substituted methyl and ethyl ethers, such as, but not limited to, methoxymethyl ether, methylthiomethyl ether, benzyloxymethyl ether, tert-butoxymethyl ether, 2-methoxyethoxymethyl ether, tetrahydropyran ether, 1-ethoxyethyl ether, allyl ether, and benzyl ether; and esters such as, but not limited to, benzoyl carbamate, formate, acetate, trichloroacetate, and trifluoroacetate.

[0197] Examples of protected amine groups include, but are not limited to, amides such as formamide, acetamide, trifluoroacetamide and benzamide; imides such as phthalimide and dithiosuccinimide; urethane esters such as tert-butyloxycarbonyl (Boc) and the like.

[0198] Examples of protected thiol groups include, but are not limited to, thioethers such as S-benzyl thioether and S-4-pyridine methyl thioether; substituted S-methyl derivatives such as hemithio, dithio, and aminothioacetal.

[0199] Stereoisomers are compounds composed of identical atoms connected in the same order but with different spatial positions. Stereoisomers include diastereomers and enantiomers.

[0200] "Physiologically acceptable salt" refers to a salt formed with an inorganic base, organic base, inorganic acid, organic acid, or basic or acidic amino acid.

[0201] Examples of suitable inorganic acids for preparing (physiologically acceptable) salts include, but are not limited to, hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, carbonic acid, sulfuric acid, and phosphoric acid.

[0202] Examples of suitable organic acids for preparing (pharmaceutically acceptable) salts include, but are not limited to, cholic acid, sorbic acid, lauric acid, acetic acid, trifluoroacetic acid, formic acid, propionic acid, succinic acid, glycolic acid, gluconic acid, digluconic acid, lactic acid, malic acid, tartaric acid, citric acid, ascorbic acid, glucuronic acid, maleic acid, fumaric acid, pyruvic acid, aspartic acid, glutamic acid, benzoic acid, anthranilic acid, methanesulfonic acid, stearic acid, salicylic acid, p-hydroxybenzoic acid, phenylacetic acid, mandelic acid, pyruvic acid, ethanesulfonic acid, etc. Benzenesulfonic acid, toluenesulfonic acid, pantothenic acid, 2-hydroxyethanesulfonic acid, p-aminobenzenesulfonic acid, cyclohexylaminosulfonic acid, β-hydroxybutyric acid, galactobionic acid, galacturonic acid, adipic acid, alginic acid, butyric acid, camphoric acid, camphorsulfonic acid, cyclopentanepropionic acid, dodecyl sulfate, glycine, glycerophosphate, heptanoic acid, hexanoic acid, nicotinic acid, 2-naphthalenesulfonic acid, oxalic acid, palmitic acid, pectic acid, 3-phenylpropionic acid, picric acid, neopentanoic acid, thiocyanate, toluenesulfonic acid, undecanoic acid, and acidic amino acids such as aspartic acid and glutamic acid.

[0203] Examples of base addition salts can include, for example, metal salts and organic salts.

[0204] Metal salts include, but are not limited to, alkali metal (Group Ia) salts, alkaline earth metal (Group IIa) salts, and other physiologically acceptable metal salts. Examples of such salts can be made from aluminum, calcium, lithium, magnesium, potassium, sodium, and zinc. For example, free acid compounds can be mixed with sodium hydroxide to form such a base addition salt.

[0205] Organic salts can be made from amines such as trimethylamine, diethylamine, N,N'-dibenzyl-ethylenediamine, chloroprocaine, ethanolamine, diethanolamine, ethylenediamine, N-methylglucosamine, procaine, and basic amino acids such as arginine, lysine, and ornithine.

[0206] As used herein, the term "pharmaceutically acceptable ester" refers to an ester that is hydrolyzed in vivo, including those that readily break down in the human body, leaving behind a parent compound or its salts. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxylic acids, particularly alkanonic acids, alkenonic acids, cycloalkanonic acids, and alkanediacids, wherein each alkyl or alkenyl moiety advantageously has no more than six carbon atoms. Representative examples of specific esters include, but are not limited to, formate esters, acetate esters, propionate esters, butyrate esters, acrylate esters, and ethyl succinate.

[0207] A solvate of a compound can be considered as an organic solvent or water adhering to the compound. Organic solvents are those known to a person skilled in the art. If water adheres to the compound, the corresponding compound is called a hydrate.

[0208] As used herein and as commonly understood by those skilled in the art, the term "polymorph" refers to different crystalline forms of the same molecular entity. Therefore, the aforementioned solvates and hydrates are not included in the definition of polymorphism due to their different chemical compositions, but are instead referred to as "pseudopolymorphs".

[0209] The term "prodrug" refers to a compound that is rapidly converted in the body to produce the parent compound of formula (I) above, for example, through hydrolysis in the blood. This is discussed in detail in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Vol. 14, ACSSymposium Series, and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987.

[0210] As used herein, the term "pharmaceuticalally acceptable prodrug" means a prodrug of the compound of the present invention that, within reasonable medical judgment, is suitable for contact with tissues of humans and lower animals without excessive toxicity, irritation, allergic reactions, etc., is commensurate with a reasonable benefit / risk ratio and is effective for its intended use, and, where possible, is in the zwitterionic form of the compound of the present invention.

[0211] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 As defined above.

[0212] In one embodiment of the present invention and / or its embodiments, R 1 Selected independently from the following

[0213] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0214] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0215] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R3’ R 2 and R 3 Selected independently from the following

[0216] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[0217] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0218] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0219] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[0220] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[0221] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl.

[0222] Optionally, in one embodiment of the invention and / or its embodiments, R 1 Selected independently from the following

[0223] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[0224] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0225] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[0226] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl.

[0227] Optionally, in one embodiment of the invention and / or its embodiments, R 1 Selected independently from the following

[0228] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[0229] Where C 1-6 -alkyl and C 1-6 The -alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0230] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl and NR 2’ R 3’ ,

[0231] Where R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl, more preferably selected from hydrogen and methyl.

[0232] In one embodiment of the present invention and / or its embodiments, R 1 Selected independently from the following

[0233] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine, especially hydrogen and methyl.

[0234] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iai), (Iaii), (Iaiii), or (Iaiv).

[0235]

[0236]

[0237] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 7 R 13 R 14 A1, A2, A3, A4, R 19 and R 25 As defined in any of the embodiments described herein.

[0238] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iai), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iaii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iaiii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iaiv), preferably in the (S)-enantiomer form.

[0239] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 7 As defined below.

[0240] In one embodiment of the present invention and / or its embodiments, R 7 Selected independently from the following

[0241] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[0242] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 -Alkoxy groups are each optionally substituted independently by one or more substituents selected from the following C groups. 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0243] R 8 and R 9 Selected independently from the following

[0244] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[0245] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0246] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycle formed together with the N atom attached thereto is optionally substituted by one or more independent substituents selected from the following.

[0247] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR 10” and C(=O)NR 11” R 12” ;

[0248] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[0249] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[0250] R 8” R 9” R 10” R 11” and R 12”Independently selected from hydrogen and C 1-6 -alkyl.

[0251] In one embodiment of the present invention and / or its embodiments, wherein R 7 Selected independently from the following

[0252] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, hydroxyl, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[0253] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4- to 10-membered heterocyclic or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0254] C 1-6 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0255] R 8 and R 9 Selected independently from the following

[0256] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[0257] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0258] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8and R 9 The heterocycle formed together with the N atom attached thereto is optionally substituted by one or more independent substituents selected from the following.

[0259] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[0260] R 10 R 11 and R 12 Independently selected from hydrogen or C 1-6 -alkyl group, preferably selected from hydrogen or C 1-3 -alkyl,

[0261] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-6 -alkyl group, preferably selected from hydrogen or C 1-3 -alkyl,

[0262] R 8” and R 9” Independently selected from hydrogen or C 1-6 -alkyl group, preferably selected from hydrogen or C 1-3 -alkyl.

[0263] In one embodiment of the present invention and / or its embodiments, R 7 Selected independently from the following

[0264] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[0265] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic or C 1-3 Each of the -alkoxy groups is optionally substituted independently by one or more substituents selected from the following.

[0266] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0267] R 8 and R 9 Selected independently from the following

[0268] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10-membered heteroaryl, or

[0269] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0270] Where C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycle formed together with the N atom attached thereto is optionally substituted by one or more independent substituents selected from the following.

[0271] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[0272] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0273] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0274] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl, preferably selected from hydrogen, methyl or ethyl.

[0275] In one embodiment of the present invention and / or its embodiments, R 7 Selected independently from the following

[0276] Hydrogen, C1-6 -alkyl, C 2-6 -Alkenyl, 4- to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[0277] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[0278] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[0279] R 8 and R 9 Selected independently from the following

[0280] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[0281] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[0282] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[0283] In one embodiment of the present invention and / or its embodiments, R 7 Selected independently from the following

[0284] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl, especially dimethylamino and morpholino-4-yl.

[0285] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibi), (Ibii), (Ibiii), (Ibiv), (Ibv), or (Ibvi).

[0286]

[0287]

[0288]

[0289] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 13 R 14 A1, A2, A3, A4, R 19 and R 25 As defined in any of the embodiments described herein.

[0290] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibvi), preferably in the (S)-enantiomer form.

[0291] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 13 and R 14 And A1, A2, A3 and A4 are defined below.

[0292] In one embodiment of the present invention and / or its embodiments,

[0293] R 13 Is it hydrogen or C? 1-3 Alkyl and

[0294] R 14 It is hydrogen, C 1-3 Alkyl or C 1-3 Alkoxy

[0295] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0296] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[0297] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0298] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl.

[0299] More preferably, in one embodiment of the invention and / or its embodiments,

[0300] R 13 Is it hydrogen or C? 1-3 Alkyl and

[0301] R 14 Is it hydrogen or C? 1-3 alkyl

[0302] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl, C 1-3 Alkoxy

[0303] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl, C1-3 Alkoxy

[0304] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl, C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl, C 1-3 Alkoxy

[0305] Of the residues A1, A2, A3, and A4, 0, 1, or 2 are N.

[0306] More preferably, in one embodiment of the invention and / or its embodiments,

[0307] R 13 It is hydrogen, methyl, or ethyl, preferably hydrogen or methyl and

[0308] R 14 It is hydrogen or methyl, preferably hydrogen.

[0309] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 alkyl,

[0310] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 alkyl,

[0311] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 alkyl,

[0312] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 alkyl,

[0313] Of the residues A1, A2, A3, and A4, 0, 1, or 2 are N.

[0314] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ici).

[0315]

[0316] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 7 R19 and R 25 As defined in any of the embodiments described herein.

[0317] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ici), preferably in the (S)-enantiomer form.

[0318] In one embodiment of the present invention and / or its embodiments,

[0319] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-, or

[0320] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing 5 or 6 carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[0321] Examples of saturated or unsaturated rings containing 5 or 6 carbon atoms (wherein the saturated ring containing 5 or 6 carbon atoms is optionally bounded by one or more C atoms). 1-3 -alkyl or =O substitution, and one or more of the carbon atoms forming a saturated ring are optionally replaced by -NH-, -N=, N-, -O-, -S(O)-, -S(O)2- or -S-; and examples of unsaturated or unsaturated rings containing 5 or 6 carbon atoms (wherein the saturated ring containing 5 or 6 carbon atoms is optionally replaced by one or more C-... 1-3 -alkyl substitution, and one or more of the carbon atoms forming an unsaturated ring optionally replaced by -NH-, -N=, N-, -O- or -S-, including but not limited to residues represented by the following structures.

[0322]

[0323] in

[0324] ------- indicates a bond with an amide group; and

[0325] The bonds representing the fusion of the above-mentioned ring system with the aromatic rings, particularly including A1, A2, A3 and A4.

[0326] In one embodiment of the present invention and / or its embodiments,

[0327] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-.

[0328] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0329] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[0330] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0331] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl.

[0332] In one embodiment of the present invention and / or its embodiments,

[0333] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, or -S-.

[0334] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0335] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0336] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0337] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0338] In one embodiment of the present invention and / or its embodiments,

[0339] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-.

[0340] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[0341] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[0342] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[0343] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[0344] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0345] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Icii), (Iciii), (Iciv), or (Icv).

[0346]

[0347] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 7 R 19 and R 25 As defined in any of the embodiments described herein.

[0348] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Icii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iciii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iciv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Icv), preferably in the (S)-enantiomer form.

[0349] In one embodiment of the present invention and / or its embodiments,

[0350] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing 5 or 6 carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[0351] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0352] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[0353] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0354] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl.

[0355] In one embodiment of the present invention and / or its embodiments,

[0356] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[0357] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0358] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0359] A3 is N or CR 17 , where R17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0360] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0361] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-.

[0362] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[0363] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[0364] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[0365] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[0366] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0367] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Icvi), (Icvii), or (Icviii).

[0368]

[0369] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 7 R 19 and R 25 As defined in any of the embodiments described herein.

[0370] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Icvi), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Icvii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Icviii), preferably in the (S)-enantiomer form.

[0371] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 19 As defined below.

[0372] In one embodiment of the present invention and / or its embodiments,

[0373] R 19 Selected independently from the following

[0374] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[0375] Where C 6-10 -aryl or 5 to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following.

[0376] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0377] R 20 and R 21 Selected independently from the following

[0378] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[0379] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0380] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C1-6 -alkoxy or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0381] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[0382] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[0383] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl.

[0384] In one embodiment of the present invention and / or its embodiments,

[0385] R 19 Selected independently from the following

[0386] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[0387] Where C 6-10 -Aryl or 5 to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following.

[0388] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, C(=O)OR 22 SO2R 22 SO2NR 23 R 24 and C(=O)NR 23 R 24 C 1-6 -alkyl, C 1-6Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[0389] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl.

[0390] In one embodiment of the present invention and / or its embodiments,

[0391] R 19 Select independently from the following C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[0392] Where C 6-10 -Aryl or 5 to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following.

[0393] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, C(=O)OR 22 and C(=O)NR 23 R 24 C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 -Alkoxy groups are optionally replaced by one or more halogens.

[0394] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl.

[0395] In one embodiment of the present invention and / or its embodiments,

[0396] R 19 Selected independently from the following

[0397] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[0398] Where C 6-10 -Aryl or 5 to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following.

[0399] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl, of which C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[0400] In one embodiment of the present invention and / or its embodiments, R 19 It is a 5- to 10-membered heteroaryl group

[0401] The 5 to 10 heteroaryl groups are optionally substituted independently by one or more substituents selected from the following.

[0402] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano and nitro and hydroxy, of which C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[0403] In one embodiment of the present invention and / or its embodiments, R 19 It is a 5- to 10-membered heteroaryl group

[0404] The 5 to 10 heteroaryl groups are optionally substituted independently by one or more substituents selected from the following.

[0405] C 1-6 -The alkyl group is optionally replaced by one or more halogens and halogens, preferably halogens.

[0406] Examples of 5- to 10-membered heteroaryl groups include, but are not limited to, pyrroloyl, imidazolyl, pyrazolyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidin-3-yl, pyrimidin-4-yl, pyrazinyl, pyridazinyl, triazolyl such as 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl and 4H-1,2,4-triazolyl, tetrazolyl such as 1H-tetrazolyl, 2H-tetrazolyl and 5H-tetrazolyl, indole, isoindole, indolinyl, indolinyl, benzimidazolyl, quinolinyl, quinolin-8-yl, isoquinolinyl, indazole, naphridinyl, benzotriazolyl, oxazolyl, isoxazolyl, oxadiazolyl such as 1,2,4 -Oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, benzoxadiazolyl, benzoxadiazolyl such as 2H-1,4-benzoxazinyl, thiazolyl, isothiazolyl, thiadiazolyl such as 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl and 1,2,5-thiadiazolyl, thiophene-2-yl, thiophene-3-ylbenzothiazolyl, benzothiadiazolyl, benzothiazinyl, benzofuranyl, quinolinyl, isoquinolinyl, cinnamyl, quinazolinyl, quinoxolinyl, triazinyl, tetraazinyl, purinyl, pteridinyl, furanyl, benzodioxoyl such as 1,3-benzodioxoyl, benzothiophene, benzodithiophene and benzooxythiophene. Preferred are pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidin-3-yl, pyrimidin-4-yl, quinoline-8-yl, thiophene-2-yl, and thiophene-3-yl.

[0407] In one embodiment of the present invention and / or its embodiments, R 19 It consists of 5 to 10 aryl compounds.

[0408] The 5 to 10 heteroaryl groups are substituted by one or more substituents independently selected from the following:

[0409] C 1-6 -The alkyl group is optionally replaced by one or more halogens and halogens, preferably halogens.

[0410] In one embodiment of the present invention and / or its embodiments, R 19 Selected from the following

[0411] 2,5-Dichloropyridin-4-yl, 2,6-Dichloropyridin-4-yl, 5-chlorothiophen-2-yl, 5-chlorothiophen-3-yl and 2,6-difluoropyridin-yl.

[0412] In one embodiment of the present invention and / or its embodiments, R 19 Selected from the following

[0413] 3,5-Dichlorophenyl, 2,3-Dichlorophenyl, 2,3,5-Trifluorophenyl, 3-Trifluoromethylphenyl, 3-Methoxyphenyl, 2,3-Dimethylphenyl, 3-Chlorophenyl, 3-Trifluoromethoxyphenyl, 3-Dimethylaminophenyl, 3,5-Difluorophenyl, 2,3-Difluorophenyl, 3,4,5-Trifluorophenyl, 2-Fluoro-3-chlorophenyl, 2-Fluoro-5-Trifluoromethylphenyl, Naphth-1-yl, 2-Fluoro-5-chlorophenyl, 3-Fluoro-5-Trifluoromethylphenyl and 2,3,5-Trichlorophenyl.

[0414] In one embodiment of the present invention and / or its embodiments, wherein R 19 It is C 6-10 -Aryl

[0415] Where C 6-10 The aryl group is optionally substituted by one or more substituents selected independently from the following groups.

[0416] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, and nitro, of which C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[0417] In one embodiment of the present invention and / or its embodiments, wherein R 19 It is C 6-10 -Aryl

[0418] Where C 6-10 The aryl group is a phenyl group that is substituted by one, two, or three independent substituents selected from the following groups.

[0419] Fluorine, chlorine, bromine, trifluoromethyl and trifluoromethoxy.

[0420] Examples of phenyl groups substituted with 1, 2, or 3 independently selected from the following substituents:

[0421] Fluorine, chlorine, bromine, methyl, methoxy, dimethylamine, trifluoromethyl, and trifluoromethoxy include, but are not limited to, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2,3-difluorophenyl, 2,4-difluorophenyl, 2,5-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,3-dichlorophenyl, 2,4-dichlorophenyl, 2,5-dichlorophenyl, 3,4-dichlorophenyl, 3,5-dichlorophenyl, 2,3-dibromophenyl, 2,4-dibromophenyl, 2,5-dibromophenyl, 3,4-dibromophenyl, 3,5-dibromophenyl, 2,3,4-dibromophenyl, 2,5-dibromophenyl, 3,4-dibromophenyl, 3,5-dibromophenyl, 2,3,4- Trifluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 2,3,4-trichlorophenyl, 2,3,5-trichlorophenyl, 3,4,5-trichlorophenyl, 2,3,4-tribromophenyl, 2,3,5-tribromophenyl, 3,4,5-tribromophenyl, 2-chloro-3-fluorophenyl, 2-chloro-4-fluorophenyl, 2-chloro-5-fluorophenyl, 3-chloro-2-fluorophenyl, 3-chloro-4-fluorophenyl, 3-chloro-5-fluorophenyl, 3-chloro-6-fluorophenyl, 4-chloro-2-fluorophenyl, 4-chloro-3-fluorophenyl, 4-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-4-fluorophenyl, 3-bromo-2-fluorophenyl, 3-bromo- 5-Fluorophenyl, 3-Bromo-6-fluorophenyl, 4-Bromo-2-chlorophenyl, 4-Bromo-3-chlorophenyl, 3,4-Dichloro-2-fluorophenyl, 3,5-Dichloro-2-fluorophenyl, 3,5-Dichloro-4-fluorophenyl, 4,5-Dichloro-3-fluorophenyl, 3,4-Dibromo-2-fluorophenyl, 3,5-Dibromo-2-fluorophenyl, 4,5-Dibromo-3-fluorophenyl, 2-Chloro-3,4-Difluorophenyl, 2-Chloro-3,5-Difluorophenyl, 3-Chloro-4,5-Difluorophenyl, 3-Chloro-5-6-Difluorophenyl, 3,4-Dibromo-2-chlorophenyl, 3,5-Dibromo-2-chlorophenyl, 4,5-Dibromo-3-chlorophenyl, 2-Bromo-3,4-Difluorophenyl, 2-Bromo- 3,5-Difluorophenyl, 3-Bromo-4,5-Difluorophenyl, 2-Bromo-3,4-Dichlorophenyl, 2-Bromo-3,5-Dichlorophenyl, 3-Bromo-4,5-Dichlorophenyl, 4-Bromo-3-chloro-2-fluorophenyl, 4-Bromo-2-chloro-3-fluorophenyl, 2-Bromo-3-chloro-4-fluorophenyl, 5-Bromo-3-chloro-2-fluorophenyl, 5-Bromo-2-chloro-3-fluorophenyl, 2-Bromo-3-chloro-5-fluorophenyl, 5-Bromo-4-chloro-3-fluorophenyl, 5-Bromo-3-chloro-4-fluorophenyl, 3-Bromo-4-chloro-5-fluorophenyl, 2-Fluoro-3-chlorophenyl, 2-Fluoro-5-trifluoromethylphenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-Dimethylphenyl, 2-fluoro-5-chlorophenyl, 2-trifluoromethoxyphenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3-fluoro-5-trifluoromethylphenyl, 2-chloro-5-trifluoromethylphenyl, 2-chloro-3-trifluoromethylphenyl, 3-chloro-5-trifluoromethylphenyl, 3-fluoro-5-trifluoromethylphenyl.

[0422] In one embodiment of the present invention and / or its embodiments, R 19 Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl, 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-chloro-3 -Fluorophenyl, 3-chloro-2-fluorophenyl, 3-chloro-5-fluorophenyl, 3-chloro-6-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl, 2-fluoro-3-chlorophenyl and 2,3,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 3-chloro-5-fluorophenyl, 2-fluoro-3-chlorophenyl, 2,3,5-trichlorophenyl and 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0423] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Idi), (Idii), (Idiii), (Idiv), (Idv), (Idvi), (Idvii), or (Idviii).

[0424]

[0425]

[0426]

[0427] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 7 R 13R 14 A1, A2, A3, A4 and R 25 As defined in any of the embodiments described herein.

[0428] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Idi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Idii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Idiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Idiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Idv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Idvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Idvii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idviii), preferably in the (S)-enantiomer form.

[0429] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 25 As defined below.

[0430] In one embodiment of the present invention and / or its embodiments, R 25 It is hydrogen or methyl, more preferably hydrogen.

[0431] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iei) or (Ieii).

[0432]

[0433] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 7 R 13 R 14 A1, A2, A3, A4 and R 19 As defined in any of the embodiments described herein.

[0434] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iei), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ieii), preferably in the (S)-enantiomer form.

[0435] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 and R 7 As defined below.

[0436] In one embodiment of the present invention and / or its embodiments,

[0437] R 1 Selected independently from the following

[0438] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0439] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0440] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[0441] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[0442] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0443] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0444] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[0445] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[0446] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[0447] R 7 Selected independently from the following

[0448] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[0449] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 -Alkoxy groups are each optionally substituted independently by one or more substituents selected from the following C groups. 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0450] R 8and R 9 Selected independently from the following

[0451] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[0452] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0453] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0454] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR 10” and C(=O)NR 11” R 12” ;

[0455] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[0456] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[0457] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl.

[0458] In one embodiment of the present invention and / or its embodiments,

[0459] R1 Selected independently from the following

[0460] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[0461] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0462] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[0463] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[0464] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl,

[0465] and

[0466] R 7 Selected independently from the following

[0467] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[0468] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic or C 1-3 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[0469] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’R 12’ ,

[0470] R 8 and R 9 Selected independently from the following

[0471] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[0472] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0473] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycle formed together with the N atom attached thereto is optionally substituted by one or more independent substituents selected from the following.

[0474] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[0475] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0476] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0477] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl, preferably selected from hydrogen, methyl or ethyl.

[0478] In one embodiment of the present invention and / or its embodiments,

[0479] R 1 Selected independently from the following

[0480] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[0481] and

[0482] R 7 Selected independently from the following

[0483] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[0484] Where C 1-6- Alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[0485] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[0486] R 8 and R 9 Selected independently from the following

[0487] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[0488] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[0489] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[0490] Appropriately, R 7 Selected independently from the following

[0491] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[0492] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ifi), (Ifii), (Ifiii), (Ifiv), (Ifv), or (Ifvi).

[0493]

[0494]

[0495] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 13 R 14 A1, A2, A3, A4, R 19 and R 25 As defined in any of the embodiments described herein.

[0496] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ifi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ifii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ifiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ifiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ifv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ifvi), preferably in the (S)-enantiomer form.

[0497] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 and R 13 R 14 A1, A2, A3, and A4 are defined below.

[0498] In one embodiment of the present invention and / or its embodiments,

[0499] R 1 Selected independently from the following

[0500] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0501] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0502] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[0503] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[0504] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0505] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0506] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[0507] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[0508] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl.

[0509] and

[0510] R 13 and R 14Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-.

[0511] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0512] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[0513] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0514] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl.

[0515] In one embodiment of the present invention and / or its embodiments,

[0516] R 1 Selected independently from the following

[0517] Hydrogen, C1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[0518] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0519] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[0520] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl.

[0521] and

[0522] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, or -S-.

[0523] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0524] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0525] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0526] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0527] In one embodiment of the present invention and / or its embodiments,

[0528] R 1 Selected independently from the following

[0529] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[0530] and

[0531] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-.

[0532] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[0533] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[0534] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[0535] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[0536] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0537] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igi), (Igii), (Igiii), (Igiv), (Igv), or (Igvi).

[0538]

[0539]

[0540] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 7 R 19 and R 25 As defined in any of the embodiments described herein.

[0541] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igvi), preferably in the (S)-enantiomer form.

[0542] In one embodiment of the present invention and / or its embodiments,

[0543] R 1 Selected independently from the following

[0544] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0545] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0546] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[0547] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10-membered heteroaryl, or

[0548] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0549] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0550] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[0551] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[0552] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl.

[0553] and

[0554] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing 5 or 6 carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[0555] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0556] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’and R 16” C is independent 1-3 -alkyl,

[0557] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0558] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl.

[0559] In one embodiment of the present invention and / or its embodiments,

[0560] R 1 Selected independently from the following

[0561] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[0562] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0563] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[0564] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl.

[0565] and

[0566] R13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[0567] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0568] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0569] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0570] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0571] In one embodiment of the present invention and / or its embodiments,

[0572] R 1 Selected independently from the following

[0573] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[0574] and

[0575] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-.

[0576] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[0577] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3Alkoxy

[0578] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[0579] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[0580] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0581] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igvii), (Igiii), (Igix), or (Igx).

[0582]

[0583]

[0584] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 7 R 19 and R 25 As defined in any of the embodiments described herein.

[0585] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Igvii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Igviii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Igix), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Igx), preferably in the (S)-enantiomer form.

[0586] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 and R 19 As defined below.

[0587] In one embodiment of the present invention and / or its embodiments,

[0588] R 1 Selected independently from the following

[0589] Hydrogen, C 1-6 -alkyl, C 1-6-alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0590] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0591] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[0592] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10-membered heteroaryl, or

[0593] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0594] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0595] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[0596] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[0597] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C1-3 -alkyl, and

[0598] R 19 Selected independently from the following

[0599] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[0600] Where C 6-10 -aryl or 5 to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following.

[0601] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0602] R 20 and R 21 Selected independently from the following

[0603] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[0604] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0605] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0606] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[0607] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[0608] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl.

[0609] Optionally, in one embodiment of the invention and / or its embodiments,

[0610] R 1 Selected independently from the following

[0611] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[0612] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0613] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[0614] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[0615] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl,

[0616] and

[0617] R 19 It is a 5- to 10-membered heteroaryl group

[0618] The 5 to 10 heteroaryl groups are optionally substituted by one or more substituents independently selected from the following.

[0619] C1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl, of which C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[0620] In one embodiment of the present invention and / or its embodiments,

[0621] R 1 Selected independently from the following

[0622] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[0623] and

[0624] R 19 The phenyl group is independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl, and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, etc. 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0625] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihi), (Ihii), (Ihiii), (Ihiv), (Ihv), or (Ihvi).

[0626]

[0627]

[0628]

[0629] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 7 R 13 R 14 A1, A2, A3, A4 and R 25 As defined in any of the embodiments described herein.

[0630] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihvi), preferably in the (S)-enantiomer form.

[0631] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 and R 25 As defined below.

[0632] In one embodiment of the present invention and / or its embodiments,

[0633] R 1 Selected independently from the following

[0634] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0635] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0636] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[0637] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[0638] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0639] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0640] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[0641] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[0642] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[0643] R 25 It is either hydrogen or methyl.

[0644] In one embodiment of the present invention and / or its embodiments,

[0645] R 1 Selected independently from the following

[0646] Hydrogen, C 1-6 -alkyl, C 1-6-alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[0647] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0648] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[0649] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[0650] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl,

[0651] and

[0652] R 25 It is either hydrogen or methyl.

[0653] In one embodiment of the present invention and / or its embodiments,

[0654] R 1 Selected independently from the following

[0655] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[0656] and

[0657] R 25 It is hydrogen or methyl, more preferably hydrogen.

[0658] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iii), (Iiii), (Iiiii), or (Iiiv).

[0659]

[0660] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 7 R 13 R 14 A1, A2, A3, A4 and R 19 As defined in any of the embodiments described herein.

[0661] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iiii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iiiii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iiiv), preferably in the (S)-enantiomer form.

[0662] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 It is hydrogen.

[0663] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 7 and R 13 R 14 A1, A2, A3 and A4 are defined below.

[0664] In one embodiment of the present invention and / or its embodiments,

[0665] R 7 Selected independently from the following

[0666] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[0667] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 -Alkoxy groups are each optionally substituted independently by one or more substituents selected from the following C groups. 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’and C(=O)NR 11’ R 12’ ,

[0668] R 8 and R 9 Selected independently from the following

[0669] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[0670] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0671] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycle formed together with the N atom attached thereto is optionally substituted by one or more independent substituents selected from the following.

[0672] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR 10” and C(=O)NR 11” R 12” ;

[0673] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[0674] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[0675] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl,

[0676] and

[0677] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-.

[0678] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0679] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[0680] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0681] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl.

[0682] In one embodiment of the present invention and / or its embodiments,

[0683] R 7 Selected independently from the following

[0684] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[0685] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic or C 1-3 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0686] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0687] R 8 and R 9 Selected independently from the following

[0688] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[0689] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0690] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycle formed together with the N atom attached thereto is optionally substituted by one or more independent substituents selected from the following.

[0691] C 1-6 -alkyl, C1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[0692] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0693] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0694] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0695] and

[0696] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, or -S-.

[0697] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0698] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0699] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0700] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0701] In one embodiment of the present invention and / or its embodiments,

[0702] R 7 Selected independently from the following

[0703] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[0704] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[0705] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[0706] R 8 and R 9 Selected independently from the following

[0707] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[0708] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[0709] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[0710] Appropriately, R 7 Selected independently from the following

[0711] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methanesulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[0712] and

[0713] R 13 and R 14Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-.

[0714] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[0715] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[0716] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[0717] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[0718] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0719] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iji), (Ijii), (Ijiii), (Ijiv), (Ijv), (Ijvi), (Ijvi), (Ijviii), or (Ijix).

[0720]

[0721]

[0722]

[0723] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 19 and R 25 As defined in any of the embodiments described herein.

[0724] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iji), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijkiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijvii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ijviii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ijix), preferably in the (S)-enantiomer form.

[0725] In one embodiment of the present invention and / or its embodiments,

[0726] R 7 Selected independently from the following

[0727] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[0728] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 -Alkoxy groups are each optionally substituted independently by one or more substituents selected from the following C groups. 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6-alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0729] R 8 and R 9 Selected independently from the following

[0730] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[0731] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0732] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0733] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR 10” and C(=O)NR 11” R 12” ;

[0734] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[0735] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[0736] R 8” R 9” R10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl,

[0737] and

[0738] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing 5 or 6 carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[0739] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0740] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[0741] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0742] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent1-3 -alkyl.

[0743] In one embodiment of the present invention and / or its embodiments,

[0744] R 7 Selected independently from the following

[0745] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[0746] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-3 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[0747] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0748] R 8 and R 9 Selected independently from the following

[0749] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10-membered heteroaryl, or

[0750] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0751] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0752] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[0753] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0754] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0755] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0756] and

[0757] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[0758] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0759] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy groups, of which 0, 1, or 2 of A1, A2, A3, and A4 are N.

[0760] In one embodiment of the present invention and / or its embodiments,

[0761] R 7 Selected independently from the following

[0762] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[0763] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[0764] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[0765] R 8 and R 9 Selected independently from the following

[0766] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[0767] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[0768] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[0769] Appropriately, R 7 Selected independently from the following

[0770] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methanesulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[0771] and

[0772] R 13 and R 14Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-.

[0773] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[0774] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[0775] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[0776] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[0777] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0778] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijx), (Ijxi), (Ijxii), (Ijxiii), (Ijxiv), or (Ijxv).

[0779]

[0780]

[0781]

[0782] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 19 and R 25 As defined in any of the embodiments described herein.

[0783] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijx), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijxi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijxii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijxiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijxiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijxv), preferably in the (S)-enantiomer form.

[0784] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 7 and R 19 As defined below.

[0785] In one embodiment of the present invention and / or its embodiments,

[0786] R 7 Selected independently from the following

[0787] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[0788] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 -Alkoxy groups are each optionally substituted independently by one or more substituents selected from the following C groups. 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR10’ and C(=O)NR 11’ R 12’ ,

[0789] R 8 and R 9 Selected independently from the following

[0790] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[0791] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0792] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycle formed together with the N atom attached thereto is optionally substituted by one or more independent substituents selected from the following.

[0793] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR 10” and C(=O)NR 11” R 12” ;

[0794] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[0795] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[0796] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6-alkyl,

[0797] and

[0798] R 19 Selected independently from the following

[0799] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[0800] Where C 6-10 -aryl or 5 to 10-membered heteroaryl groups are each optionally substituted by one or more substituents independently selected from the following.

[0801] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0802] R 20 and R 21 Selected independently from the following

[0803] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[0804] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0805] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0806] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[0807] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[0808] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl.

[0809] In one embodiment of the present invention and / or its embodiments,

[0810] R 7 Selected independently from the following

[0811] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[0812] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic or C 1-3 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[0813] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0814] R 8 and R 9 Selected independently from the following

[0815] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[0816] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0817] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0818] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[0819] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0820] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0821] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0822] and

[0823] R 19 It is a 5- to 10-membered heteroaryl group

[0824] The 5 to 10 heteroaryl groups are optionally substituted independently by one or more substituents selected from the following.

[0825] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl groups

[0826] Where C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C 1-6 -alkyl, C1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[0827] In one embodiment of the present invention and / or its embodiments,

[0828] R 7 Selected independently from the following

[0829] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[0830] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups is optionally substituted independently by one or more substituents selected from the following.

[0831] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[0832] R 8 and R 9 Selected independently from the following

[0833] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[0834] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[0835] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[0836] Appropriately, R 7 Selected independently from the following

[0837] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methanesulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[0838] and

[0839] R 19 Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0840] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iki), (Ikii), (Ikiii), (Ikiv), (Ikv), (Ikvi), (Ikvii), (klviii), or (Ikix).

[0841]

[0842]

[0843]

[0844]

[0845] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 13 R 14 A1, A2, A3, A4 and R 25 As defined in any of the embodiments described herein.

[0846] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iki), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikvii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ikviii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ikix), preferably in the (S)-enantiomer form.

[0847] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 7 and R 25 As defined below.

[0848] In one embodiment of the present invention and / or its embodiments,

[0849] R 7 Selected independently from the following

[0850] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[0851] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 -Alkoxy groups are each optionally substituted independently by one or more substituents selected from the following C groups. 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R,

[0852] R 8 and R 9 Selected independently from the following

[0853] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[0854] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0855] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0856] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR 10” and C(=O)NR 11” R 12” ;

[0857] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[0858] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[0859] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl,

[0860] and

[0861] R 25 It is either hydrogen or methyl.

[0862] In one embodiment of the present invention and / or its embodiments,

[0863] R 7 Selected independently from the following

[0864] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[0865] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic or C 1-3 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[0866] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0867] R8 and R 9 Selected independently from the following

[0868] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[0869] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0870] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0871] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[0872] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0873] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0874] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[0875] and

[0876] R 25 It is either hydrogen or methyl.

[0877] In one embodiment of the present invention and / or its embodiments,

[0878] R 7 Selected independently from the following

[0879] Hydrogen, C1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[0880] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups is optionally substituted independently by one or more substituents selected from the following.

[0881] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[0882] R 8 and R 9 Selected independently from the following

[0883] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[0884] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[0885] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[0886] Appropriately, R 7 Selected independently from the following

[0887] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methanesulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[0888] and

[0889] R 25 It is hydrogen or methyl, more preferably hydrogen.

[0890] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ili), (Ilii), (Iliii), (Iliv), (Ilv), or (Ilvi).

[0891]

[0892]

[0893]

[0894] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 13 R 14 A1, A2, A3, A4 and R 19 As defined in any of the embodiments described herein.

[0895] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ili), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ilii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iliii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iliv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ilv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ilvi), preferably in the (S)-enantiomer form.

[0896] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 13 R 14 A1, A2, A3, A4, and R 19 As defined below.

[0897] In one embodiment of the present invention and / or its embodiments,

[0898] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-.

[0899] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0900] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[0901] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0902] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl,

[0903] and

[0904] R 19 Selected independently from the following

[0905] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[0906] Where C 6-10 -Aryl or 5 to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following.

[0907] C1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0908] R 20 and R 21 Selected independently from the following

[0909] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[0910] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0911] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy group, or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0912] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[0913] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[0914] R 20’ R 21’ R 22’ R23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl.

[0915] In one embodiment of the present invention and / or its embodiments,

[0916] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, or -S-.

[0917] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0918] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0919] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0920] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0921] and

[0922] R 19 It is a 5- to 10-membered heteroaryl group

[0923] The 5 to 10 heteroaryl groups are optionally substituted independently by one or more substituents selected from the following.

[0924] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl groups

[0925] Where C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C 1-6 -alkyl, C 1-6Each alkoxy group may optionally be replaced by one or more halogens.

[0926] In one embodiment of the present invention and / or its embodiments,

[0927] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-.

[0928] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[0929] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[0930] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[0931] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[0932] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0933] and

[0934] R 19Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0935] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imi), (Imii), (Imiii), (Imiv), (Imv), (Imvi), (Imvii), (Imviii), or (Imix).

[0936]

[0937]

[0938]

[0939] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 7 and R 25 As defined in any of the embodiments described herein.

[0940] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imvii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Imviii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Imix), preferably in the (S)-enantiomer form.

[0941] In one embodiment of the present invention and / or its embodiments,

[0942] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing 5 or 6 carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[0943] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0944] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R16’ and R 16” C is independent 1-3 -alkyl,

[0945] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0946] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl,

[0947] and

[0948] R 19 Selected independently from the following

[0949] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[0950] Where C 6-10 -Aryl or 5 to 10-membered heteroaryl groups are each optionally substituted by one or more substituents independently selected from the following.

[0951] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0952] R 20 and R 21 Selected independently from the following

[0953] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[0954] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0955] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy group, or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[0956] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[0957] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[0958] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl.

[0959] In one embodiment of the present invention and / or its embodiments,

[0960] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[0961] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0962] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkyl groups, wherein 0, 1, or 2 of A1, A2, A3, and A4 are nitrogen atoms.

[0963] and

[0964] R 19 It is a 5- to 10-membered heteroaryl group

[0965] The 5 to 10 heteroaryl groups are optionally substituted by one or more substituents independently selected from the following.

[0966] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl groups

[0967] Where C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[0968] In one embodiment of the present invention and / or its embodiments,

[0969] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-.

[0970] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[0971] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[0972] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[0973] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[0974] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0975] and

[0976] R 19 Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0977] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imx), (Imxi), (Imxii), (Imxiii), (Imxiv), or (Imxv).

[0978]

[0979]

[0980] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R7 and R 25 As defined in any of the embodiments described herein.

[0981] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imx), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imxi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imxii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imxiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imxiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imxv), preferably in the (S)-enantiomer form.

[0982] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 13 R 14 A1, A2, A3, A4, and R 25 As defined below.

[0983] In one embodiment of the present invention and / or its embodiments,

[0984] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-.

[0985] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[0986] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3Alkoxy or NR 16’ R 16” , where R 16’ and R 16” Independently is C 1-3 -alkyl,

[0987] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[0988] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl,

[0989] and

[0990] R 25 It is either hydrogen or methyl.

[0991] In one embodiment of the present invention and / or its embodiments,

[0992] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, or -S-.

[0993] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0994] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0995] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[0996] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[0997] and

[0998] R 25 It is either hydrogen or methyl.

[0999] In one embodiment of the present invention and / or its embodiments,

[1000] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-.

[1001] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[1002] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[1003] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[1004] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[1005] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1006] and

[1007] R 25 It is hydrogen or methyl, more preferably hydrogen.

[1008] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ini), (Inii), (Iniii), (Iniv), (Inv), or (Invi).

[1009]

[1010]

[1011]

[1012] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 7 and R 19 As defined in any of the embodiments described herein.

[1013] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ini), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iniii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iniv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Invi), preferably in the (S)-enantiomer form.

[1014] In one embodiment of the present invention and / or its embodiments,

[1015] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing 5 or 6 carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[1016] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[1017] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[1018] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[1019] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl,

[1020] and

[1021] R 25 It is either hydrogen or methyl.

[1022] In one embodiment of the present invention and / or its embodiments,

[1023] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[1024] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1025] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1026] A3 is N or CR 17 , where R 17Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1027] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1028] and

[1029] R 25 It is either hydrogen or methyl.

[1030] In one embodiment of the present invention and / or its embodiments,

[1031] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-.

[1032] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[1033] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[1034] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[1035] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[1036] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1037] and

[1038] R 25 It is hydrogen or methyl, more preferably hydrogen.

[1039] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Invii), (Inviii), (Inix), or (Inx).

[1040]

[1041]

[1042] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 7 and R 19 As defined in any of the embodiments described herein.

[1043] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Invii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Inviii), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Inix), preferably in the (S)-enantiomer form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Inx), preferably in the (S)-enantiomer form.

[1044] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 19 and R 25 As defined below.

[1045] In one embodiment of the present invention and / or its embodiments,

[1046] R 19 Selected independently from the following

[1047] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[1048] Where C 6-10 -Aryl or 5 to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following.

[1049] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[1050] R 20 and R 21 Selected independently from the following

[1051] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[1052] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1053] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy group, or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1054] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[1055] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[1056] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl,

[1057] and

[1058] R 25 It is either hydrogen or methyl.

[1059] In one embodiment of the present invention and / or its embodiments,

[1060] R 19 It is a 5- to 10-membered heteroaryl group

[1061] The 5 to 10 heteroaryl groups are optionally substituted by one or more substituents independently selected from the following.

[1062] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl groups

[1063] Where C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[1064] and

[1065] R 25 It is either hydrogen or methyl.

[1066] In one embodiment of the present invention and / or its embodiments,

[1067] R 19 Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl, and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[1068] and

[1069] R 25 It is hydrogen or methyl, more preferably hydrogen.

[1070] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iooi), (Ioii), (Ioiii), (Ioiv), (Iov), or (Iovi).

[1071]

[1072]

[1073]

[1074] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 R 7 and R 13 R 14 A1, A2, A3, and A4 are defined as in any of the embodiments described herein.

[1075] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioov), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iovi), preferably in the (S)-enantiomer form.

[1076] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 R 7 and R 13 R 14 A1, A2, A3 and A4 are defined below.

[1077] Optionally, in one embodiment of the present invention and / or its embodiments,

[1078] R 1 Selected independently from the following

[1079] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[1080] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1081] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[1082] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1083] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1084] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1085] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[1086] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[1087] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[1088] R 7 Selected independently from the following

[1089] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[1090] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 -Alkoxy groups are each optionally substituted independently by one or more substituents selected from the following C groups. 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1091] R 8 and R 9 Selected independently from the following

[1092] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[1093] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1094] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1095] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR 10” and C(=O)NR 11” R 12” ;

[1096] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[1097] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[1098] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl,

[1099] and

[1100] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S,

[1101] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[1102] A2 is N or CR 16 , where R16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[1103] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[1104] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl.

[1105] In one embodiment of the present invention and / or its embodiments,

[1106] R 1 Selected independently from the following

[1107] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[1108] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1109] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[1110] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[1111] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl,

[1112] and

[1113] R 7 Selected independently from the following

[1114] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[1115] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic or C 1-3 Each of the -alkoxy groups is optionally substituted independently by one or more substituents selected from the following.

[1116] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1117] R 8 and R 9 Selected independently from the following

[1118] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1119] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1120] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9The heterocycle formed together with the N atom attached thereto is optionally substituted by one or more independent substituents selected from the following.

[1121] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[1122] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1123] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1124] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1125] and

[1126] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, or -S-.

[1127] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1128] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1129] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1130] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1131] In one embodiment of the present invention and / or its embodiments,

[1132] R 1 Selected independently from the following

[1133] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[1134] and

[1135] R 7 Selected independently from the following

[1136] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[1137] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups is optionally substituted independently by one or more substituents selected from the following.

[1138] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[1139] R 8 and R 9 Selected independently from the following

[1140] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[1141] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[1142] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[1143] Appropriately, R 7 Selected independently from the following

[1144] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methanesulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[1145] and

[1146] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-.

[1147] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[1148] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[1149] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[1150] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[1151] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1152] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipi), (Ipii), (Ipiii), (Ipiv), (Ipv), (Ipvi), (Ipvii), (Ipviii), (Ipix), (Ipx), (Ipxi), or (Ipxii).

[1153]

[1154]

[1155]

[1156]

[1157] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 19 and R 25 As defined in any of the embodiments described herein.

[1158] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipvii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipviii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipix), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipx), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxii), preferably in the (S)-enantiomer form.

[1159] Optionally, in one embodiment of the present invention and / or its embodiments,

[1160] R 1 Selected independently from the following

[1161] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[1162] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1163] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[1164] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1165] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1166] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1167] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[1168] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[1169] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[1170] R 7 Selected independently from the following

[1171] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[1172] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following C 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1173] R 8 and R 9 Selected independently from the following

[1174] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[1175] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1176] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1177] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR 10” and C(=O)NR 11” R 12” ;

[1178] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[1179] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[1180] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl,

[1181] and

[1182] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing 5 or 6 carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally substituted with -NH-, -N=, =N-, -O- or -S-.

[1183] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[1184] A2 is N or CR 16 , where R 16Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[1185] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[1186] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl.

[1187] In one embodiment of the present invention and / or its embodiments,

[1188] R 1 Selected independently from the following

[1189] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[1190] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1191] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[1192] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[1193] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl,

[1194] and

[1195] R 7 Selected independently from the following

[1196] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[1197] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic or C 1-3 Each of the -alkoxy groups is optionally substituted independently by one or more substituents selected from the following.

[1198] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1199] R 8 and R 9 Selected independently from the following

[1200] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1201] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1202] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1203] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[1204] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1205] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1206] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1207] and

[1208] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[1209] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1210] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1211] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1212] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1213] In one embodiment of the present invention and / or its embodiments,

[1214] R 1 Selected independently from the following

[1215] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[1216] and

[1217] R 7 Selected independently from the following

[1218] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[1219] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups is optionally substituted independently by one or more substituents selected from the following.

[1220] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[1221] R 8 and R 9 Selected independently from the following

[1222] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[1223] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[1224] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[1225] Appropriately, R 7 Selected independently from the following

[1226] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methanesulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[1227] and

[1228] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-.

[1229] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[1230] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[1231] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[1232] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[1233] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1234] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxiii), (Ipxiv), (Ipxv), (Ipxvi), (Ipxvii), (Ipxviii), (Ipxix), or (Ipxx).

[1235]

[1236]

[1237] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 19 and R 25 As defined in any of the embodiments described herein.

[1238] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxvii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxviii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxix), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipxx), preferably in the form of (S)-enantiomer.

[1239] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 R 7 and R 19 As defined below.

[1240] Optionally, in one embodiment of the present invention and / or its embodiments,

[1241] R 1 Selected independently from the following

[1242] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[1243] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1244] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[1245] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1246] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1247] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1248] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[1249] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[1250] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[1251] R 7 Selected independently from the following

[1252] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[1253] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 The -alkoxy group is optionally substituted independently by one or more substituents selected from the following.

[1254] C 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1255] R 8 and R 9 Selected independently from the following

[1256] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[1257] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1258] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1259] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9”C(=O)OR 10” and C(=O)NR 11” R 12” ;

[1260] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[1261] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[1262] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl,

[1263] and

[1264] R 19 Selected independently from the following

[1265] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[1266] Where C 6-10 -Aryl or 5 to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following.

[1267] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[1268] R 20 and R 21 Selected independently from the following

[1269] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[1270] R20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1271] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy group, or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1272] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[1273] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[1274] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl.

[1275] In one embodiment of the present invention and / or its embodiments,

[1276] R 1 Selected independently from the following

[1277] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[1278] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1279] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[1280] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[1281] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl,

[1282] and

[1283] R 7 Selected independently from the following

[1284] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[1285] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic or C 1-3 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[1286] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1287] R 8 and R 9 Selected independently from the following

[1288] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1289] R 8 and R 9Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1290] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1291] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[1292] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1293] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1294] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1295] and

[1296] R 19 It is a 5- to 10-membered heteroaryl group

[1297] The 5 to 10 heteroaryl groups are optionally substituted independently by one or more substituents selected from the following.

[1298] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl groups

[1299] Where C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[1300] In one embodiment of the present invention and / or its embodiments,

[1301] R 1 Selected independently from the following

[1302] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[1303] and

[1304] R 7 Selected independently from the following

[1305] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[1306] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups is optionally substituted independently by one or more substituents selected from the following.

[1307] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[1308] R 8 and R 9 Selected independently from the following

[1309] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[1310] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[1311] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[1312] Appropriately, R 7 Selected independently from the following

[1313] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methanesulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[1314] and

[1315] R 19 Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[1316] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqi), (Iqii), (Iqiii), (Iqiv), (Iqv), (Iqvi), (Iqvii), or (Iqviii).

[1317]

[1318]

[1319]

[1320] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 13 R 14 A1, A2, A3, A4 and R 25 As defined in any of the embodiments described herein.

[1321] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqvii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqviii), preferably in the (S)-enantiomer form.

[1322] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 R 7 and R 25 As defined below.

[1323] Optionally, in one embodiment of the invention and / or its embodiments,

[1324] R 1 Selected independently from the following

[1325] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[1326] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1327] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[1328] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1329] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1330] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1331] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[1332] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[1333] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[1334] R 7 Selected independently from the following

[1335] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[1336] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 -Alkoxy groups are each optionally substituted independently by one or more substituents selected from the following C groups. 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1337] R 8 and R 9 Selected independently from the following

[1338] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[1339] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1340] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1341] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR10” and C(=O)NR 11” R 12” ;

[1342] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[1343] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[1344] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl,

[1345] and

[1346] R 25 It is either hydrogen or methyl.

[1347] In one embodiment of the present invention and / or its embodiments,

[1348] R 1 Selected independently from the following

[1349] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[1350] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1351] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[1352] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[1353] R 2’ and R 3’Independently selected from hydrogen and C 1-3 -alkyl,

[1354] and

[1355] R 7 Selected independently from the following

[1356] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[1357] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic or C 1-3 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[1358] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1359] R 8 and R 9 Selected independently from the following

[1360] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1361] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1362] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1363] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[1364] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1365] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1366] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1367] and

[1368] R 25 It is either hydrogen or methyl.

[1369] In one embodiment of the present invention and / or its embodiments,

[1370] R 1 Selected independently from the following

[1371] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[1372] and

[1373] R 7 Selected independently from the following

[1374] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[1375] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[1376] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[1377] R 8 and R 9 Selected independently from the following

[1378] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[1379] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[1380] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[1381] Appropriately, R 7 Selected independently from the following

[1382] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methanesulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[1383] and

[1384] R 25 It is hydrogen or methyl, more preferably hydrogen.

[1385] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iri), (Irii), (Iriii), (Iriv), (Irv), (Irvi), (Irvii), or (Irviii).

[1386]

[1387]

[1388]

[1389] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 13 R 14 A1, A2, A3, A4 and R 19As defined in any of the embodiments described herein.

[1390] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iri), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Irii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iriii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iriv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Irv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Irvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Irvii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Irviii), preferably in the (S)-enantiomer form.

[1391] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 R 13 R 14 A1, A2, A3 and A4 are defined below.

[1392] Optionally, in one embodiment of the present invention and / or its embodiments,

[1393] R 1 Selected independently from the following

[1394] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[1395] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1396] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR2’ R 3’ R 2 and R 3 Selected independently from the following

[1397] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1398] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1399] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1400] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[1401] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[1402] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[1403] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-.

[1404] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[1405] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[1406] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[1407] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl,

[1408] and

[1409] R 19 Selected independently from the following

[1410] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[1411] Where C 6-10 -Aryl or 5 to 10-membered heteroaryl groups are each optionally substituted by one or more substituents independently selected from the following.

[1412] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10-Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[1413] R 20 and R 21 Selected independently from the following

[1414] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[1415] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1416] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy group, or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1417] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[1418] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[1419] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl.

[1420] In one embodiment of the present invention and / or its embodiments,

[1421] R 1 Selected independently from the following

[1422] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[1423] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1424] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[1425] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[1426] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl,

[1427] and

[1428] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, or -S-.

[1429] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1430] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkyl groups, wherein 0, 1, or 2 of A1, A2, A3, and A4 are nitrogen atoms.

[1431] and

[1432] R 19 It is a 5- to 10-membered heteroaryl group

[1433] The 5 to 10 heteroaryl groups are optionally substituted independently by one or more substituents selected from the following.

[1434] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl groups

[1435] Where C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[1436] Optionally, in one embodiment of the present invention and / or its embodiments,

[1437] R 1 Selected independently from the following

[1438] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[1439] and

[1440] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-.

[1441] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[1442] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[1443] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[1444] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[1445] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1446] and

[1447] R 19 Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[1448] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isi), (Isii), (Isiii), (Isiv), (Isv), (Isvi), (Isvii), (Isviii), (Isix), (Isx), (Isxi), or (Isxii).

[1449]

[1450]

[1451]

[1452]

[1453] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R7 and R 25 As defined in any of the embodiments described herein.

[1454] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isvii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isviii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isix), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxii), preferably in the (S)-enantiomer form.

[1455] Optionally, in one embodiment of the invention and / or its embodiments,

[1456] R 1 Selected independently from the following

[1457] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[1458] Where C 1-6 -alkyl or C1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1459] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[1460] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1461] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1462] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1463] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[1464] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[1465] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[1466] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing 5 or 6 carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3-alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[1467] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[1468] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[1469] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[1470] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl,

[1471] and

[1472] R 19 Selected independently from the following

[1473] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[1474] Where C 6-10-aryl or 5 to 10-membered heteroaryl groups are each optionally substituted by one or more substituents independently selected from the following.

[1475] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[1476] R 20 and R 21 Selected independently from the following

[1477] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[1478] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1479] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy group, or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1480] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[1481] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[1482] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl.

[1483] In one embodiment of the present invention and / or its embodiments,

[1484] R 1 Selected independently from the following

[1485] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[1486] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1487] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[1488] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[1489] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl,

[1490] and

[1491] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[1492] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1493] A2 is N or CR 16 , where R 16Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1494] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1495] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1496] and

[1497] R 19 It is a 5- to 10-membered heteroaryl group

[1498] The 5 to 10 heteroaryl groups are optionally substituted by one or more substituents independently selected from the following.

[1499] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl groups

[1500] Where C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[1501] Optionally, in one embodiment of the present invention and / or its embodiments,

[1502] R 1 Selected independently from the following

[1503] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[1504] and

[1505] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-.

[1506] A1 is N or CR 15 , where R 15Independently hydrogen or C 1-3 Alkoxy

[1507] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[1508] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[1509] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy,

[1510] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1511] and

[1512] R 19 Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[1513] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxiii), (Ixiv), (Isxv), (Isxvi), (Isxvii), (Isxviii), (Isxix), or (Isxx).

[1514]

[1515]

[1516] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 7 and R 25 As defined in any of the embodiments described herein.

[1517] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxvii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxviii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxix), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isxx), preferably in the form of (S)-enantiomer.

[1518] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 R 13 R 14 A1, A2, A3, A4 and R 25 As defined below.

[1519] Optionally, in one embodiment of the present invention and / or its embodiments,

[1520] R 1 Selected independently from the following

[1521] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R6 ,

[1522] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1523] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[1524] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1525] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1526] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1527] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[1528] R 4 R 5 and R 6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[1529] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[1530] R 13 and R 14Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally substituted with -NH-, -O-, -S(O)-, -S(O)2- or -S-.

[1531] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[1532] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[1533] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[1534] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl,

[1535] and

[1536] R 25 It is either hydrogen or methyl.

[1537] In one embodiment of the present invention and / or its embodiments,

[1538] R 1 Selected independently from the following

[1539] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[1540] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1541] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[1542] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[1543] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl,

[1544] and

[1545] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, or -S-.

[1546] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1547] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1548] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1549] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1550] and

[1551] R 25 It is either hydrogen or methyl.

[1552] In one embodiment of the present invention and / or its embodiments,

[1553] R 1 Selected independently from the following

[1554] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[1555] and

[1556] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-.

[1557] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[1558] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[1559] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[1560] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[1561] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1562] and

[1563] R 25 It is hydrogen or methyl, more preferably hydrogen.

[1564] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itti), (Itii), (Itiii), (Ittiv), (Itv), (Itvi), (Itvii), (Itviii), (Itix), (Itx), (Itxi), or (Itxii).

[1565]

[1566]

[1567]

[1568] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 7 and R 19 As defined in any of the embodiments described herein.

[1569] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itti), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ittiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itvii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itviii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itix), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itx), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxii), preferably in the (S)-enantiomer form.

[1570] Optionally, in one embodiment of the present invention and / or its embodiments,

[1571] R 1 Selected independently from the following

[1572] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[1573] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1574] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[1575] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1576] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1577] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1578] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[1579] R 4 R 5 and R6 Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[1580] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[1581] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing 5 or 6 carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[1582] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[1583] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[1584] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[1585] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl,

[1586] and

[1587] R 25 It is either hydrogen or methyl.

[1588] In one embodiment of the present invention and / or its embodiments,

[1589] R 1 Selected independently from the following

[1590] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[1591] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1592] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[1593] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[1594] R 2’ and R 3’ Independently selected from hydrogen and C 1-3 -alkyl,

[1595] and

[1596] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[1597] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1598] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1599] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1600] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1601] and

[1602] R 25 It is either hydrogen or methyl.

[1603] In one embodiment of the present invention and / or its embodiments,

[1604] R 1 Selected independently from the following

[1605] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[1606] and

[1607] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-.

[1608] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[1609] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[1610] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[1611] A4 is N or CR 18 , where R18 Independently hydrogen or C 1-3 Alkoxy

[1612] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1613] and

[1614] R 25 It is hydrogen or methyl, more preferably hydrogen.

[1615] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxiii), (Itxiiii), (Itxv), (Itxvi), (Itxvii), (Itxviii), (Itxix), or (Itxx).

[1616]

[1617]

[1618] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 7 and R 19 As defined in any of the embodiments described herein.

[1619] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxvii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxviii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxix), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxx), preferably in the form of (S)-enantiomer.

[1620] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 1 R 19and R 25 As defined below.

[1621] R 1 Selected independently from the following

[1622] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl, NR 2 R 3 C(=O)OR 4 and C(=O)NR 5 R 6 ,

[1623] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1624] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ R 2 and R 3 Selected independently from the following

[1625] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1626] R 2 and R 3 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1627] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 2 and R 3 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1628] C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 1-6 -alkoxy,

[1629] R 4 R 5 and R 6 Independently selected from hydrogen and C1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl,

[1630] R 2’ and R 3’ Independently selected from hydrogen and C 1-6 -alkyl, preferably selected from hydrogen and C 1-3 -alkyl, and

[1631] R 19 Selected independently from the following

[1632] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[1633] Where C 6-10 -aryl or 5 to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following. 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[1634] R 20 and R 21 Selected independently from the following

[1635] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[1636] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1637] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy group, or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1638] C 1-6 -alkyl, C 3-10-cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[1639] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[1640] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl,

[1641] and

[1642] R 25 It is either hydrogen or methyl.

[1643] In one embodiment of the present invention and / or its embodiments,

[1644] R 1 Selected independently from the following

[1645] Hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 ,

[1646] Where C 1-6 -alkyl or C 1-6 Each alkoxy group is optionally substituted by one or more substituents independently selected from the following.

[1647] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, hydroxyl and NR 2’ R 3’ ,

[1648] R 5 and R 6 Independently selected from hydrogen and C 1-3 -alkyl,

[1649] R 2’ and R 3’ Independently selected from hydrogen and C 1-3-alkyl,

[1650] and

[1651] R 19 It is a 5- to 10-membered heteroaryl group

[1652] The 5 to 10 heteroaryl groups are optionally substituted by one or more substituents independently selected from the following.

[1653] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl groups

[1654] Where C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[1655] and

[1656] R 25 It is either hydrogen or methyl.

[1657] In one embodiment of the present invention and / or its embodiments,

[1658] R 1 Selected independently from the following

[1659] Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluorine, and chlorine.

[1660] and

[1661] R 19Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl, and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[1662] and

[1663] R 25 It is hydrogen or methyl, more preferably hydrogen.

[1664] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iui), (Iuii), (Iuiii), (Iuiv), (Iuv), (Iuvi), (Iuvii), (Iuviii), (Iuix), (Iux), (Iuxi), or (Iuxii).

[1665]

[1666]

[1667]

[1668] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 7 and R 13 R 14 A1, A2, A3, and A4 are defined as in any of the embodiments described herein.

[1669] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iui), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuiii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuiv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuvii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuviii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuix), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iux), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuxi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuxii), preferably in the (S)-enantiomer form.

[1670] This invention provides compounds according to the invention and / or embodiments thereof, wherein R 7 R 13 R 14 A1, A2, A3 and A4 are defined below.

[1671] Optionally, in one embodiment of the invention and / or its embodiments,

[1672] R 7 Selected independently from the following

[1673] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR 10 SR10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[1674] Where C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 -Alkoxy groups are each optionally substituted independently by one or more substituents selected from the following C groups. 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1675] R 8 and R 9 Selected independently from the following

[1676] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[1677] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1678] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1679] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR 10” and C(=O)NR 11” R 12” ;

[1680] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[1681] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[1682] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl,

[1683] and

[1684] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing 5 or 6 carbon atoms, wherein the saturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-.

[1685] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[1686] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[1687] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[1688] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” C is independent 1-3 -alkyl,

[1689] and

[1690] R 19 Selected independently from the following

[1691] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[1692] Where C 6-10 -Aryl or 5 to 10-membered heteroaryl groups are each optionally substituted independently by one or more substituents selected from the following.

[1693] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[1694] R 20 and R 21 Selected independently from the following

[1695] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[1696] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1697] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy group, or C 6-10 -Aryl or derived from R 20 and R 21 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1698] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[1699] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[1700] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl.

[1701] In one embodiment of the present invention and / or its embodiments,

[1702] R 7 Selected independently from the following

[1703] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[1704] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic or C 1-3 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[1705] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1706] R 8 and R 9 Selected independently from the following

[1707] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1708] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1709] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1710] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[1711] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1712] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1713] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1714] and

[1715] R 13 and R 14 Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, or -S-.

[1716] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1717] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1718] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1719] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1720] and

[1721] R 19 It is a 5- to 10-membered heteroaryl group

[1722] The 5 to 10 heteroaryl groups are optionally substituted independently by one or more substituents selected from the following.

[1723] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, and hydroxyl groups

[1724] Where C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[1725] In one embodiment of the present invention and / or its embodiments,

[1726] R 7 Selected independently from the following

[1727] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9 ,

[1728] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[1729] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[1730] R 8 and R 9 Selected independently from the following

[1731] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[1732] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[1733] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[1734] Appropriately, R 7 Selected independently from the following

[1735] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methanesulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[1736] and

[1737] R 13 and R 14Together with the atoms they are attached to, they form a saturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-.

[1738] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[1739] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[1740] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[1741] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[1742] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1743] and

[1744] R 19 Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[1745] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivi), (Ivii), (Iviii), (Iviv), (Ivv), (Ivvi), (Ivvii), (Ivviii), (Ivix), (Ivx), (Ivxi) or (Ivxii).

[1746]

[1747]

[1748]

[1749]

[1750]

[1751] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 and R 25 As defined in any of the embodiments described herein.

[1752] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iviii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iviv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivv), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivvi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivvii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivviii), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivix), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivx), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivxi), preferably in the (S)-enantiomer form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivxii), preferably in the (S)-enantiomer form.

[1753] Optionally, in one embodiment of the present invention and / or its embodiments,

[1754] R 7 Selected independently from the following

[1755] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8 R 9 C(=O)OR 10 SR 10 SOR 10 SO2R 10 and C(=O)NR 11 R 12 ,

[1756] Where C1-6 -alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 to 10-membered heterocyclic or C 1-6 -Alkoxy groups are each optionally substituted independently by one or more substituents selected from the following C groups. 1-6 -alkyl, C 3-10 -cycloalkyl, 5 to 10-membered heterocyclic, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1757] R 8 and R 9 Selected independently from the following

[1758] Hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic and 5 to 10-membered heteroaryl, or

[1759] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1760] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 to 10-membered heterocyclic or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1761] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxyl, NR 8” R 9” C(=O)OR 10” and C(=O)NR 11” R 12” ;

[1762] R 10 R 11 and R 12 Independently selected from hydrogen and C 1-6 -alkyl,

[1763] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen and C 1-6 -alkyl,

[1764] R 8” R 9” R 10” R 11” and R 12” Independently selected from hydrogen and C 1-6 -alkyl,

[1765] and

[1766] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing 5 or 6 carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[1767] A1 is N or CR 15 , where R 15 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” C is independent 1-3 -alkyl,

[1768] A2 is N or CR 16 , where R 16 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” C is independent 1-3 -alkyl,

[1769] A3 is N or CR 17 , where R 17 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17’ R 17” , where R 17’ and R 17” C is independent 1-3 -alkyl,

[1770] A4 is N or CR 18 , where R 18 Independently, it is hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 18’ R 18” , where R 18’ and R 18” Independently is C 1-3 -alkyl,

[1771] and

[1772] R 19 Selected independently from the following

[1773] C 6-10 -Aryl and 5 to 10-membered heteroaryl groups

[1774] Where C 6-10 -aryl or 5 to 10-membered heteroaryl groups are each optionally substituted by one or more substituents independently selected from the following.

[1775] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, nitro, hydroxyl, NR 20 R 21 C(=O)OR 22 and C(=O)NR 23 R 24 ,

[1776] R 20 and R 21 Selected independently from the following

[1777] Hydrogen, C 1-6 -alkyl, C 3-10 -Cycloalkyl and C 6-10 -Aryl or

[1778] R 20 and R 21 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1779] Where C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy group, or C 6-10 -Aryl or derived from R 20 and R 21The heterocycles formed together with the N atoms attached thereto are each optionally substituted by one or more independent substituents selected from the following.

[1780] C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 to 10-membered heterocyclic group, C 6-10 -Aryl, 5- to 10-membered heteroaryl, halogen, cyano, hydroxyl, NR 20’ R 21’ C(=O)OR 22’ and C(=O)NR 23’ R 24’ ,

[1781] R 22 R 23 and R 24 Independently selected from hydrogen and C 1-6 -alkyl,

[1782] R 20’ R 21’ R 22’ R 23’ and R 24’ Independently selected from hydrogen and C 1-6 -alkyl.

[1783] In one embodiment of the present invention and / or its embodiments,

[1784] R 7 Selected independently from the following

[1785] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group, C 1-3 -alkoxy, hydroxyl, NR 8 R 9 SR 10 SOR 10 and SO2R 10 ,

[1786] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-3 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[1787] C 1-3 -alkyl, 5 to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxyl, oxo, NR 8’ R 9’ C(=O)OR 10’and C(=O)NR 11’ R 12’ ,

[1788] R 8 and R 9 Selected independently from the following

[1789] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl, C 6-10 -Aryl and 5 to 10 heteroaryl groups, or

[1790] R 8 and R 9 Together with the N atom it is attached to, it forms a saturated or unsaturated heterocycle with 3 to 12 ring atoms, wherein one ring atom is N and 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1791] Where C 1-6 -alkyl, C 6-10 -aryl or 5 to 10-membered heteroaryl or R 8 and R 9 The heterocycles formed together with the N atom attached thereto are each optionally substituted by one or more independent substituents selected from the following: C 1-6 -alkyl, C 1-6 -alkoxy, hydroxyl and NR 8” R 9” ;

[1792] R 10 Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1793] R 8’ R 9’ R 10’ R 11’ and R 12’ Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1794] R 8” and R 9” Independently selected from hydrogen or C 1-3 -alkyl group, preferably selected from hydrogen, methyl, or ethyl.

[1795] and

[1796] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, or -S-.

[1797] A1 is N or CR 15 , where R 15 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1798] A2 is N or CR 16 , where R 16 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1799] A3 is N or CR 17 , where R 17 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy group, A4 is N or CR 18 , where R 18 Independently, it is hydrogen and C 1-3 Alkyl or C 1-3 Alkoxy

[1800] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1801] and

[1802] R 19 It is a 5- to 10-membered heteroaryl group

[1803] The 5 to 10 heteroaryl groups are optionally substituted by one or more substituents independently selected from the following.

[1804] C 1-6 -alkyl, C 1-6- Alkyl, halogen, cyano, nitro, and hydroxyl groups

[1805] Where C 1-6 -alkyl, C 1-6 Each of the -alkoxy groups is optionally substituted by one or more substituents independently selected from the following: halogen, cyano, hydroxyl, preferably C. 1-6 -alkyl, C 1-6 Each alkoxy group may optionally be replaced by one or more halogens.

[1806] In one embodiment of the present invention and / or its embodiments,

[1807] R 7 Selected independently from the following

[1808] Hydrogen, C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic groups, C 1-6 -alkoxy, NR 8 R 9,

[1809] Where C 1-6 -alkyl, C 2-6 -Alkenyl, 4 to 10-membered heterocyclic group or C 1-6 Each of the -alkoxy groups may optionally be independently substituted by one or more substituents selected from the following.

[1810] C 1-6 -alkyl, C 1-6 -alkoxy groups and halogens,

[1811] R 8 and R 9 Selected independently from the following

[1812] Hydrogen, C 1-6 -alkyl, C 3-6 -cycloalkyl,

[1813] Where C 1-6 -alkyl or C 3-6 -The cycloalkyl group is optionally substituted by one or more substituents independently selected from the following.

[1814] C 1-6 -alkyl, C 1-6 -alkoxy and hydroxyl groups.

[1815] Appropriately, R 7 Selected independently from the following

[1816] Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methanesulfonyl, methylsulfenyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxyethylamino, cyclopropylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidine-1-yl, 3-fluoroazacyclobutan-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, azacyclobutan-1-yl, tetrahydro-2H-pyran-4-yl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl.

[1817] and

[1818] R 13 and R 14 Together with the atoms they are attached to, they form an unsaturated ring containing five or six carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-.

[1819] A1 is N or CR 15 , where R 15 Independently hydrogen or C 1-3 Alkoxy

[1820] A2 is N or CR 16 , where R 16 Independently hydrogen or C 1-3 Alkoxy

[1821] A3 is N or CR 17 , where R 17 Independently hydrogen or C 1-3 Alkoxy

[1822] A4 is N or CR 18 , where R 18 Independently hydrogen or C 1-3 Alkoxy

[1823] In A1, A2, A3, and A4, 0, 1, or 2 are N.

[1824] and

[1825] R 19 Independently selected from 3,5-dichlorophenyl, 2,3-dichlorophenyl, 2,3,5-trifluorophenyl, 3-trifluoromethylphenyl, 3-methoxyphenyl, 2,3-dimethylphenyl, 3-chlorophenyl, 3-trifluoromethoxyphenyl, 3-dimethylaminophenyl, 3,5-difluorophenyl, 2,3-difluorophenyl, 3,4,5-trifluorophenyl, 2-fluoro-3-chlorophenyl, 2-fluoro-5-trifluoromethylphenyl, naphth-1-yl, 2-fluoro-5-chlorophenyl, 3-fluoro-5-trifluoromethylphenyl and 2,3,5-trichlorophenyl, preferably 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 2-Chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 3-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl and 3,4,5-trichlorophenyl, more preferably 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 3,5-dichloro-4-fluorophenyl, especially 2,3,5-trifluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[1826] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivxiii), (Ivxiv), (Ivxv), (Ivxvi), (Ivxvii), (Ivxviii), (Ivxix), or (Ivxx).

[1827]

[1828]

[1829]

[1830] Or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs, and mixtures thereof, wherein R 1 and R 25 As defined in any of the embodiments described herein.

[1831] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivxiii), preferably in the (S)-enantiomer form. ...

Claims

1. A compound of formula (I) Formula (I) in R 1 Selected from hydrogen and methyl, R 7 Independently selected from: dimethylamino, morpholino-4-yl, 4-methylpiperazin-1-yl, 3,3-difluoroazacyclobutan-1-yl, 4-oxo-1-piperidinyl, 3-fluoroazacyclobutan-1-yl, methoxyethylamino, azacyclobutan-1-yl, cyclopropylamino, hydroxyethylamino, 2-hydroxyethylmethylamino, methoxy, ethoxy, tetrahydro-2H-pyran-4-yl, ethyl, isopropyl, piperidin-1-yl, and 4,4-difluoropiperidin-1-yl. R 13 It is methyl. R 14 It is hydrogen, or R 13 and R 14 Together with the atoms to which it is attached, it forms an unsaturated ring containing five or six carbon atoms, wherein the unsaturated ring is optionally bounded by one or more C atoms. 1-3 -alkyl substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-. A1, A2, A3, and A4 are CH. R 19 It was C 1-6 -alkyl, C 1-6 -Alkoxy or halogen-substituted phenyl, wherein the C 1-6 -alkyl or C 1-6 -Alkoxy groups may optionally be replaced by halogens. R 25 It's hydrogen. Or a physiologically acceptable salt.

2. A compound of formula (I), Formula (I) in, A1, A2, A3, and A4 are CH. in: 。 3. A method for preparing a compound according to formula (I): Formula (I), The method includes the following steps: Compound of formula (A) Formula (A) Reaction with compound of formula (B) Formula (B) Where R 1 R 7 R 13 R 14 A1, A2, A3, A4, R 19 and R 25 As defined in claim 1 or 2, To obtain the compound according to formula (I).

4. A veterinary composition comprising - The compound according to formula (I) according to claim 1 or 2, and - One or more physiologically acceptable excipients.

5. Use of the compound of formula (I) according to claim 1 or 2, or the veterinary composition according to claim 4, in the preparation of a medicament for treating diseases caused by worms in animals.

6. The use according to claim 5, wherein the animal is a dog.

7. The use according to claim 5, wherein the disease is heartworm disease.

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