Anthelmintic compounds containing a quinoline structure

Abstract

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

Description

[0001] The present invention relates to novel anthelmintic compounds. These compounds can be used, for example, for treating classes of helminthiases caused by helminths such as Dirofilaria, in particular Dirofilaria immitis. Background Art

[0002] A number of serious animal diseases are caused by helminths, which can be classified into the following categories: a) cestodes, for example, Anoplocephala; Dipylidium; Diphyllobothrium; Echinococcus; Moniezia; Taenia; b) trematodes, for example, Dicrocoelium; Fasciola; Paramphistomum; Schistosoma; or c) nematodes, for example, Haemonchus; Ancylostoma; Anecator spp.; Ascaridia; Ascaris; Brugia; Bunostomum; Capillaria; Chabertia; Cooperia; Cyathostomum; Cylicocyclus; Cylicodontophorus; Cylicostephanus; Dictyocaulus; Haemonchus; Dirofilaria; Dracunculus; Enterobius; Filaroides; Habronema; Haemonchus; Heterakis; Hyostrongylus; Muellerius spp.; Necator; Nematodirus; Onchocerca; Loa; Ostertagia; Oxyuris; Parascaris; Stephanurus; Strongylus; Syngamus; Toxocara; Strongyloides; Trichuris; Trichostrongylus; Triodontophorus; Ancylostoma; and / or Wuchereria.

[0003] Helminthiases caused by the above helminths are also referred to as helminth infections. These helminths usually live in the gastrointestinal tract of the host, but they may also burrow into other organs, where they can cause physiological damage. For example, Ascaridia is reported to cause small intestine infections in affected animals, especially feathered animals such as birds, resulting in partial or even complete gastrointestinal obstruction. In addition, another helminth, Haemonchus, is known to affect animals such as sheep and goats, where this infestation usually results in attachment to the gastric mucosa to suck blood from the host. As a result, the affected animals show anemia and shortness of breath. Further, Nematodirus is known to form nodules in the intestines of its infected hosts, which can lead to dysentery.

[0004] In addition, heartworm disease, also known as cardiovascular filariasis, is a serious and mostly fatal disease that can affect the internal organs such as the lungs and heart of pets and certain other mammals. This disease is caused by the parasitic nematode Dirofilaria immitis, which can reach a length of about 30 cm and a thickness of about 1 mm in its adult state. These nematodes live in the heart, lungs, and associated 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, usually ultimately resulting in the death of the host.

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

[0006] Heartworms must go through different stages before becoming adult worms in an infected host animal. Mosquitoes play a crucial role in the life cycle of heartworms as they are required as intermediate hosts. Adult female heartworms living in an infected host give birth to larvae called microfilariae, which can circulate in the blood for up to two years and are ingested by blood-sucking mosquitoes. When a mosquito bites and sucks blood from such an infected host, it takes away the said microfilariae, which start to develop inside the mosquito, and thus the first and second larval stages (L1) and (L2) of heartworm development occur inside the mosquito. Once the larvae mature to the third larval stage (L3), the infective larval stage, the mosquito locates and bites a host, and these infective larvae are deposited on the skin surface of the host and enter the new host through the mosquito bite, remaining under the skin at the bite site. After further growth in a short period of about 2 weeks, they develop to the fourth larval stage (L4) and migrate to the chest and abdominal muscles. 45 to 60 days after infection, the larvae turn into immature adult worms (fifth larval stage; L5), and between 75 and 120 days after infection (mosquito bite), these immature heartworms enter the bloodstream and are carried to the heart and lung systems, where their body size increases significantly in the next approximately three months. Seven months after infection (mosquito bite), the adult worms mate, and the female starts to produce the above-mentioned microfilariae. Mature heartworms can survive for about 7 years in dogs and about 3 years in cats. Due to the long lifespan of these worms, each mosquito season leads to an increase in the number of heartworms in infected pets.

[0007] Due to the widespread use of anthelmintic compounds, highly drug-resistant worm populations have been reported to have emerged. The emergence of such drug resistance to known anthelmintics is thought to pose an increasing problem for the successful treatment of the above-mentioned disease.

[0008] Both WO2018 / 087036A1 and WO2019 / 025341A1 disclose a compound considered to be an anthelmintic, namely a quinoline 3-carboxamide derivative having the following structure

[0009]

[0010] wherein the residues R 1 、R 2 、R 3 、R 4 、R 5 、R 6 、A and Q are defined accordingly.

[0011] These molecules are thought to be regulators of the nematode calcium-activated potassium channel slo-1, which can be considered the worm ortholog of the human KCa1.1 channel (potassium calcium-activated channel subfamily M alpha-1), encoded by the KCNMA1 gene (KCa1.1 and KCNMA1 are often used interchangeably). Slo-1 exhibits calcium-activated potassium channel activity and voltage-gated potassium channel activity. The Slo-1 channel plays an important role in neuromuscular washout and secretory cells, etc. Therefore, slo-1 regulators have been reported to be involved in several processes, including behavioral responses to ethanol, locomotion, and pharyngeal pumping. More specifically, it disrupts neuromuscular transmission, leading to flaccid paralysis, and also affects feeding and egg-laying. In addition, it slows down the development of the corresponding worm larvae and adults.

[0012] However, especially in view of the emergence of resistance to known anthelmintic compounds, there is still an urgent need for new active pharmaceutical ingredients that can address worm infections.

[0013] Accordingly, an object of the present invention is to overcome one or more deficiencies of the prior art.

[0014] One aim is to provide new anthelmintic compounds which can be used to address infections in mammals, especially pets such as cats and dogs, particularly dogs. In particular, one aim is to provide new anthelmintic compounds which can be used to address 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, Oesophagostomum venulosum, Chabertia ovina, Dictyocaulus viviparous, Dictyocaulus filaria, Dirofilaria immitis, Dirofilaria repens; b) trematodes: Fasciola hepatica, Fascioloides magna, Dicrocoelium dentriticum, Paramphistomum cervi, c) cestodes: Monezia expansai, especially Ascaridia galli, Haemonchus contortus, Oesophagostomum dentatum and Acanthocheilonema viteae, and infections by Dirofilaria immitis, especially by Dirofilaria immitis (heartworm).

[0015] Another object is to provide novel anthelmintic compounds that can be used for treating mammalian infections, where these compounds are compatible with standard antiparasitic treatments for pets, especially cats and dogs, and particularly dogs. In particular, an object is to provide novel anthelmintic compounds that can be used to address infections in pets such as cats and dogs and can be administered orally or topically.

[0016] More particularly, an object is to provide novel anthelmintic compounds that can be used to address infections in mammals caused by parasites, especially infections caused by Dirofilaria immitis (heartworm), without having a negative impact on the host due to unwanted side effects.

[0017] In addition, an object is that the novel anthelmintic compounds can be used in different treatment regimens, especially monthly or longer treatment regimens. Summary of the Invention

[0018] Surprisingly, at least one object can be met by providing a compound according to formula (I):

[0019]

[0020] wherein

[0021] R 1 is independently selected from

[0022] hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy, C 1-6 -alkylthio, halogen, cyano, nitro, hydroxy, 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 ,

[0023] where each C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C1-6 -alkoxy or C 1-6 -alkylthio is optionally substituted by one or more substituents independently selected from

[0024] C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy, C 1-6 -alkylthio, halogen, cyano, nitro, hydroxy, 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’ ,

[0025] R 2 and R 3 are independently selected from

[0026] hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy-C 1-6 -alkyl, C-alkyl substituted by 3-10 -cycloalkyl, C-alkyl substituted by 1-6 -a 5- to 10-membered heterocyclic group, C-alkyl substituted by 1-6 -an aryl, C-alkyl substituted by 6-10 -a 5- to 10-membered heteroaryl, or 1-6 C-alkyl substituted by 1-6 or

[0027] R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O,

[0028] wherein each C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10-cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy-C 1-6 -alkyl, C1-6-alkyl substituted with C3-10-cycloalkyl, C 1-6 -alkyl, C 6-10 -alkyl substituted with C 1-6 -aryl or C 1-6 -alkyl substituted with 5- to 10-membered heteroaryl or a heterocycle formed by R 2 and R 3 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[0029] C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxy, 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” ;

[0030] R 4 、R 5 and R 6 are independently selected from hydrogen and C 1-6 -alkyl,

[0031] R 2’ 、R 3’ 、R 4’ 、R 5’ and R 6’ are independently selected from hydrogen and C 1-6 -alkyl,

[0032] R 2” 、R 3” 、R 4” 、R 5” and R 6” are independently selected from hydrogen and C 1-6 -alkyl,

[0033] R 7 is independently selected from

[0034] Hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4- to 10-membered heterocyclic group, C 6-10 aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy, C 1-6 -alkylthio, halogen, cyano, nitro, hydroxy, 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 ,

[0035] wherein each C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 4- to 10-membered heterocyclic group, C 6-10 aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy or C 1-6 -alkylthio is optionally independently substituted with one or more substituents selected from the following

[0036] C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy, C 1-6 -alkylthio, halogen, cyano, nitro, hydroxy, mercapto, 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’ ,

[0037] R 8 and R 9 are independently selected from

[0038] hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy-C 1-6 -alkyl, C1-6-alkyl substituted with C3-10-cycloalkyl, C 1-6 -alkyl, C 6-10 -alkyl substituted with C 1-6 -aryl, C 1-6 -alkyl, or

[0039] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O,

[0040] wherein each C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy-C 1-6- alkyl, C1-6-alkyl substituted with C3-10-cycloalkyl, C 1-6 -alkyl, C 6-10 -alkyl substituted with C 1-6 -aryl or C 1-6 -alkyl substituted with 5- to 10-membered heteroaryl or C 8 and R 9 the heterocycle formed together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[0041] C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR 8” R 9” 、C(=O)OR 10” 、SR 10” 、SOR10” , SO2R 10” , SO2NR 11” R 12” and C(=O)NR 11” R 12” ;

[0042] R 10 , R 11 and R 12 are independently selected from hydrogen and C 1-6 -alkyl,

[0043] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen and C 1-6 -alkyl,

[0044] R 8” , R 9” , R 10” , R 11” and R 12” are independently selected from hydrogen and C 1-6 -alkyl,

[0045] R 13 is hydrogen or C 1-3 alkyl,

[0046] R 14 is hydrogen, C 1-3 alkyl, C 1-3 alkoxy, NR 14’ R 14” wherein R 14’ and R 14” are independently C 1-3 -alkyl or

[0047] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the ring containing 5 or 6 carbon atoms is optionally substituted by one or more C 1-3 -alkyl or =O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S-, or

[0048] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein the ring containing 5 or 6 carbon atoms is optionally substituted by one or more C 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-

[0049] A1 is N or CR 15 , where R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , where R 15’ and R 15” are independently C 1-3 -alkyl,

[0050] A2 is N or CR 16 , where R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” , where R 16’ and R 16” are independently C 1-3 -alkyl,

[0051] A3 is N or CR 17 , where R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 17’ R 17” , where R 17’ and R 17” are independently C 1-3 -alkyl,

[0052] A4 is N or CR 18 , where R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 18’ R 18” , where R 18’ and R 18” are independently C 1-3 -alkyl,

[0053] R 19 is independently selected from C 6-10 -aryl and 5- to 10-membered heteroaryl,

[0054] where each C 6-10 -aryl or 5- to 10-membered heteroaryl is optionally substituted by one or more substituents independently selected from the following

[0055] C 1-6-alkyl, C 2-6 -alkenyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy, C 1-6 -alkylthio, halogen, cyano, nitro, hydroxy, 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 ,

[0056] R 20 and R 21 are independently selected from

[0057] 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, 5- to 10-membered heteroaryl-substituted C 1-6 -alkyl, or

[0058] R 20 and R 21 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0059] wherein each C 1-6 -alkyl, C 2-6 -alkenyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy or C 1-6 -alkylthio or the heterocycle formed by R 20 and R 21 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from the following

[0060] C 1-6 -alkyl, C 2-6 -alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C6-10 -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’

[0061] R 22 , R 23 and R 24 are independently selected from hydrogen and C 1-6 -alkyl,

[0062] R 20’ , R 21’ , R 22’ , R 23’ and R 24’ are independently selected from hydrogen and C 1-6 -alkyl,

[0063] R 25 are independently selected from hydrogen and C 1-6 -alkyl,

[0064] or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph, prodrug, or mixture thereof.

[0065] In one embodiment of the present invention and / or its embodiments,

[0066] R 1 Independently selected from

[0067] Hydrogen, C 1-6 -alkyl, C 1-6 -Alkoxy, halogen, hydrogen, nitro, hydroxyl, NR 2 R 3 、C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0068] Each of the C 1-6 -alkyl or C 1-6 -alkoxy is optionally substituted by one or more substituents independently selected from the following

[0069] C 1-6 -alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxyl and NR2’ R 3’ ,

[0070] R 2 and R 3 are independently selected from

[0071] hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl, or

[0072] R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 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;

[0073] wherein each C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 2 and R 3 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from

[0074] C 1-6 -alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy,

[0075] R 4 , R 5 and R 6 are independently selected from hydrogen and C 1-6 -alkyl,

[0076] R 2’ and R 3’ are independently selected from hydrogen and C 1-6 -alkyl.

[0077] In one embodiment of the present invention and / or its embodiments,

[0078] R 1 is independently selected from

[0079] hydrogen, C 1-6 -alkyl, C 1-6 -alkoxy and halogen,

[0080] wherein each C 1-6 -alkyl or C 1-6 -alkoxy is optionally substituted with one or more substituents independently selected from

[0081] C1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxy, and NR 2’ R 3’ ,

[0082] wherein R 2’ and R 3 ' are independently selected from hydrogen and C 1-3 -alkyl.

[0083] In one embodiment of the present invention and / or its embodiments,

[0084] R 1 is independently selected from

[0085] hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride.

[0086] In one embodiment of the present invention and / or its embodiments,

[0087] R 7 is independently selected from

[0088] 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, hydroxy, NR 8 R 9 , C(=O)OR 10 , SR 10 , SOR 10 , SO2R 10 , and C(=O)NR 11 R 12 ,

[0089] wherein each C 1-6 -alkyl, C 2-6 -alkenyl, C 3-10 -cycloalkyl, 4- to 10-membered heterocyclic group, or C 1-6 -alkoxy is optionally substituted with one or more substituents independently selected from the following

[0090] C 1-6 -alkyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ , and C(=O)NR 11’ R 12’ ,

[0091] R8 and R 9 are independently selected from

[0092] hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, a 5- to 10-membered heterocyclic group, and a 5- to 10-membered heteroaryl, or

[0093] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2, or 3 other ring atoms are selected from N, S, and O;

[0094] wherein each C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10- -aryl, a 5- to 10-membered heterocyclic group, and a 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from

[0095] C 1-6 -alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8” R 9” 、C(=O)-OR 10” and C(=O)NR 11” R 12” ;

[0096] R 10 、R 11 and R 12 are independently selected from hydrogen and C 1-6 -alkyl,

[0097] R 8’ 、R 9’ 、R 10’ 、R 11’ and R 12’ are independently selected from hydrogen and C 1-6 -alkyl,

[0098] R 8” 、R 9” 、R 10” 、R 11” and R 12” are independently selected from hydrogen and C 1-6 -alkyl.

[0099] In one embodiment of the present invention and / or its embodiments,

[0100] R 7 independently selected from

[0101] hydrogen, C 1-6 -alkyl, C 2-6 -alkenyl, a 4- to 10-membered heterocyclic group, 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 ,

[0102] wherein each C 1-6 -alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocyclic group or C 1-6 -alkoxy is optionally substituted by one or more substituents independently selected from the following

[0103] C 1-6 -alkyl, a 5- to 10-membered heterocyclic group, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0104] R 8 and R 9 are independently selected from the following

[0105] hydrogen, C 1-6 -alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl, or

[0106] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0107] wherein C 1-6 -alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from the following

[0108] C 1-6 -alkyl, C 1-6 -alkoxy, hydroxy and NR8” R 9” ;

[0109] R 10 、R 11 and R 12 are independently selected from hydrogen or C 1-6 -alkyl,

[0110] R 8’ 、R 9’ 、R 10’ 、R 11’ and R 12’ are independently selected from hydrogen or C 1-6 -alkyl,

[0111] R 8” and R 9” are independently selected from hydrogen or C 1-6 -alkyl.

[0112] In one embodiment of the present invention and / or its embodiments,

[0113] R 7 is independently selected from

[0114] methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl.

[0115] In one embodiment of the present invention and / or its embodiments,

[0116] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the ring containing 5 or 6 carbon atoms is optionally substituted by one or more C 1-3 -alkyl or =O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S-,

[0117] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R15’ and R 15” is independently C 1-3 -alkyl,

[0118] A2 is N or CR 16 , where R 16 is independently hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy or NR 16’ R 16” , where R 16’ and R 16” is independently C 1-3 -alkyl,

[0119] A3 is N or CR 17 , where R 17 is independently hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy or NR 17’ R 17” , where R 17’ and R 17” is independently C 1-3 -alkyl,

[0120] A4 is N or CR 18 , where R 18 is independently hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy or NR 18’ R 18” , where R 18’ and R 18” is independently C 1-3 -alkyl,

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

[0122] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, where the ring containing 5 or 6 carbon atoms is optionally substituted by one or more C 1-3 -alkyl, and / or where one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[0123] A1 is N or CR 15 , where R 15 is independently hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy or NR 15’ R 15” , where R 15’ and R 15”Independently is C 1-3 -alkyl

[0124] A2 is N or CR 16 wherein R 16 independently is hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy or NR 16’ R 16” wherein R 16’ and R 16” independently are C 1-3 -alkyl

[0125] A3 is N or CR 17 wherein R 17 independently is hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy or NR 17’ R 17” wherein R 17’ and R 17” independently are C 1-3 -alkyl

[0126] A4 is N or CR 18 wherein R 18 independently is hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy or NR 18’ R 18” wherein R 18’ and R 18” independently are C 1-3 -alkyl

[0127] In one embodiment of the present invention and / or its embodiments,

[0128] Zero, one or two of the residues A1, A2, A3 and A4 are N.

[0129] In one embodiment of the present invention and / or its embodiments,

[0130] A1 is CR 15 , A2 is CR 16 , A3 is CR 17 and A4 is CR 18 .

[0131] In one embodiment of the present invention and / or its embodiments,

[0132] R 19 independently is selected from

[0133] C 6-10 -aryl and 5- to 10-membered heteroaryl

[0134] Each C 6-10 -aryl or 5- to 10-membered heteroaryl is optionally substituted by one or more substituents independently selected from

[0135] C 1-6 -alkyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy, halogen, hydrogen, nitro, hydroxy, NR 20 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0136] R 20 and R 21 are independently selected from

[0137] hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl and C 6-10 -aryl, or

[0138] R 20 and R 21 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 of the other ring atoms are selected from N, S and O;

[0139] Each C 1-6 -alkyl, C 3-10 -cycloalkyl or C 6-10 -aryl or the heterocycle formed by R 20 and R 21 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from

[0140] C 1-6 -alkyl, C 3-10 -cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 -aryl, 5- to 10-membered heteroaryl, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 20’ R 21’ , C(=O)OR 22’ and C(=O)NR 23’ R 24’

[0141] R 22 , R 23 and R 24 are independently selected from hydrogen and C 1-6 -alkyl,

[0142] R 20’ , R 21’ , R 22’ , R 23’ and R 24’ are independently selected from hydrogen and C 1-6 -alkyl.

[0143] In one embodiment of the present invention and / or its embodiments,

[0144] R 19 Independently selected from

[0145] C 6-10 - aryl and 5- to 10-membered heteroaryl,

[0146] Each C 6-10 -aryl or 5 to 10 membered heteroaryl is optionally substituted by one or more substituents independently selected from

[0147] C 1-6 -alkyl, C 1-6 - alkoxy, halogen, cyano, nitro and hydroxy.

[0148] In one embodiment of the present invention and / or its embodiments,

[0149] R 19 It is C 6-10- Aryl, where C 6-10- Aryl is optionally substituted with one or more substituents independently selected from

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

[0151] In one embodiment of the present invention and / or its embodiments,

[0152] R 19 It is C 6-10- Aryl, where C 6-10 -Aryl is phenyl substituted with 1, 2 or 3 substituents independently selected from fluoride, chloride and bromide.

[0153] In one embodiment of the present invention and / or its embodiments, R 25 It's hydrogen.

[0154] In one embodiment of the invention and / or its embodiments, the compound according to formula (I) is present in the form of the (S)-enantiomer.

[0155] Furthermore, the present invention provides a process for preparing a compound according to formula (I), comprising the following steps:

[0156] React the compound of formula (A)

[0157]

[0158] with the compound of formula (B),

[0159]

[0160] wherein R 1 、R 7 、R 13 、R 14 、A1, A2, A3, A4, R 19 and R 25 are defined as in any one of the embodiments disclosed herein to obtain a compound according to formula (I).

[0161] In addition, the present invention provides a veterinary pharmaceutical composition comprising

[0162] - a compound according to formula (I) as defined in any one of the embodiments described herein, and

[0163] - one or more physiologically acceptable excipients.

[0164] 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, glidants, disintegrants and preservatives and mixtures thereof.

[0165] In addition, the present invention provides a compound according to formula (I) as defined in any one of the embodiments described herein or a veterinary pharmaceutical composition according to the present invention for use as a medicament.

[0166] In addition, the present invention provides a compound according to formula (I) as defined in any one of the embodiments described herein or a veterinary pharmaceutical composition according to the present invention for treating a disorder / disease caused by worms.

[0167] In one embodiment of the present invention and / or its embodiments, the disease is filariasis, particularly heartworm disease.

[0168] In one embodiment of the present invention and / or its embodiments, the worm is Dirofilaria immitis. Detailed Description

[0169] It has been found that the compounds according to formula (I) or their stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof can be used for the treatment of conditions / diseases caused by helminths such as Ostertagia ostertagi, Cooperia oncophora, Cooperia punctata, Trichostrongylus axei, Haemonchus placei, Haemonchus contortus, Nematodirus helvetianus, Nematodirus spathiger, Trichostrongylus colubriformis, Trichostrongylus circumcincta, Oesophagostomum venulosum, Chabertia ovina, Dictyocaulus viviparous, Dictyocaulus filaria, Dirofilaria immitis, Dirofilaria repens; b) trematodes: Fasciola hepatica, Fascioloides magna, Dicrocoelium dendriticum, Paramphistomum cervi, c) cestodes: Monezia expansa. In particular, Ascaridia galli, Haemonchus contortus, Oesophagostomum dentatum and Dirofilaria immitis. Specifically, the compounds according to the invention and / or any of its embodiments can be used for the treatment of helminth infections such as filariasis, in particular heartworm disease. Optionally, the compounds according to the invention and / or any of its embodiments can be used for the treatment of conditions / diseases caused by helminths such as nematodes, in particular Dirofilaria immitis, wherein the condition / disease caused by Dirofilaria immitis is heartworm disease.

[0170] Advantageously, the compounds according to the invention and / or any of its embodiments are effective against worms such as Dirofilaria immitis, but ineffective against bacteria that are particularly relevant to the health of mammals, especially dogs, such as Acinetobacter baumanii or Staphylococcus spp. or Streptococcus spp.

[0171] The inventors have found that the compounds of the invention meet these requirements and are thus very useful in the treatment (and prevention) of diseases caused by worms such as heartworm disease.

[0172] The following abbreviations and definitions are used throughout this application.

[0173] Generally, reference to an element means including all isotopes of that element. For example, if a group is defined as including hydrogen or a residue is hydrogen, it also includes deuterium and tritium.

[0174] The term "C 1-6- alkyl" refers to an alkyl group having 1 to 6 carbon atoms and no heteroatoms. Thus, the term includes straight-chain alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, and hexyl. The term also includes branched-chain isomers of straight-chain alkyl groups, including but not limited to those provided as examples below: -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. Thus, 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.

[0175] Accordingly, the term "C 1-3- alkyl" refers to an alkyl group having 1 to 3 carbon atoms and no heteroatoms. Thus, the term includes straight-chain alkyl groups such as methyl, ethyl, and propyl. The term also includes the branched-chain isomer of the straight-chain alkyl group, i.e., CH(CH3)2. Thus, the term "C 1-3- alkyl" includes primary alkyl groups having 1 to 3 carbon atoms and secondary alkyl groups having 3 carbon atoms

[0176] The term "C 2-6 alkenyl" refers to straight-chain and branched-chain alkenyl groups, for example, with respect to "C 2-6Those described by "alkyl", except that there is at least one double bond between two carbon atoms. Examples 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, hexadienyl, etc.

[0177] The term "C 2-6- alkynyl" refers to straight-chain and branched alkynyls, such as those described for "C 2-6- alkyl" above, except that there is 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.

[0178] The term "C 3-10 -cycloalkyl" refers to a non-aromatic monocyclic alkyl group having 3 to 10 carbon atoms or a non-aromatic polycyclic alkyl group having 3 to 10 carbon atoms, where the group consists only of carbon and hydrogen atoms. The cycloalkyl group can contain a fused or bridged ring system having 3 to 10 carbon atoms. Non-aromatic monocyclic alkyl groups having 3 to 10 carbon atoms include but are not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, etc. Non-aromatic polycyclic alkyl groups having 3 to 10 carbon atoms include but are not limited to adamantane, norbornane, decahydronaphthyl, 7,7-dimethyl-bicyclo[2.2.1]heptyl, etc.

[0179] The term "5- to 10-membered heterocyclic group" refers to a cyclic group in which 5 to 10 members (atoms) form a backbone, and the backbone of the cyclic compound contains 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, the "5- to 10-membered heterocyclic group" can be a monocyclic, bicyclic, or polycyclic group, which can include a fused ring or bridged ring system, and a part of the fused ring system can be aromatic; the nitrogen, carbon, or sulfur atoms in the "5- to 10-membered heterocyclic group" can be optionally oxidized; the nitrogen atom can be optionally quaternized; and the heterocyclic group residue can be partially saturated.

[0180] Examples of heterocyclic groups include, but are not limited to, pyrrolinyl, 3H-pyrazolyl, 4H-pyrazolyl, dihydropyridyl, pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, homopiperazinyl, indolinyl, quinuclidinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, dihydrodithienyl, dihydrodisulfinyl, tetrahydrothiophene, tetrahydropyran, benzothiazinyl such as 2H-1,4-benzothiazinyl, dihydrobenzothiazinyl such as 2H-3,4-dihydrobenzothiazinyl, benzodioxolyl such as 1,3-benzodioxolyl, dihydrooxathienyl, 1,4-oxathienyl. 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 (sulfoxides and sulfones), such as tetrahydrothiophene, tetrahydrothiophene oxide, and tetrahydrothiophene-1,1-dioxide, and thiomorpholine, thiomorpholine oxide, and thiomorpholine-1,1-dioxide.

[0181] The term "C 6-10 aryl" refers to a group having an aromatic backbone structure, where the ring atoms of the aromatic backbone structure are carbon atoms. In other words, "C 6-10 aryl" does not contain heteroatoms such as N, S, O in the aromatic backbone structure.

[0182] Examples of aryl groups include, but are not limited to, phenyl, biphenyl, and naphthyl.

[0183] The term "5- to 10-membered heteroaryl" refers to an aromatic group in which 5 to 10 members (atoms) form a backbone, and the backbone of the cyclic compound contains 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 specifically stated in the specification, the "5- to 10-membered heterocyclic group" can be a monocyclic, bicyclic, or polycyclic group, which can include a fused ring system.

[0184] Examples of 5- to 10-membered heteroaryls include, but are not limited to, pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, triazolyls such as 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl, and 4H-1,2,4-triazolyl, tetrazolyls such as 1H-tetrazolyl, 2H-tetrazolyl, and 5H-tetrazolyl, indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, quinolinyl, isoquinolinyl, indazolyl, naphthyridinyl, benzotriazolyl, oxazolyl, isoxazolyl, oxadiazolyls such as 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, benzoxazolyl, benzoxadiazolyl, benzoxazinyl such as 2H-1,4-benzoxazinyl, thiazolyl, isothiazolyl, thiadiazolyls such as 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, thienyl, benzothiazolyl, benzothiadiazolyl, benzothiazinyl, benzofuranyl, quinolinyl, isoquinoline, cinnamyl, quinazolinyl, quinoxalinyl, triazinyl, tetrazinyl, purinyl, pteridinyl, furyl, benzodioxolyl such as 1,3-benzodioxolyl, benzothienyl, benzodithienyl, and benzothiazinyl.

[0185] The term "C 1-6- alkoxy" refers to a group based on an alkyl group having 1 to 6 carbon atoms bonded to oxygen. Alkyl groups having 1 to 6 carbon atoms refer to straight-chain and branched-chain groups such as those described for "C 1-6- alkyl" defined above.

[0186] Accordingly, the term "C 1-3- alkoxy" refers to a group based on an alkyl group having 1 to 3 carbon atoms bonded to oxygen. Alkyl groups having 1 to 3 carbon atoms refer to straight-chain and branched-chain groups such as those described for "C 1-3- alkyl" defined above.

[0187] The term "C 1-6- alkylthio" refers to a group based on an alkyl group having 1 to 6 carbon atoms bonded to sulfur. Alkyl groups having 1 to 6 carbon atoms refer to straight-chain and branched-chain groups such as those described for "C 1-6- alkyl" defined above.

[0188] "Optionally substituted" means that one or more hydrogens of a group are optionally substituted by one or more defined substituents.

[0189] Other amines, hydroxyl groups, and thiol groups can be protected. The term "protected" with respect to these groups refers to forms of these functionalities having protecting groups to prevent undesired reactions of the groups. These protecting groups are known to those skilled in the art, such as those from Protective Groups in Organic Synthesis; Wuts, P.G.M. John Wiley & Sons, New York, NY (53rd Edition, 2014). The procedures described therein can be used to add or remove the protecting groups.

[0190] Examples of protected hydroxyl groups include, but are not limited to, silyl ethers, such as those obtained by reaction of a hydroxyl group with a reagent such as, but not limited to, tert-butyldimethyl-chlorosilane, trimethylchlorosilane, triisopropylchlorosilane, triethylchlorosilane; substituted methyl ethers and ethyl ethers, such as, but not limited to, methoxymethyl ether, methylthiomethyl ether, benzyloxymethyl ether, tert-butoxymethyl ether, 2-methoxyethoxymethyl ether, tetrahydropyranyl ether, 1-ethoxyethyl ether, allyl ether, benzyl ether; esters such as, but not limited to, benzoylformate, formate, acetate, trichloroacetate, and trifluoroacetate.

[0191] Examples of protected amino groups include, but are not limited to, amides, such as formamide, acetamide, trifluoroacetamide, and benzamide; imides, such as phthalimide and dithiosuccinimide; carbamates, such as tert-butoxycarbonyl (Boc), etc.

[0192] Examples of protected thiol groups include, but are not limited to, thioethers, such as S-benzyl thioether and S-4-pyridylmethyl thioether; substituted S-methyl derivatives, such as hemithioacetals, dithioacetals, and aminothioacetals, etc.

[0193] Stereoisomers include compounds that are composed of the same atoms connected in the same order but differ in the positions of the atoms in space. Stereoisomers include diastereoisomers and enantiomers.

[0194] "Physiologically acceptable salts" refer to salts formed with inorganic bases, organic bases, inorganic acids, organic acids, or basic or acidic amino acids.

[0195] 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.

[0196] 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, pamoic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic acid, pantothenic acid, 2-hydroxyethanesulfonic acid, p-aminobenzenesulfonic acid, cyclohexylaminosulfonic acid, β-hydroxybutyric acid, galactonic acid, galacturonic acid, adipic acid, alginic acid, butyric acid, camphoric acid, camphorsulfonic acid, cyclopentanepropionic acid, dodecylsulfuric acid, enanthic acid, glycerophosphoric acid, heptanoic acid, hexanoic acid, nicotinic acid, 2-naphthalenesulfonic acid, oxalic acid, palmitic acid, pectic acid, 3-phenylpropionic acid, picric acid, pivalic acid, thiocyanic acid, toluenesulfonic acid, undecanoic acid, and acidic amino acids such as aspartic acid and glutamic acid.

[0197] Examples of base addition salts can include, for example, metal salts and organic salts.

[0198] 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, the free acid compound can be mixed with sodium hydroxide to form such a base addition salt.

[0199] Organic salts can be made from amines such as trimethylamine, diethylamine, N,N'-dibenzylethylenediamine, chloroprocaine, ethanolamine, diethanolamine, ethylenediamine, N-methylglucamine, procaine, and basic amino acids such as arginine, lysine, and ornithine.

[0200] As used herein, the term "pharmaceutically acceptable ester" refers to an ester that hydrolyzes in vivo, including those that readily decompose in the human body to leave the parent compound or its salt. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxylic acids, particularly alkanoic acids, alkenoic acids, cycloalkanoic acids, and alkanedioic acids, where each alkyl or alkenyl moiety advantageously has no more than 6 carbon atoms. Representative examples of specific esters include, but are not limited to, formates, acetates, propionates, butyrates, acrylates, and ethyl succinates.

[0201] A solvate of a compound can be considered a compound in which an organic solvent or water is attached to the compound. Organic solvents are those known to the person skilled in the art. If water is attached to the compound, the corresponding compound is called a hydrate.

[0202] As used herein and as generally understood by those skilled in the art, the term "polymorph" refers to different crystalline forms of the same molecular entity. Thus, due to their different chemical compositions, the above-mentioned solvates and hydrates are not included in the definition of polymorphs, but are referred to as "pseudopolymorphs".

[0203] The term "prodrug" refers to a compound that is rapidly converted in vivo to produce the parent compound of formula ((I) above, for example by hydrolysis in the blood. Detailed discussions are provided in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery Systems, Volume 14, A.C.S. Symposium Series and Edward B. Roche, Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987.

[0204] As used herein, the term "pharmaceutically acceptable prodrug" refers to a prodrug of a compound of the present invention that, within the scope of reasonable medical judgment, is suitable for contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, etc., commensurate with a reasonable benefit / risk ratio and effective for its intended use, and, where possible, the zwitterionic form of the compound of the present invention.

[0205] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 1 As defined above.

[0206] In one embodiment of the present invention and / or its embodiments, R 1 is independently selected from:

[0207] hydrogen, C 1-6- alkyl, C 1-6- alkoxy, halogen, amino, nitro, hydroxy, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0208] wherein each C 1-6- alkyl or C 1-6- alkoxy is optionally substituted with one or more substituents independently selected from

[0209] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, hydroxy and NR 2’ R3’ ,

[0210] R 2 and R 3 are independently selected from

[0211] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[0212] R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0213] wherein each C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 2 and R 3 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from

[0214] C 1-6- alkyl, C 3-10- cycloalkyl and C 1-6- alkoxy,

[0215] R 4 , R 5 and R 6 are independently selected from hydrogen and C 1-6- alkyl, preferably selected from hydrogen and C 1-3- alkyl, R 2’ and R 3’ are independently selected from hydrogen and C 1-6- alkyl, preferably selected from hydrogen and C 1-3- alkyl.

[0216] Optionally, in one embodiment of the present invention and / or its embodiments, R 1 is independently selected from

[0217] hydrogen, C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro and C(=O)NR 5 R 6 , wherein each C 1-6- alkyl or C 1-6- alkoxy is optionally substituted with one or more substituents independently selected from

[0218] C 1-6- alkyl, C1-6- Alkoxy, halogen, cyano, nitro, hydroxy and NR 2’ R 3’ ,

[0219] R 5 and R 6 are independently selected from hydrogen and C 1-3- alkyl

[0220] R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl

[0221] Optionally, in one embodiment of the present invention and / or its embodiments, R 1 is independently selected from

[0222] hydrogen, C 1-6- alkyl, C 1-6- alkoxy and halogen

[0223] wherein C 1-6- alkyl and C 1-6- alkoxy are optionally substituted by one or more substituents independently selected from the following

[0224] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy and NR 2’ R 3’ ,

[0225] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably selected from hydrogen and methyl

[0226] In one embodiment of the present invention and / or its embodiments, R 1 is independently selected from

[0227] hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride

[0228] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iai), (Iaii), (Iaiii), (Iaiv), (Iav) or (Iavi):

[0229]

[0230]

[0231] 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.

[0232] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iai), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iaii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iaiii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iaiv), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iav), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iavi), preferably in the (S)-enantiomeric form.

[0233] The present invention provides a compound according to the invention and / or its embodiments, wherein R 7 is as defined above.

[0234] In one embodiment of the invention and / or its embodiments, R 7 is independently selected from 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, hydroxy, NR 8 R 9 , C(=O)OR 10 , SR 10 , SOR 10 , SO2R 10 and C(=O)NR 11 R 12 ,

[0235] wherein each C 1-6- alkyl, C 2-6- alkenyl, C 3-10- cycloalkyl, 4- to 10-membered heterocyclic group or C 1-6- alkoxy is optionally substituted with one or more substituents independently selected from the following

[0236] C 1-6- alkyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 1-6-alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0237] R 8 and R 9 are independently selected from

[0238] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group, and 5- to 10-membered heteroaryl, or

[0239] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2, or 3 other ring atoms are selected from N, S, and O;

[0240] wherein the C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group, or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[0241] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8” R 9” , C(=O)OR 10” and C(=O)NR 11” R 12” ;

[0242] R 10 , R 11 and R 12 are independently selected from hydrogen and C 1-6- alkyl,

[0243] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen and C 1-6- alkyl,

[0244] R 8” , R 9” , R 10” , R11” and R 12” are independently selected from hydrogen and C 1-6- alkyl groups.

[0245] In one embodiment of the present invention and / or its embodiments, wherein R 7 is independently selected from

[0246] 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 ,

[0247] wherein each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-6- alkoxy is optionally substituted with one or more substituents independently selected from the following

[0248] C 1-6- alkyl, 5- to 10-membered heterocyclic groups, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0249] R 8 and R 9 are independently selected from

[0250] hydrogen, C 1-6- alkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[0251] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0252] wherein C 1-6- alkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the group formed by R 8 and R 9The heterocyclic ring formed together with the N atom to which it is attached is optionally substituted by one or more substituents independently selected from the following

[0253] C 1-6- Alkyl, C 1-6- Alkoxy, hydroxyl and NR 8” R 9” ;

[0254] R 10 , R 11 and R 12 are independently selected from hydrogen or C 1-6- Alkyl, preferably selected from hydrogen or C 1-3- alkyl,

[0255] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen or C 1-6- Alkyl, preferably selected from hydrogen or C 1-3- alkyl,

[0256] R 8” and R 9” are independently selected from hydrogen or C 1-6- Alkyl, preferably selected from hydrogen or C 1-3- alkyl.

[0257] In one embodiment of the present invention and / or its embodiments, R 7 Independently selected from

[0258] 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 ,

[0259] Each of the C 1-6- Alkyl, C 2-6- alkenyl, 4 to 10 membered heterocyclic group or C 1-3- The alkoxy group is optionally substituted with one or more substituents independently selected from the following

[0260] C 1-3- Alkyl, 5- to 10-membered heterocyclic group, C 1-6- Alkoxy, halogen, cyano, hydroxyl, NR 8’ R 9’ 、C(=O)OR 10’ and C(=O)NR 11’ R12’ ,

[0261] R 8 and R 9 are independently selected from

[0262] hydrogen, C 1-6- alkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[0263] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0264] wherein C 1-6- alkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from

[0265] C 1-6- alkyl, C 1-6- alkoxy, hydroxy and NR 8” R 9” ;

[0266] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[0267] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[0268] R 8” and R 9” are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl.

[0269] In one embodiment of the present invention and / or its embodiments, R 7Independently selected from: methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, mesyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl.

[0270] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibi), (Ibii), (Ibiii), (Ibiv), (Ibv), (Ibvi), (Ibvii), (Ibviii), (Ibix), (Ibx), (Ibxi) or (Ibxii)

[0271]

[0272]

[0273]

[0274]

[0275] 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 are defined as in any of the embodiments described herein.

[0276] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibvi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibvii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibviii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibix), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibx), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibxi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ibixii), preferably in the (S)-enantiomeric form.

[0277] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 13 and R 14 and A1, A2, A3, A4 are as defined above.

[0278] In one embodiment of the present invention and / or its embodiments,

[0279] R 13 is hydrogen or C 1-3 alkyl and

[0280] R 14 is hydrogen, C 1-3 alkyl or C 1-3 alkoxy.

[0281] More preferably, in one embodiment of the present invention and / or its embodiments,

[0282] R 13 is hydrogen or C 1-3 alkyl and

[0283] R 14 is hydrogen or C 1-3 alkyl group.

[0284] More preferably, in one embodiment of the present invention and / or its embodiments,

[0285] R 13 is hydrogen, methyl or ethyl, preferably hydrogen or methyl and

[0286] R 14 is hydrogen or methyl, preferably hydrogen.

[0287] A1 is N or CR 15 , where R 15 is independently hydrogen, halogen, C 1-3 alkyl group, C 1-3 alkoxy group, or NR 15’ R 15” , where R 15’ and R 15” are independently C 1-3- alkyl group,

[0288] A2 is N or CR 16 , where R 16 is independently hydrogen, halogen, C 1-3 alkyl group, C 1-3 alkoxy group, or NR 16’ R 16” , where R 16’ and R 16” are independently C 1-3- alkyl group,

[0289] A3 is N or CR 17 , where R 17 is independently hydrogen, halogen, C 1-3 alkyl group, C 1-3 alkoxy group, or NR 17’ R 17” , where R 17’ and R 17” are independently C 1-3- alkyl group,

[0290] A4 is N or CR 18 , where R 18 is independently hydrogen, halogen, C 1-3 alkyl group, C 1-3 alkoxy group, or NR 18’ R 18” , where R 18’ and R 18” are independently C 1-3- alkyl group.

[0291] More preferably, in one embodiment of the present invention and / or its embodiments

[0292] R 13 is hydrogen or C 1-3 alkyl and R 14 is hydrogen or C 1-3 alkyl,

[0293] A1 is N or CR 15 wherein R 15 is independently hydrogen, C 1-3 alkyl, C 1-3 alkoxy,

[0294] A2 is N or CR 16 wherein R 16 is independently hydrogen, C 1-3 alkyl, C 1-3 alkoxy,

[0295] A3 is N or CR 17 wherein R 17 is independently hydrogen, C 1-3 alkyl, C 1-3 alkoxy,

[0296] A4 is N or CR 18 wherein R 18 is independently hydrogen, C 1-3 alkyl, C 1-3 alkoxy,

[0297] wherein 0, 1 or 2 of the residues A1, A2, A3 and A4 are N.

[0298] More preferably, in one embodiment of the present invention and / or its embodiments

[0299] R 13 is hydrogen, methyl or ethyl, preferably hydrogen or methyl and R 14 is hydrogen or methyl, preferably hydrogen,

[0300] A1 is N or CR 15 wherein R 15 is independently hydrogen or C 1-3 alkyl,

[0301] A2 is N or CR 16 wherein R 16 is independently hydrogen or C 1-3 alkyl,

[0302] A3 is N or CR 17 wherein R 17 is independently hydrogen or C 1-3 alkyl,

[0303] A4 is N or CR 18 , where R 18 is independently hydrogen or C 1-3 alkyl

[0304] where zero, one or two of the residues A1, A2, A3 and A4 are N.

[0305] In another embodiment of the present invention and / or its embodiments,

[0306] A1 is CR 15 , where R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , where R 15’ and R 15” are independently C 1-3- alkyl

[0307] A2 is CR 16 , where R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” , where R 16’ and R 16” are independently C 1-3- alkyl

[0308] A3 is CR 17 , where R 17 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0309] A4 is CR 18 , where R 18 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy.

[0310] In another embodiment of the present invention and / or its embodiments,

[0311] R 13 is hydrogen or C 1-3- alkyl

[0312] R 14 is hydrogen, C 1-3- alkyl, or C 1-3- alkoxy

[0313] A1 is CR 15 , where R15 is hydrogen, a halogen, C 1-3- alkyl, C 1-3- alkoxy, or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0314] A2 is CR 16 , wherein R 16 is hydrogen, a halogen, C 1-3- alkyl, C 1-3 -alkoxy, or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl,

[0315] A3 is CR 17 , wherein R 17 is hydrogen or C 1-3- alkyl,

[0316] A4 is CR 18 , wherein R 18 is hydrogen or C 1-3- alkyl.

[0317] In another embodiment of the present invention and / or its embodiments,

[0318] R 13 is hydrogen, methyl or ethyl, preferably hydrogen or methyl,

[0319] R 14 is hydrogen or methyl, preferably hydrogen,

[0320] A1 is CR 15 , wherein R 15 is hydrogen or C 1-3 alkyl, preferably hydrogen or methyl,

[0321] A2 is CR 16 , wherein R 16 hydrogen or C 1-3 alkyl, preferably hydrogen or methyl,

[0322] A3 is CR 17 and A4 is CR 18 , wherein R 17 and R 18 is hydrogen.

[0323] In another embodiment of the present invention and / or its embodiments,

[0324] R 13is hydrogen, methyl or ethyl, preferably hydrogen or methyl,

[0325] R 14 is hydrogen or methyl, preferably hydrogen,

[0326] A1 is CR 15 and A2 is CR 16 and A3 is CR 17 and A4 is CR 18 wherein R 15 、R 16 、R 17 and R 18 is hydrogen.

[0327] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ic).

[0328]

[0329] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 、R 7 、R 19 and R 25 are defined as in any of the embodiments described herein.

[0330] In one embodiment of the present invention and / or its embodiments, the compound is as shown in formula (Ic), preferably in the (S)-enantiomeric form.

[0331] In one embodiment of the present invention and / or its embodiments, R 13 and R 14 together with the atoms to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the ring containing 5 or 6 carbon atoms is optionally substituted by one or more C 1-3 -alkyl or =O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S-, or

[0332] R 13 and R 14 together with the atoms to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally substituted by one or more C 1-3- alkyl, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-.

[0333] Examples of non-aromatic or aromatic rings containing 5 or 6 carbon atoms, wherein the non-aromatic ring containing 5 or 6 carbon atoms is optionally substituted by one or more C1-3 -alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S-; or the aromatic ring containing 5 or 6 carbon atoms is optionally substituted by one or more C 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-, including but not limited to the residues represented by the following structures.

[0334]

[0335] wherein

[0336] represents bonding to the amide group; and

[0337] represents the bond of the above ring system fused to an aromatic ring. The aromatic ring particularly includes A1, A2, A3 and A4.

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

[0339] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally substituted by one or more C 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-,

[0340] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0341] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl,

[0342] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl.

[0343] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl.

[0344] In one embodiment of the present invention and / or its embodiments,

[0345] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O- or -S-

[0346] A1 is N or CR 15 , wherein R 15 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy.

[0347] A2 is N or CR 16 , wherein R 16 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy.

[0348] A3 is N or CR 17 , wherein R 17 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy, A4 is N or CR 18 , wherein R 18 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy.

[0349] wherein 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0350] In one embodiment of the present invention and / or its embodiments,

[0351] R 13 and R 14 together with the atom to which it is attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally substituted by one or more C 1-3- alkyl or =O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-,

[0352] A1 is N or CR 15 wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[0353] A2 is N or CR 16 wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[0354] A3 is N or CR 17 wherein R 17 is independently hydrogen or C 1-3 alkoxy,

[0355] A4 is N or CR 18 wherein R 18 is independently hydrogen or C 1-3 alkoxy,

[0356] wherein 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0357] In one embodiment of the present invention and / or its embodiments, none of A1, A2, A3 and A4 is N.

[0358] In one embodiment of the present invention and / or its embodiments, A1 is N. In one embodiment of the present invention and / or its embodiments, A2 is N. In one embodiment of the present invention and / or its embodiments, A3 is N. In one embodiment of the present invention and / or its embodiments, A4 is N.

[0359] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Idi), (Idii), (Idiii), (Idiv), (Idv), (Idvi) or (Idvii)

[0360]

[0361]

[0362] or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph, prodrug, and mixtures thereof, wherein R 1 、R 7 、R 19 and R 25 are as defined in any of the embodiments described herein.

[0363] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idi), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idiii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idiv), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idv), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idvi), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idvii), preferably in the (S)-enantiomeric form.

[0364] In one embodiment of the invention and / or its embodiments,

[0365] R 13 and R 14 together with the atoms to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally substituted by one or more C 1-3- alkyl groups, and / or wherein one or more of the ring-forming carbon atoms are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[0366] A1 is N or CR 15 wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0367] A2 is N or CR 16 wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl

[0368] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl

[0369] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl

[0370] In one embodiment of the present invention and / or its embodiments

[0371] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-

[0372] A1 is N or CR 15 , wherein R 15 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0373] A2 is N or CR 16 , wherein R 16 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0374] A3 is N or CR 17 , wherein R 17 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy, A4 is N or CR 18 , wherein R 18 is independently hydrogen, C 1-3 alkyl or C1-3 Alkoxy

[0375] wherein zero, one or two of A1, A2, A3 and A4 are N.

[0376] In one embodiment of the present invention and / or its embodiments,

[0377] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N- or -S-.

[0378] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy

[0379] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy

[0380] A3 is N or CR 17 , wherein R 17 is independently hydrogen or C 1-3 alkoxy

[0381] A4 is N or CR 18 , wherein R 18 is independently hydrogen or C 1-3 alkoxy

[0382] wherein zero, one or two of A1, A2, A3 and A4 are N.

[0383] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Idviii), (Idix), (Idx), (Idxi), (Idxii), (Idxiii), (Idxiv) or (Idxv)

[0384]

[0385]

[0386]

[0387] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 , R 7 , R 19 and R 25As defined in any of the embodiments described herein.

[0388] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idviii), preferably in the form of the (S)-enantiomer. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idix), preferably in the form of the (S)-enantiomer. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idx), preferably in the form of the (S)-enantiomer. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idxi), preferably in the form of the (S)-enantiomer. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idxii), preferably in the form of the (S)-enantiomer. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idxiii), preferably in the form of the (S)-enantiomer. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idxiv), preferably in the form of the (S)-enantiomer. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Idxv), preferably in the form of the (S)-enantiomer.

[0389] The present invention provides a compound according to the invention and / or its embodiments, wherein R 19 As defined above.

[0390] In one embodiment of the invention and / or its embodiments, R 19 is independently selected from

[0391] C 6-10- aryl and 5- to 10-membered heteroaryl,

[0392] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted by one or more substituents independently selected from

[0393] 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, hydrogen, nitro, hydroxy, NR 20 R 21 、C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0394] R 20 and R 21 are independently selected from

[0395] Hydrogen, C 1-6- Alkyl, C 3-10- Cycloalkyl and C 6-10- Aryl or

[0396] R 20 and R 21 together with the N atom to which it is attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0397] wherein each C 1-6- alkyl, C 3-10- cycloalkyl or C 6-10- aryl or formed by R 20 and R 21 the heteroatom together with the N atom to which it is attached is optionally substituted by one or more substituents independently selected from

[0398] 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, hydroxy, NR 20’ R 21’ , C(=O)OR 22’ and C(=O)NR 23’ R 24’

[0399] R 22 , R 23 and R 24 are independently selected from hydrogen and C 1-6- alkyl,

[0400] R 20’ , R 21’ , R 22’ , R 23’ and R 24’ are independently selected from hydrogen and C 1-6- alkyl.

[0401] In one embodiment of the present invention and / or its embodiments, R 19 is independently selected from the following

[0402] C 6-10- aryl and 5- to 10-membered heteroaryl,

[0403] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted by one or more substituents independently selected from the following

[0404] C 1-6- alkyl, C1-6- Alkoxy, halogen, hydrogen, nitro, hydroxy, C(=O)OR 22 , SO2R 22 , SO2NR 23 R 24 and C(=O)NR 23 R 24 ,

[0405] R 22 , R 23 and R 24 are independently selected from hydrogen and C 1-6- alkyl.

[0406] In one embodiment of the present invention and / or its embodiments, R 19 is independently selected from

[0407] C 6-10- aryl and 5- to 10-membered heteroaryl,

[0408] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[0409] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0410] R 22 , R 23 and R 24 are independently selected from hydrogen and C 1-6- alkyl, preferably selected from hydrogen and C 1-3- alkyl.

[0411] In one embodiment of the present invention and / or its embodiments, R 19 is independently selected from C 6-10- aryl and 5- to 10-membered heteroaryl

[0412] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[0413] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro and hydroxy.

[0414] In one embodiment of the present invention and / or its embodiments, R 19 is a 5- to 10-membered heteroaryl

[0415] wherein the 5- to 10-membered heteroaryl is optionally substituted by one or more substituents independently selected from the following: C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, and hydroxy.

[0416] In one embodiment of the present invention and / or its embodiments, R 19 is a 5- to 10-membered heteroaryl

[0417] wherein the 5- to 10-membered heteroaryl is optionally substituted by one or more substituents independently selected from the following: C 1-6- alkyl and halogen, preferably halogen.

[0418] Examples of 5- to 10-membered heteroaryl groups include but are not limited to pyrrolyl, 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, indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, quinolin-4-yl, quinolin-8-yl, isoquinolinyl, indazolyl, naphthyridinyl, benzotriazolyl, oxazolyl, isoxazolyl, oxadiazolyl such as 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, benzoxazolyl, 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, 1,2,5-thiadiazolyl, thiophen-2-yl, thiophen-3-yl benzothiazolyl, benzothiadiazolyl, benzothiazinyl, benzofuranyl, quinolinyl, isoquinoline, cinnamyl, quinazolinyl, quinoxalinyl, triazinyl, tetrazinyl, purinyl, pteridinyl, furyl, benzodioxolyl such as 1,3-benzodioxolyl, benzothienyl, benzodithienyl, and benzoxathienyl. Preferred are pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidin-3-yl, pyrimidin-4-yl, quinolin-8-yl, thiophen-2-yl, and thiophen-3-yl.

[0419] In one embodiment of the present invention and / or its embodiments, R 19 is a 5- to 10-membered heteroaryl,

[0420] wherein the 5- to 10-membered heteroaryl is substituted by one or more substituents independently selected from C 1-6- alkyl and halogen, preferably halogen.

[0421] In one embodiment of the present invention and / or its embodiments, R 19 is selected from: pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, 2,5-dichloropyridin-4-yl, 2,6-dichloropyridin-4-yl, 5-chlorothiophen-2-yl, 5-chlorothiophen-3-yl, pyrimidin-4-yl, quinolin-4-yl, quinolin-8-yl, and 2,6-difluoropyridinyl.

[0422] In one embodiment of the present invention and / or its embodiments, wherein R 19 is C 6-10- aryl,

[0423] wherein the C 6-10 aryl is optionally substituted with one or more substituents independently selected from

[0424] C 1-6- alkyl, halogen, cyano, and nitro.

[0425] In one embodiment of the present invention and / or its embodiments, wherein R 19 is C 6-10- aryl,

[0426] wherein the C 6-10 aryl is a phenyl substituted with one, two, or three substituents independently selected from

[0427] fluoride, chloride, and bromide.

[0428] Examples of phenyl groups substituted with one, two or three substituents independently selected from fluoride, chloride and bromide 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, 2,3-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-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, 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, 4-bromo-2-chlorobromophenyl, 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, 3,4-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 and 3-bromo-4-chloro-5-fluorophenyl.

[0429] 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, 5-chloro-3-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, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0430] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iei), (Ieii), (Ieiii) or (Ieiv)

[0431]

[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 25 are defined as in any of the embodiments described herein.

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

[0435] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 25 is as defined above.

[0436] In one embodiment of the present invention and / or its embodiments, R 25 is hydrogen or C 1-3- alkyl.

[0437] In one embodiment of the present invention and / or its embodiments, R 25 is hydrogen or methyl.

[0438] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ifi) or (Ifii)

[0439]

[0440] 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 are defined as in any of the embodiments described herein.

[0441] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ifi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ifii), preferably in the (S)-enantiomeric form.

[0442] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 1 and R 7 are as defined above.

[0443] In one embodiment of the present invention and / or its embodiments,

[0444] R 1 is independently selected from

[0445] hydrogen, C 1-6- alkyl, C 1-6- alkoxy, halogen, amino, nitro, hydroxy, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0446] wherein each C 1-6- alkyl or C 1-6- alkoxy is optionally substituted with one or more substituents independently selected from

[0447] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, hydroxy, and NR 2’ R 3’ ,

[0448] R 2 and R 3 are independently selected from

[0449] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, and 5- to 10-membered heteroaryl, or

[0450] R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2, or 3 other ring atoms are selected from N, S, and O;

[0451] wherein each C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, or 5- to 10-membered heteroaryl or the heterocycle formed by R 2 and R 3 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from

[0452] C 1-6- alkyl, C 3-10- cycloalkyl, and C 1-6- alkoxy,

[0453] R 4 、R 5 and R 6 are independently selected from hydrogen and C 1-6- alkyl, preferably selected from hydrogen and C 1-3- alkyl,

[0454] R 2’ and R 3’ are independently selected from hydrogen and C 1-6- alkyl, preferably selected from hydrogen and C 1-3- alkyl,

[0455] and

[0456] R 7 is independently selected from

[0457] 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, hydroxy, NR 8 R 9 、C(=O)OR 10 、SR 10 、SOR 10, SO2R 10 and C(=O)NR 11 R 12 ,

[0458] wherein each C 1-6- alkyl, C 2-6- alkenyl, C 3-10- cycloalkyl, 4- to 10-membered heterocyclic group or C 1-6- alkoxy is optionally substituted by one or more substituents independently selected from

[0459] C 1-6- alkyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0460] R 8 and R 9 are independently selected from

[0461] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group and 5- to 10-membered heteroaryl, or

[0462] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0463] wherein C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from

[0464] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8” R 9” , C(=O)-OR 10” and C(=O)NR 11” R 12” ;

[0465] R10 、R 11 and R 12 are independently selected from hydrogen and C 1-6- alkyl

[0466] R 8’ 、R 9’ 、R 10’ 、R 11’ and R 12’ are independently selected from hydrogen and C 1-6- alkyl

[0467] R 8” 、R 9” 、R 10” 、R 11” and R 12” are independently selected from hydrogen and C 1-6- alkyl

[0468] In one embodiment of the present invention and / or its embodiments

[0469] R 1 is independently selected from

[0470] hydrogen, C 1-6- alkyl, C 1-6- alkoxy and halogen

[0471] wherein C 1-6- alkyl and C 1-6- alkoxy are optionally substituted by one or more substituents independently selected from the following

[0472] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy and NR 2’ R 3’

[0473] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably from hydrogen and methyl

[0474] and

[0475] R 7 is independently selected from

[0476] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 、SR 10 、SOR 10 and SO2R 10 ​​

[0477] wherein each C 1-6- alkyl group, C 2-6- alkenyl group, 4- to 10-membered heterocyclic group or C 1-3- alkoxy group is optionally substituted with one or more substituents independently selected from the following

[0478] C 1-3- alkyl group, 5- to 10-membered heterocyclic group, C 1-6- alkoxy group, halogen, cyano group, hydroxyl group, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0479] R 8 and R 9 are independently selected from

[0480] hydrogen, C 1-6- alkyl group, C 6-10- aryl group and 5- to 10-membered heteroaryl group, or

[0481] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0482] wherein the C 1-6- alkyl group, C 6-10- aryl group or 5- to 10-membered heteroaryl group or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[0483] C 1-6- alkyl group, C 1-6- alkoxy group, hydroxyl group and NR 8” R 9” ;

[0484] R 10 is independently selected from hydrogen or C 1-3- alkyl group, preferably selected from hydrogen, methyl or ethyl

[0485] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl group, preferably selected from hydrogen, methyl or ethyl,

[0486] R 8”and R 9” are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl.

[0487] In one embodiment of the present invention and / or its embodiments,

[0488] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride,

[0489] and

[0490] R 7 is independently selected from methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methylsulfonylmethylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, morpholin-4-yl, pyrrolin-1-yl, 3-hydroxy-pyrrolidine, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl.

[0491] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Igi), (Igii), (Igiii), (Igiv), (Igv) or (Igvi)

[0492]

[0493]

[0494] 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 are defined as in any of the embodiments described herein.

[0495] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Igvi), preferably in the (S)-enantiomeric form.

[0496] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 1 and R 13 , R 14 , A1, A2, A3 and A4 are as defined above.

[0497] In one embodiment of the present invention and / or its embodiments

[0498] R 1 is independently selected from

[0499] hydrogen, C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, hydroxy, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0500] wherein each C 1-6- alkyl or C 1-6- alkoxy is optionally substituted with one or more substituents independently selected from the following

[0501] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, hydroxy and NR 2’ R 3’ ,

[0502] R 2 and R 3 are independently selected from

[0503] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10-aryl and 5- to 10-membered heteroaryl, or

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

[0505] wherein each C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 2 and R 3 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from

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

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

[0508] R 2’ and R 3’ are 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 14 together with the atoms to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally substituted with one or more C 1-3- alkyl or =O, and / or wherein 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 wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15’ R 15” wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0512] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy, or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3 -alkyl,

[0513] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy, or NR 17’ R 17” , wherein R 17’ and R 17” are independently C 1-3- -alkyl,

[0514] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy, or NR 18’ R 18” , wherein R 18’ and R 18” are independently C 1-3- -alkyl.

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

[0516] R 1 is independently selected from

[0517] hydrogen, C 1-6- -alkyl, C 1-6- -alkoxy and halogen,

[0518] wherein C 1-6- -alkyl and C 1-6- -alkoxy are optionally substituted with one or more substituents independently selected from the following

[0519] C 1-6- -alkyl, C 1-6- -alkoxy, halogen, cyano, hydroxy and NR 2’ R 3’ ,

[0520] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- -alkyl, more preferably selected from hydrogen and methyl,

[0521] and

[0522] R 13 and R 14 together with the atom(s) to which it is attached form a non-aromatic ring containing 5 or 6 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 wherein R 15 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0524] A2 is N or CR 16 wherein R 16 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0525] A3 is N or CR 17 wherein R 17 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0526] A4 is N or CR 18 wherein R 18 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0527] wherein 0, 1 or 2 of A1, A2, A3 and A4 are N

[0528] In one embodiment of the present invention and / or its embodiments

[0529] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride

[0530] and

[0531] R 13 and R 14 together with the atom(s) to which it is attached form a non-aromatic ring containing 5 or 6 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 wherein R 15 is independently hydrogen or C 1-3 alkoxy

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

[0534] A3 is N or CR 17 , where R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[0535] A4 is N or CR 18 , where R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

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

[0537] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ihi), (Ihii), (Ihiii), (Ihiv), (Ihv) or (Ihvi)

[0538]

[0539]

[0540] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, where R 7 , R 19 and R 25 are defined as 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 (Ihi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihv). In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ihvi), preferably in the (S)-enantiomeric form.

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

[0543] R 1 is independently selected from

[0544] Hydrogen, C 1-6- Alkyl, C 1-6- Alkoxy, halogen, hydrogen group, nitro group, hydroxy group, NR 2 R 3 , C(=O)OR 4 And C(=O)NR 5 R 6 ,

[0545] Wherein each C 1-6- Alkyl or C 1-6- Alkoxy is optionally substituted by one or more substituents independently selected from the following

[0546] C 1-6- Alkyl, C 1-6- Alkoxy, halogen, cyano group, nitro group, hydroxy group and N R2’ R 3’ ,

[0547] R 2 And R 3 Are independently selected from

[0548] Hydrogen, C 1-6- Alkyl, C 3-10- Cycloalkyl, C 6-10- Aryl and 5- to 10-membered heteroaryl, or

[0549] R 2 And R 3 Together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0550] Wherein each C 1-6- Alkyl, C 3-10- Cycloalkyl, C 6-10- Aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 2 And R 3 Together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from the following

[0551] C 1-6- Alkyl, C 3-10- Cycloalkyl and C 1-6- Alkoxy,

[0552] R 4 , R 5 And R 6 Are independently selected from hydrogen and C 1-6- Alkyl, preferably selected from hydrogen and C 1-3- Alkyl,

[0553] R 2’and R 3’ are independently selected from hydrogen and C 1-6- alkyl, preferably selected from hydrogen and C 1-3- alkyl,

[0554] and

[0555] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally substituted by one or more C 1-3- alkyl, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[0556] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0557] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl,

[0558] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0559] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3-Alkyl

[0560] Optionally, in one embodiment of the present invention and / or its embodiments

[0561] R 1 is independently selected from

[0562] hydrogen, C 1-6- alkyl, C 1-6- alkoxy and halogen,

[0563] wherein the C 1-6- alkyl and C 1-6- alkoxy are optionally substituted with one or more substituents independently selected from the following

[0564] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxyl and NR 2’ R 3’ ,

[0565] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably selected from hydrogen and methyl,

[0566] and

[0567] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[0568] A1 is N or CR 15 , wherein R 15 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy,

[0569] A2 is N or CR 16 , wherein R 16 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy,

[0570] A3 is N or CR 17 , wherein R 17 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy,

[0571] A4 is N or CR 18 , wherein R 18 is independently hydrogen, C 1-3 alkyl or C 1-3Alkoxy

[0572] wherein zero, one or two of A1, A2, A3 and A4 are N.

[0573] In one embodiment of the present invention and / or its embodiments,

[0574] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride,

[0575] and

[0576] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N =, = N- or -S-,

[0577] A1 is N or CR 15 wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[0578] A2 is N or CR 16 wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[0579] A3 is N or CR 17 wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[0580] A4 is N or CR 18 wherein R 18 is independently hydrogen or C1-3 alkoxy, preferably hydrogen,

[0581] wherein zero, one or two of A1, A2, A3 and A4 are N.

[0582] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ihvii), (Ihviii), (Ihix), (Ihx), (Ihxi) or (Ihxii)

[0583]

[0584]

[0585] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 7 、R 19and R 25 as defined in any of the embodiments described herein.

[0586] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ihvii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ihviii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ihix), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ihx), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ihxi). In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ihxii), preferably in the (S)-enantiomeric form.

[0587] The invention provides a compound according to the invention and / or its embodiments, wherein R 1 and R 19 as defined above.

[0588] In one embodiment of the invention and / or its embodiments,

[0589] R 1 is independently selected from

[0590] hydrogen, C 1-6- alkyl, C 1-6- alkoxy, halogen, amino, nitro, hydroxy, NR 2 R 3 、C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0591] wherein each C 1-6- alkyl or C 1-6- alkoxy is optionally substituted with one or more substituents independently selected from: C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, hydroxy and NR 2’ R 3’ ,

[0592] R 2 and R 3 are independently selected from

[0593] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[0594] R 2 and R 3 together with the N atom to which it is attached forms a saturated or unsaturated heterocycle having 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;

[0595] wherein each C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 2 and R 3 together with the N atom to which it is attached is optionally substituted by one or more substituents independently selected from

[0596] C 1-6- alkyl, C 3-10- cycloalkyl and C 1-6- alkoxy,

[0597] R 4 、R 5 and R 6 are independently selected from hydrogen and C 1-6- alkyl, preferably selected from hydrogen and C 1-3- alkyl,

[0598] R 2’ and R 3’ are independently selected from hydrogen and C 1-6- alkyl, preferably selected from hydrogen and C 1-3- alkyl,

[0599] and

[0600] R 19 is independently selected from

[0601] C 6-10- aryl and 5- to 10-membered heteroaryl,

[0602] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted by one or more substituents independently selected from: 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, hydroxy, NR 20 R 21 、C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0603] R20 and R 21 are independently selected from

[0604] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, and C 6-10- aryl, or

[0605] R 20 and R 21 together with the N atom to which it is attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2, or 3 other ring atoms are selected from N, S, and O;

[0606] wherein each C 1-6- alkyl, C 3-10- cycloalkyl, or C 6-10- aryl, or the heterocycle formed by R 20 and R 21 together with the N atom to which it is attached is optionally substituted by one or more substituents independently selected from

[0607] 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, hydroxy, NR 20’ R 21’ , C(=O)OR 22’ and C(=O)NR 23’ R 24’

[0608] R 22 , R 23 , and R 24 are independently selected from hydrogen and C 1-6- alkyl.

[0609] R 20’ , R 21’ , R 22’ , R 23’ , and R 24’ are independently selected from hydrogen and C 1-6- alkyl.

[0610] Optionally, in one embodiment of the present invention and / or its embodiments

[0611] R 1 is independently selected from

[0612] hydrogen, C 1-6- alkyl, C 1-6- alkoxy, and halogen.

[0613] wherein C 1-6-The alkyl group and C 1-6- The alkoxy group is optionally substituted by one or more substituents independently selected from the following: C 1-6- alkyl group, C 1-6- alkoxy group, halogen, cyano group, hydroxyl group and NR 2’ R 3’ ,

[0614] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl group, more preferably selected from hydrogen and methyl,

[0615] and

[0616] R 19 is independently selected from

[0617] C 6-10- aryl group and 5- to 10-membered heteroaryl group

[0618] wherein each C 6-10- aryl group or 5- to 10-membered heteroaryl group is optionally substituted by one or more substituents independently selected from the following: C 1-6- alkyl group, C 1-6- alkoxy group, halogen, cyano group, nitro group and hydroxyl group.

[0619] In one embodiment of the present invention and / or its embodiments,

[0620] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride,

[0621] and

[0622] R 19 is independently selected from 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, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0623] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iii), (Iiii), (Iiiii), (Iiiv), (Iiv) or (Iivi)

[0624]

[0625]

[0626]

[0627] or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph, prodrug thereof, and mixtures thereof, wherein R 7 、R 13 、R 14 、A1, A2, A3, A4 and R 25 are as defined in any of the embodiments described herein.

[0628] In one embodiment of the invention and / or an embodiment thereof, the compound is according to formula (Iii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or an embodiment thereof, the compound is according to formula (Iiii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or an embodiment thereof, the compound is according to formula (Iiiii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or an embodiment thereof, the compound is according to formula (Iiiv, preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or an embodiment thereof, the compound is according to formula (Iiv), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or an embodiment thereof, the compound is according to formula (Iivi), preferably in the (S)-enantiomeric form.

[0629] The present invention provides a compound according to the invention and / or an embodiment thereof, wherein R 1 and R 25 are as defined above.

[0630] In one embodiment of the invention and / or an embodiment thereof, R 1 is independently selected from the following

[0631] hydrogen, C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, hydroxy, NR 2 R 3 、C(=O)OR 4 and C(=O)NR 5 R 6 ,

[0632] wherein each C 1-6- alkyl or C 1-6- alkoxy is optionally substituted with one or more substituents independently selected from the following

[0633] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, hydroxy and NR 2’ R 3’ ,

[0634] R 2 and R 3 are independently selected from

[0635] hydrogen, C 1-6 -alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl, or

[0636] R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0637] wherein each C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 2 and R 3 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from

[0638] C 1-6- alkyl, C 3-10- cycloalkyl and C 1-6- alkoxy,

[0639] R 4 、R 5 and R 6 are independently selected from hydrogen and C 1-6- alkyl, preferably selected from hydrogen and C 1-3- alkyl,

[0640] R 2’ and R 3’ are independently selected from hydrogen and C 1-6- alkyl, preferably selected from hydrogen and C 1-3- alkyl,

[0641] and

[0642] R 25 is hydrogen or C 1-3- alkyl.

[0643] In one embodiment of the present invention and / or its embodiments, R 1 are independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride,

[0644] and

[0645] R 25 is hydrogen or methyl.

[0646] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iji), (Ijii), (Ijiii) or (Ijiv)

[0647]

[0648]

[0649] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 7 、R 13 、R 14 、A1, A2, A3 and A4 are defined as in any of the embodiments described herein.

[0650] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iji), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ijiv), preferably in the (S)-enantiomeric form.

[0651] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 7 and R 13 、R 14 、A1, A2; A3 and A4 are as defined above.

[0652] In one embodiment of the present invention and / or its embodiments

[0653] R 7 is independently selected from the following

[0654] 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, hydroxy, NR 8 R 9 、C(=O)OR 10 、SR 10 、SOR 10 、SO2R 10 and C(=O)NR 11 R 12 ,

[0655] wherein each C1-6- alkyl, C 2-6- alkenyl, C 3-10- cycloalkyl, 4- to 10-membered heterocyclic group, or C 1-6- alkoxy is optionally substituted with one or more substituents independently selected from the following

[0656] C 1-6- alkyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0657] R 8 and R 9 are independently selected from the following

[0658] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group, and 5- to 10-membered heteroaryl, or

[0659] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2, or 3 other ring atoms are selected from N, S, and O;

[0660] wherein C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group, or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[0661] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8” R 9” , C(=O)-OR 10” and C(=O)NR 11” R 12” ;

[0662] R 10 , R 11 and R 12 are independently selected from hydrogen and C 1-6- alkyl,

[0663] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen and C 1-6- alkyl,

[0664] R 8” , R 9” , R 10” , R 11” and R 12” are independently selected from hydrogen and C 1-6- alkyl,

[0665] and

[0666] R 13 and R 14 Together with the atoms to which they are attached, they form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally replaced by one or more C 1-3- alkyl or =O, 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-,

[0667] A1 is N or CR 15 , where R 15 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, or NR 15’ R 15” , where R 15’ and R 15” Independently C 1-3- alkyl,

[0668] A2 is N or CR 16 , where R 16 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, or NR 16’ R 16” , where R 16’ and R 16” Independently C 1-3- alkyl,

[0669] A3 is N or CR 17 , where R 17 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy, or NR 17’ R 17” , where R 17’ and R 17” Independently C 1-3- alkyl,

[0670] A4 is N or CR 18 , where R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 18’ R 18” , where R 18’ and R 18” are independently C 1-3- alkyl.

[0671] In one embodiment of the present invention and / or its embodiments

[0672] R 7 is independently selected from the following

[0673] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 , SR 10 , SOR 10 and SO2R 10 ,

[0674] where each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally substituted by one or more substituents independently selected from the following: C 1-3- alkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0675] R 8 and R 9 are independently selected from the following

[0676] hydrogen, C 1-6- alkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[0677] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, where 1 ring atom is N and where 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0678] where C 1-6-alkyl, C 6-10- aryl, or 5- to 10-membered heteroaryl, or a heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from: C 1-6- alkyl, C 1-6 -alkoxy, hydroxy, and NR 8” R 9” ;

[0679] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl, or ethyl

[0680] R 8’ 、R 9’ 、R 10’ 、R 11’ and R 12’ is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl, or ethyl,

[0681] R 8” and R 9” is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl, or ethyl,

[0682] and

[0683] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the ring-forming carbon atoms are optionally replaced by -NH-, -O-, or -S-,

[0684] A1 is N or CR 15 wherein R 15 is independently hydrogen, C 1-3 alkyl, or C 1-3 alkoxy,

[0685] A2 is N or CR 16 wherein R 16 is independently hydrogen, C 1-3 alkyl, or C 1-3 alkoxy,

[0686] A3 is N or CR 17 wherein R 17 is independently hydrogen, C 1-3 alkyl, or C 1-3 alkoxy,

[0687] A4 is N or CR 18 wherein R 18 is independently hydrogen, C1-3 alkyl or C 1-3 alkoxy,

[0688] wherein zero, one or two of A1, A2, A3 and A4 are N.

[0689] In one embodiment of the present invention and / or its embodiments,

[0690] R 7 is independently selected from methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, propyl, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, morpholin-4-yl, (methoxyethyl)(methyl)amino, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl,

[0691] and

[0692] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-,

[0693] A1 is N or CR 15 , where R 15 is independently hydrogen or C 1-3 alkoxy,

[0694] A2 is N or CR 16 , where R 16 is independently hydrogen or C 1-3 alkoxy,

[0695] A3 is N or CR 17 , where R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[0696] A4 is N or CR 18 , where R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[0697] wherein zero, one or two of A1, A2, A3 and A4 are N.

[0698] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iki), (Ikii), (Ikiii), (Ikiv), (Ikv), (Ikvi), (Ikvii), (Ikviii) or (Ikix)

[0699]

[0700]

[0701]

[0702] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 、R 19 and R 25 are defined as in any of the embodiments described herein.

[0703] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iki), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikvi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikvii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikviii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikix), preferably in the (S)-enantiomeric form.

[0704] In one embodiment of the present invention and / or its embodiments,

[0705] R 7 is independently selected from the following

[0706] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, C 3-10- cycloalkyl, 4- to 10-membered heterocyclic group, C1-6- alkoxy, halogen, cyano, hydroxy, NR 8 R 9 , C(=O)OR 10 , SR 10 , SOR 10 , SO2R 10 and C(=O)NR 11 R 12 ,

[0707] wherein each C 1-6- alkyl, C 2-6- alkenyl, C 3-10- cycloalkyl, 4- to 10-membered heterocyclic group or C 1-6- the alkoxy is optionally substituted independently by one or more substituents selected from

[0708] C 1-6- alkyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0709] R 8 and R 9 are independently selected from

[0710] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group and 5- to 10-membered heteroaryl, or

[0711] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0712] wherein the C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted independently by one or more substituents selected from

[0713] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy, NR8” R 9” 、C(=O)-OR 10” and C(=O)NR 11” R 12” ;

[0714] R 10 , R 11 and R 12 are independently selected from hydrogen and C 1-6- alkyl,

[0715] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen and C 1-6- alkyl,

[0716] R 8” , R 9” , R 10” , R 11” and R 12” are independently selected from hydrogen and C 1-6- alkyl,

[0717] and

[0718] R 13 and R 14 Together with the atoms to which they are attached, they form an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally replaced by one or more C 1-3- alkyl, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[0719] A1 is N or CR 15 , where R 15 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15’ R 15” , where R 15’ and R 15” Independently C 1-3- alkyl,

[0720] A2 is N or CR 16 , where R 16 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16’ R 16” , where R 16’ and R 16” Independently C 1-3- alkyl,

[0721] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl.

[0722] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl.

[0723] In one embodiment of the present invention and / or its embodiments

[0724] R 7 is independently selected from the following

[0725] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 , SR 10 , SOR 10 and SO2R 10 ,

[0726] wherein each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally substituted with one or more substituents independently selected from the following: C 1-3- alkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0727] R 8 and R 9 are independently selected from the following

[0728] hydrogen, C 1-6- alkyl, C6-10- an aryl group and a 5- to 10-membered heteroaryl group, or

[0729] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0730] wherein C 1-6- alkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocyclic ring formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from: C 1-6- alkyl, C 1-6- alkoxy, hydroxy and NR 8” R 9” ;

[0731] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl

[0732] R 8’ 、R 9’ 、R 10’ 、R 11’ and R 12’ is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[0733] R 8” and R 9” is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[0734] and

[0735] R 13 and R 14 together with the atoms to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[0736] A1 is N or CR 15 ,wherein R 15 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy,

[0737] A2 is N or CR 16 ,wherein R 16 is independently hydrogen, C 1-3 alkyl or C1-3 Alkoxy

[0738] A3 is N or CR 17 , wherein R 17 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0739] A4 is N or CR 18 , wherein R 18 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0740] wherein 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0741] In one embodiment of the present invention and / or its embodiments,

[0742] R 7 is independently selected from methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, propyl, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, morpholin-4-yl, (methoxyethyl)(methyl)amino, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl,

[0743] and

[0744] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N- or -S-,

[0745] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy

[0746] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy

[0747] A3 is N or CR 17 , wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[0748] A4 is N or CR18 , wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[0749] wherein zero, one or two of A1, A2, A3 and A4 are N.

[0750] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ikx), (Ikxi), (Ikxii), (Ikxiii), (Ikxiv), (Ikxv), (Ikxvi), (Ikvii) or (Ikxviii)

[0751]

[0752]

[0753]

[0754] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 , R 19 and R 25 are defined as in any of the embodiments described herein.

[0755] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikx), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikxi), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikxii), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikxiii), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikxiv), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikxv), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikxvi), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikvii), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ikxviii), preferably in the (S) - enantiomeric form.

[0756] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 7 and R 19 are as defined above.

[0757] In one embodiment of the present invention and / or its embodiments,

[0758] R 7 is independently selected from the following

[0759] 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, hydroxy, NR 8 R 9 、C(=O)OR 10 、SR 10 、SOR 10 、SO2R 10 and C(=O)NR 11 R 12 ,

[0760] wherein each C 1-6- alkyl, C 2-6- alkenyl, C 3-10- cycloalkyl, 4- to 10-membered heterocyclic group or C 1-6- alkoxy is optionally substituted with one or more substituents independently selected from the following

[0761] C 1-6- alkyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ 、C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0762] R 8 and R 9 are independently selected from the following

[0763] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group and 5- to 10-membered heteroaryl, or

[0764] R 8 and R 9Together with the N atom to which it is attached, form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0765] wherein C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group or 5- to 10-membered heteroaryl or a heterocycle formed by R 8 and R 9 together with the N atom to which it is attached is optionally substituted with one or more substituents independently selected from

[0766] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8” R 9” , C(=O)-OR 10” and C(=O)NR 11” R 12” ;

[0767] R 10 、R 11 and R 12 are independently selected from hydrogen and C 1-6- alkyl,

[0768] R 8’ 、R 9’ 、R 10’ 、R 11’ and R 12’ are independently selected from hydrogen and C 1-6- alkyl,

[0769] R 8” 、R 9” 、R 10” 、R 11” and R 12” are independently selected from hydrogen and C 1-6- alkyl,

[0770] and

[0771] R 19 is independently selected from

[0772] C 6-10- aryl and 5- to 10-membered heteroaryl,

[0773] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from C 1-6- alkyl, C 3-10- cycloalkyl, C 1-6- alkoxy, 5- to 10-membered heterocyclic group, C6-10- aryl, 5- to 10-membered heteroaryl, halogen, hydrogen, nitro, hydroxy, NR 20 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0774] R 20 and R 21 are independently selected from the following

[0775] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl and C 6-10- aryl or

[0776] R 20 and R 21 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0777] wherein each C 1-6- alkyl, C 3-10- cycloalkyl or C 6-10- aryl or the heterocycle formed by R 20 and R 21 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from the following

[0778] 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, hydroxy, NR 20’ R 21’ , C(=O)OR 22’ and C(=O)NR 23’ R 24’

[0779] R 22 , R 23 and R 24 are independently selected from hydrogen and C 1-6- alkyl,

[0780] R 20’ , R 21’ , R 22’ , R 23’ and R 24’ are independently selected from hydrogen and C 1-6- alkyl.

[0781] In one embodiment of the present invention and / or its embodiments

[0782] R 7 are independently selected from the following

[0783] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, a 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 , SR 10 , SOR 10 and SO2R 10 ,

[0784] wherein each C 1-6- alkyl, C 2-6- alkenyl, a 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally substituted with one or more substituents independently selected from the following

[0785] C 1-3- alkyl, a 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0786] R 8 and R 9 are independently selected from the following

[0787] hydrogen, C 1-6- alkyl, C 6-10- aryl and a 5- to 10-membered heteroaryl, or

[0788] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0789] wherein C 1-6- alkyl, C 6-10- aryl or a 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[0790] C 1-6- alkyl, C 1-6- alkoxy, hydroxy and NR 8” R 9” ;

[0791] R 10 are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl

[0792] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[0793] R 8” and R 9” are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[0794] and

[0795] R 19 is independently selected from the following

[0796] C 6-10- aryl and 5- to 10-membered heteroaryl

[0797] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[0798] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro and hydroxy.

[0799] In one embodiment of the present invention and / or its embodiments,

[0800] R 7 is independently selected from methyl, ethyl, isopropyl, propyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl,

[0801] and

[0802] R 19Independently selected from 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, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0803] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ili), (Ilii), (Iliii), (Iliv), (Ilv), (Ilvi), (Ilvii), (Ilviii) or (Ilix)

[0804]

[0805]

[0806]

[0807] 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 are defined as in any of the embodiments described herein.

[0808] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ili), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ilii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iliii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iliv), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ilv), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ilvi), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ilvii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ilviii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ilix), preferably in the form of the (S)-enantiomer.

[0809] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 7 and R 25 are as defined above.

[0810] In one embodiment of the present invention and / or its embodiments,

[0811] R 7 is independently selected from the following

[0812] 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, hydroxy, NR 8 R 9 、C(=O)OR 10 、SR 10 、SOR 10 、SO2R 10 and C(=O)NR 11 R 12 ,

[0813] wherein each C 1-6- alkyl, C 2-6- alkenyl, C 3-10- cycloalkyl, 4- to 10-membered heterocyclic group or C 1-6-The alkoxy group is optionally substituted by one or more substituents independently selected from the following

[0814] C 1-6- alkyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[0815] R 8 and R 9 are independently selected from the following

[0816] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group and 5- to 10-membered heteroaryl, or

[0817] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0818] wherein C 1-6- alkyl, C 3-10- cycloalkyl, C 6-10- aryl, 5- to 10-membered heterocyclic group or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from the following

[0819] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8” R 9” , C(=O)-OR 10” and C(=O)NR 11” R 12” ;

[0820] R 10 , R 11 and R 12 are independently selected from hydrogen and C 1-6- alkyl,

[0821] R 8’ , R 9’ , R 10’ , R 11’ and R12’ independently selected from hydrogen and C 1-6- alkyl,

[0822] R 8” 、R 9” 、R 10” 、R 11” and R 12” are independently selected from hydrogen and C 1-6- alkyl,

[0823] and

[0824] R 25 is hydrogen or C 1-3- alkyl.

[0825] In one embodiment of the present invention and / or its embodiments,

[0826] R 7 is independently selected from methyl, ethyl, isopropyl, propyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl,

[0827] and

[0828] R 25 is hydrogen or methyl, preferably hydrogen.

[0829] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Imi), (Imii), (Imiii), (Imiv), (Imv) or (Imiv)

[0830]

[0831]

[0832] 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 are defined as in any of the embodiments described herein.

[0833] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imi), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imiii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imiv), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imv), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Imvi), preferably in the form of the (S)-enantiomer.

[0834] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 13 , R 14 , A1, A2, A3 and A4 and R 19 are as defined above.

[0835] In one embodiment of the present invention and / or its embodiments,

[0836] R 13 and R 14 together with the atoms to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally substituted by one or more C 1-3- alkyl or =O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-,

[0837] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0838] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 16’ R 16” , wherein R 16’ and R 16” are independently C1-3- alkyl

[0839] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 17’ R 17” , wherein R 17’ and R 17” are independently C 1-3- alkyl

[0840] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 18’ R 18” , wherein R 18’ and R 18” are independently C 1-3- alkyl

[0841] and

[0842] R 19 is independently selected from

[0843] C 6-10- aryl and 5- to 10-membered heteroaryl

[0844] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted by one or more substituents independently selected from the following: 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, hydrogen group, nitro, hydroxy, NR 20 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0845] R 20 and R 21 are independently selected from the following

[0846] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl and C 6-10- aryl or

[0847] R 20 and R 21Together with the N atom to which it is attached, it forms a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0848] wherein each C 1-6- alkyl, C 3-10- cycloalkyl or C 6-10- aryl or the heterocycle formed by R 20 and R 21 together with the N atom to which it is attached is optionally substituted by one or more substituents independently selected from the following

[0849] 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, hydroxy, NR 20’ R 21’ 、C(=O)OR 22’ and C(=O)NR 23’ R 24’

[0850] R 22 、R 23 and R 24 are independently selected from hydrogen and C 1-6- alkyl,

[0851] R 20’ 、R 21’ 、R 22’ 、R 23’ and R 24’ are independently selected from hydrogen and C 1-6- alkyl.

[0852] In one embodiment of the present invention and / or its embodiments,

[0853] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O- or -S-,

[0854] A1 is N or CR 15 wherein R 15 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy,

[0855] A2 is N or CR 16 wherein R 16 is independently hydrogen, C 1-3 alkyl or C 1-3Alkoxy

[0856] A3 is N or CR 17 , wherein R 17 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0857] A4 is N or CR 18 , wherein R 18 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0858] wherein 0, 1 or 2 of A1, A2, A3 and A4 are N

[0859] and

[0860] R 19 is independently selected from the following

[0861] C 6-10- aryl and 5- to 10-membered heteroaryl

[0862] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[0863] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro and hydroxy

[0864] In one embodiment of the present invention and / or its embodiments

[0865] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-

[0866] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy

[0867] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy

[0868] A3 is N or CR 17 , wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen

[0869] A4 is N or CR18 , wherein R 18 is independently hydrogen or a C 1-3 alkoxy group, preferably hydrogen,

[0870] wherein zero, one or two of A1, A2, A3 and A4 are N,

[0871] and

[0872] R 19 is independently selected from 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, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0873] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ini), (Inii), (Iniii), (Iniv), (Inv), (Invi), (Invii), (Inviii) or (Inix)

[0874]

[0875]

[0876]

[0877]

[0878] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 , R 7 and R 25 are as defined in any of the embodiments described herein.

[0879] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ini), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iniii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iniv), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inv), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Invi), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Invii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inviii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inix), preferably in the form of the (S)-enantiomer.

[0880] In one embodiment of the present invention and / or its embodiments,

[0881] R 13 and R 14 together with the atom to which it is attached form an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally substituted by one or more C 1-3- alkyl groups, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[0882] A1 is N or CR 15 wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0883] A2 is N or CR 16 wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” wherein R 16’and R 16” independently is C 1-3- alkyl,

[0884] A3 is N or CR 17 , where R 17 independently is hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , where R 15’ and R 15” independently is C 1-3- alkyl,

[0885] A4 is N or CR 18 , where R 18 independently is hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , where R 15’ and R 15” independently is C 1-3- alkyl,

[0886] and

[0887] R 19 independently selected from the following

[0888] C 6-10- aryl and 5- to 10-membered heteroaryl,

[0889] where each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted by one or more substituents independently selected from the following: 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, hydroxy, NR 20 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0890] R 20 and R 21 independently selected from the following

[0891] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl and C 6-10- aryl or

[0892] R 20 and R 21Together with the N atom to which it is attached, form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0893] wherein each C 1-6- alkyl, C 3-10- cycloalkyl or C 6-10- aryl or the heterocycle formed by R 20 and R 21 together with the N atom to which it is attached is optionally substituted by one or more substituents independently selected from

[0894] 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, hydroxy, NR 20’ R 21’ 、C(=O)OR 22’ and C(=O)NR 23’ R 24’

[0895] R 22 、R 23 and R 24 are independently selected from hydrogen and C 1-6- alkyl,

[0896] R 20’ 、R 21’ 、R 22’ 、R 23’ and R 24’ are independently selected from hydrogen and C 1-6- alkyl.

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

[0898] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-;

[0899] A1 is N or CR 15 wherein R 15 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy,

[0900] A2 is N or CR 16 wherein R 16 is independently hydrogen, C 1-3alkyl or C1-3 alkoxy

[0901] A3 is N or CR 17 , where R 17 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0902] A4 is N or CR 18 , where R 18 is independently hydrogen, C 1-3 alkyl or C 1-3 alkoxy

[0903] where 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0904] and

[0905] R 19 is independently selected from the following

[0906] C 6-10- aryl and 5- to 10-membered heteroaryl

[0907] where each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[0908] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro and hydroxy.

[0909] In one embodiment of the present invention and / or its embodiments,

[0910] R 13 and R 14 together with the atoms to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, where one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-,

[0911] R 13 and R 14 together with the atoms to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, where one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N- or -S-,

[0912] A1 is N or CR 15 , where R 15 is independently hydrogen or C 1-3 alkoxy

[0913] A2 is N or CR 16 , where R 16 is independently hydrogen or C 1-3 alkoxy

[0914] A3 is N or CR 17 , where R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[0915] A4 is N or CR 18 , where R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen, where 0, 1 or 2 of A1, A2, A3 and A4 are N,

[0916] and

[0917] R 19 is independently selected from 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, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0918] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Inx), (Inxi), (Inxii), (Inxiii), (Inxiv), (Inxv), (Inxvi), (Inxvii) or (Inxviii)

[0919]

[0920]

[0921]

[0922] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, where R 1 , R 7 and R 25 are defined as in any of the embodiments described herein.

[0923] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inx), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inxi), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inxii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inxiii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inxiv), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inxv), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inxvi), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inxvii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Inxviii), preferably in the form of the (S)-enantiomer.

[0924] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 13 , R 14 , A1, A2, A3 and A4 and R 25 are as defined above.

[0925] In one embodiment of the present invention and / or its embodiments,

[0926] R 13 and R 14 together with the atoms to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally substituted by one or more C 1-3- alkyl or =O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-,

[0927] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0928] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl,

[0929] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 17’ R 17” , wherein R 17’ and R 17” are independently C 1-3- alkyl,

[0930] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 18’ R 18” , wherein R 18’ and R 18” are independently C 1-3- alkyl, and

[0931] R 25 is hydrogen or C 1-3- alkyl.

[0932] In one embodiment of the present invention and / or its embodiments,

[0933] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-,

[0934] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[0935] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[0936] A3 is N or CR 17 , wherein R17 is independently hydrogen or C 1-3 an alkoxy group, preferably hydrogen,

[0937] A4 is N or CR 18 , where R 18 is independently hydrogen or C 1-3 an alkoxy group, preferably hydrogen,

[0938] where 0, 1 or 2 of A1, A2, A3 and A4 are N,

[0939] and

[0940] R 25 is hydrogen or methyl, preferably hydrogen.

[0941] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ioi), (Ioii), (Ioiii), (Ioiv), (Iov) or (Iovi)

[0942]

[0943]

[0944] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, where R 1 , R 7 and R 19 are defined as in any of the embodiments described herein.

[0945] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iov), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iovi), preferably in the (S)-enantiomeric form.

[0946] In one embodiment of the present invention and / or its embodiments,

[0947] R 13 and R 14Together with the atom to which it is attached, it forms an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally substituted with one or more C 1-3- alkyl groups, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[0948] A1 is N or CR 15 wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0949] A2 is N or CR 16 wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” wherein R 16’ and R 16” are independently C 1-3- alkyl,

[0950] A3 is N or CR 17 wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0951] A4 is N or CR 18 wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” wherein R 15’ and R 15” are independently C 1-3- alkyl,

[0952] and

[0953] R 25 is hydrogen or C 1-3- alkyl.

[0954] In one embodiment of the present invention and / or its embodiments,

[0955] R 13 and R 14 together with the atom to which it is attached forms an aromatic ring having 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N- or -S-

[0956] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy

[0957] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy

[0958] A3 is N or CR 17 , wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen

[0959] A4 is N or CR 18 , wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen

[0960] wherein 0, 1 or 2 of A1, A2, A3 and A4 are N

[0961] and

[0962] R 25 is hydrogen or methyl, preferably hydrogen

[0963] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iovii), (Ioviii), (Ioix), (Iox), (Ioxi) or (Ioxii)

[0964]

[0965]

[0966] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 , R 7 and R 19 are as defined in any of the embodiments described herein

[0967] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iovii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioviii), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioix), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iox), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioxi), preferably in the form of the (S)-enantiomer. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ioxii), preferably in the form of the (S)-enantiomer.

[0968] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 19 and R 25 are as defined above.

[0969] In one embodiment of the present invention and / or its embodiments,

[0970] R 19 is independently selected from the following

[0971] C 6-10 -aryl and 5- to 10-membered heteroaryl,

[0972] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[0973] 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, hydrogen group, nitro, hydroxy, NR 20 R 21 、C(=O)OR 22 and C(=O)NR 23 R 24 ,

[0974] R 20 and R 21 is independently selected from the following

[0975] hydrogen, C 1-6- alkyl, C 3-10- cycloalkyl and C 6-10- aryl or

[0976] R20 and R 21 together with the N atom to which it is attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[0977] wherein each C 1-6- alkyl, C 3-10- cycloalkyl or C 6-10- aryl or the heterocycle formed by R 20 and R 21 together with the N atom to which it is attached is optionally substituted by one or more substituents independently selected from the following

[0978] 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, hydroxy, NR 20’ R 21’ 、C(=O)OR 22’ and C(=O)NR 23’ R 24’

[0979] R 22 、R 23 and R 24 are independently selected from hydrogen and C 1-6- alkyl,

[0980] R 20’ 、R 21’ 、R 22’ 、R 23’ and R 24’ are independently selected from hydrogen and C 1-6- alkyl,

[0981] and

[0982] R 25 is hydrogen or C 1-3- alkyl.

[0983] In one embodiment of the present invention and / or its embodiments,

[0984] R 19 is independently selected from 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, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl,

[0985] and

[0986] R 25 is hydrogen or methyl, preferably hydrogen.

[0987] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ipi), (Ipii), (Ipiii), (Ipiv), (Ipv) or (Ipvi)

[0988]

[0989]

[0990]

[0991] 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.

[0992] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ipi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to (Ipii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to (Ipiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to (Ipiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to (Ipv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to (Ipvi), preferably in the (S)-enantiomeric form.

[0993] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 1 、R 7 and R 13 、R 14 、A1, A2, A3 and A4 are defined as above.

[0994] Optionally, in one embodiment of the present invention and / or its embodiments,

[0995] R 1 is independently selected from the following

[0996] hydrogen, C1-6- alkyl, C 1-6- alkoxy, and halogen,

[0997] wherein the C 1-6- alkyl and C 1-6- alkoxy are optionally independently substituted with one or more substituents selected from the following

[0998] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy, and NR 2’ R 3’ ,

[0999] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably selected from hydrogen and methyl,

[1000] and

[1001] R 7 is independently selected from the following

[1002] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 , SR 10 , SOR 10 and SO2R 10 ,

[1003] wherein each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally independently substituted with one or more substituents selected from the following

[1004] C 1-3- alkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1005] R 8 and R 9 are independently selected from the following

[1006] hydrogen, C 1-6- alkyl, C 6-10- aryl, and 5- to 10-membered heteroaryl, or

[1007] R8 and R 9 together with the N atom to which it is attached forms a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 1 ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1008] wherein C 1-6- alkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which it is attached is optionally substituted by one or more substituents independently selected from the following

[1009] C 1-6- alkyl, C 1-6- alkoxy, hydroxy mixed with NR 8” R 9” ,

[1010] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1011] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1012] R 8” and R 9” are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1013] and

[1014] R 13 and R 14 together with the atom to which it is attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally substituted by one or more C 1-3 -alkyl or =O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-,

[1015] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15’ R 15” , wherein R 15’ and R 15”Independently is C 1-3- alkyl,

[1016] A2 is N or CR 16 , where R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 16’ R 16” , where R 16’ and R 16” are independently C 1-3- alkyl,

[1017] A3 is N or CR 17 , where R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 17’ R 17” , where R 17’ and R 17” are independently C 1-3- alkyl,

[1018] A4 is N or CR 18 , where R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 18’ R 18” , where R 18’ and R 18” are independently C 1-3- alkyl.

[1019] In one embodiment of the present invention and / or its embodiments,

[1020] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride,

[1021] and

[1022] R 7 is independently selected from methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl,

[1023] and

[1024] R 13 and R 14 together with the atom to which it is attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-

[1025] A1 is N or CR 15 wherein R 15 is independently hydrogen or C 1-3 alkoxy

[1026] A2 is N or CR 16 wherein R 16 is independently hydrogen or C 1-3 alkoxy

[1027] A3 is N or CR 17 wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen

[1028] A4 is N or CR 18 wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen

[1029] wherein 0, 1 or 2 of A1, A2, A3 and A4 are N.

[1030] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iqi), (Iqii), (Iqiii), (Iqiv), (Iqv) or (Iqvi)

[1031]

[1032]

[1033] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 19 and R 25 are defined as in any of the embodiments described herein.

[1034] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqvi), preferably in the (S)-enantiomeric form.

[1035] Optionally, in one embodiment of the present invention and / or its embodiments

[1036] R 1 is independently selected from

[1037] hydrogen, C 1-6- alkyl, C 1-6- alkoxy and halogen,

[1038] wherein C 1-6- alkyl and C 1-6- alkoxy are optionally substituted by one or more substituents independently selected from

[1039] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy and NR 2’ R 3’ ,

[1040] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably selected from hydrogen and methyl, and

[1041] R 7 is independently selected from

[1042] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 , SR 10 , SOR 10 and SO2R 10 ,

[1043] wherein each C 1-6-alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, or C 1-3- alkoxy is optionally substituted with one or more substituents independently selected from the following

[1044] C 1-3- alkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano,

[1045] hydroxy, NR 8’ R 9’ 、C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1046] R 8 and R 9 are independently selected from the following

[1047] hydrogen, C 1-6- alkyl, C 6-10- aryl, and 5- to 10-membered heteroaryl, or

[1048] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2, or 3 other ring atoms are selected from N, S, and O;

[1049] wherein C 1-6- alkyl, C 6-10- aryl, or 5- to 10-membered heteroaryl, or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[1050] C 1-6- alkyl, C 1-6- alkoxy, hydroxy, and NR 8” R 9” ,

[1051] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl, or ethyl,

[1052] R 8’ 、R 9’ 、R 10’ 、R 11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl, or ethyl,

[1053] R 8” and R9” independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1054] and

[1055] R 13 and R 14 together with the atom to which it is attached form an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally substituted by one or more C1-3-alkyl groups, and / or wherein one or more of the ring-forming carbon atoms are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[1056] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1057] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl,

[1058] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1059] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl.

[1060] In one embodiment of the present invention and / or its embodiments,

[1061] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride,

[1062] and

[1063] R 7 is independently selected from methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl,

[1064] and

[1065] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-,

[1066] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[1067] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[1068] A3 is N or CR 17 , wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1069] A4 is N or CR 18 , wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1070] wherein 0, 1, or 2 of A1, A2, A3, and A4 are N.

[1071] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iqvii), (Iqviii), (Iqix), (Iqx), (Iqxi), or (Iqxii)

[1072]

[1073]

[1074] or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph, prodrug, and mixtures thereof, wherein R 19 and R 25 are as defined 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 (Iqvii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqviii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqix), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqx), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqxi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iqxii), preferably in the (S)-enantiomeric form.

[1076] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 1 , R 7 and R 19 are as defined above.

[1077] Optionally, in one embodiment of the present invention and / or its embodiments,

[1078] R 1 is independently selected from the following

[1079] hydrogen, C 1-6- alkyl, C 1-6- alkoxy, and halogen,

[1080] wherein the C 1-6- alkyl and C 1-6- alkoxy are optionally substituted with one or more substituents independently selected from the following

[1081] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy, and NR 2’ R 3’ ,

[1082] wherein R2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably from hydrogen and methyl,

[1083] and

[1084] R 7 is independently selected from the following

[1085] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 , SR 10 , SOR 10 and SO2R 10 ,

[1086] wherein each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally substituted with one or more substituents independently selected from the following

[1087] C 1-3- alkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1088] R 8 and R 9 are independently selected from the following

[1089] hydrogen, C 1-6- alkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[1090] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1091] wherein C 1-6- alkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[1092] C 1-6- alkyl, C 1-6- alkoxy, hydroxy, and NR 8” R 9” ;

[1093] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl, or ethyl,

[1094] R 8’ 、R 9’ 、R 10’ 、R 11’ and R 12’ is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl, or ethyl,

[1095] R 8” and R 9” is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl, or ethyl,

[1096] and

[1097] R 19 is independently selected from the following

[1098] C 6-10- aryl and 5- to 10-membered heteroaryl

[1099] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[1100] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, and hydroxy.

[1101] In one embodiment of the present invention and / or its embodiments,

[1102] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride,

[1103] and

[1104] R 7independently selected from methyl, ethyl, isopropyl, propyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, mesyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl,

[1105] and

[1106] R 19 is selected from 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, particularly 2,3,5-trifluorophenyl, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[1107] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iri), (Irii), (Iriii), (Iriv), (Irv) or (Irvi)

[1108]

[1109]

[1110] 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 are defined as in any of the embodiments described herein.

[1111] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iri), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Irii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iriii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iriv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Irv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Irvi), preferably in the (S)-enantiomeric form.

[1112] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 1 , R 7 and R 25 are as defined above.

[1113] Optionally, in one embodiment of the present invention and / or its embodiments

[1114] R 1 is independently selected from the following

[1115] hydrogen, C 1-6- alkyl, C 1-6- alkoxy and halogen,

[1116] wherein C 1-6- alkyl and C 1-6- alkoxy are optionally substituted by one or more substituents independently selected from the following

[1117] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy and NR 2’ R 3’ ,

[1118] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably selected from hydrogen and methyl,

[1119] and

[1120] R 7 is independently selected from the following

[1121] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3-Alkoxy, hydroxy, NR 8 R 9 、SR 10 、SOR 10 and SO2R 10 ,

[1122] wherein each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally substituted independently by one or more substituents selected from

[1123] C 1-3- alkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ 、C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1124] R 8 and R 9 are independently selected from

[1125] hydrogen, C 1-6- alkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[1126] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1127] wherein C 1-6- alkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted independently by one or more substituents selected from

[1128] C 1-6- alkyl, C 1-6- alkoxy, hydroxy and NR 8” R 9” ;

[1129] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1130] R 8’ 、R 9’ 、R 10’ 、R11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1131] R 8” and R 9” are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1132] and

[1133] R 25 is hydrogen or C 1-3- alkyl.

[1134] Optionally, in one embodiment of the present invention and / or its embodiments

[1135] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride,

[1136] and

[1137] R 7 is independently selected from methyl, ethyl, isopropyl, propyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl,

[1138] and

[1139] R 25 is hydrogen or methyl, preferably hydrogen.

[1140] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Isi), (Isii), (Isiii) or (Isiv)

[1141]

[1142]

[1143] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 13 , R 14 , A1, A2, A3, A4 and R 29 are defined as in any of the embodiments described herein.

[1144] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isi), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isii), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isiii), preferably in the (S) - enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Isiv), preferably in the (S) - enantiomeric form.

[1145] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 1 、R 13 、R 14 、A1, A2, A3, A4 and R 19 are as defined above.

[1146] Optionally, in one embodiment of the present invention and / or its embodiments,

[1147] R 1 is independently selected from the following

[1148] hydrogen, C 1-6- alkyl, C 1-6- alkoxy and halogen,

[1149] wherein C 1-6- alkyl and C 1-6- alkoxy are optionally substituted by one or more substituents independently selected from the following

[1150] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy and NR 2’ R 3’ ,

[1151] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably selected from hydrogen and methyl,

[1152] and

[1153] R 13 and R 14 together with the atom to which they are attached form a non - aromatic ring containing 5 or 6 carbon atoms, wherein the non - aromatic ring is optionally substituted by one or more C 1-3- alkyl or = O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by - NH -, - O -, - S (O) -, - S (O) 2 - or - S -,

[1154] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1155] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl,

[1156] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 17’ R 17” , wherein R 17’ and R 17” are independently C 1-3- alkyl,

[1157] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 18’ R 18” , wherein R 18’ and R 18” are independently C 1-3- alkyl,

[1158] and

[1159] R 19 is independently selected from the following

[1160] C 6-10- aryl and 5- to 10-membered heteroaryl

[1161] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[1162] C 1-6-alkyl, C 1-6- alkoxy, halogen, cyano, nitro, and hydroxy.

[1163] In one embodiment of the present invention and / or its embodiments,

[1164] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride,

[1165] and

[1166] R 13 and R 14 together with the atom to which it is attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-,

[1167] A1 is N or CR 15 , where R 15 is independently hydrogen or C 1-3 alkoxy,

[1168] A2 is N or CR 16 , where R 16 is independently hydrogen or C 1-3 alkoxy,

[1169] A3 is N or CR 17 , where R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1170] A4 is N or CR 18 , where R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1171] where 0, 1, or 2 of A1, A2, A3, and A4 are N,

[1172] and

[1173] R 19 is independently selected from 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, particularly 2,3,5-trifluorophenyl, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[1174] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iti), (Itii), (Itiii), (Itiv), (Itv) or (Itvi)

[1175]

[1176]

[1177] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 7 and R 25 are defined as in any of the embodiments described herein.

[1178] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iti), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itvi), preferably in the (S)-enantiomeric form.

[1179] Optionally, in one embodiment of the present invention and / or its embodiments

[1180] R 1 is independently selected from

[1181] hydrogen, C 1-6- alkyl, C 1-6- alkoxy and halogen,[[]]END]]

[1182] wherein C 1-6- alkyl and C 1-6- alkoxy are optionally substituted with one or more substituents independently selected from

[1183] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy and NR 2’ R 3’ ,

[1184] wherein R 2’ and R 3’ are independently selected from hydrogen and C1-3- An alkyl group, more preferably selected from hydrogen and methyl,

[1185] and

[1186] R 13 and R 14 together with the atom to which it is attached form an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally substituted by one or more C 1-3- alkyl groups, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[1187] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1188] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl,

[1189] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1190] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1191] and

[1192] R 19 independently selected from the following

[1193] C 6-10- aryl and 5- to 10-membered heteroaryl

[1194] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[1195] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, and hydroxy.

[1196] In one embodiment of the present invention and / or its embodiments,

[1197] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride,

[1198] and

[1199] R 13 and R 14 together with the atom to which it is attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-,

[1200] A1 is N or CR 15 wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[1201] A2 is N or CR 16 wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[1202] A3 is N or CR 17 wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1203] A4 is N or CR 18 wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1204] wherein 0, 1, or 2 of A1, A2, A3, and A4 are N,

[1205] and

[1206] R 19Independently selected from 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, particularly 2,3,5-trifluorophenyl, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[1207] In one embodiment of the present invention and / or its embodiments, the compound is as shown in formula (Itvii), (Itviii), (Itix), (Itx), (Itxi) or (Itxii)

[1208]

[1209]

[1210] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 7 and R 25 are defined as in any of the embodiments described herein.

[1211] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itvii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itviii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itix), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itx), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Itxii), preferably in the (S)-enantiomeric form.

[1212] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 1 , R 13 , R 14 , A1, A2, A3, A4 and R 25 are as defined above.

[1213] Optionally, in one embodiment of the present invention and / or its embodiments,

[1214] R 1 is independently selected from the following

[1215] Hydrogen, C 1-6- Alkyl, C 1-6- Alkoxy and halogen,

[1216] wherein C 1-6- alkyl and C 1-6- alkoxy are optionally independently substituted by one or more substituents selected from the following

[1217] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy and NR 2’ R 3’ ,

[1218] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably selected from hydrogen and methyl,

[1219] and

[1220] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally substituted by one or more C 1-3- alkyl or =O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-,

[1221] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1222] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl,

[1223] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C1-3 an alkoxy group, or NR 17’ R 17” , wherein R 17’ and R 17” independently is C 1-3- alkyl

[1224] A4 is N or CR 18 , wherein R 18 independently is hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy group, or NR 18’ R 18” , wherein R 18’ and R 18” independently is C 1-3- alkyl

[1225] and

[1226] R 25 is hydrogen or C 1-3- alkyl

[1227] In one embodiment of the present invention and / or its embodiments,

[1228] R 1 independently is selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride,

[1229] and

[1230] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-,

[1231] A1 is N or CR 15 , wherein R 15 independently is hydrogen or C 1-3 alkoxy group,

[1232] A2 is N or CR 16 , wherein R 16 independently is hydrogen or C 1-3 alkoxy group,

[1233] A3 is N or CR 17 , wherein R 17 independently is hydrogen or C 1-3 alkoxy group, preferably hydrogen,

[1234] A4 is N or CR 18 , wherein R 18 independently is hydrogen or C 1-3 alkoxy group, preferably hydrogen,

[1235] Zero, one or two of A1, A2, A3 and A4 are N,

[1236] and

[1237] R 25 is hydrogen or methyl, preferably hydrogen.

[1238] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iui), (Iuii), (Iuiii), (Iuiv), (Iuv) or (Iuvi)

[1239]

[1240]

[1241]

[1242] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 7 and R 19 are defined as in any of the embodiments described herein.

[1243] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iui), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuvi), preferably in the (S)-enantiomeric form.

[1244] Optionally, in one embodiment of the present invention and / or its embodiments,

[1245] R 1 is independently selected from the following

[1246] hydrogen, C 1-6- alkyl, C 1-6- alkoxy and halogen,

[1247] wherein C 1-6- alkyl and C 1-6-The alkoxy group is optionally substituted by one or more substituents independently selected from the following

[1248] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy and NR 2’ R 3’ ,

[1249] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably selected from hydrogen and methyl,

[1250] and

[1251] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally substituted by one or more C1-3-alkyl groups, and / or wherein one or more of the ring-forming carbon atoms are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[1252] A1 is N or CR 15 wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1253] A2 is N or CR 16 wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” wherein R 16’ and R 16” are independently C 1-3- alkyl,

[1254] A3 is N or CR 17 wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1255] A4 is N or CR18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1256] and

[1257] R 25 is hydrogen or C 1-3- alkyl.

[1258] In one embodiment of the present invention and / or its embodiments,

[1259] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride,

[1260] and

[1261] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N- or -S-,

[1262] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[1263] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[1264] A3 is N or CR 17 , wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1265] A4 is N or CR 18 , wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1266] wherein 0, 1 or 2 of A1, A2, A3 and A4 are N,

[1267] and

[1268] R 25 is hydrogen or methyl, preferably hydrogen.

[1269] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iuvii), (Iuviii), (Iuix), (Iux), (Iuxi) or (Iuxii)

[1270]

[1271]

[1272] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 7 and R 19 are defined as in any of the embodiments described herein.

[1273] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuvii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuviii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuix), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iux), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuxi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iuxii), preferably in the (S)-enantiomeric form.

[1274] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 1 , R 19 and R 25 are as defined above.

[1275] Optionally, in one embodiment of the present invention and / or its embodiments

[1276] R 1 is independently selected from

[1277] hydrogen, C 1-6- alkyl, C 1-6- alkoxy and halogen,

[1278] wherein C 1-6- alkyl and C 1-6- alkoxy are optionally substituted by one or more substituents independently selected from

[1279] C1-6- alkyl, C 1-6- alkoxy, halogen, cyano, hydroxy and NR 2’ R 3’ ,

[1280] wherein R 2’ and R 3’ are independently selected from hydrogen and C 1-3- alkyl, more preferably selected from hydrogen and methyl,

[1281] and

[1282] R 19 is independently selected from the following

[1283] C 6-10- aryl and 5- to 10-membered heteroaryl

[1284] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[1285] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro and hydroxy,

[1286] and

[1287] R 25 is hydrogen or C 1-3- alkyl.

[1288] In one embodiment of the present invention and / or its embodiments,

[1289] R 1 is independently selected from hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride,

[1290] and

[1291] R 19 is independently selected from 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, 3,5-trifluorophenyl, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl, and

[1292] R 25 is hydrogen or methyl, preferably hydrogen.

[1293] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ivi), (Ivii), (Iviii) or (Iviv)

[1294]

[1295]

[1296] or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph, prodrug, and mixtures thereof, wherein R 7 and R 13 、R 14 、A1, A2, A3 and A4 are as defined in any of the embodiments described herein.

[1297] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ivii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iviii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iviv), preferably in the (S)-enantiomeric form.

[1298] The present invention provides a compound according to the present invention and / or its embodiments, wherein R7, R 13 、R 14 、A1, A2, A3, A4 and R 19 are as defined above.

[1299] Optionally, in one embodiment of the present invention and / or its embodiments,

[1300] R 7 is independently selected from the following

[1301] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 、SR 10 、SOR 10 and SO2R 10 ,

[1302] wherein each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally substituted with one or more substituents independently selected from the following

[1303] C 1-3-alkyl, 5- to 10-membered heterocyclic group, C1-6-alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1304] R 8 and R 9 are independently selected from the following

[1305] hydrogen, C 1-6- alkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[1306] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1307] wherein the C 1-6- alkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[1308] C 1-6- alkyl, C 1-6- alkoxy, hydroxy and NR 8” R 9” ;

[1309] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1310] R 8’ 、R 9’ 、R 10’ 、R 11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1311] R 8” and R 9” are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1312] and

[1313] R 13 and R 14Together with the atom to which it is attached, form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally substituted by one or more C 1-3- alkyl or =O, and / or wherein one or more of the ring-forming carbon atoms are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-,

[1314] A1 is N or CR 15 wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15’ R 15” wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1315] A2 is N or CR 16 wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 16’ R 16” wherein R 16’ and R 16” are independently C 1-3- alkyl,

[1316] A3 is N or CR 17 wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 17’ R 17” wherein R 17’ and R 17” are independently C 1-3- alkyl,

[1317] A4 is N or CR 18 wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 18’ R 18” wherein R 18’ and R 18” are independently C 1-3- alkyl,

[1318] and

[1319] R 19 is independently selected from the following

[1320] C 6-10- aryl and 5- to 10-membered heteroaryl

[1321] Each C 6-10- The aryl or 5- to 10-membered heteroaryl is optionally substituted independently by one or more substituents selected from the following

[1322] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, and hydroxy.

[1323] In one embodiment of the present invention and / or its embodiments,

[1324] R 7 is independently selected from methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl,

[1325] and

[1326] R 13 and R 14 together with the atom to which it is attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-,

[1327] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[1328] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[1329] A3 is N or CR 17 , wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1330] A4 is N or CR 18 , wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1331] wherein 0, 1, or 2 of A1, A2, A3, and A4 are N,

[1332] and

[1333] R 19 independently selected from 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, particularly 2,3,5-trifluorophenyl, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[1334] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iwi), (Iwii), (Iwiii), (Iwiv), (Iwv), (Iwvi), (Iwvii), (Iwviii), (Iwix), (Iwx), (Iwxi) or (Iwxi)

[1335]

[1336]

[1337]

[1338]

[1339] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 and R 25 are defined as in any of the embodiments described herein.

[1340] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwvi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwvii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwviii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwix), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwx), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwixii), preferably in the (S)-enantiomeric form.

[1341] Optionally, in one embodiment of the present invention and / or its embodiments,

[1342] R 7 is independently selected from the following

[1343] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 、SR 10 、SOR 10 and SO2R 10 ,

[1344] wherein each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally substituted by one or more substituents independently selected from the following

[1345] C 1-3- alkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1346] R 8 and R 9 are independently selected from the following

[1347] hydrogen, C 1-6- alkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[1348] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1349] wherein C 1-6- alkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from the following

[1350] C 1-6- alkyl, C 1-6- alkoxy, hydroxy and NR 8” R 9” ;

[1351] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1352] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1353] R 8” and R 9” are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl, and

[1354] R 13 and R 14Together with the atom to which it is attached, form an aromatic ring containing 5 or 6 carbon atoms, where the aromatic ring is optionally substituted by one or more C 1-3- alkyl groups, and / or where one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[1355] A1 is N or CR 15 where R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” where R 15’ and R 15” are independently C 1-3- alkyl,

[1356] A2 is N or CR 16 where R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” where R 16’ and R 16” are independently C 1-3- alkyl,

[1357] A3 is N or CR 17 where R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” where R 15’ and R 15” are independently C 1-3- alkyl,

[1358] A4 is N or CR 18 where R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” where R 15’ and R 15” are independently C 1-3- alkyl,

[1359] and

[1360] R 19 is independently selected from

[1361] C 6-10- aryl and 5- to 10-membered heteroaryl

[1362] Each C 6-10- The aryl or 5- to 10-membered heteroaryl is optionally substituted independently by one or more substituents selected from the following

[1363] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, and hydroxy.

[1364] In one embodiment of the present invention and / or its embodiments,

[1365] R 7 is independently selected from methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)l(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl,

[1366] and

[1367] R 13 and R 14 together with the atom to which it is attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-,

[1368] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[1369] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[1370] A3 is N or CR 17 , wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1371] A4 is N or CR 18 , wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1372] wherein 0, 1, or 2 of A1, A2, A3, and A4 are N,

[1373] and

[1374] R 19 independently selected from 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, particularly 2,3,5-trifluorophenyl, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[1375] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iwxiii), (Iwxiv), (Iwxv), (Iwxvi), (Iwxvii), (Iwxviii), (Iwxix), (Iwxx), (Iwxxi), (Iwxxii), (Iwxxiii) or (Iwxxiv)

[1376]

[1377]

[1378]

[1379]

[1380]

[1381] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 and R 25 are defined as in any of the embodiments described herein.

[1382] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxvi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxvii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxviii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxix), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxx), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxxi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxxii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxxiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iwxxiv), preferably in the (S)-enantiomeric form.

[1383] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 7 、R 13 、R 14 、A1, A2, A3, A4 and R 25 are as defined above.

[1384] Optionally, in one embodiment of the present invention and / or its embodiments,

[1385] R 7 is independently selected from the following

[1386] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, a 4- to 10-membered heterocyclic group, C 1-3 -alkoxy, hydroxy, NR 8 R 9 、SR 10 、SOR 10and SO2R 10 ,

[1387] wherein each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally substituted with one or more substituents independently selected from the following

[1388] C 1-3- alkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1389] R 8 and R 9 are independently selected from the following

[1390] hydrogen, C 1-6- alkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[1391] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1392] wherein the C 1-6- alkyl, C 6-10- aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[1393] C 1-6- alkyl, C 1-6- alkoxy, hydroxy and NR 8” R 9” ,

[1394] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1395] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1396] R 8” and R 9” are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1397] and

[1398] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally substituted by one or more C 1-3- alkyl or =O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-,

[1399] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1400] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl,

[1401] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 17’ R 17” , wherein R 17’ and R 17” are independently C 1-3- alkyl,

[1402] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 18’ R 18” , wherein R18’ and R 18” is independently C 1-3- alkyl, and

[1403] R 25 is hydrogen or C 1-3- alkyl.

[1404] In one embodiment of the present invention and / or its embodiments,

[1405] R 7 is independently selected from methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl,

[1406] and

[1407] R 13 and R 14 together with the atom to which it is attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the ring-forming carbon atoms are optionally replaced by -NH- or -O-,

[1408] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[1409] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[1410] A3 is N or CR 17 , wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1411] A4 is N or CR 18 , wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1412] wherein 0, 1 or 2 of A1, A2, A3 and A4 are N,

[1413] and

[1414] R 25is hydrogen or methyl, preferably hydrogen.

[1415] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ixi), (Ixii), (Ixiii), (Ixiv), (Ixv) or (Ixvi)

[1416]

[1417]

[1418] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 and R 19 are defined as in any of the embodiments described herein.

[1419] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ixi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ixii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ixiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ixiv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ixv), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Ixvi), preferably in the (S)-enantiomeric form.

[1420] Optionally, in one embodiment of the present invention and / or its embodiments

[1421] R 7 is independently selected from the following

[1422] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 、SR 10 、SOR 10 and SO2R 10 ,

[1423] wherein each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally substituted with one or more substituents independently selected from the following

[1424] C 1-3- alkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1425] R 8 and R 9 are independently selected from the following

[1426] hydrogen, C 1-6- alkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[1427] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1428] wherein C 1-6- alkyl, C6-10-aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted by one or more substituents independently selected from the following

[1429] C 1-6- alkyl, C 1-6- alkoxy, hydroxy and NR 8” R 9” ,

[1430] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1431] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1432] R 8” and R 9” are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1433] and

[1434] R13 and R 14 together with the atom to which it is attached forms an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally substituted by one or more C 1-3- alkyl groups, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[1435] A1 is N or CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1436] A2 is N or CR 16 , wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” , wherein R 16’ and R 16” are independently C 1-3- alkyl,

[1437] A3 is N or CR 17 , wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1438] A4 is N or CR 18 , wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1439] and

[1440] R 25 is hydrogen or C 1-3- alkyl.

[1441] In one embodiment of the present invention and / or its embodiments,

[1442] R 7 is independently selected from methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, mesyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl,

[1443] and

[1444] R 13 and R 14 together with the atom to which it is attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, or -S-,

[1445] A1 is N or CR 15 wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[1446] A2 is N or CR 16 wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[1447] A3 is N or CR 17 wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1448] A4 is N or CR 18 wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1449] wherein 0, 1, or 2 of A1, A2, A3, and A4 are N,

[1450] and

[1451] R 25 is hydrogen or methyl, preferably hydrogen.

[1452] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Ixvii), (Ixviii), (Ixix), (Ixx), (Ixxi), or (Ixxii)

[1453]

[1454]

[1455] or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph, prodrug, and mixtures thereof, wherein R 1 and R 19 are as defined in any of the embodiments described herein.

[1456] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ixvii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ixix), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ixx), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ixxi), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Ixxii), preferably in the (S)-enantiomeric form.

[1457] The present invention provides a compound according to the invention and / or its embodiments, wherein R 7 , R 19 and R 25 are as defined above.

[1458] Optionally, in one embodiment of the invention and / or its embodiments,

[1459] R 7 is independently selected from the following

[1460] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group, C 1-3- alkoxy, hydroxy, NR 8 R 9 , SR 10 , SOR 10 and SO2R 10 ,

[1461] wherein each C 1-6- alkyl, C 2-6- alkenyl, 4- to 10-membered heterocyclic group or C 1-3- alkoxy is optionally substituted with one or more substituents independently selected from the following

[1462] C 1-3- alkyl, 5- to 10-membered heterocyclic group, C 1-6- alkoxy, halogen, cyano, hydroxy, NR 8’ R 9’ , C(=O)OR 10’ and C(=O)NR 11’ R 12’ ,

[1463] R 8 and R 9 are independently selected from the following

[1464] hydrogen, C 1-6- alkyl, C 6-10- aryl and 5- to 10-membered heteroaryl, or

[1465] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein one ring atom is N and wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1466] wherein the C 1-6- alkyl, C 6-10 -aryl or 5- to 10-membered heteroaryl or the heterocycle formed by R 8 and R 9 together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following

[1467] C 1-6- alkyl, C 1-6- alkoxy, hydroxy and NR 8” R 9” ;

[1468] R 10 is independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1469] R 8’ , R 9’ , R 10’ , R 11’ and R 12’ are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1470] R 8” and R 9” are independently selected from hydrogen or C 1-3- alkyl, preferably selected from hydrogen, methyl or ethyl,

[1471] and

[1472] R19 Independently selected from the following

[1473] C 6-10- Aryl and 5- to 10-membered heteroaryl

[1474] Wherein each C 6-10- The aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[1475] C 1-6- Alkyl, C 1-6- Alkoxy, halogen, cyano, nitro and hydroxy,

[1476] And

[1477] R 25 Is hydrogen or C 1-3- Alkyl.

[1478] In one embodiment of the present invention and / or its embodiments,

[1479] R 7 Independently selected from methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methanesulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl,

[1480] And

[1481] R 19 Independently selected from 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, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl,

[1482] And

[1483] R 25 Is hydrogen or methyl, preferably hydrogen.

[1484] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Iyi), (Iyii), (Iyiii) or (Iyiv)

[1485]

[1486]

[1487] or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph, prodrug, and mixtures thereof, wherein R 1 、R 13 、R 14 、A1, A2, A3, and A4 are as defined in any of the embodiments described herein.

[1488] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iyi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iyii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iyiii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iyiv), preferably in the (S)-enantiomeric form.

[1489] The present invention provides a compound according to the present invention and / or its embodiments, wherein R 13 、R 14 、A1, A2, A3, A4, R 19 and R 25 are as defined above.

[1490] Optionally, in one embodiment of the present invention and / or its embodiments,

[1491] R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the non-aromatic ring is optionally substituted by one or more C 1-3- alkyl or =O, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -O-, -S(O)-, -S(O)2-, or -S-,

[1492] A1 is N or CR 15 ,wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15’ R 15” ,wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1493] A2 is N or CR 16 ,wherein R 16Independently is hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 16’ R 16” wherein R 16’ and R 16” independently are C 1-3- alkyl,

[1494] A3 is N or CR 17 wherein R 17 independently is hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 17’ R 17” wherein R 17’ and R 17” independently are C 1-3- alkyl,

[1495] A4 is N or CR 18 wherein R 18 independently is hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 18’ R 18” wherein R 18’ and R 18” independently are C 1-3- alkyl,

[1496] and

[1497] R 19 is independently selected from the following

[1498] C 6-10- aryl and 5 - to 10 - membered heteroaryl

[1499] wherein each C 6-10- aryl or 5 - to 10 - membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[1500] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro, and hydroxy,

[1501] and

[1502] R 25 is hydrogen or C 1-3- alkyl.

[1503] In one embodiment of the present invention and / or its embodiments,

[1504] R 13 and R 14Together with the atom to which it is attached, form a non-aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH- or -O-.

[1505] A1 is N or CR 15 , wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[1506] A2 is N or CR 16 , wherein R 16 is independently hydrogen or C 1-3 alkoxy,

[1507] A3 is N or CR 17 , wherein R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1508] A4 is N or CR 18 , wherein R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1509] wherein 0, 1 or 2 of A1, A2, A3 and A4 are N,

[1510] and

[1511] R 19 is independently selected from 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, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl,

[1512] and

[1513] R 25 is hydrogen or methyl, preferably hydrogen.

[1514] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Izi), (Izii), (Iziii), (Iziv), (Izv) or (Izvi)

[1515]

[1516]

[1517] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R1 and R 7 as defined in any of the embodiments described herein.

[1518] In one embodiment of the invention and / or its embodiments, the compound is according to formula (Izi), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Izii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iziii), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Iziv), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Izv), preferably in the (S)-enantiomeric form. In one embodiment of the invention and / or its embodiments, the compound is according to formula (Izvi), preferably in the (S)-enantiomeric form.

[1519] Optionally, in one embodiment of the invention and / or its embodiments,

[1520] R 13 and R 14 together with the atom to which it is attached form an aromatic ring containing 5 or 6 carbon atoms, wherein the aromatic ring is optionally substituted by one or more C1-3-alkyl groups, and / or wherein one or more of the ring-forming carbon atoms are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[1521] A1 is N or CR 15 , wherein R 15 independently is hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” independently are C 1-3- alkyl,

[1522] A2 is N or CR 16 , wherein R 16 independently is hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” , wherein R 16’ and R 16” independently are C 1-3- alkyl,

[1523] A3 is N or CR 17 , wherein R17 Independently is hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” wherein R 15’ and R 15” independently is C 1-3- alkyl,

[1524] A4 is N or CR 18 wherein R 18 independently is hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 15’ R 15” wherein R 15’ and R 15” independently is C 1-3- alkyl,

[1525] and

[1526] R 19 is independently selected from the following

[1527] C 6-10- aryl and 5- to 10-membered heteroaryl

[1528] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[1529] C 1-6- alkyl, C 1-6- alkoxy, halogen, cyano, nitro and hydroxy,

[1530] and

[1531] R 25 is hydrogen or C 1-3- alkyl.

[1532] Optionally, in one embodiment of the present invention and / or its embodiments,

[1533] R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, wherein one or more of the ring-forming carbon atoms are optionally replaced by -NH-, -N=, =N- or -S-,

[1534] A1 is N or CR 15 wherein R 15 is independently hydrogen or C 1-3 alkoxy,

[1535] A2 is N or CR 16 wherein R16 is independently hydrogen or C 1-3 alkoxy,

[1536] A3 is N or CR 17 , where R 17 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1537] A4 is N or CR 18 , where R 18 is independently hydrogen or C 1-3 alkoxy, preferably hydrogen,

[1538] where 0, 1 or 2 of A1, A2, A3 and A4 are N,

[1539] and

[1540] R 19 is independently selected from 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, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl,

[1541] and

[1542] R 25 is hydrogen or methyl, preferably hydrogen.

[1543] In one embodiment of the present invention and / or its embodiments, the compound is represented by formula (Izvii), (Izviii), (Izix), (Izx), (Izxi) or (Izxii)

[1544]

[1545]

[1546]

[1547] or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, where R 1 and R 7 are defined as in any of the embodiments described herein.

[1548] In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Iziii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Izviii), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Izix), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Izx), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Izxi), preferably in the (S)-enantiomeric form. In one embodiment of the present invention and / or its embodiments, the compound is according to formula (Izxii), preferably in the (S)-enantiomeric form.

[1549] The compounds according to the present invention can be considered as an "active" agent, which is herein considered as a substance capable of inhibiting worms such as Dirofilaria, especially Dirofilaria immitis. The term "inhibiting growth" refers to a decrease in the growth rate of the worm population. Thus, the term includes cases where the number of worms increases but at a reduced rate, cases where the inhibition of population growth stops, and cases where the number of worms in the population decreases or even disappears.

[1550] Furthermore, the present invention provides a method for preparing a compound according to formula (I), comprising the following steps

[1551] reacting a compound of formula (A)

[1552]

[1553] with a compound of formula (B)

[1554]

[1555] wherein

[1556] R 1 is independently selected from the following

[1557] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy, C 1-6- alkylthio, halogen, cyano, nitro, hydroxy, 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 ,

[1558] wherein each C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10 aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy or C 1-6- alkylthio is optionally independently substituted with one or more substituents selected from the following

[1559] C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy, C 1-6- alkylthio, halogen, cyano, nitro, hydroxy, 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’ ,

[1560] R 2 and R 3 are independently selected from the following

[1561] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy-C 1-6- alkyl, C 3-10- alkyl substituted with C 1-6- cycloalkyl, C 1-6- alkyl substituted with a 5- to 10-membered heterocyclic group, C 6-10- alkyl substituted with C 1-6- aryl and C alkyl substituted with a 5- to 10-membered heteroaryl1-6- alkyl, or

[1562] R 2 and R 3 together with the N atom to which it is attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 of the other ring atoms are selected from N, S and O,

[1563] wherein each C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy-C 1-6- alkyl, C 3-10- alkyl substituted with cycloalkyl, 1-6- alkyl substituted with a 5- to 10-membered heterocyclic group, 1-6- alkyl, C 6-10- alkyl substituted with aryl, 1-6- alkyl or C 1-6- alkyl substituted with a 5- to 10-membered heteroaryl or a heterocycle formed by R 2 and R 3 together with the N atom to which it is attached is optionally substituted with one or more substituents independently selected from

[1564] C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy, carbonyl, halogen, cyano, hydroxy, 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” ;

[1565] R 4 、R 5 and R 6 are independently selected from hydrogen and C 1-6- alkyl,

[1566] R 2’ 、R 3’ 、R 4’ 、R5’ and R 6’ are independently selected from hydrogen and C 1-6- alkyl

[1567] R 2” 、R 3” 、R 4” 、R 5” and R 6” are independently selected from hydrogen and C 1-6- alkyl

[1568] R 7 is independently selected from the following

[1569] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 4- to 10-membered heterocyclic group, C 6-10 aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy, C 1-6- alkylthio, halogen, cyano, nitro, hydroxy, 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 ,

[1570] wherein each C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 4- to 10-membered heterocyclic group, C 6-10 aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy or C 1-6- alkylthio is optionally substituted by one or more substituents independently selected from the following

[1571] C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy, C 1-6- alkylthio, halogen, cyano, nitro, hydroxy, mercapto, NR 8’ R 9’ 、C(=O)OR10’ , SR 10’ , SOR 10’ , SO2R 10’ , SO2NR 11’ R 12’ and C(=O)NR 11’ R 12’ ,

[1572] R 8 and R 9 are independently selected from the following

[1573] hydrogen, C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy-C 1-6- alkyl, C 3-10- alkyl substituted with C 1-6- cycloalkyl, C 1-6- alkyl substituted with a 5- to 10-membered heterocyclic group, C 6-10- alkyl substituted with C 1-6- aryl, C 1-6- alkyl substituted with a 5- to 10-membered heteroaryl, C

[1574] R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O,

[1575] wherein each C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy-C 1-6- alkyl, C 3-10- alkyl substituted with C 1-6- cycloalkyl, C 1-6- alkyl substituted with a 5- to 10-membered heterocyclic group, C 6-10- alkyl substituted with C 1-6- aryl, C 1-6- alkyl or C 8 and R 9 the heterocycle formed together with the N atom to which they are attached is optionally substituted with one or more substituents independently selected from the following C 1-6- alkyl, C2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, 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” ;

[1576] R 10 , R 11 , and R 12 are independently selected from hydrogen and C 1-6- alkyl,

[1577] R 8’ , R 9’ , R 10’ , R 11’ , and R 12’ are independently selected from hydrogen and C 1-6- alkyl,

[1578] R 8” , R 9” , R 10” , R 11” , and R 12” are independently selected from hydrogen and C 1-6- alkyl,

[1579] R 13 is hydrogen or C 1-3 alkyl,

[1580] R 14 is hydrogen, C 1-3 alkyl, C 1-3 alkoxy, NR 14’ R 14” , wherein R 14’ , and R 14” are independently C 1-3- alkyl or

[1581] R 13 , and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, wherein the ring containing 5 or 6 carbon atoms is optionally substituted by one or more C 1-3-alkyl or =O substitution, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S-,

[1582] or

[1583] R 13 and R 14 together with the atom to which it is attached form an aromatic ring containing 5 or 6 carbon atoms, wherein the ring containing 5 or 6 carbon atoms is optionally substituted by one or more C 1-3 -alkyl, and / or one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S-,

[1584] A1 is N or CR 15 wherein R 15 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 15’ R 15” wherein R 15’ and R 15” are independently C 1-3- alkyl,

[1585] A2 is N or CR 16 wherein R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 16’ R 16” wherein R 16’ and R 16” are independently C 1-3- alkyl,

[1586] A3 is N or CR 17 wherein R 17 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 17’ R 17” wherein R 17’ and R 17” are independently C 1-3- alkyl,

[1587] A4 is N or CR 18 wherein R 18 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy, or NR 18’ R 18” wherein R 18’ and R 18”is independently C 1-3- alkyl,

[1588] R 19 is independently selected from the following C 6-10- aryl and 5- to 10-membered heteroaryl,

[1589] wherein each C 6-10- aryl or 5- to 10-membered heteroaryl is optionally substituted with one or more substituents independently selected from the following

[1590] C 1-6- alkyl, C 2-6- alkenyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy, C 1-6- alkylthio, halogen, cyano, nitro, hydroxy, 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 ,

[1591] R 20 and R 21 are independently selected from the following

[1592] 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, C1-C6-alkyl substituted with C 6-10- aryl, C-alkyl substituted with 5- to 10-membered heteroaryl 1-6- alkyl, or

[1593] R 20 and R 21 together with the N atom to which they are attached form a saturated or unsaturated heterocycle having 3 to 12 ring atoms, wherein 0, 1, 2 or 3 other ring atoms are selected from N, S and O;

[1594] wherein each C 1-6- alkyl, C 2-6- alkenyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy or C1-6- alkylthio or R 20 and R 21 the heterocycle formed together with the N atom to which it is attached is optionally substituted with one or more substituents independently selected from the following

[1595] C 1-6- alkyl, C 2-6- alkenyl, C 2-6- alkynyl, C 3-10- cycloalkyl, 5- to 10-membered heterocyclic group, C 6-10- aryl, 5- to 10-membered heteroaryl, C 1-6- alkoxy, carbonyl, halogen, cyano, hydroxy, 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’

[1596] R 22 , R 23 and R 24 are independently selected from hydrogen and C 1-6- alkyl,

[1597] R 20’ , R 21’ , R 22’ , R 23’ and R 24’ are independently selected from hydrogen and C 1-6- alkyl,

[1598] R 25 is independently selected from hydrogen and C 1-6- alkyl,

[1599] to obtain a compound according to formula (I).

[1600] In one embodiment of the present invention and / or its embodiments, with respect to R 1 , R 7 , R 13 , R 14 , A1, A2, A3, A4, R 19 and R 25 the same applies to the description of the compounds of the present invention above.

[1601] The compounds of formula (A) and formula (B) are commercially available or can be obtained by synthesis.

[1602] In one embodiment of the present invention and / or its implementation manners, the amine of formula (A) and the carboxylic acid of formula (B) can form the corresponding amide group in an organic solvent in the presence of a coupling agent.

[1603] The coupling agent can be considered as a substance that generally promotes the formation of esters or amides. The coupling agent reacts with the carboxyl group by forming an active intermediate, which then further reacts with an alcohol or an amine to form the final product, namely an ester or an amide.

[1604] Examples of coupling agents include, but are not limited to, carbodiimides such as N,N'-dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC•HCl), and N-cyclohexyl-N'-(2-morpholinoethyl)carbodiimide-methyl-p-toluenesulfonate (CMC), phosphonium salts such as benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate (PyBOP), amine salts such as 3-[bis(dimethylamino)methyl]-3H-benzotriazol-1-oxide hexafluorophosphate (HBTU), and carbonyldiimidazole (CDI).

[1605] In one embodiment of the present invention and / or its implementation manners, the coupling agent is selected from N,N'-dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDC•HCl), and carbonyldiimidazole (CDI). A more preferred coupling agent is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride.

[1606] Organic solvents are known to those skilled in the art.

[1607] Suitable organic solvents for the method according to the present invention can be, for example, acetonitrile, dioxane, tetrahydrofuran (THF), and dimethylformamide (DMF), dimethyl sulfoxide (DMSO), preferably dimethylformamide (DMF).

[1608] In one embodiment of the present invention and / or its implementation manners, the method can be carried out in the presence of an auxiliary basic compound. Suitable basic compounds include, but are not limited to, pyridines such as 4-(dimethylamino)pyridine (DMAP), amidines such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and amines such as triethylamine and diisopropylethylamine (DIPEA), preferably 4-(dimethylamino)pyridine (DMAP).

[1609] In one embodiment of the present invention and / or its embodiments, the method can be carried out at a temperature of 5° to 120°C, preferably 20 to 100°C.

[1610] In an alternative embodiment of the present invention and / or its embodiments, the carboxylic acid according to formula (B) can be reacted with thionyl chloride or oxalyl chloride, preferably oxalyl chloride, to form the corresponding acyl chloride. Subsequently, the corresponding acyl chloride can be reacted with the amine according to formula (A) to obtain the compound of formula (I).

[1611] In an alternative embodiment of the present invention and / or its embodiments, the alternative method can be carried out in an organic solvent and / or in the presence of an auxiliary basic compound.

[1612] Suitable organic solvents can be, for example, acetonitrile, toluene, dioxane, tetrahydrofuran, chloroform or dichloromethane.

[1613] Regarding the auxiliary basic compound, the same as above, pyridine, DMAP, triethylamine and diisopropylethylamine are preferred.

[1614] Furthermore, the present invention provides a veterinary pharmaceutical composition comprising a compound according to the present invention and one or more physiologically acceptable excipients.

[1615] The veterinary pharmaceutical composition of the present invention and / or its embodiments comprises a therapeutically effective amount of the compound of the present invention and / or its embodiments, which is formulated together with one or more physiologically acceptable excipients.

[1616] Physiologically acceptable excipients are known in the art. For example, they are described in "Gennaro, Remington: The Science and Practice of Pharmacy" (20th edition, 2000). All these physiologically acceptable excipients must be substantially pharmaceutically or veterinarily pure and non-toxic in the amounts used and must be compatible with the active ingredient.

[1617] In a preferred embodiment of the present invention and / or its embodiments, one or more physiologically acceptable excipients are selected from carriers, binders, antioxidants, buffers, sugar components, surfactants, lubricants, stabilizers, flow agents, disintegrants and preservatives and mixtures thereof.

[1618] As used herein, the term "carrier" refers to any type of non-toxic, inert, solid, semi-solid or liquid filler or diluent that carries / encapsulates any type of material. Some examples of materials that can be used as physiologically acceptable carriers are, but are not limited to, sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as carboxymethyl cellulose, ethyl cellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository wax; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; esters such as ethyl oleate and ethyl laurate; agar.

[1619] An adhesive is a substance that can bond other substances together. An adhesive (in the case where the adhesive is a polymer) preferably has a melting temperature or glass transition temperature (T g ) within the range of 25 to 100 °C, preferably 35 to 85 °C, particularly 40 to 70 °C. The glass transition temperature is the temperature at which a polymer becomes brittle upon cooling and softens upon heating. This means that a hydrophilic polymer will soften at a temperature above the glass transition temperature (T g ) and can be plastically deformed without breaking. The glass transition temperature or melting point is determined by methods known to those skilled in the art.

[1620] In a preferred embodiment of the present invention and / or its embodiments, the adhesive is selected from polyethylene glycol, polypropylene glycol, polyethylene glycol-polypropylene glycol copolymer, microcrystalline wax, glycerol monostearate, hydrogenated castor oil, polyethylene glycol hydroxystearate glycerol ester, polysaccharides, polyvinylpyrrolidone, polyvinyl alcohol, poly(meth)acrylate, polyvinylpyrrolidone-polyacetate copolymer and mixtures thereof.

[1621] An antioxidant is a substance used to inhibit oxidation. Antioxidants suitable for inclusion in the soft chew veterinary dosage form of the present invention include, but are not limited to, ascorbic acid, glutathione, tocopherols and their esters, tertiary butylhydroquinone (TBHQ), butylated hydroxyanisole (BHA also known as 2-tert-butyl-4-hydroxyanisole, 3-tert-butyl-4-hydroxyanisole or mixtures thereof) and butylated hydroxytoluene (BHT also known as 2,6-di-tert-butyl-4-methylphenol). Preferably, the antioxidant is present in aggregates. In a preferred embodiment of the present invention and / or its embodiments, the antioxidant included in the veterinary pharmaceutical preparation can be in the range of 0.001 to 1.00% by weight.

[1622] A buffer is a substance that maintains / regulates the pH value of a product. Non-limiting examples of buffers are bicarbonates, dihydrogen phosphates, hydrogen phosphates.

[1623] Sugar components are used to sweeten the taste of the product. It includes natural sugars (carbohydrates) and sugar substitutes. In a preferred embodiment of the present invention and / or its embodiments, the buffering agent contained in the veterinary pharmaceutical preparation can be in the range of 1 to 10% by weight.

[1624] Surfactants can be regarded as substances that reduce the interfacial tension between two phases. Common surfactants are alkyl sulfates (such as sodium lauryl sulfate), alkyl trimethyl ammonium salts, alcohol ethoxylates, etc. In a preferred embodiment of the present invention and / or its embodiments, the surfactant contained in the veterinary pharmaceutical preparation can be in the range of 0.1 to 10.0% by weight.

[1625] Lubricants generally can be considered as substances suitable for reducing friction, such as static friction, sliding friction, and rolling friction. The lubricant is preferably a stearate or a fatty acid, more preferably an alkaline earth metal stearate, such as magnesium stearate. In a preferred embodiment of the present invention and / or its embodiments, the lubricant contained in the veterinary pharmaceutical preparation can be in the range of 0.1 to 10.0% by weight.

[1626] Stabilizers are physiologically acceptable excipients that help preserve the product. Examples include but are not limited to alginates, carrageenans, gelatin, pectin, and natural gums. In a preferred embodiment of the present invention and / or its embodiments, the surfactant contained in the veterinary pharmaceutical preparation can be in the range of 0.01 to 3.0% by weight.

[1627] Glidants, also known as flow aids, can be used to improve fluidity. Traditionally, talc has been used as a flow aid, but now it has been almost completely replaced by colloidal silica. In a preferred embodiment of the present invention and / or its embodiments, the glidant contained in the veterinary pharmaceutical preparation can be in the range of 1 to 3% by weight.

[1628] Disintegrants, also known as disintegrating agents, are compounds that enhance the ability of a dosage form, preferably a tablet, to break into smaller fragments when in contact with a liquid, preferably water. Non-limiting examples of disintegrants include sodium carboxymethyl starch, sodium starch glycolate, cross-linked polyvinylpyrrolidone, sodium carboxymethyl glycolate, preferably sodium starch glycolate. In a preferred embodiment of the present invention and / or its embodiments, the surfactant contained in the veterinary pharmaceutical preparation can be in the range of 1.0 to 7.0% by weight.

[1629] Preservatives are substances that can be added to prevent microbial growth or decomposition by adverse chemical changes. Non-limiting examples include lactic acid, benzoic acid benzoates, and parabens. In a preferred embodiment of the present invention and / or its embodiments, the surfactant contained in the veterinary pharmaceutical preparation can be in the range of 0.01 to 1.0% by weight.

[1630] The compounds according to the present invention can be administered in various dosage forms. The term "dosage form" refers to a product in which the compound according to the present invention is formulated to be suitable for administration to an animal by a contemplated route of administration. Such dosage forms are sometimes referred to herein as formulations or pharmaceutical compositions.

[1631] The pharmaceutical compositions and / or embodiments thereof of the present invention can be administered to an animal orally, rectally, vaginally, parenterally, topically, buccally or nasally.

[1632] In a preferred embodiment of the present invention and / or its embodiments, the dosage form for oral administration can be a liquid or solid dosage form.

[1633] Liquid dosage forms of the compound are generally solutions, suspensions or emulsions. A solution is a mixture of two or more components that forms a single phase that is uniform at the molecular level. A suspension consists of insoluble solid particles dispersed in a liquid medium, and the solid particles account for about 0.5% to about 30% of the suspension. The liquid can be aqueous, oily or both. An emulsion is a heterogeneous dispersion of one immiscible liquid in another; its stability depends on an emulsifier. Dry powder (or granules) for reconstitution is mixed with a diluent (e.g., water) and reconstituted into a solution or suspension immediately before injection. The main advantage of this dosage form is that it overcomes the problem of instability of solutions or suspensions.

[1634] Liquid preparations for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, infusions, feed or drinking water preparations and elixirs. A gastric lavage fluid is a liquid oral preparation that is administered directly into the mouth / throat of an animal, especially a dog, by a "stomach tube gun" or syringe or other suitable device. When the composition is administered in the drinking water of the animal recipient or as an infusion, it may be convenient to use a solution or suspension preparation. For example, such a preparation can be a concentrated suspension mixed with water or a dry preparation mixed and suspended in water. In addition to the active compound, liquid dosage forms can contain inert diluents commonly used in the art, such as water or other solvents, solubilizers and emulsifiers, such as ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butanediol, dimethylformamide, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive castor oil and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol and fatty acid esters of sorbitol and mixtures thereof. In addition to the inert diluent, oral compositions can also contain adjuvants such as wetting agents, emulsifiers and suspending agents, sweetening agents, flavoring agents and aromatics.

[1635] Solid dosage forms for oral administration include capsules, tablets, dragees, pills, powders, and granules, chewable snacks, premixes, and boluses. In such solid dosage forms, the active compound is admixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or calcium phosphate dibasic and / or a) fillers or extenders such as starch, lactose, sucrose, glucose, mannitol, and silicic acid; b) binders such as carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidone, sucrose, and acacia; c) humectants such as glycerol; d) disintegrants such as agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; e) solution retarders such as paraffin; f) absorption promoters such as quaternary ammonium compounds; g) wetting agents such as ethanol and glyceryl monostearate; h) absorbents such as kaolin and bentonite; i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets, and pills, the dosage form may also contain buffering agents.

[1636] The active compound can also be in microencapsulated form with one or more excipients as described above. Solid dosage forms of tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulation art such as enteric coatings, controlled release coatings, and other coatings. In such solid dosage forms, the active compound can be admixed with at least one inert diluent such as sucrose, lactose, or starch. Such dosage forms may also contain, as is conventional, other substances in addition to the inert diluent, for example, tableting lubricants and other tableting aids such as magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets, and alkyls, the dosage form may also contain buffering agents. It may optionally contain opacifying agents and may also be a composition that releases the active substance only or preferably in a certain part of the intestine, optionally in a delayed manner. Examples of embedding compositions include polymers and waxes.

[1637] Similar types of solid compositions can also be used as fillers in soft and hard gelatin capsules, using excipients such as lactose or milk sugar and high molecular weight polyethylene glycols.

[1638] Solid oral formulations are administered directly to animals (tablets, capsules) or in a feed mixture or via medicated feed blocks.

[1639] When an oral formulation is administered via the feed of a non-human animal, for example, it can be fed as a discrete feed or as a chewable snack. Or (or additionally), it can, for example, be intimately dispersed in the animal recipient's regular feed, used as a top dressing, or added to the finished feed in solid particulate, paste, or liquid form. When an oral formulation is administered as a feed additive, it may be convenient to prepare a "premix" in which the oral formulation is dispersed in a small amount of liquid or solid carrier. The "premix" is then dispersed in the animal's regular feed using, for example, a conventional mixer.

[1640] In a preferred embodiment of the present invention and / or its embodiments, the dosage form for rectal and vaginal administration can be considered a semi-solid preparation.

[1641] The composition for rectal or vaginal administration can be prepared by mixing the compound of the present invention with a suitable non-irritating excipient or carrier such as cocoa butter, polyethylene glycol or suppository wax, which is solid at ambient temperature but liquid at body temperature and thus melts in the rectal or vaginal cavity and releases the active compound.

[1642] In a preferred embodiment of the present invention and / or its embodiments, the dosage form can be used for parenteral administration. One route of administration (route of administration) is parenteral administration, especially injection administration (e.g., subcutaneous injection, intravenous injection, intramuscular injection, etc.). Parenteral formulations and delivery systems for non-oral routes include liquids (e.g., solutions for reconstitution, suspensions, emulsions and dry powders), semi-solids and solids (e.g., implants). Most implants used in veterinary medicine are compressed tablets or dispersed matrix systems in which the drug is uniformly dispersed in a non-degradable polymer or extruded product. In one embodiment, the compound of the present invention is administered subcutaneously.

[1643] Injectable preparations, such as sterile injectable aqueous or oily suspensions, can be formulated according to known techniques using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation can also be a sterile injectable solution, suspension or emulsion in a non-toxic parenterally acceptable diluent or solvent, such as a solution in 1,3-butanediol. Acceptable carriers and solvents that can be used include water, Ringer's solution and isotonic sodium chloride solution. In addition, sterile fixed oils are commonly used as a solvent or suspending medium. For this purpose, any mild non-volatile oil can be used, including synthetic mono- or di-glycerides of fatty acids. In addition, fatty acids such as oleic acid can be used in the preparation of injectables.

[1644] The injectable preparation can be sterilized, for example, by filtration through a bacteria-retaining filter, or by incorporating a sterilizing agent in the form of a sterile solid composition, which can be dissolved or dispersed in sterile water or other sterile injectable media before use.

[1645] To prolong the action of a drug, it is generally necessary to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be achieved by using a liquid suspension of a poorly water-soluble crystalline or amorphous material. The absorption rate of the drug depends on its dissolution rate, which in turn may depend on crystal size and crystal form. Alternatively, delayed absorption of a parenteral dosage form of a drug can be achieved by dissolving or suspending the drug in an oil vehicle. Injectable long-acting formulations are made by forming a microencapsulated matrix of the drug in a biodegradable polymer such as polylactic-co-glycolic acid. The drug release rate can be controlled according to the ratio of the drug to the pre-polymer and the nature of the specific polymer used. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Long-acting injectable formulations can also be prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues.

[1646] In a preferred embodiment of the present invention and / or its embodiments, dosage forms suitable for topical administration (also referred to as transdermal administration) of the compounds of the present invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants or patches. The active ingredient is mixed with a pharmaceutically acceptable carrier and any required preservatives or buffers under sterile conditions. Ophthalmic formulations, ear drops, etc. are also considered to be within the scope of the present invention.

[1647] In addition to the active compounds of the present invention, ointments, pastes, creams and gels may also contain excipients such as animal and vegetable fats, oils, waxes, paraffin wax, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silicic acid, talc and zinc oxide or mixtures thereof.

[1648] The compounds of the present invention can also be formulated as topical powders and sprays, which may contain excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances in addition to the compounds of the present invention.

[1649] Sprays may also contain conventional propellants such as chlorofluorocarbons.

[1650] Transdermal patches have the additional advantage of providing controlled delivery of the compound to the body. Such dosage forms can be prepared by dissolving or dispersing the compound in a suitable medium. Absorption enhancers can also be used to increase the flux of the compound through the skin.

[1651] The rate can be controlled by providing a rate-controlling membrane or by dispersing the compound in a polymer matrix or gel.

[1652] In a preferred embodiment of the present invention and / or its embodiments, dosage forms suitable for oral administration of the compounds of the present invention include orally disintegrating tablets (ODTs), films, sublingual drops, lozenges, effervescent oral tablets, toothpastes and mouthwashes.

[1653] In a preferred embodiment of the present invention and / or its embodiments, the dosage form for nasal administration of the compounds of the present invention includes a liquid spray or an inhalable dry powder. The liquid aerosol preparation can be mainly atomized into particle sizes that can be delivered to the terminal bronchioles and respiratory bronchioles.

[1654] The liquid aerosol and the inhalable dry powder preparation are preferably delivered through the bronchial tree to the terminal bronchioles and ultimately to the parenchymal tissue.

[1655] The aerosolized preparation of the present invention can be delivered using an aerosol-forming device, such as an injector, a vibrating perforated plate, or an ultrasonic nebulizer, preferably selected to allow the formation of aerosol particles having a mass median diameter mainly between 1 and 5 μm.

[1656] In addition, the preparation preferably has a balanced osmotic pressure ionic strength and chloride concentration and a minimum nebulizable volume capable of delivering an effective dose of the compound of the present invention to the infected part. In addition, the nebulized preparation preferably does not negatively impair the function of the airways and does not cause undesirable side effects.

[1657] Aerosolization devices suitable for administering the aerosol preparation of the present invention include, for example, jet, vibrating perforated plate, ultrasonic nebulizers, and electrically powered dry powder inhalers, which are capable of atomizing the preparation of the present invention into aerosol particles in the particle size range of 1 - 5 μm. In the present application, it mainly means that at least 70% but preferably more than 90% of all the generated aerosol particles are in the range of 1 to 5 μm. The jet nebulizer decomposes the liquid solution into aerosol droplets by air pressure. The vibrating perforated plate nebulizer works on the principle of using the acoustic vacuum generated by a rapidly vibrating perforated plate to extrude the solvent droplets through the perforated plate. The ultrasonic nebulizer works on the principle that the piezoelectric crystal shears the liquid into small aerosol droplets.

[1658] Depending on, for example, the route of administration, the concentration of the compound of the present invention in the dosage form can vary widely. Generally, the concentration of the compound of the present invention or its embodiments in the preparation according to the present invention or its embodiments is 1 to 70% by weight, based on the total weight of the preparation. In some embodiments, the concentration is from 1 to 50% by weight, or from 10 to 50% by weight. In other embodiments, the concentration is from 35 to 65% by weight, from 40 to 60% by weight, or about 50% by weight.

[1659] The preferred concentration of the compound of the present invention or its embodiments dissolved in drinking water is 0.01 to 0.05% by weight, especially 0.01 to 0.025%, and in feed it is 100 to 400 ppm (g / metric ton), especially 100 to 200 ppm.

[1660] In a preferred embodiment of the present invention or its embodiments, the veterinary pharmaceutical composition of the present invention and / or its embodiments comprises a therapeutically effective amount of the compound of the present invention and / or its embodiments as a single active agent.

[1661] In a preferred embodiment of the present invention or its embodiments, the veterinary pharmaceutical composition of the present invention and / or its embodiments comprises a combination of a therapeutically effective amount of the compound of the present invention and / or its embodiments with one or more other known active agents. These one or more other known active agents may have a spectrum similar to that of the compounds of the present invention to synergistically enhance the treatment of infections covered by the spectrum of the compounds of the present invention. Alternatively, when multiple organisms are suspected, these one or more other known active agents may have a different spectrum from that of the compounds of the present invention, where an active agent with a different spectrum may be required in addition to the compounds of the present invention. Treatment may include administering a composition having the compound of the present invention and one or more other known active agents, or administering the compound of the present invention, followed or preceded by the administration of one or more additional active agents.

[1662] For further aspects regarding the formulation of drugs and various excipients, see, for example, Gennaro, A.R. et al., eds., Remington: The Science and Practice of Pharmacy (Lippincott Williams & Wilkins, 20th Ed., 2000). In addition, formulation methods are well known in the art and are disclosed, for example, in Remington: The Science and Practice of Pharmacy, Mack Publishing Company, Easton, Pa., 19th Edition (1995).

[1663] As shown above, the compounds according to the present invention can be considered an "active" agent, which is considered a substance that inhibits the growth of worms such as Dirofilaria, particularly Dirofilaria immitis. The term "inhibiting growth" refers to a decrease in the growth rate of the worm population.

[1664] In a preferred embodiment, a compound according to the present invention is used for treating worm infections, such as infections caused by one or more worms selected from the following: a) cestodes: for example, Anoplocephala spp.; Dipylidium spp.; Diphyllobothrium spp.; Echinococcus spp.; Moniezia spp.; Taenia spp.; b) trematodes, for example, Dicrocoelium spp.; Fasciola spp.; Paramphistomum spp.; Schistosoma spp.; or c) nematodes, for example, Acanthocheilonema spp.; Ancylostoma 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.; Dictyocaulus spp.; Dracunculus spp.; Enterobius spp.; Filaroides spp.; Habronema spp.; Haemonchus spp.; Heterakis spp.; Hyostrongylus spp.; Meulleriusspp.; Necator spp.; Nematodirus spp.; Onchocerca spp.; Loa loa; Ostertagia spp.; Oxyuris spp.; Parascaris spp.; Stephanurus spp.; Strongylus spp.; Syngamus spp.; Toxocara spp.; Strongyloides stercoralis; Trichuris spp.; Trichostrongylus spp.; Triodontophorus spp.; Uncinaria spp.; and / or Wuchereria spp.; preferably nematodes; especially Dirofilaria spp.; Haemonchus spp.; Ascaris spp.; Strongylus spp.; especially Dirofilaria immitis.

[1665] It should be understood that the terms "treating" or "treatment" as used herein include prophylactic, remedial prophylactic, therapeutic or curative treatment. Prophylactic or remedial prophylactic treatment, i.e., deworming, is usually used to prevent worm infections, thereby controlling parasitic infections in animals. In addition, worms can infect humans and thus pose a threat to human health. Prophylactic treatment includes treatments carried out regularly, such as 1 - 6 times a year, or 2 - 4 times a year or 1 - 4 times a month, or even continuously through drinking water. Remedial prophylactic treatment includes treating all animals, for example, in the same area when some animals are diagnosed to prevent the spread of parasites to other animals. Remedial prophylaxis and prophylactic treatment may also occur seasonally, for example, when vectors are particularly active.

[1666] In therapeutic or curative treatment, the compound is administered after clinical diagnosis. In this method, the cost of the anthelmintic is reduced, and if only some animals are treated, the likelihood of selecting for drug resistance is significantly reduced, which will ensure the presence of a susceptible parasite population in the herd or flock. However, its disadvantage is that it requires regular testing, increasing labor input.

[1667] The present invention provides a compound according to the present invention or a veterinary pharmaceutical composition according to the present invention, which is used as a medicine. In a preferred embodiment, the compound according to the present invention or the veterinary pharmaceutical composition according to the present invention is suitable for use as a medicine for treating worm infections such as filariasis, especially heartworm disease.

[1668] The compound according to the present invention or the veterinary pharmaceutical composition according to the present invention is used for preparing a medicine. In a preferred embodiment, the compound according to the present invention or the veterinary pharmaceutical composition according to the present invention is used for preparing a medicine for treating worm infections such as filariasis, especially heartworm disease.

[1669] In addition, the present invention provides the use of a compound according to the present invention or a veterinary pharmaceutical composition according to the present invention in the preparation of a medicine.

[1670] In addition, the present invention provides the use of a compound according to the present invention or a veterinary pharmaceutical composition according to the present invention in the preparation of a medicine for treating worm infections such as filariasis, especially heartworm disease. Preferably, the compound of the present invention or the veterinary pharmaceutical composition according to the present invention is used for preparing a medicine for treating worm infections such as filariasis, especially heartworm disease.

[1671] In addition, the present invention provides a compound according to the present invention or a composition of the present invention for treating a disorder / disease caused by worms, preferably one or more worms selected from the following: a) cestodes: for example, Anoplocephala spp.; Dipylidium spp.; Diphyllobothrium spp.; Echinococcus spp.; Moniezia spp.; Taenia spp.; b) trematodes, for example, Dicrocoelium spp.; Fasciola spp.; Paramphistomum spp.; Schistosoma spp.; or c) nematodes, for example, Acanthocheilonema spp.; Ancylostoma 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.; Dictyocaulus spp.; Dracunculus spp.; Enterobius spp.; Filaroides spp.; Habronema spp.; Haemonchus spp.; Heterakis spp.; Hyostrongylus spp.; Muellerius spp.; Necator spp.; Nematodirus spp.; Onchocerca spp.; Loa loa; Ostertagia spp.; Oxyuris spp.; Parascaris spp.; Stephanurus spp.; Strongylus spp.; Syngamus spp.; Toxocara spp.; Trichuris spp.; Trichostrongylus spp.; Triodontophorus spp.; Uncinaria spp.; and / or Wuchereria spp.; more preferably nematodes, especially Dirofilaria spp.; Haemonchus spp.; Ascaris spp.; Strongylus spp. and Oesophagostomum dentatum, especially Dirofilaria immitis.

[1672] In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention or the composition of the present invention is used for treating worm infections, such as filariasis, especially heartworm disease. In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention or the composition of the present invention is used for treating a disorder / disease caused by a worm, wherein the worm is Dirofilaria, more particularly Dirofilaria immitis or Dirofilaria repens.

[1673] In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention or the composition of the present invention is used for treating blood coagulation disorders. In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention or the composition of the present invention is used for treating a disorder / disease caused by a worm, wherein the worm is Haemonchus and especially Haemonchus placei and Haemonchus contortus.

[1674] In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention or the composition of the present invention is used for treating ascariasis. In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention or the composition of the present invention is used for treating a disorder / disease caused by a worm, wherein the worm is Ascaridia galli.

[1675] In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention or the composition of the present invention is used for treating nodular nematodiasis. In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention or the composition of the present invention is used for treating a disorder / disease caused by a worm, wherein the worm is Oesophagostomum and especially Oesophagostomum venulosum and Oesophagostomum dentalum.

[1676] In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention or the composition of the present invention is used for treating trichostrongylosis. In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention or the composition of the present invention is used for treating a disorder / disease caused by a worm, wherein the worm is Trichostrongylus and especially Trichostrongylus axei and Trichostrongylus colubriformis.

[1677] In a preferred embodiment of the present invention or an embodiment thereof, the compounds according to the present invention or the compositions of the present invention are used for treating Ostertagia infection. In a preferred embodiment of the present invention or an embodiment thereof, the compounds according to the present invention or the compositions of the present invention are used for treating a disorder / disease caused by a worm, wherein the worm is of the genus Ostertagia and in particular Ostertagia ostertagi.

[1678] In a preferred embodiment of the present invention or an embodiment thereof, the compounds according to the present invention or the compositions of the present invention are used for treating Cooperia infection. In a preferred embodiment of the present invention or an embodiment thereof, the compounds according to the present invention or the compositions of the present invention are used for treating a disorder / disease caused by a worm, wherein the worm is of the genus Cooperia and in particular Cooperia oncophora.

[1679] In a preferred embodiment of the present invention or an embodiment thereof, the compounds according to the present invention or the compositions of the present invention are used for treating Nematodirus infection. In a preferred embodiment of the present invention or an embodiment thereof, the compounds according to the present invention or the compositions of the present invention are used for treating a disorder / disease caused by a worm, wherein the worm is of the genus Nematodirus and in particular Nematodirus helvetianus, Nematodirus spathiger.

[1680] It is expected that the compounds according to the present invention and compounds corresponding to the uses according to the present invention can be used for treating animals, including humans and non-human animals, especially non-human mammals. Such non-human mammals include, for example, domestic mammals (e.g., pigs, domestic ruminants such as cows, sheep, goats, etc.), laboratory mammals (e.g., mice, rats, gerbils, etc.), companion mammals (e.g., dogs, cats, horses, etc.), and wild and zoo mammals (e.g., buffalo, deer, etc.). It is expected that the compounds are also suitable for treating non-mammals such as poultry (e.g., t...

Claims

1. A compound of formula (I) wherein R 1 independently selected from: Hydrogen, C 1-6 -alkyl, halogen, Wherein C 1-6 - the alkyl group is optionally substituted by one or more substituents independently selected from halogen, R 7 independently selected from: methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylsulfinyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl; R 13 is hydrogen or C 1-3 alkyl group, R 14 is hydrogen or C 1-3 alkyl or R 13 and R 14 together with the atom(s) to which it is attached form an aromatic ring having 5 or 6 carbon atoms, wherein the ring having 5 or 6 carbon atoms is optionally substituted by one or more C 1-3 -alkyl groups, and / or wherein one or more of the carbon atoms forming the ring are optionally replaced by -NH-, -N=, =N-, -O- or -S- A1 is CR 15 , wherein R 15 is independently hydrogen, halogen, C 1-3 -alkyl, C 1-3 -alkoxy or NR 15’ R 15” , wherein R 15’ and R 15” are independently C 1-3 -alkyl, A2 is CR 16 , where R 16 is independently hydrogen, halogen, C 1-3 alkyl, C 1-3 alkoxy or NR 16’ R 16” , where R 16’ and R 16” are independently C 1-3 -alkyl, A3 is CR 17 , where R 17 is hydrogen, A4 is CR 18 , where R 18 is hydrogen, R 19 is C 6-10 -aryl, Wherein C 6-10 -aryl is a phenyl group optionally substituted by 1, 2 or 3 substituents independently selected from: F, Cl and Br; R 25 independently selected from hydrogen and C 1-6 -alkyl or a stereoisomer, physiologically acceptable salt and mixture thereof.

2. The compound according to claim 1, wherein R 1 is independently selected from: Hydrogen, methyl, trifluoromethyl, ethyl, F and Cl.

3. The compound according to claim 1, which exists in the form of the (S)-enantiomer.

4. A process for preparing a compound of formula (I) according to any one of claims 1 to 3, which comprises the steps of reacting a compound of formula (A) with a compound of formula (B), wherein R 1 、R 7 、R 13 、R 14 、A1, A2, A3, A4, R 19 and R 25 are as defined in any one of claims 1 to 3, to obtain a compound of formula (I).

5. A veterinary pharmaceutical composition comprising - a compound of formula (I) according to any one of claims 1 to 3, and - one or more physiologically acceptable excipients.

6. The veterinary pharmaceutical composition according to claim 5, wherein the one or more physiologically acceptable excipients are selected from carriers, fillers, flavoring agents, binders, antioxidants, buffers, sugar components, lubricants, surfactants, stabilizers, glidants, disintegrants and preservatives, and mixtures thereof.

7. Use of a compound of formula (I) according to any one of claims 1 to 3 or the veterinary pharmaceutical composition according to claim 5 or 6 in the manufacture of a medicament for the treatment of a disorder / disease caused by worms.

8. The use according to claim 7, wherein the disease is heartworm disease.

9. The use according to claim 7, wherein the worm is Dirofilaria immitis.

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