Anthelmintic compounds comprising quinoline structure

Abstract

To provide new anthelmintic compounds that can, for example, be used in the treatment of the kind of worm disease caused by helminths such as Dirofilaria, in particular Dirofilaria immitis.SOLUTION: There is provided a compound of Formula (I) or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph, prodrug and mixtures thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to novel anthelmintic compounds. These compounds are useful for, for example, treating dogs. Heartworms, especially Dirofilaria immitis It can be used to treat types of helminthiasis caused by helminths such as [Background technology]

[0002] Several important animal diseases are caused by helminths, which are of the following groups: a) Tapeworms For example, Anaplocephala species; Dipylidium ipylidium species; Diphyllobothrium genus Species: Echinococcus species; Moniezia ) species; Taenia species; b) Trematodes: e.g. Dicrocoelium coelium species; Fasciola species; Paramphistomum (P aramphistomum species; Schistosoma species; c ) nematodes, e.g. Acanthocheilonema Genus and species; Ancylostoma species; Anecator species; Ascaridia species; Ascaris species; Brugi Brugia species; Bunostomum species; Capillaria (C apillaria species; Chabertia species; Coupelia (C ooperia species; Cyathostomum species; Silicosik Cylicodontphorus species; Cylicodont ophorus species; Cylicostephanus species; Craterostomum species; Dictyocaulus ocaulus species; Dipetalonema species; Dirofilari Dirofilaria species; Dracunculus species; Enterobius species; Filaroides ) genus species; Habronema genus species; Haemonchus Genus and species: Heterakis; Hyostrogillus ylus species;Metastrongylus species;Metastrongylus Meullerius species; Necator species; Nematodirus Nematodirus species; Nippostrongylu s) genus and species; Oesophagostomum genus and species; Onchocerca Onchocerca species; Onchocercidae species ;Ostertagia species;Oxyuris species ; Parascaris species; Stephanuru s) genus species; Strongylus genus species; Syngamu Toxocara species; Strongyloides species loides species; Teladorsagia species; Toxascaly Toxascaris species; Trichinella species; Trichinella species Squirrel (Trichuris species); Trichostrongy lus genus species; Triodontophorous genus species; Un Uncinaria species and / or Wuchereria species They can be divided into species.

[0003] The above helminths cause helminthiasis, also known as parasitic infection. They often live in the digestive tract, but can also infiltrate other organs and cause physiological disorders there. For example, Ascaridia species can cause infections of the small intestine. It has been reported to cause partial or total obstruction of the digestive tract in affected animals, especially feathered animals such as birds. Furthermore, another helminth, Haemonchus species, is known to It is known to affect animals such as horses and goats, and such infestations occur by sucking blood from the host. This often results in the animal adhering to the abdominal mucosa, causing anemia and shortness of breath. In addition, Oesophagostomum species is known to form nodules in the intestine of infected hosts and can cause dysentery. There is.

[0004] In addition, canine heartworm disease, also known as cardiovascular dirofilariasis, is a disease that can infect pets and certain other animals. It is a severe and mostly fatal disease that can affect internal organs such as the lungs and heart of mammals. The disease is caused by parasitic lines that can be up to 30 cm long and about 1 mm thick in adult form. Dirofilaria immitis (Dirofilaria immitis) These nematodes attack the heart, lungs, and kidneys. It lives in the blood vessels that connect the body to the lungs and can cause severe lung disease, heart failure, and damage to internal organs such as the liver and kidneys. Therefore, heartworm infection can cause complications in the host, typically leading to the host's death. To make.

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

[0006] Heartworms must pass through different stages before becoming adults that can infect a host animal. Mosquitoes are required as intermediate hosts in the life cycle of heartworm. The female heartworm adults that live in the infected host are born as larvae. They are called microfilariae and can circulate in the bloodstream for as long as two years. , which are ingested by blood-sucking mosquitoes, which bite such infected hosts and take in blood. The mosquito then ingests the microfilariae, which then begin to develop inside the mosquito's body. The first and second larval stages (L1) and (L2) of heartworm development occur within the mosquito. The larvae mature into the third larval stage (L3), which is the infective stage, and then the mosquito finds a host. Upon biting, these infective larvae are deposited on the host's skin surface and move from the mosquito bite to a new host. They mainly penetrate and remain under the skin at the site of the bite. After a short further development period of about two weeks, the young The worms develop into the fourth larval stage (L4), chest or abdomen of muscle 45-60 days after infection The larvae develop into immature adults (fifth larval stage; L5) and live for 75-12 hours after infection (mosquito bite). At day 0, the immature heartworms enter the bloodstream and are transported to the heart and pulmonary system, where they subsequently It takes about three months for the worms to grow significantly. They reach adulthood within seven months of infection (mosquito bite). The worms have mated, and the females begin to produce the microfilariae described above. These worms can live for up to about 7 years in dogs and up to about 3 years in cats. Because of this, the number of heartworms in infected pets increases every mosquito season. This could result in: Summary of the Invention [Problem to be solved by the invention]

[0007] It has been reported that the extensive use of anthelmintic compounds has led to the development of highly resistant helminth populations. The development of such resistance to known anthelmintics has led to the failure of successful treatment of the disease. It is thought to be a major problem above.

[0008] WO2018 / 087036A1 and WO2019 / 025341A1 are both anthelmintics The present invention discloses a compound believed to be a quinoline 3-carboxamide derivative having the following structure: is doing. [ka] In the formula, the residue R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , A and Q are defined accordingly.

[0009] This molecule is thought to be a modulator of the Caenorhabditis elegans calcium-activated potassium channel slo-1. slo-1 is found to be a transcription factor for the KCNMA1 gene (KCa1.1 and KCNMA1 are often Human KCa1.1 channels (potassium calcium channels) encoded by It can be considered as a helminth orthologue of the calcium-activated channel subfamily Mα1. Slo-1 regulates calcium-activated potassium channel activity and voltage-gated potassium channels. The Slo-1 channel exhibits channel activity, particularly in the neuromuscular system and secretory cells. Therefore, Slo-1 modulators may improve the response to ethanol. It has been reported to be involved in several processes, including motor responses, locomotion, and pharyngeal pumping. More specifically, it inhibits neuromuscular transmission, causing flaccid paralysis and It affects feeding and egg-laying. In addition, it retards the development of larvae and adults of the corresponding helminths. .

[0010] Even so, helminths are still at high risk of developing intolerances, especially given the development of resistance to known anthelmintic compounds. There remains an urgent need for new active pharmaceutical ingredients that can combat infections caused by do.

[0011] SUMMARY OF THE INVENTION It is therefore an object of the present invention to overcome one or more of the shortcomings of the prior art.

[0012] To combat infectious diseases in mammals, especially pets such as cats and dogs, especially dogs The present invention aims to provide novel anthelmintic compounds that can be used in the treatment of parasitic worms. Insects, such as Ostertagia ostertagi ), Cooperia oncophora, Cooperia Cooperia punctata, Trichostrongylus axe Trichostrongylus axei, Haemonchus prasei (Haem onchus placei), Haemonchus contortus (Haemonchus c ontortus, Nematodirus hel vetianus), Nematodirus spathiger iger), Trichostrongylus colubriformis (Trichostrongy lus colubriformis, Trichostrongylus silkicinctus (Tr ichostrongylus circumcincta), Esophagostomum ve Oesophagostomum venulosum, Chabelcia o Chabertia ovina, Dictyocaulus biviparous yocaulus viviparous, Dictyocaulus filariasis (Dict yocaulus filaria), Dirofilaria immitis (Dirofila ria immitis), Dirofilaria repens pens);b) Flukes: Fasciola hepatica ), Fascioloides magna, Dicrochoe Dicrocoelium dentriticum, Para Paramphistomum cervi, c) Cestodes: Monezia expansai, especially Ascarizia Galli (Ascaridia galli), Haemonchus contortus (Haemonchus hus contortus), Esophagostomum dentatum (Oesophago stomum dentatum), and Acanthocheironema vitae (Acanth ocheilonema viteae) and Dirofilaria immitis (D Infection in mammals with irofilaria immitis, especially dirofilariasis Caused by Dirofilaria immitis (heartworm) The aim is to provide new anthelmintic compounds that can be used to combat infections. be.

[0013] Another object is to develop novel antimicrobial agents that can be used to combat infectious diseases in mammals. Insecticidal compounds, which compounds are effective in treating pets, particularly cats and dogs, especially dogs. The objective of the present invention is to provide anthelmintic compounds that are compatible with standard antiparasitic treatments. It can be used to treat infections in pets such as cats and dogs and is administered orally or It is an object to provide novel anthelmintic compounds that can be administered topically.

[0014] More specifically, infections in mammals by parasitic helminths, especially Dirofilaria immitis Treating infection with Dirofilaria immitis (dog heartworm) can be used to treat a variety of conditions, but do not adversely affect the host with unwanted side effects. It is an object to provide novel anthelmintic compounds.

[0015] Furthermore, the novel antiparasitic compounds can be administered in different treatment regimens, particularly monthly or longer treatment regimens. The purpose is to be able to use it in paintings. [Means for solving the problem]

[0016] Surprisingly, at least one of these objectives can be achieved by the compounds according to formula (I) or their derivatives. isomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs or It has been found that providing a mixture can be satisfactory. [ka]

[0017] During the ceremony, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3- 10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 Aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -alkoxy, C 1-6 -Alkyl mercapto, halogen, cyano, nitrite B, hydroxy, mercapto, NR 2 R 3 , COOH, C(=O)OR 4 , S.R. 4 , SO R 4 , SO2R 4 , SO2NR 5 R 6 and C(=O)NR 5 R 6 Independently selected from the group consisting of Selected, Each C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10 Aryl, 5-10 membered heteroaryl Lu, C 1-6 -alkoxy or C 1-6 -Alkyl mercapto C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -alkoxy, C 1-6 -Alkyl mercapto, halogen, cyano, nitrite B, hydroxy, mercapto, NR 2′ R 3′ , C(=O)OR 4′ , S.R. 4′ , SOR 4′ , SO2R 4′ , SO2NR 5′ R 6′ and C(=O)NR 5′ R 6′ A group consisting of may be substituted by one or more substituents independently selected from

[0018] R 2 and R 3 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3- 10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Lille, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -cycloalkyl Replaced C 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C6 -10 -aryl-substituted C 1-6 -substituted with alkyl and 5-10 membered heteroaryl C 1-6 -alkyl, or R 2 and R 3 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, and 0, 1, 2 or 3 further ring atoms are N , S and O; Each C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -substituted with cycloalkyl C 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6- 10 -aryl-substituted C 1-6 -substituted with alkyl or 5-10 membered heteroaryl C 1-6 -alkyl or R 2 and R 3 are formed together with the N atom to which they are attached The heterocycle is C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -Alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto , N.R. 2″ R 3″ , C(=O)OR 4″ , S.R. 4″ , SOR 4 , SO2R 4″ , SO2N R 5″ R 6″ and C(=O)NR 5″ R 6″one or more substituents independently selected from the group consisting of may be substituted with a substituent;

[0019] R 4 , R 5 and R 6 is hydrogen and C 1-6 -alkyl; R 2′ , R 3′ , R 4′ , R 5′ and R 6′ is hydrogen and C 1-6 -Independent of alkyl Selected by R 2″ , R 3″ , R 4″ , R 5″ and R 6″ is hydrogen and C 1-6 -Independent of alkyl Selected by

[0020] R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3- 10 -cycloalkyl, 4-10 membered heterocycle, C 6-10 Aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -alkoxy, C 1-6 -Alkyl mercapto, halogen, cyano, nitrite B, hydroxy, mercapto, NR 8 R 9 , COOH, C(=O)OR 10 , S.R. 10 , SOR 10 , SO2R 10 , SO2NR 11 R 12 and C(=O)NR 11 R 12 Because are independently selected from the group Each C 1-6-Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 4-10 membered heterocycle, C 6-10 Aryl, 5-10 membered heteroaryl Lu, C 1-6 -alkoxy or C 1-6 -Alkyl mercapto C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -alkoxy, C 1-6 -Alkyl mercapto, halogen, cyano, nitrite B, hydroxy, mercapto, NR 8′ R 9′ , C(=O)OR 10′ , S.R. 10′ , S OR 10′ , SO2R 10′ , SO2NR 11′ R 12′ and C(=O)NR 11′ R 1 2′ and optionally substituted with one or more substituents independently selected from the group consisting of:

[0021] R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3- 10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Lille, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10-cycloalkyl Replaced C 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C6 -10 -aryl-substituted C 1-6 -substituted with alkyl, 5-10 membered heteroaryl C 1-6 -alkyl, or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, and 0, 1, 2 or 3 further ring atoms are N , S and O; Each C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -substituted with cycloalkyl C 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6- 10 -aryl-substituted C 1-6 -substituted with alkyl or 5-10 membered heteroaryl C 1-6 -alkyl or R 8 and R 9 are formed together with the N atom to which they are attached The heterocycle is C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10-aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -Alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto , N.R. 8″ R 9″ , C(=O)OR 10″ , S.R. 10″ , SOR 10″ ,SO2R 10″ , SO2NR 11″ R 12″ and C(=O)NR 11″ R 12″ Independently selected from the group consisting of may be substituted with one or more substituents selected from the group consisting of aryl, ...

[0022] R 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen and C 1-6 -Alkyl are independently selected from R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -Alkyl are independently selected from

[0023] R 13 is hydrogen or C 1-3 is alkyl, R 14 is hydrogen, C 1-3 Alkyl, C 1-3 Alkoxy, NR 14′ R 14″ and R 14′ and R 14″ is independently C 1-3 -alkyl, or R 13 and R14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the ring containing 5 or 6 carbon atoms has one or more C 1-3 -alkyl or ═O, and / or the ring carbons One or more of -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S- may be replaced by, or R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the ring containing 5 or 6 carbon atoms has one or more C1 -3 and / or one or more of the ring carbons may be substituted by -alkyl. may be replaced by -NH-, -N=, =N-, -O- or -S-;

[0024] A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1- 3-alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C1 -3 -alkyl, A3 is N or CR 17 and R 17are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independently C 1- 3-alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen C 1-3 Alkyl, C1 -3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independently C 1- 3-alkyl,

[0025] R 19 is C 6-10 -independently from the group consisting of aryl and 5-10 membered heteroaryl Selected, Each C 6-10 -aryl or 5-10 membered heteroaryl, C 1-6 -Alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 5 ~10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, C 1-6 -Arco Kishi, C 1-6 -Alkyl mercapto, halogen, cyano, nitro, hydroxy, mercapto Puto, NR 20 R 21 , C(=O)OR 22 , S.R. 22 , SOR 22 , SO2R 22 , S O2NR 23 R 24 and C(=O)NR 23 R 24 One or more independently selected from the group consisting of may be substituted with the above substituents,

[0026] R 20 and R 21 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5-10 membered heteroaryl, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 6-10 - C1-C6-alkyl substituted with aryl, C substituted with 5-10 membered heteroaryl 1-6 -alkyl, or R 20 and R 21 have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C 1-6 -Alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 5 ~10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, C 1-6 -Arco Kishi or C 1-6 -alkylmercapto or R 20 and R 21 are the N to which they are bonded The heterocycle formed together with the atoms is C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -Alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto , N.R. 20′ R 21′ , C(=O)OR 22′ , S.R. 22′ , SOR 22′ , SO2R 2 2′ , SO2NR 23′ R 24′ and C(=O)NR 23′ R 24′ Independent from the group consisting of and optionally substituted with one or more substituents selected from

[0027] R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -Arki are independently selected from the R 25 is hydrogen and C 1-6 -alkyl.

[0028] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Droxi, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R 6 Independent from the group consisting of Selected by Each C 1-6 -alkyl or C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Roxy and NR 2′ R 3′ substituted with one or more substituents independently selected from the group consisting of It may be R 2 and R 3 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and and 5- to 10-membered heteroaryl, or R 2 and R 3 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- Aryl or 5-10 membered heteroaryl or R 2 and R 3 are formed along with the N atoms to which they are attached The heterocycle is C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -Alkoxy? and optionally substituted with one or more substituents independently selected from the group consisting of: R 4 , R 5 and R 6 is hydrogen and C 1-6 -alkyl; R 2′ and R 3′ is hydrogen and C 1-6 -alkyl.

[0029] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by Each C 1-6 -alkyl or C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2′ R 3′ may be substituted with one or more substituents independently selected from the group consisting of Ku, R 2′ and R 3 ′ is hydrogen and C 1-3 -alkyl.

[0030] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride.

[0031] In one embodiment of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8 R 9 , C(=O)OR 10 , S.R. 10 , SOR 10 , SO2R 10 and C(=O)NR 11 R 12 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C2-6-alkenyl, C3-10 -cycloalkyl, 4 ~10-membered heterocycle or C 1-6 -alkoxy is C 1-6 -Alkyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 1- 6-alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ , C(=O)OR 10 ′ , and C(=O)NR 11′ R 12′ one or more substituents independently selected from the group consisting of may be substituted with R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, independently selected from the group consisting of 5- to 10-membered heterocycle and 5- to 10-membered heteroaryl; or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- Aryl, 5~ 10-membered heterocycle, and 5-10-membered heteroaryl or R 8 and R 9 But they are combined The heterocycle formed together with the N atom is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy, N R 8″ R 9″ , C(=O)-OR 10″and C(=O)NR 11″ R 12″ A group consisting of may be substituted with one or more substituents independently selected from: R 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen and C 1-6 -Alkyl are independently selected from R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -Alkyl are selected independently.

[0032] In one embodiment of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-6 - Alkoxy, hydroxy, NR 8 R 9 , C(=O)OR 10 , S.R. 10 , SOR 10 , S O2R 10 and C(=O)NR 11 R 12 are independently selected from the group consisting of: Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-6 - Alkoxy is C 1-6 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, chlorine Ano, Hydroxy, NR 8′ R9′ , C(=O)OR 10′ and C(=O)NR 11′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl, and 5- to 10-membered heteroaryl or is R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of: R 10 , R 11 and R 12 is hydrogen or C 1-6 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-6 -Alkyl are independently selected.

[0033] R 8″ and R9″ is hydrogen or C 1-6 -alkyl. In one embodiment of the present invention and / or embodiments thereof, R 7 teeth, Methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, Isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, Dimethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydro (methoxyethyl)(methyl)aminomethoxyethylamino, (methoxyethyl)(methyl) Amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine- From the group consisting of 1-yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl are independently selected.

[0034] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the ring containing 5 or 6 carbon atoms has one or more C 1-3 -alkyl or ═O, and / or the ring carbons One or more of -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S- may be replaced by A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C1 -3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independently C1 -3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen C 1-3 Alkyl, C1 -3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independently C 1- It is 3-alkyl.

[0035] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the ring containing 5 or 6 carbon atoms has one or more C1 -3 and / or one or more of the ring carbons may be substituted by -alkyl. may be replaced by -NH-, -N=, =N-, -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C1 -3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independently C1 -3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen C 1-3 Alkyl, C1 -3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independently C 1- It is 3-alkyl.

[0036] In one embodiment of the present invention and / or embodiments thereof, 0, 1 or 2 residues of A1, A2, A3 and A4 are N.

[0037] In one embodiment of the present invention and / or embodiments thereof, A1 is CR 15 and A2 is CR 16 and A3 is CR 17 and A4 is CR 1 8 is.

[0038] In one embodiment of the present invention and / or embodiments thereof, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5-10 membered heteroaryl, C 1-6 -Alkyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 6- 10 -aryl, 5-10 membered heteroaryl, C 1-6 -Alkoxy, halogen, cyano , nitro, hydroxy, NR 20 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24 and optionally substituted with one or more substituents independently selected from the group consisting of: R 20 and R 21 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 6-10 -aryl or R 20 and R 21 have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl or C 6-10 -aryl or R 20 and R 21 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 6-1 0-aryl, 5-10 membered heteroaryl, C 1-6 -alkoxy, halogen, cyano, Hydroxy, NR 20′ R 21′ , C(=O)OR 22′ and C(=O)NR 23′ R 2 4′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -Arki are selected independently from the

[0039] In one embodiment of the present invention and / or embodiments thereof, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5-10 membered heteroaryl, C1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of hydroxy.

[0040] In one embodiment of the present invention and / or embodiments thereof, R 19 is C 6-10 -aryl, wherein C 6-10 -aryl is C 1-6 -independently selected from the group consisting of alkyl, halogen, cyano and nitro It may be substituted with one or more substituents.

[0041] In one embodiment of the present invention and / or embodiments thereof, R 19 is C 6-10 -aryl, wherein C 6-10 -aryl is one, two or more independently selected from the group consisting of fluoride, chloride and bromide; Preferably, it is phenyl substituted with three substituents.

[0042] In one embodiment of the present invention and / or embodiments thereof, R 25 is hydrogen.

[0043] In one embodiment of the present invention and / or embodiments thereof, the compound according to formula (I) The product exists in the form of the (S)-enantiomer.

[0044] Furthermore, the present invention provides a method for producing a compound according to formula (I), comprising the steps of: Compounds of formula (A): [ka] to a compound of formula (B): [ka] [R1 , R 7 , R 13 , R 14 , A1, A2, A3, A4, R 19 and R 25 is this specification ] to form a compound of formula (I) The present invention provides a method for producing a compound comprising the steps of:

[0045] Furthermore, the present invention provides a compound according to formula (I) as defined in any one of the embodiments described herein, and -One or more physiologically acceptable excipients The present invention provides a veterinary drug composition comprising:

[0046] In one embodiment of the present invention and / or embodiments thereof, said one or more physiologically acceptable The excipients used include carriers, fillers, flavoring agents, binders, antioxidants, buffers, sugar components, lubricants, It is selected from surfactants, stabilizers, flow agents, disintegrants and preservatives and mixtures thereof.

[0047] Furthermore, the present invention relates to a method for treating a rheumatoid arthritis, ... There is provided a compound according to formula (I) as defined above or a veterinary composition according to the invention.

[0048] Furthermore, the present invention relates to a method for treating disorders / diseases caused by helminths, comprising: There is provided a compound according to formula (I) or a veterinary composition according to the invention.

[0049] In one embodiment of the invention and / or embodiments thereof, the disease is filariasis, in particular The disease is canine heartworm disease.

[0050] In one embodiment of the invention and / or embodiments thereof, the helminth is Dirofilaria -Immitis (Dirofilaria immitis). DETAILED DESCRIPTION OF THE INVENTION

[0051] Compounds according to formula (I) or stereoisomers, physiologically acceptable salts, esters, solvates, Polymorphs, prodrugs and mixtures thereof are available from Ostertagia ostertagii (Oste rtagia ostertagi), Cooperia oncophora (Cooperia oncophora), Cooperia punctata ), Trichostrongylus axei , Haemonchus placei, Haemonchus contortus Haemonchus contortus, Nematogyrus helveticus (Nematodirus helvetianus), Nematodirus spathiger (N ematodirus spathiger), Trichostrongylus colubrillus Miss (Trichostrongylus colubriformis), Tricost Trichostrongylus circumcinctus cta), Oesophagostomum venulosum (Oesophagostomum venulosum ulosum), Chabertia ovina, Dictyo Dictyocaulus viviparous, Dictyocaulus viviparous Dictyocaulus filaria, Dirofilaria Dirofilaria immitis, Dirofilaria repens b) Trematodes: Fasciola hepatica (F asciola hepatica, Fascioloides magna (Fascioloi des magna), Dicrocoelium dentriticum (Dicrocoelium dentriticum), Paramphistomum cervi (Paramphistom um cervi), c) Cestodes: Monezia expansa nsa), especially Ascaridia galli, Haemonchus Haemonchus contortus, Esophagostomum by helminths such as Oesophagostomum dentatum and Dirofilaria immitis It has been found that the present invention is useful in the treatment of disorders / diseases caused by the The compounds and / or any of their embodiments are useful in treating helminth infections, such as filariasis and and in particular in the treatment of canine heartworm disease. Any of these embodiments may be directed against helminths, such as nematodes, and in particular Dirofilaria immichii. Treatment of disorders / diseases caused by Dirofilaria immitis It is useful in the treatment of Dirofilaria immitis. The disorder / disease caused by Dirofilariasis is heartworm disease.

[0052] Advantageously, the compounds according to the invention and / or any of their embodiments are Zilof Against helminths such as Dirofilaria immitis Although effective, bacteria that are particularly relevant to mammalian health, especially canine health, such as Acinetobacter Acinetobacter baumannii (Acinetobacter b aumaii or Staphylococcus species or Staphylococcus It is not effective against Streptococcus species.

[0053] The present inventors believe that the compounds of the present invention will satisfy such a need and therefore be useful in treating canine heartworm disease and other diseases. have been shown to be very useful in the treatment (and prevention) of diseases caused by helminths. Found it.

[0054] The following abbreviations and definitions are used throughout this application:

[0055] Generally, when a particular element is mentioned, the reference includes all isotopes of that element. For example, if a group is defined as including hydrogen or If the residue contains H, it also includes deuterium and tritium.

[0056] "C 1-6 The term "-alkyl" refers to alkyl groups having 1 to 6 carbon atoms and no heteroatoms. Thus, the term refers to alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, propyl, propyl, pentyl ... Thus, the term includes straight chain alkyl groups such as methyl, ethyl, and hexyl. The term also includes straight chain alkyl groups such as propyl, butyl, pentyl, and hexyl. It also includes branched isomers of straight chain alkyl groups, such as, for example, -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 and Others include, but are not limited to, the following. 1-6 -Alkyl The term "alkyl" refers to a primary alkyl group having 1 to 6 carbon atoms, a primary alkyl group having 3 to 6 carbon atoms, These include secondary alkyl groups having 4 to 6 carbon atoms and tertiary alkyl groups having 4 to 6 carbon atoms.

[0057] In response, "C 1-3 The term "-alkyl" refers to 1 to 3 alkyl groups containing no heteroatoms. Thus, the term includes methyl, ethyl, and propyl. The term also includes branched isomers of straight chain alkyl groups. , i.e., CH(CH3)2. Therefore, "C 1-3 The term "-alkyl" refers to ~ Primary alkyl groups having 3 carbon atoms and secondary alkyl groups having 3 carbon atoms Includes.

[0058] "C 2-6 The term "alkenyl" refers to an alkenyl group having at least one double bond between two carbon atoms. Except for the fact that it exists between 2-6 -alkyl" It refers to straight-chain and branched alkenyl groups. Examples include, among others, -CH=CH2, -C(CH3)= CH2, -CH=CH(CH3), -CH=C(CH3)2, -CH=CH(CH3), -C(CH3)=CH(CH3), -C(CH2CH3)H=CH2, -CH2=CH( CH2CH3), -CH2CH2-CH=CH2, CH2CH2-C(CH3)=CH2 , CH2CH2-CH=C(CH3)H, -CH=CH-(CH2)2CH3, -CH= C(CH3)-CH2CH3, -(CH2)3-CH=CH2, -(CH2)4-CH= CH2, -(CH2)2-CH=C(CH3)2, butadienyl, pentadienyl, and Examples include, but are not limited to, hexadienyl.

[0059] "C 2-6 The term "alkynyl" refers to a group of carbon atoms having at least one triple bond. Except for the fact that it exists between 2-6 -alkyl" It refers to straight-chain and branched alkynyl groups. Examples include, among others, -C≡CH, -C≡CCH3, - C≡C-CH2CH3, -CH2-C≡CH, -CH(CH3)-C≡CH, -C(CH 3)2-C≡CH, -CH2-C≡CCH3, -CH(CH3)-C≡CCH3, -C( CH3)2-C≡CCH 3、 -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., but are not limited to these. It's not that.

[0060] "C 3-10 The term "-cycloalkyl" refers to a non-aromatic alkyl group having 3 to 10 carbon atoms. It refers to an aromatic monocyclic alkyl group or a non-aromatic polycyclic alkyl group having 3 to 10 carbon atoms. The group consists of only carbon and hydrogen atoms. Cycloalkyl is a group containing 3 to 10 carbon atoms. The aromatic hydrocarbon group may include fused or bridged ring systems having 3 to 10 carbon atoms. Cyclic alkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. , cycloheptyl, cyclooctyl, etc., but are not limited to these. Non-aromatic polycyclic alkyl groups having up to 10 carbon atoms include adamantane. ntine), norbornane, decalinyl, 7,7-dimethyl-bicyclo[2.2.1] Heptanyl, but not limited to.

[0061] The term "5- to 10-membered heterocycle" refers to a ring in which 5 to 10 members (atoms) form a skeleton, and The skeleton 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 term "5- to 10-membered heterocyclic ring" refers to a fused system. or bridged systems, and may be monocyclic, bicyclic or polycyclic groups, Part of the ring system may be aromatic; nitrogen, carbon or sulfur in a "5- to 10-membered heterocycle" the nitrogen atom may be oxidized; the nitrogen atom may be quaternized; and the heterocyclic residue The radicals of the group can be partially saturated.

[0062] Examples of heterocyclic rings include pyrrolinyl, 3H-pyrazolyl, and 4H-pyrazolyldihydropyridyl. , pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, homopiperazinyl, Indolinyl, quinuclidinyl, morpholinyl, thiomorpholinyl thiazolidinyl, dihydrochloride Dihydrodithionyl, dihydrodithionyl, tetrahydrothiophene, tetrahydrothiopyra benzothiazinyl, e.g. 2H-1,4-benzothiazinyl, dihydrobenzothiazinyl 2H-3,4-dihydrobenzothiazinyl, benzodioxolyl, e.g., 1 ,3-benzodioxoyl, dihydrooxathiinyl, 1,4-oxathianyl, etc. Further examples of heterocyclic groups include, but are not limited to, heterocyclic groups containing one or more S in the ring. Atoms double-bonded to one or two oxygen atoms (sulfoxides and sulfones) The above-mentioned compounds, for example, tetrahydrothiophene, tetrahydrothiophene oxide, and and tetrahydrothiophene-1,1-dioxide and thiomorpholine, Examples include, but are not limited to, thiomorpholine-1,1 dioxide and thiomorpholine-1,1 dioxide. It's not that.

[0063] "C 6-10 The term "aryl" refers to an aromatic group in which the ring atoms of the aromatic backbone are carbon atoms. It refers to a group having a cyclic skeletal structure. 6-10 "Aryl" refers to the aromatic skeleton structure does not contain heteroatoms such as N, S, or O.

[0064] Examples of aryl groups include, but are not limited to, phenyl, biphenyl, and naphthyl. It is not something that is done.

[0065] The term "5- to 10-membered heteroaryl" refers to a heteroaryl having 5 to 10 members (atoms) forming a backbone and The skeleton of the cyclic compound contains at least one carbon atom and at least one heteroatom. Refers to an aromatic group. Examples of heteroatoms include, but are not limited to, N, O, and S. Unless otherwise specifically stated in this specification, the term "5- to 10-membered heterocycle" refers to a single ring. It can be a cyclic, bicyclic or polycyclic group, which can include fused ring systems.

[0066] Examples of 5- to 10-membered heteroaryl groups include pyrrolyl, imidazolyl, pyrazolyl, pyridyl pyrimidyl, pyrazinyl, pyridazinyl, triazolyl, e.g., 1H-1,2,3- Triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl and 4H-1,2,4-triazlyl, tetrazolyl, e.g., 1H-tetrazolyl Tolazolyl, 2H-tetrazolyl and 5H-tetrazoyl, India aryl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, quinolyl , isoquinolyl, indazolyl, naphthyridinyl, benzotriazolyl, oxazolyl, Isoxazolyl, oxadiazolyl, for example 1,2,4-oxadiazolyl, 1,3, 4-oxadiazolyl, 1,2,5-oxadiazolyl, benzoxazolyl, benzo thiadiazolyl, benzoxazinyl, e.g., 2H-1,4-benzoxazinylthiazolyl thiadiazolyl, isothiazolyl, thiadiazolyl, for example 1,2,3-thiadiazolyl, 1,2, 4-Thiadiazolyl, 1,3,4-Thiadiazolyl, 1,2,5-Thiadiazolyl, Thie nyl, benzothiazolyl, benzothiadiazolyl, benzothiazinyl, benzofuranyl, Quinolinyl, isoquinoline, cinnolinyl, quinaxolinyl )Quinoxalinyl, triazinyl, tetrazinyl, purinyl, pteridinyl, furyl, benzyl Benzodioxolyl, for example 1,3-benzodioxolyl, benzothienyl, benzodithiyl Examples include, but are not limited to, benzoxathiinyl and benzoxathiinyl.

[0067] "C 1-6 The term "alkoxy" refers to a group having 1 to 6 carbon atoms attached to an oxygen atom. It refers to a group based on an alkyl group. An alkyl group having 1 to 6 carbon atoms is as defined above. "C 1-6 -alkyl" refers to straight and branched chains such as those described for "-alkyl".

[0068] Correspondingly, "C 1-3The term "-alkoxy" refers to a 1-3 carbon atom attached to an oxygen atom. The alkyl group having 1 to 3 carbon atoms is defined as The above definition of "C 1-3 -alkyl" refers to straight and branched chains such as those described for "-alkyl".

[0069] "C 1-6 The term "-alkylmercapto" refers to a group of 1 to 6 carbon atoms attached to a sulfur atom. The alkyl group having 1 to 6 carbon atoms is a group based on the above alkyl group. Defined in "C 1-6 -alkyl" refers to straight and branched chains such as those described for "-alkyl".

[0070] "Optionally substituted" means that one or more hydrogen atoms of a group are substituted with one or more of the defined substituents. Refers to any substitution.

[0071] Further amine, hydroxyl and mercapto groups can be protected. The term "protected" in this context refers to a group that is protected to prevent undesired reactions. Such a protecting group refers to a form of these functional groups that has a protective group. Groups in Organic Synthesis;Wuts, PG M., John Wiley & Sons, New York, NY, (5 3 th Protecting groups are known to those skilled in the art from the literature (Eds. 1999, 1:100-110, 1999, pp. 111-114). These can be added or removed using the procedures described in .

[0072] Examples of protected hydroxyl groups include t-butyldimethyl-chlorosilane, trimethyl Chlorosilanes, triisopropylchlorosilane, triethylchlorosilane, etc. (These silyl ethers, such as, but not limited to, those obtained by reaction with reagents such as: Methoxymethyl ether, methylthiomethyl ether, benzyloxymethyl ether, t-Butoxymethyl ether, 2-methoxyethoxymethyl ether, tetrahydropyridine 1-ethoxyethyl ether, allyl ether, benzyl ether, etc. Substituted methyl and ethyl ethers of (including but not limited to); Benzoyl formate, formate, acetate, trichloroacetate and trichloroacetate and esters such as, but not limited to, trifluoroacetic acid esters. However, the present invention is not limited to these.

[0073] Examples of protected amine groups include formamide, acetamide, trifluoroacetamide, amides such as phthalimide and dithiosuccinimide; imides such as phthalimide and dithiosuccinimide carbamates such as tert-butyloxycarbonyl (Boc) and others However, it is not limited to these.

[0074] Examples of protected mercapto groups include S-benzyl thioether and S-4-picolyl. thioethers such as thioethers; substituted thioethers such as hemithio, dithio and aminothioacetals; Examples include, but are not limited to, substituted S-methyl derivatives and others.

[0075] Stereoisomers consist of the same atoms joined in the same order, but with the atoms spaced apart. Stereoisomers include compounds in which the nuclei are in different positions. Includes.

[0076] "Physiologically acceptable salts" include salts of inorganic bases, organic bases, inorganic acids, organic acids, or basic or is referred to as a salt with an acidic amino acid.

[0077] Examples of suitable inorganic acids for forming (physiologically acceptable) salts include hydrochloric acid, hydrobromic acid, iodine, and the like. These include, but are not limited to, hydrochloric acid, nitric acid, carbonic acid, sulfuric acid, and phosphoric acid. stomach.

[0078] Examples of organic acids suitable for forming (pharmaceutically acceptable) salts include 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, Chloric acid, maleic acid, fumaric acid, pyruvic acid, aspartic acid, glutamic acid, benzoic acid Acid, anthranilic acid, mesylic acid, stearic acid, salicylic acid, p-hydroxybenzoic acid, Phenylacetic acid, mandelic acid, embonic acid, ethanesulfonic acid, benzenesulfonic acid, toluene ethanesulfonic acid, pantothenic acid, 2-hydroxyethanesulfonic acid, sulfanilic acid, Cyclohexylaminosulfonic acid, β-hydroxybutyric acid, galactaric acid, galacturonic acid, Adipic acid, alginic acid, butyric acid, camphoric acid, camphorsulfonic acid, cyclopentane Propionic acid, dodecyl sulfate, glycoheptanoic acid, glycerophosphate, heptanoic acid, hexa nicotinic acid, 2-naphthalenesulfonic acid, oxalic acid, palmoic acid , pectic acid, 3-phenylpropionic acid, picric acid, pivalic acid, thiocyanic acid, tocopherol acidic amino acids such as aspartic acid and glutamic acid. However, it is not limited to these.

[0079] Examples of base addition salts may include, for example, metallic salts and organic salts.

[0080] Metal salts include alkali metal (group Ia) salts, alkaline earth metal (group IIa) salts, and other organic salts. Such salts include, but are not limited to, physiologically acceptable metal salts. Examples are aluminum, calcium, lithium, magnesium, potassium, sodium and For example, the free acid compound can be mixed with sodium hydroxide and They can form base addition salts such as:

[0081] The organic salts are trimethylamine, diethylamine, N,N'-dibenzylethylenediamine, amine, chloroprocaine, ethanolamine, diethanolamine, ethylenediamine, N -methylglucamine, procaine and basic amino acids such as arginine, lysine and oleic acid It can be prepared from amines such as lunithine.

[0082] As used herein, the term "pharmaceutically acceptable ester" refers to an in vivo It refers to an ester that is easily hydrolyzed in the human body to give the parent compound or its salt. Suitable ester groups include, for example, pharmaceutically acceptable aliphatic carbohydrates. derived from carboxylic acids, especially alkanoic acids, alkenoic acids, cycloalkanoic acids and alkanediacids and the like, each alkyl or alkenyl moiety advantageously having 6 or fewer carbon atoms. Representative examples of specific esters include formates, acetates, and propionates. esters, butyrate esters, acrylate esters, and ethylsuccinate esters. However, the present invention is not limited to these.

[0083] 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 known to those skilled in the art. When water is added to a compound, the corresponding compound is known as a hydrate.

[0084] The term "polymorph" as used herein, and as commonly understood by those skilled in the art, The term refers to different crystalline forms of the same molecular entity. Thus, due to their different chemical compositions, Solvates and hydrates of the compound are not included in the definition of polymorphs, but are instead referred to as "pseudopolymorphs." It is called.

[0085] The term "prodrug" refers to a drug that is rapidly degraded in vivo, for example by hydrolysis in blood. It refers to compounds that are converted to yield the parent compound of formula (I) above. A detailed discussion is given in T. Hig uchi and V. Stella, Pro-drugs as Novel D elivery Systems, Vol. 14 of the ACS Symposium Series and Edward B. Roche, ed., Bioreversible Carriers in Drug Design, American Pharmaceutical Association and Pergamon Press, 1987.

[0086] As used herein, the term "pharmaceutically acceptable prodrug" means a within the bounds of sound medical judgment, without excessive toxicity, irritation, or allergic reaction to humans. Suitable for use in contact with tissues of animals and lower animals, and is commensurate with a reasonable benefit / risk ratio. and prodrugs of the compounds of the present invention that are effective in their intended uses, as well as potential Where possible, the term refers to the zwitterionic form of the compounds of the present invention.

[0087] The present invention is 1 is defined as above, and / or an embodiment thereof Provides form.

[0088] In an embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Droxi, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R 6 Independent from the group consisting of Selected by Each C 1-6 -alkyl or C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Roxy and NR 2′ R 3′ substituted with one or more substituents independently selected from the group consisting of It may be R 2 and R 3 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and and 5- to 10-membered heteroaryl, or R 2 and R 3 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Each C 1-6-Alkyl, C 3-10 -cycloalkyl, C 6-10- Aryl or 5 ~10-membered heteroaryl or R 2 and R 3 are formed with the N atoms to which they are attached The heterocycle is C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -Alkoxy may be substituted with one or more substituents independently selected from the group consisting of R 4 , R 5 and R 6 is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1- 3-alkyl; R 2′ and R 3′ is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1-3 -alkyl.

[0089] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth,

[0090] Hydrogen, C 1-6 -Alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and C (=O)NR 5 R 6 are independently selected from the group consisting of: Each C 1-6 -alkyl or C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydro KI and NR 2 ′R 3 substituted by one or more substituents independently selected from the group consisting of It may be R 5 and R 6 is hydrogen and C 1-3 -alkyl; R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl.

[0091] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - independently selected from the group consisting of alkoxy and halogen Selected, C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxy and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of , R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are selected independently from the In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chlorine and independently selected from the group consisting of:

[0092] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iai): (Iaii), (Iaiii), (Iaiv), (Iav) or (Iavi) [ka] TIFF2025134777000006.tif222152TIFF2025134777000007.tif57149, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 7 , R 13 , R 14 , A1, A2, A3, A4, R 19 and R 25 is defined as in any of the embodiments described herein.

[0093] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iai) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Iaii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Iaiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iaiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I av), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Iavi) and preferably in the form of the (S)-enantiomer.

[0094] The present invention is 7 is defined as above, and / or an embodiment thereof Provides form.

[0095] In an embodiment of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4 10-membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8 R 9 , C (=O)OR 10 , S.R. 10 , SOR 10 , SO2R 10 and C(=O)NR 11 R 12 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4 10-membered heterocycle or C 1-6 -alkoxy is C 1-6 -Alkyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 12′ and substituted with one or more substituents independently selected from the group consisting of It may be replaced, R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, independently selected from the group consisting of 5- to 10-membered heterocycle and 5- to 10-membered heteroaryl; or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 10-membered heterocycle or 5-10-membered heteroaryl or R 8 and R 9 But they are combined The heterocycle formed together with the N atom is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy, N R 8″ R 9″ , C(=O)OR 10″ and C(=O)NR 11″ R 12″ From the group consisting of optionally substituted with one or more independently selected substituents; R 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen and C 1-6 -Alkyl are independently selected from R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -Alkyl are independently selected.

[0096] In an embodiment of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-6 -a Alkoxy, Hydroxy, NR 8 R 9 , C(=O)OR 10 , S.R. 10 , SOR 10 , SO 2nd Round 10 and C(=O)NR 11 R 12 are independently selected from the group consisting of: Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-6 -a Lucox is C 1-6 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, sia No, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 1 2′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6-Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of: R 10 , R 11 and R 12 is hydrogen or C 1-6 - alkyl, preferably hydrogen or C 1-3 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-6 -Alkyl and preferably hydrogen or C 1-3 -alkyl; R 8″ and R 9″ is hydrogen or C 1-6 -alkyl, preferably hydrogen or C 1-3 -alkyl.

[0097] In an embodiment of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 -a Alkoxy, Hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 A group consisting of are independently selected from Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 -a Lucox is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, sia No, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 1 2′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of: R 10 is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl Selected to be a R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl. In an embodiment of the present invention and / or embodiments thereof, R 7 is methyl, ethyl, Pyr, isopropyl, isopropenyl methoxy, ethoxy, isopropoxy, hydroxy , methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethyl Amino, (ethyl)(methyl)amino, isopropylamino, dimethylamino, (isopropyl (hydroxyethyl)(methyl)amino, hydroxyethylamino, (hydroxyethyl)(methyl) Amino, methoxyethylamino, (methoxyethyl)(methyl)amino, morpholine-4 -yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoro independently selected from the group consisting of azetidinyl and 3,3-difluoroazetidinyl.

[0098] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ibi): (Ibii)(Ibiii).(Ibiv), (Ibv)(Ibvi), (Ibvii) , (Ibviii)(Ibix), (Ibx), (Ibxi) or (Ibxii) [ka] TIFF2025134777000009.tif212156TIFF2025134777000010.tif244158TIFF2025134777000011.tif119150, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 , R 13 , R 14, A1, a2, A3, A4, R 19 and R 25 is defined as in any of the embodiments described herein.

[0099] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Ibi) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Ibii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Ibiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Ibiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I bv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Ibvi): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Ibvii), preferably In the form of the (S)-enantiomer. wherein the compound is according to formula (Ibviii), preferably an (S)-enanthate In an embodiment of the present invention and / or embodiments thereof, the compound The product is according to formula (Ibix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Ibx) and preferably in the form of the (S)-enantiomer. and / or in an embodiment thereof, the compound is according to formula (Ibxi): It is preferably in the form of the (S)-enantiomer. In an embodiment, the compound is according to formula (Ibxii), preferably (S) - in the form of enantiomers.

[0100] The present invention is 13 and R 14 and A1, A2, A3, A4 are defined as above , provide compounds according to the invention and / or embodiments thereof.

[0101] In an embodiment of the present invention and / or in an embodiment thereof, R 13 is hydrogen or C 1-3 is alkyl, R 14 is hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0102] More preferably, in accordance with the present invention and / or embodiments thereof: R 13 is hydrogen or C 1-3 is alkyl, R 14 is hydrogen or C 1-3 It is alkyl.

[0103] More preferably, in accordance with the present invention and / or embodiments thereof: R 13 is hydrogen, methyl or ethyl, preferably hydrogen or methyl, R 14 is hydrogen or methyl, preferably hydrogen.

[0104] A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independently C 1-3 - alkyl.

[0105] More preferably, in accordance with the present invention and / or embodiments thereof: R 13 is hydrogen or C1-3 alkyl, and R 14 is hydrogen or C 1-3 With alkyl can be, A1 is N or CR 15 and R 15 are independently hydrogen, C 1-3 Alkyl, C 1-3 a It is alkoxy A2 is N or CR 16 and R 16 are independently hydrogen, C 1-3 Alkyl, C 1-3 a It is alkoxy A3 is N or CR 17 and R 17 are independently hydrogen, C 1-3 Alkyl, C 1-3 a It is alkoxy A4 is N or CR 18 and R 18 are independently hydrogen, C 1-3 Alkyl, C 1-3 a It is alkoxy 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0106] More preferably, in accordance with the present invention and / or embodiments thereof: R 13 is hydrogen, methyl or ethyl, preferably hydrogen or methyl, and R 14 is water hydrogen or methyl, preferably hydrogen; A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 is alkyl, A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 is alkyl, A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3is alkyl, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 is alkyl, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0107] In another embodiment of the present invention and / or in embodiments thereof, A1 is CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl, C1 -3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A2 is CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl, C1 -3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is CR 17 and R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 Al It is Kokish A4 is CR 18 and R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 Al This is Koxi.

[0108] In another embodiment of the present invention and / or in embodiments thereof, R 13 is hydrogen or C 1-3 -alkyl, R 14 is hydrogen, C 1-3 -alkyl, or C 1-3 -alkoxy, A1 is CR 15 and R 15 is hydrogen, halogen, C 1-3 -Alkyl, C 1-3 -alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A2 is CR 16 and R 16 is hydrogen, halogen, C 1-3 -Alkyl, C 1-3 -alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is CR 17 and R 17 is hydrogen or C 1-3 -alkyl, A4 is CR 18 and R 18 is hydrogen or C 1-3 - alkyl.

[0109] In another embodiment of the present invention and / or in embodiments thereof, R 13 is hydrogen, methyl or ethyl, preferably hydrogen or methyl, R 14 is hydrogen or methyl, preferably hydrogen, A1 is CR 15 and R 15 is hydrogen or C 1-3 alkyl, preferably hydrogen or is methyl, A2 is CR 16 and R 16is hydrogen or C 1-3 Alkyl, preferably hydrogen or methyl Chill, A3 is CR 17 and A4 is CR 18 and R 17 and R 18 is hydrogen.

[0110] In another embodiment of the present invention and / or in embodiments thereof, R 13 is hydrogen, methyl or ethyl, preferably hydrogen or methyl, R 14 is hydrogen or methyl, preferably hydrogen, A1 is CR 15 and A2 is CR 16 and A3 is CR 17 and A4 is , C.R. 18 and R 15 , R 16 , R 17 and R 18 is hydrogen.

[0111] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ic): [ka] or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph thereof R 1 , R 7 , R 19 and R 25 is described herein In any of the embodiments,

[0112] In an embodiment of the invention and / or embodiments thereof, the compound is according to formula (Ic) and preferably in the form of the (S)-enantiomer.

[0113] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 But those Together with the atoms to which it is attached, it forms a non-aromatic ring containing 5 or 6 carbon atoms. and the ring containing 5 or 6 carbon atoms has one or more C 1-3 -Alkyl or =O and / or one or more of the ring carbons may be substituted by -NH-, -N= , =N-, -O-, -S(O)-, -S(O)2- or -S- Alternatively, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, It may be replaced by -O- or -S-.

[0114] The non-aromatic or aromatic ring containing 5 or 6 carbon atoms, is a group consisting of one or more non-aromatic rings containing six carbon atoms. 1-3 -Alkyl or =O and / or one or more of the ring carbon atoms may be -NH-, -N=, =N-, may be replaced by -O-, -S(O)-, -S(O)2- or -S-; or The aromatic ring containing 5 or 6 carbon atoms has one or more C 1-3 -Alkyl and / or one or more of the ring carbons may be substituted with -NH-, -N=, ═N Examples of compounds which may be replaced by -, -O- or -S- include compounds of the following structure: Examples of such residues include, but are not limited to, residues represented by the following: [ka] During the ceremony, ······ indicates a bond to an amide group; -·- means that the ring system is fused with an aromatic ring, especially the aromatic rings A1, A2, A3 and A4. The figure shows the bond.

[0115] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 - alkyl.

[0116] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -O-, or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A2 is N or CR 16 and R 16 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A3 is N or CR 17 and R 17 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A4 is N or CR 18 and R 18are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0117] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH- or - may be replaced by O-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 It is alkoxy , A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 It is alkoxy , 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0118] In one embodiment of the present invention and / or embodiments thereof, A1, A2, A3 and A4 There is nothing that is N.

[0119] In one embodiment of the present invention and / or embodiments thereof, A1 is N. In one embodiment and / or embodiments thereof, A2 is N. In one embodiment of the present invention and / or an embodiment thereof, A3 is N. In an embodiment, A4 is N.

[0120] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Idi): (Idii), (Idiii), (Idiv), (Idv), (Idvi) or (Idv ii) [ka] TIFF2025134777000015.tif230150, or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs R 1 , R 7 , R 19 and R 25 is described herein In any of the embodiments,

[0121] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Idi) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Idii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Idiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Idiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I dv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Idvi) and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Idvii), preferably It is in the form of the (S)-enantiomer.

[0122] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 - alkyl.

[0123] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- , optionally replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A2 is N or CR 16 and R 16 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A3 is N or CR 17 and R 17 are independently hydrogen, C1-3 Alkyl or C 1- 3 alkoxy, A4 is N or CR 18 and R 18 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0124] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 It is alkoxy , A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 It is alkoxy , 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0125] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Idvii i), (Idix), (Idx), (Idxi), (Idxii), (Idxiii), (Idxiv) or (Idxv) [ka] TIFF2025134777000017.tif228163TIFF2025134777000018.tif113149, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 , R 7 , R 19 and R 25 is described herein In any of the embodiments,

[0126] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Idvii i), preferably in the form of the (S)-enantiomer. In some forms and / or embodiments thereof, the compound is according to formula (Idix): and preferably in the form of the (S)-enantiomer. In an embodiment, the compound is according to formula (Idx), preferably (S) In an embodiment of the present invention and / or in its embodiment, The compound is according to formula (Idxi), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound has the formula ( Idxii), preferably in the form of the (S)-enantiomer. In certain and / or embodiments thereof, the compound has the formula (Idxiii) and preferably in the form of the (S)-enantiomer. and / or in embodiments thereof, the compound is according to formula (Idxiv): It is preferably in the form of the (S)-enantiomer. In an embodiment, the compound is according to formula (Idxv), preferably (S)- It is in the form of an enantiomer.

[0127] The present invention is 19 The compound according to the present invention and / or its embodiment, An embodiment is provided.

[0128] In one embodiment of the present invention and / or embodiments thereof, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; Each C 6-10 -aryl or 5-10 membered heteroaryl, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, halogen, cyano, Nitro, Hydroxy, NR 20 R 21 , C(=O)OR 22 and C(=O)NR 23 R 2 4 and optionally substituted with one or more substituents independently selected from the group consisting of: R 20 and R 21 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 6-10 -aryl or R 20 and R 21have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl or C 6-10 -aryl or R 20 and R 21 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, halogen, cyano, Hydroxy, NR 20′ R 21′ , C(=O)OR 22′ and C(=O)NR 23′ R 2 4′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -Arki are selected independently from the

[0129] In an embodiment of the present invention and / or embodiments thereof, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; Each C 6-10 -aryl or 5-10 membered heteroaryl, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydro Kishi, C(=O)OR 22 , SO2R 22 , SO2NR 23 R 24 and C(=O)NR 2 3 R 24 and optionally substituted with one or more substituents independently selected from the group consisting of: R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl.

[0130] In an embodiment of the present invention and / or embodiments thereof, R 19 is C 6-10 -Allie and 5- to 10-membered heteroaryl; Each C 6-10 -aryl or 5-10 membered heteroaryl, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, C(= O)OR 22 and C(=O)NR 23 R 24 one or more substituents independently selected from the group consisting of may be substituted with a substituent, R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1-3 -alkyl.

[0131] In an embodiment of the present invention and / or embodiments thereof, R 19 is C 6-10 -Allie and 5- to 10-membered heteroaryl; Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -alkoxy, halogen, cyano, nitro and hydro and optionally substituted with one or more substituents independently selected from the group consisting of:

[0132] In an embodiment of the present invention and / or embodiments thereof, R 19 is a 5- to 10-membered heteroaromatic It is a reel, The 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, Ha one or more substituents independently selected from the group consisting of halogen, cyano, nitro, and hydroxy; may be substituted with.

[0133] In an embodiment of the present invention and / or embodiments thereof, R 19 is a 5- to 10-membered heteroaromatic It is a reel, The 5- to 10-membered heteroaryl is C 1-6 - alkyl and halogen, preferably halo and optionally substituted with one or more substituents independently selected from the group consisting of:

[0134] Examples of 5- to 10-membered heteroaryl groups include pyrrolyl, imidazolyl, pyrazolyl, pyridyl pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, pyridin-4-yl pyrimidin-3-yl, pyrimidin-4-yl, pyrazinyl, pyridazinyl, triazolyl, For example, 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1, 2,4-Triazolyl and 4H-1,2,4-triazlyl, tetrazolyl Tetrazolyl, such as 1H-tetrazolyl, 2H-tetrazolyl and 5H-tetrazolyl trazoyl), indolyl, isoindolyl, indolinyl, indolizinyl, benzyl Zoimidazolyl, quinolin-4-yl, quinolin-8-yl, isoquinolyl, indazolyl , naphthyridinyl, benzotriazolyl, oxazolyl, isoxazolyl, oxadiazolyl Zolyl, for example 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2 ,5-oxadiazolyl, benzoxazolyl, benzoxadiazolyl, benzoxa Thiazolyl, e.g., 2H-1,4-benzoxazinyl, thiazolyl, isothiazolyl, thiazolyl Azolyl, for example 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3, 4-Thiadiazolyl, 1,2,5-Thiadiazolyl, thien-2-yl, thien-3-yl Benzothiazolyl, benzothiadiazolyl, benzothiazinyl, benzofuranyl, quinoline cinnolinyl, isoquinoline, cinnolinyl, quinaxolinyl Noxalinyl, triazinyl, tetrazinyl, purinyl, pteridinyl, furyl, benzo Dioxolyl, such as 1,3-benzodioxoyl, benzothienyl, benzodithiinyl and benzoxathiinyl. The pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2 -yl, pyrimidin-3-yl, pyrimidin-4-yl, quinolin-8-yl, thien- 2-yl and thien-3-yl.

[0135] In an embodiment of the present invention and / or embodiments thereof, R 19 is a 5- to 10-membered heteroaromatic It is a reel, The 5- to 10-membered heteroaryl is C 1-6 - alkyl and halogen, preferably halogen and substituted with one or more substituents independently selected from the group consisting of halogens.

[0136] In an embodiment of the present invention and / or embodiments thereof, R 19 is pyridin-2-yl , pyridin-3-yl, pyridin-4-yl 2,5-dichloropyridin-4-yl, 2, 6-Dichloropyridin(pyridn)-4-yl, 5-chlorothien-2-yl, 5- Chlorothien-3-yl, pyrimidin-4-yl, quinolin-4-yl, quinolin-8-yl yl and 2,6-difluoropyridin-yl.

[0137] In an embodiment of the present invention and / or embodiments thereof, R 19 is C 6-10 -aryl and Said C 6-10 The aryl is C 1-6 - independently selected from the group consisting of alkyl, halogen, cyano and nitro The group may be substituted with one or more substituents.

[0138] In an embodiment of the present invention and / or embodiments thereof, R 19 is C 6-10 -aryl and C 6-10 Aryl is independently selected from the group consisting of fluoride, chloride and bromide. and phenyl substituted with one, two or three substituents selected from the group consisting of phenyl, phenyl, phenyl substituted with one, two or three substituents selected from the group consisting of ...

[0139] one, two or more independently selected from the group consisting of fluoride, chloride and bromide; Examples of phenyl substituted with three or more substituents include 2-fluorophenyl, 3-fluorophenyl, and 4-fluorophenyl. phenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chloro Phenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2,3-di Fluorophenyl, 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 2-chloro-3-fluorophenyl, 3,4,5-tribromophenyl, 2-chloro-3-fluorophenyl, -chloro-4-fluorophenyl, 2-chloro-5-fluorophenyl, 3-chloro-2 -fluorophenyl, 3-chloro-4-fluorophenyl, 3-chloro-5-fluorophenyl phenyl, 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 nyl, 4-bromo-2-chlorobromophenyl, 4-bromo-3-chlorophenyl, 3, 4-Dichloro-2-fluoro-phenyl, 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-3,4-difluorophenyl Bromo-3,5-difluorophenyl, 3-bromo-4,5-difluorophenyl, 2-bromo- Bromo-3,4-dichlorophenyl, 2-bromo-3,5-dichlorophenyl, 3-bromo -4,5-dichlorophenyl, 4-bromo-3-chloro-2-fluorophenyl, 4-bromo-3-chloro-2-fluorophenyl Bromo-2-chloro-3-fluorophenyl, 2-bromo-3-chloro-4-fluorophenyl nyl, 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 and the like. do not have.

[0140] Preferred are 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl. Phenyl 3,5-difluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl 2-chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro- 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-2-fluorophenyl Fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl phenyl, 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 trifluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl phenyl, 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.

[0141] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iei): (Ieii), (Ieiii) or (Ieiv) [ka] TIFF2025134777000020.tif211147 or its stereoisomers, physiologically acceptable salts, esters, solvates and polymorphs R 1 , R 7 , R 13 , R 14 , A1, A2, A3, A4 and R 25 is defined as in any of the embodiments described herein.

[0142] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iei) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Ieii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Ieiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Ieiv), preferably in the form of the (S)-enantiomer It is a posture.

[0143] The present invention is 25 The compound according to the present invention and / or its embodiment, An embodiment is provided.

[0144] In an embodiment of the present invention and / or embodiments thereof, R 25 is hydrogen or C 1-3 -a It's Rukiru.

[0145] In an embodiment of the present invention and / or embodiments thereof, R 25 is hydrogen or methyl .

[0146] In an embodiment of the invention and / or embodiments thereof, the compound has the formula (Ifi) or Ifii [ka] or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph thereof R 1 , R 7 , R 13 , R 14 , A1, A2, A3, A4 and R 19 is defined as in any of the embodiments described herein.

[0147] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Ifi) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Ifii), preferably Preferably it is in the form of the (S)-enantiomer.

[0148] The present invention is 1 and R 7 is defined as above, and / or The embodiments are provided below.

[0149] In an embodiment of the present invention and / or in an embodiment thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Droxi, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R 6 Independent from the group consisting of Selected by Each C 1-6 -alkyl or C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Roxy and NR 2′ R 3′ substituted with one or more substituents independently selected from the group consisting of It may be R 2 and R 3 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and and 5- to 10-membered heteroaryl, or R 2 and R 3 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- Aryl or 5 ~10-membered heteroaryl or R 2 and R 3 are formed together with the N atom to which they are attached The heterocycle is C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -Alkoxy may be substituted with one or more substituents independently selected from the group consisting of R 4 , R 5 and R 6 is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1- 3-alkyl; R 2′ and R 3′ is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1-3 -alkyl; R 7 teeth, Hydrogen, C 1-6 -Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8 R 9 , C(=O)OR 10 , S.R. 10 , SOR 10 , SO2R 10 and C(=O)NR 11 R 12 are independently selected from the group consisting of: Each C 1-6-Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4 ~10-membered heterocycle or C 1-6 -alkoxy is C 1-6 -Alkyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 1- 6-alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ , C(=O)OR 10 ′ and C(=O)NR 11′ R 12′ and one or more substituents independently selected from the group consisting of may be substituted, R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, independently selected from the group consisting of 5- to 10-membered heterocycle and 5- to 10-membered heteroaryl; or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 10-membered heterocycle or 5-10-membered heteroaryl or R 8 and R 9 But they are combined The heterocycle formed together with the N atom is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy, N R 8″ R 9″, C(=O)-OR 10″ and C(=O)NR 11″ R 12″ A group consisting of may be substituted with one or more substituents independently selected from: R 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen and C 1-6 -Alkyl are independently selected from R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -Alkyl are independently selected.

[0150] In an embodiment of the present invention and / or in an embodiment thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, chlorine Ano, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of: R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl.

[0151] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 7 teeth, Methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, di Methylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydro (xyethyl)(methyl)amino, methoxyethylamino, morpholin-4-yl, pyrrolidin 3-hydroxy-pyrrolidine 3-fluoroazetidinyl and 3,3-difluoroazetidinyl and independently selected from the group consisting of: fluoroazetidinyl.

[0152] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Igi): (Igii), (Igiii), (Igiv), (Igv) or (Igvi) [ka] TIFF2025134777000023.tif176145 or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs R 13 , R 14 , A1, A2, A3, A4, R 19 and R 25 is defined as in any of the embodiments described herein.

[0153] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Igi) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Igii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Igiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Igiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I gv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Igvi): and preferably in the form of the (S)-enantiomer.

[0154] The present invention is 1 and R 13 , R 14 , A1, A2, A3 and A4 are defined as above The present invention provides compounds according to the present invention and / or embodiments thereof,

[0155] In an embodiment of the present invention and / or in an embodiment thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Droxi, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R 6 Independent from the group consisting of Selected by Each C 1-6 -alkyl or C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Roxy and NR 2′ R 3′ substituted with one or more substituents independently selected from the group consisting of It may be R 2 and R 3 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and and 5- to 10-membered heteroaryl, or R 2 and R 3 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl or 5 ~10-membered heteroaryl or R 2 and R 3 are formed together with the N atom to which they are attached The heterocycle is C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -Alkoxy may be substituted with one or more substituents independently selected from the group consisting of R 4 , R 5 and R 6 is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1- 3-alkyl; R 2′ and R 3′ is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1-3 -alkyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independent C 1-3 - alkyl.

[0156] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6-alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -O- or - may be replaced by S-, A1 is N or CR 15 and R 15 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A2 is N or CR 16 and R 16 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A3 is N or CR 17 and R 17 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A4 is N or CR 18 and R 18 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0157] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0158] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Ihi): (Ihii)(Ihiii), (Ihiv), (Ihv) or (Ihvi) [ka] TIFF2025134777000025.tif228157 or its stereoisomers, physiologically acceptable salts, esters, solvates and polymorphs R 7 , R 19 and R 25 is the implementation described herein. It is defined as either in the form

[0159] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Ihi) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Ihii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Ihiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Ihiv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I In accordance with an embodiment of the present invention and / or its embodiments, the compound The compound is according to formula (Ihvi), preferably in the form of the (S)-enantiomer. be.

[0160] In an embodiment of the present invention and / or in an embodiment thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Droxi, NR 2 R 3 , C(=O)OR 4 and C(=O)NR5 R 6 Independent from the group consisting of Selected by Each C 1-6 -alkyl or C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Roxy and NR 2′ R 3′ substituted with one or more substituents independently selected from the group consisting of It may be R 2 and R 3 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and and 5- to 10-membered heteroaryl, or R 2 and R 3 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- Aryl or 5 ~10-membered heteroaryl or R 2 and R 3 are formed together with the N atom to which they are attached The heterocycle is C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -Alkoxy may be substituted with one or more substituents independently selected from the group consisting of R 4 , R 5 and R 6 is hydrogen and C 1-6-alkyl, preferably hydrogen and C 1- 3-alkyl; R 2′ and R 3′ is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1-3 -alkyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 - alkyl.

[0161] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- , optionally replaced by -O- or -S-; A1 is N or CR15 and R 15 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A2 is N or CR 16 and R 16 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A3 is N or CR 17 and R 17 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A4 is N or CR 18 and R 18 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0162] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0163] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Ihvii ), (Ihviii)(Ihix), (Ihx), (Ihxi) or (Ihxii): [ka] TIFF2025134777000027.tif221151 or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs R 7 , R 19 and R 25 is the implementation described herein. It is defined as either in the form

[0164] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Ihvii ), preferably in the form of the (S)-enantiomer. In certain aspects and / or embodiments thereof, the compound is according to formula (Ihviii): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Ihix), preferably In the embodiment of the present invention and / or its embodiments, wherein the compound is according to formula (Ihx), preferably the (S)-enantiomer In an embodiment of the invention and / or embodiments thereof, the compound is of the formula (Ihxi). In the embodiments of the present invention and / or in the embodiments thereof, The compound is according to formula (Ihxii), preferably the (S)-enantiomer It is in the form of:

[0165] The present invention is 1 and R 19 is defined as above, and / or An embodiment thereof is provided.

[0166] In an embodiment of the present invention and / or in an embodiment thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Droxi, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R 6 Independent from the group consisting of Selected by Each C 1-6 -alkyl or C 1-6 -alkoxy is C 1-6 -Alkyl, C 1- 6-alkoxy, halogen, cyano, nitro, hydroxy and NR 2′ R 3′ A group consisting of and optionally substituted by one or more substituents independently selected from R 2 and R 3 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10-cycloalkyl, C 6-10- Aryl and and 5- to 10-membered heteroaryl, or R 2 and R 3 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- Aryl or 5 ~10-membered heteroaryl or R 2 and R 3 are formed with the N atoms to which they are attached The heterocycle is C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -Alkoxy may be substituted with one or more substituents independently selected from the group consisting of R 4 , R 5 and R 6 is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1- 3-alkyl; R 2′ and R 3′ is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1-3 -alkyl; R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5-10 membered heteroaryl is C 1-6 -alkyl, C 3-10-cycloalkyl, C 1-6 -alkoxy, 5-10 membered heterocycle, C 6-10 - Aryl, 5-10 membered heteroaryl, halogen, cyano, nitro, hydroxy, NR 2 0 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24 Independently selected from the group consisting of and optionally substituted with one or more substituents such as R 20 and R 21 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 6-10 -aryl or R 20 and R 21 have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl or C 6-10 -aryl or R 20 and R 21 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, halogen, cyano, Hydroxy, NR 20′ R 21′ , C(=O)OR 22′ and C(=O)NR 23′ R 2 4′and optionally substituted with one or more substituents independently selected from the group consisting of: R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -Arki are selected independently from the

[0167] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxy and NR 2 ′R 3 Independently from the group consisting of optionally substituted with one or more selected substituents; R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -alkyl, C 1-6independently selected from the group consisting of alkoxy, halogen, cyano, nitro and hydroxy It may be substituted with one or more selected substituents.

[0168] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro and 3,5-dichlorophenyl.

[0169] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iii): (Iiii), (Iiiii), (Iiiv), (Iiv) or (Iivi) [ka] TIFF2025134777000029.tif210158TIFF2025134777000030.tif138147, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 7 , R 13 , R 14 , A1, A2, A3, A4 and BiR 25is defined as in any of the embodiments described herein.

[0170] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iii) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (III), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (III), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iiiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I iv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Iivi): and preferably in the form of the (S)-enantiomer.

[0171] The present invention is 1 and R 25 is defined as above, and / or An embodiment thereof is provided.

[0172] In an embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Droxi, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R6 Independent from the group consisting of Selected by Each C 1-6 -alkyl or C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy Roxy and NR 2′ R 3′ substituted with one or more substituents independently selected from the group consisting of It may be R 2 and R 3 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -Aryl and and 5- to 10-membered heteroaryl, or R 2 and R 3 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- Aryl or 5 ~10-membered heteroaryl or R 2 and R 3 are formed together with the N atom to which they are attached The heterocycle is C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -Alkoxy may be substituted with one or more substituents independently selected from the group consisting of R 4 , R 5 and R 6 is hydrogen and C 1-6 -alkyl, preferably hydrogen and C1- 3-alkyl; R 2′ and R 3′ is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1-3 -alkyl; R 25 is hydrogen or C 1-3 - alkyl. In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chlorine are independently selected from the group consisting of: R 25 is hydrogen or methyl.

[0173] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iji): (Ijii), (Ijiii) or (Ijiv) [ka] or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph thereof R 7 , R 13 , R 14 , A1, A2, A3 and A4 is defined as in any of the embodiments described herein.

[0174] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iji) and preferably in the form of the (S)-enantiomer. and / or in embodiments thereof, the compound is according to formula (Ijii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Ijiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Ijiv), preferably in the form of the (S)-enantiomer It is a posture.

[0175] The present invention is 7 and R 13 , R 14 , A1, A2; A3 and A4 are defined as above The present invention provides compounds according to the present invention and / or embodiments thereof,

[0176] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8 R 9 , C(=O)OR 10 , S.R. 10 , SOR 10 , SO2R 10 and C(=O)NR 11 R 12 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4 ~10-membered heterocycle or C 1-6 -alkoxy is C 1-6 -Alkyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 1- 6-alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ , C(=O)OR 10 ′ and C(=O)NR 11′ R 12′ and one or more substituents independently selected from the group consisting of may be substituted, R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, independently selected from the group consisting of 5- to 10-membered heterocycle and 5- to 10-membered heteroaryl; or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 10-membered heterocycle or 5-10-membered heteroaryl or R 8 and R 9 But they are combined The heterocycle formed together with the N atom is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy, N R 8″ R 9″ , C(=O)-OR 10″ and C(=O)NR 11″ R 12″ A group consisting of may be substituted with one or more substituents independently selected from: R 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R 9′ , R10′ , R 11′ and R 12′ is hydrogen and C 1-6 -Alkyl are independently selected from R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -Alkyl are independently selected from R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independent C 1-3 - alkyl.

[0177] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen hydroxy, cyano, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 1 1′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 are bonded to the N atom to form a heterocycle, 1- 6-Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ From the group consisting of optionally substituted with one or more optionally selected substituents; R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -O- or - may be replaced by S-, A1 is N or CR 15 and R 15 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A2 is N or CR 16 and R 16 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A3 is N or CR 17 and R 17 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A4 is N or CR 18 and R 18 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0178] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, propyl, isopropenyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethicone ethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxy (methyl)amino, methoxyethylamino, morpholin-4-yl, (methoxy Diethyl)(methyl)amino, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine-1 -yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Selected to be a R 13 and R 14 Five or six carbon atoms together with the atoms to which they are attached and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0179] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iki): (Ikii), (Ikiii), (Ikiv), (Ikv), (Ikvi), (Ikvi i), (Ikviii) or (Ikix) [ka] TIFF2025134777000033.tif240159TIFF2025134777000034.tif133152, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 , R 19 and R 25 is the implementation described herein. It is defined as either in the form

[0180] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iki) and preferably in the form of the (S)-enantiomer. and / or in an embodiment thereof, the compound is according to formula (Ikii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Ikiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Ikiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I kv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Ikvi): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Ikvii), preferably In the form of the (S)-enantiomer. wherein the compound is according to formula (Ikviii), preferably an (S)-enanthate In an embodiment of the present invention and / or embodiments thereof, the compound The product is according to formula (Ikix), preferably in the form of the (S)-enantiomer. do.

[0181] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8 R 9 , C(=O)OR 10 , S.R. 10 , SOR 10 , SO2R 10 and C(=O)NR 11 R 12 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4 ~10-membered heterocycle or C 1-6 -alkoxy is C 1-6 -Alkyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 1- 6-alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ , C(=O)OR 10 ′ and C(=O)NR 11′ R 12′ and one or more substituents independently selected from the group consisting of may be substituted, R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C6-10 -aryl, independently selected from the group consisting of 5- to 10-membered heterocycle and 5- to 10-membered heteroaryl; or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 10-membered heterocycle or 5-10-membered heteroaryl or R 8 and R 9 But they are combined The heterocycle formed together with the N atom is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy, N R 8″ R 9″ , C(=O)-OR 10″ and C(=O)NR 11″ R 12″ A group consisting of may be substituted with one or more substituents independently selected from: R 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen and C 1-6 -Alkyl are independently selected from R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -Alkyl are independently selected from R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 - alkyl.

[0182] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen hydroxy, cyano, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 1 1′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 are bonded to the N atom to form a heterocycle, 1- 6-Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ From the group consisting of optionally substituted with one or more optionally selected substituents; R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- , optionally replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A2 is N or CR 16 and R 16 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A3 is N or CR 17 and R 17 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A4 is N or CR 18 and R 18 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0183] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, propyl, isopropenyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethicone ethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxy (methyl)amino, methoxyethylamino, morpholin-4-yl, (methoxy Diethyl)(methyl)amino, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine-1 -yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Selected to be a R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0184] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Ikx): (Ikxi), (Ikxii), (Ikxiii), (Ikxiv), (Ikxv), ( Ikxvi), (Ikvii) or (Ikxviii) [ka] TIFF2025134777000036.tif235160TIFF2025134777000037.tif67148, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 , R 19 and R 25 is the implementation described herein. It is defined as either in the form

[0185] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Ikx) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Ikxi), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Ikxii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Ikxiii) and is preferably the (S)-enantiomer In an embodiment of the invention and / or embodiments thereof, the compound is of the formula (Ikxiv), preferably in the form of the (S)-enantiomer. In an embodiment of the invention and / or embodiments thereof, the compound is according to formula (Ikxv) and preferably in the form of the (S)-enantiomer. In / or embodiments thereof, the compound is according to formula (Ikxvi), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Ikxvii), preferably (S) In an embodiment of the present invention and / or in its embodiment, The compound is according to formula (Ikxviii) and is preferably the (S)-enantiomer. It is in the form of a mar.

[0186] The present invention is 7 and R 19 is defined as above, and / or An embodiment thereof is provided.

[0187] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8 R 9 , C(=O)OR 10 , S.R. 10 , SOR 10 , SO2R 10 and C(=O)NR 11 R 12 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4 ~10-membered heterocycle or C 1-6 -alkoxy is C 1-6 -Alkyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 1- 6-alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ , C(=O)OR 10 ′ and C(=O)NR 11′ R 12′ and one or more substituents independently selected from the group consisting of may be substituted, R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, independently selected from the group consisting of 5- to 10-membered heterocycle and 5- to 10-membered heteroaryl; or R 8and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 10-membered heterocycle or 5-10-membered heteroaryl or R 8 and R 9 But they are combined The heterocycle formed together with the N atom is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy, N R 8″ R 9″ , C(=O)-OR 10″ and C(=O)NR 11″ R 12″ A group consisting of may be substituted with one or more substituents independently selected from: R 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen and C 1-6 -Alkyl are independently selected from R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -Alkyl are independently selected from R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 ~10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, halogen, cyano , nitro, hydroxy, NR 20 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24 and optionally substituted with one or more substituents independently selected from the group consisting of: R 20 and R 21 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 6-10 -aryl or R 20 and R 21 have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl or C 6-10 -aryl or R 20 and R 21 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, halogen, cyano, Hydroxy, NR 20′ R21′ , C(=O)OR 22′ and C(=O)NR 23′ R 2 4′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -Arki are selected independently from the

[0188] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, chlorine Ano, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of: R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 19 teeth, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of hydroxy.

[0189] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Methyl, ethyl, isopropyl, propyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethicone ethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxy (Methoxyethyl)(methyl)amino, methoxyethylamino, (Methoxyethyl)(methyl)amino amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine-1 -yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Selected to be a R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro and 3,5-dichlorophenyl.

[0190] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (IIi): (Ilii), (Iliiii), (Iliv), (Ilv), (Ilvi), (Ilvi i), (Ilviii) or (Ilix): [ka] TIFF2025134777000039.tif215155TIFF2025134777000040.tif236147, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 , R 13 , R 14 , A1, A2, A3, A4 and BiR 25 is defined as in any of the embodiments described herein.

[0191] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Ili) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Ilii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Iliii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iliv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I lv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Ilvi) and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Ilvii), preferably In the form of the (S)-enantiomer. wherein the compound is according to formula (Ilviii), preferably an (S)-enanthate In an embodiment of the present invention and / or embodiments thereof, the compound The product is according to formula (Ilix) and is preferably in the form of the (S)-enantiomer. .

[0192] The present invention is 7 and R 25 is defined as above, and / or An embodiment thereof is provided.

[0193] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C2-6-alkenyl, C 3-10 -cycloalkyl, 4-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8 R 9 , C(=O)OR 10 , S.R. 10 , SOR 10 , SO2R 10 and C(=O)NR 11 R 12 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C2-6-alkenyl, C3-10 -cycloalkyl, 4 ~10-membered heterocycle or C 1-6 -alkoxy is C 1-6 -Alkyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 1- 6-alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ , C(=O)OR 10 ′ and C(=O)NR 11′ R 12′ and one or more substituents independently selected from the group consisting of may be substituted, R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, independently selected from the group consisting of 5- to 10-membered heterocycle and 5- to 10-membered heteroaryl; or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5 10-membered heterocycle or 5-10-membered heteroaryl or R 8 and R 9 But they are combined The heterocycle formed together with the N atom is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy, N R 8″ R 9″ , C(=O)-OR 10″and C(=O)NR 11″ R 12″ A group consisting of may be substituted with one or more substituents independently selected from: R 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen and C 1-6 -Alkyl are independently selected from R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -Alkyl are independently selected from R 25 is hydrogen or C 1-3 - alkyl.

[0194] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Methyl, ethyl, isopropyl, propyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethicone ethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxy (Methoxyethyl)(methyl)amino, methoxyethylamino, (Methoxyethyl)(methyl)amino amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine-1 -yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Selected to be a R25 is hydrogen or methyl, preferably hydrogen.

[0195] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Imi): (Imii), (Imiii), (Imiv), (Imv) or (Imiv): [ka] TIFF2025134777000042.tif137155, or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs R 1 , R 13 R 14 , A1, A2, A3, A4 and R 19 is defined as in any of the embodiments described herein.

[0196] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Imi) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Imii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Imiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Imiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I mv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Imvi): and preferably in the form of the (S)-enantiomer.

[0197] The present invention is 13 , R 14 , A1, A2, A3 and A4 and R 19 is defined as above The present invention provides compounds according to the present invention and / or embodiments thereof, which are defined as

[0198] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independent C 1-3 -alkyl, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5-10 membered heterocycle, C 6-10 - Aryl, 5-10 membered heteroaryl, halogen, cyano, nitro, hydroxy, NR 2 0 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24 Independently selected from the group consisting of and optionally substituted with one or more substituents such as R 20 and R 21 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 6-10 -aryl or R 20 and R 21 have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl or C 6-10 -aryl or R 20 and R 21 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, halogen, cyano, Hydroxy, NR 20′ R 21′ , C(=O)OR 22′ and C(=O)NR 23′ R 2 4′ are independently selected from R 22 , R 23 and R 24 is hydrogen and C 1-6 - independently selected from the group consisting of alkyl and optionally substituted by one or more substituents such as R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -Arki are selected independently from the

[0199] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -O- or - may be replaced by S-, A1 is N or CR 15 and R 15 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A2 is N or CR 16 and R 16 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A3 is N or CR 17 and R 17 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A4 is N or CR 18 and R 18 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of hydroxy.

[0200] In one embodiment of the present invention and / or embodiments thereof, R 13 and R14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro and 3,5-dichlorophenyl.

[0201] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Ini): (Inii), (Iniii), (Iniv), (Inv), (Invi), (Invi i), (Inviii) or (Inix): [ka] TIFF2025134777000044.tif216155TIFF2025134777000045.tif214158TIFF2025134777000046.tif67153, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 , R 7 and R 25 is an embodiment described herein. It is defined as either

[0202] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Ini) and preferably in the form of the (S)-enantiomer. and / or in embodiments thereof, the compound is according to formula (Inii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Iniii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iniv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I nv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Invi): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Invii), preferably In the form of the (S)-enantiomer. wherein the compound is according to formula (Inviii), preferably an (S)-enanthate In an embodiment of the present invention and / or embodiments thereof, the compound The product is according to formula (Inix), preferably in the form of the (S)-enantiomer. do.

[0203] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 - alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5-10 membered heterocycle, C 6-10 - Aryl, 5-10 membered heteroaryl, halogen, cyano, nitro, hydroxy, NR 2 0 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24 Independently selected from the group consisting of and optionally substituted with one or more substituents such as R 20 and R21 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 6-10 -aryl or R 20 and R 21 have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl or C 6-10 -aryl or R 20 and R 21 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, halogen, cyano, Hydroxy, NR 20′ R 21′ , C(=O)OR 22′ and C(=O)NR 23′ R 2 4′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -Arki are selected independently from the

[0204] Optionally, in embodiments of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- , optionally replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A2 is N or CR 16 and R 16 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A3 is N or CR 17 and R 17 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, A4 is N or CR 18 and R 18 are independently hydrogen, C 1-3 Alkyl or C 1- 3 alkoxy, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of hydroxy. In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, and 0, 1 or 2 of A1, A2, A3 and A4 are N. the law of nature, R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro and 3,5-dichlorophenyl.

[0205] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Inx): (Inxi), (Inxii), (Inxiii), (Inxiv), (Inxv), ( Inxvi), (Inxvii) or (Inxviii): [ka] TIFF2025134777000048.tif212157TIFF2025134777000049.tif208154, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 , R 7 and R 25 is an embodiment described herein. It is defined as either

[0206] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Inx) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Inxi), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Inxii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Inxiii) and is preferably the (S)-enantiomer In an embodiment of the invention and / or embodiments thereof, the compound is of the formula (Inxiv), preferably in the form of the (S)-enantiomer. In an embodiment of the invention and / or embodiments thereof, the compound is according to formula (Inxv) and preferably in the form of the (S)-enantiomer. In / or embodiments thereof, the compound is according to formula (Inxvi), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Inxvii), preferably (S) In an embodiment of the present invention and / or in its embodiment, The compound is according to formula (Inxviii) and is preferably the (S)-enantiomer. It is in the form of a mar.

[0207] The present invention is 13 , R 14 , A1, A2, A3 and A4 and R 25 is defined as above The present invention provides compounds according to the present invention and / or embodiments thereof, which are defined as

[0208] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independent C 1-3 -alkyl, R 25 is hydrogen or C 1-3 - alkyl.

[0209] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 25 is hydrogen or methyl, preferably hydrogen.

[0210] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Ioi): (Ioii), (Ioiii), (Ioiv), (Iov) or (Iovi): [ka] TIFF2025134777000051.tif224148 or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs R1 , R 7 and R 19 is an embodiment described herein. It is defined as either

[0211] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Ioi) and preferably in the form of the (S)-enantiomer. and / or in embodiments thereof, the compound is according to formula (Ioii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Ioiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Ioiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I ov), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Iovi): and preferably in the form of the (S)-enantiomer.

[0212] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-; A1 is N or CR15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, R 25 is hydrogen or C 1-3 - alkyl.

[0213] In one embodiment of the present invention and / or embodiments thereof, R13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 25 is hydrogen or methyl, preferably hydrogen.

[0214] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iovii ), (Ioviii), (Ioix), (Iox), (Ioxi) or (Ioxii): [ka] TIFF2025134777000053.tif158152 or its stereoisomers, physiologically acceptable salts, esters, solvates and polymorphs R 1 , R 7 and R 19is an embodiment described herein. It is defined as either

[0215] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iovii ), preferably in the form of the (S)-enantiomer. In certain aspects and / or embodiments thereof, the compound is according to formula (Ioviii): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Ioix), preferably In the embodiment of the present invention and / or its embodiments, The compound is according to formula (Iox), preferably the (S)-enantiomer In an embodiment of the invention and / or embodiments thereof, the compound is of the formula (Ioxi), preferably in the form of the (S)-enantiomer. In certain embodiments and / or embodiments thereof, the compound is represented by formula (Ioxii): and preferably in the form of the (S)-enantiomer.

[0216] The present invention is 19 and R 25 is defined as above, and / or provides an embodiment thereof.

[0217] In one embodiment of the present invention and / or embodiments thereof, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C1-6 -Alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 ~10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, halogen, cyano , nitro, hydroxy, NR 20 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24 and optionally substituted with one or more substituents independently selected from the group consisting of: R 20 and R 21 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 6-10 -aryl or R 20 and R 21 have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl or C 6-10 -aryl or R 20 and R 21 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 1-6 -alkoxy, 5 10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, halogen, cyano, Hydroxy, NR 20′ R 21′ , C(=O)OR 22′ and C(=O)NR 23′ R 2 4′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -Arki are independently selected from the R 25 is hydrogen or C 1-3 - alkyl.

[0218] In one embodiment of the present invention and / or embodiments thereof, R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro independently selected from the group consisting of 3,5-dichlorophenyl and 3,5-dichlorophenyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0219] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ipi): (Ipii), (Ipiii), (Ipiv), (Ipv) or (Ipvi): [ka] TIFF2025134777000055.tif221153TIFF2025134777000056.tif72150, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 , R 7 and R 13 , R 14 , A1, A2, A3 and A4 are defined as in any of the embodiments described herein.

[0220] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Ipi) and preferably in the form of the (S)-enantiomer. and / or in an embodiment thereof, the compound is according to formula (Ipii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Ipiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Ipiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I pv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Ipvi): and preferably in the form of the (S)-enantiomer.

[0221] The present invention is 1 , R 7 and R 13 , R 14 , A1, A2, A3 and A4 are as above The present invention provides compounds according to the invention and / or embodiments thereof, as defined in

[0222] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, chlorine Ano, Hydroxy, NR 8′ R 9′ , C(=O)OR10′ and C(=O)NR 11′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3- alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independent C 1-3 - alkyl.

[0223] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 7 teeth, Methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, di Methylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydro (xyethyl)(methyl)amino, methoxyethylamino, morpholin-4-yl, pyrrolidin 3-hydroxy-pyrrolidin-1-yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0224] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iqi): (Iqii), (Iqiii), (Iqiv), (Iqv) or (Iqvi) [ka] TIFF2025134777000058.tif220154TIFF2025134777000059.tif73156, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 19 and R 25 is an embodiment of the present invention. It is defined as either

[0225] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iqi) and preferably in the form of the (S)-enantiomer. and / or in embodiments thereof, the compound is according to formula (Iqii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Iqiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iqiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I qv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Iqvi): and preferably in the form of the (S)-enantiomer.

[0226] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, chlorine Ano, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 - alkyl.

[0227] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 7 teeth, Methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, di Methylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydro (xyethyl)(methyl)amino, methoxyethylamino, morpholin-4-yl, pyrrolidin 3-hydroxy-pyrrolidin-1-yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N.

[0228] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iqvii ), (Iqviii), (Iqix), (Iqx), (Iqxi) or (Iqxii) [ka] TIFF2025134777000061.tif198155, or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs R 19 and R 25 is an embodiment of the present invention. It is defined as either

[0229] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iqvii ), preferably in the form of the (S)-enantiomer. In certain aspects and / or embodiments thereof, the compound is according to formula (Iqviii): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Iqix), preferably ( In the embodiment of the present invention and / or its embodiments, The compound is according to formula (Iqx), preferably the (S)-enantiomer In an embodiment of the invention and / or embodiments thereof, the compound is of the formula (Iqxi), preferably in the form of the (S)-enantiomer. In certain and / or embodiments thereof, the compound is according to formula (Iqxii) and preferably in the form of the (S)-enantiomer.

[0230] The present invention is 1 , R 7 and R 19 is defined as above, and and / or embodiments thereof.

[0231] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6-alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, chlorine Ano, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of: R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5-10 membered heteroaryl, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of hydroxy.

[0232] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 7 teeth, Methyl, ethyl, isopropyl, propyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethicone ethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxy (Methoxyethyl)(methyl)amino, methoxyethylamino, (Methoxyethyl)(methyl)amino amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine-1 -yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Selected to be a R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro The aryl group is selected from the group consisting of 3,5-dichlorophenyl and 3,5-dichlorophenyl.

[0233] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iri): (Irii), (Iriii), (Iriv), (Irv) or (Irvi) [ka] TIFF2025134777000063.tif223156TIFF2025134777000064.tif83152, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 13 , R 14 , A1, A2, A3, A4 and R 2 5 is defined as in any of the embodiments described herein.

[0234] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iri) and preferably in the form of the (S)-enantiomer. and / or in an embodiment thereof, the compound is according to formula (Irii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Iriii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iriv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I rv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Irvi): and preferably in the form of the (S)-enantiomer.

[0235] The present invention is 1 , R 7 and R 25 is defined as above, and and / or embodiments thereof.

[0236] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, chlorine Ano, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of: R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 25 is hydrogen or C 1-3 - alkyl.

[0237] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 7 teeth, Methyl, ethyl, isopropyl, propyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethicone ethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxy (Methoxyethyl)(methyl)amino, methoxyethylamino, (Methoxyethyl)(methyl)amino amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine-1 -yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Selected to be a R 25 is hydrogen or methyl, preferably hydrogen.

[0238] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Isi): (Isii), (Isiii) or (Isiv) [ka] TIFF2025134777000066.tif123155, or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs R 13 , R 14 , A1, A2, A3, A4 and R 2 9 is defined as in any of the embodiments described herein.

[0239] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Isi) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Isii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Isiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Isiv), preferably in the form of the (S)-enantiomer It is an attitude.

[0240] The present invention is 1 , R 13 , R 14 , A1, A2, A3, A4 and R 19 As shown above, Provided are compounds according to the invention and / or embodiments thereof as defined.

[0241] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R16″ and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independent C 1-3 -alkyl, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of hydroxy.

[0242] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro and 3,5-dichlorophenyl.

[0243] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iti): (Itii), (Itiii), (Itiv), (Itv) or (Itvi): [ka] TIFF2025134777000068.tif199150TIFF2025134777000069.tif139149, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 7 and R 25 is any of the embodiments described herein. It is defined as either

[0244] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iti) and preferably in the form of the (S)-enantiomer. and / or in embodiments thereof, the compound is according to formula (Itii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Itiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Itiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I tv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Itvi): and preferably in the form of the (S)-enantiomer.

[0245] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of hydroxy.

[0246] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro and 3,5-dichlorophenyl.

[0247] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Itvii ), (Itviii), (Itix), (Itx), (Itxi) or (Itxii) [ka] TIFF2025134777000071.tif196157TIFF2025134777000072.tif137158, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 7 and R 25 is any of the embodiments described herein. It is defined as either

[0248] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Itvii ), preferably in the form of the (S)-enantiomer. In certain aspects and / or embodiments thereof, the compound is according to formula (Itviii): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Itix), preferably In the embodiment of the present invention and / or its embodiments, wherein the compound is according to formula (Itx), preferably the (S)-enantiomer In an embodiment of the invention and / or embodiments thereof, the compound is of the formula (Itxi), preferably in the form of the (S)-enantiomer. In certain and / or embodiments thereof, the compound is according to formula (Itxii): and preferably in the form of the (S)-enantiomer.

[0249] The present invention is 1 , R 13 , R 14 , A1, A2, A3, A4 and R 25 As shown above, Provided are compounds according to the invention and / or embodiments thereof as defined.

[0250] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independent C 1-3 -alkyl, R 25 is hydrogen or C 1-3 - alkyl.

[0251] In one embodiment of the present invention and / or embodiments thereof, R1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 25 is hydrogen or methyl, preferably hydrogen.

[0252] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iui): (Iuii), (Iuiii), (Iuiv), (Iuv) or (Iuvi) [ka] TIFF2025134777000074.tif212157 or its stereoisomers, physiologically acceptable salts, esters, solvates and polymorphs R 7 and R 19 is any of the embodiments described herein. It is defined as either

[0253] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iui) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Iuii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Iuiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iuiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I UV), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Iuvi): and preferably in the form of the (S)-enantiomer.

[0254] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6-alkoxy is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, hydroxy and and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of Ku, R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, R 25 is hydrogen or C 1-3 - alkyl.

[0255] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 25 is hydrogen or methyl, preferably hydrogen.

[0256] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iuvii ), (Iuviii), (Iuix), (Iux), (Iuxi) or (Iuxii) [ka] TIFF2025134777000076.tif205154TIFF2025134777000077.tif54147, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 7 and R 19 is any of the embodiments described herein. It is defined as either

[0257] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iuvii ), preferably in the form of the (S)-enantiomer. In certain aspects and / or embodiments thereof, the compound is according to formula (Iuviii): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Iuix), preferably In the embodiment of the present invention and / or its embodiments, The compound is according to formula (Iux), preferably the (S)-enantiomer In an embodiment of the invention and / or embodiments thereof, the compound is of the formula (Iuxi), preferably in the form of the (S)-enantiomer. In certain and / or certain embodiments thereof, the compound is of formula (Iuxii) and preferably in the form of the (S)-enantiomer.

[0258] The present invention is 1 , R 19 and R 25 The compounds according to the present invention are as defined above. and / or embodiments thereof.

[0259] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 - Independently from the group consisting of alkoxy and halogen Selected by C 1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxy and NR 2 ′R 3 and optionally substituted with one or more substituents independently selected from the group consisting of , R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl are independently selected from the R 19 teeth, C6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of: R 25 is hydrogen or C 1-3 - alkyl.

[0260] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride; R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro independently selected from the group consisting of 3,5-dichlorophenyl and 3,5-dichlorophenyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0261] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ivi): (Ivii), (Iviii) or (Iviv) [ka] TIFF2025134777000079.tif204151 or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs R 7 and R 13 , R 14 , A1, A2, A3 and A 4 is defined as in any of the embodiments described herein.

[0262] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Ivi) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Ivii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Iviii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iviv), preferably in the form of the (S)-enantiomer It is an attitude.

[0263] The present invention is 7 , R 13 , R 14 , A1, A2, A3, A4 and R 19 As shown above, Provided are compounds according to the invention and / or embodiments thereof as defined.

[0264] Optionally, in embodiments of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, chlorine Ano, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of: R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independent C 1-3 -alkyl, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of hydroxy.

[0265] In one embodiment of the present invention and / or embodiments thereof, R 7 teeth, Methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, di Methylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydro (methoxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl) Amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine- From the group consisting of 1-yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Independently selected, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro and 3,5-dichlorophenyl.

[0266] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iwi): (Iwii), (Iwiii), (Iwiv), (Iwv), (Iwvi), (Iwvi i), (Iwviii), (Iwix), (Iwx), (Iwxi) or (Iwxii) [ka] TIFF2025134777000081.tif243157TIFF2025134777000082.tif203160TIFF2025134777000083.tif223151TIFF2025134777000084.tif78152, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 and R 25 is any of the embodiments described herein. It is defined as either

[0267] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iwi) and preferably in the form of the (S)-enantiomer. and / or in embodiments thereof, the compound is according to formula (Iwii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Iwiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iwiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I The preferred form of the compound is the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Iwvi) and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Iwvii), preferably In the form of the (S)-enantiomer. wherein the compound is according to formula (Iwviii), preferably (S)-enanthracene In an embodiment of the present invention and / or embodiments thereof, the compound The product is according to formula (Iwix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iwx) and preferably in the form of the (S)-enantiomer. and / or in an embodiment thereof, the compound is according to formula (Iwxi): It is preferably in the form of the (S)-enantiomer. In an embodiment, the compound is according to formula (Iwxii), preferably (S) - in the form of enantiomers.

[0268] Optionally, in embodiments of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, chlorine Ano, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of: R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of hydroxy.

[0269] In one embodiment of the present invention and / or embodiments thereof, R 7 teeth, Methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, di Methylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydro (methoxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl) Amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine- From the group consisting of 1-yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Independently selected, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro and 3,5-dichlorophenyl.

[0270] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iwxii i), (Iwxiv), (Iwxv), (Iwxvi), (Iwxvii), (Iwxv iii), (Iwxix), (Iwxx), (Iwxxi), (Iwxxii), (Iw xxiii) or (Iwxxiv): [ka] TIFF2025134777000086.tif213158TIFF2025134777000087.tif230162TIFF2025134777000088.tif238163TIFF2025134777000089.tif77148, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 and R 25 is any of the embodiments described herein. It is defined as either

[0271] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iwxii i), preferably in the form of the (S)-enantiomer. In some forms and / or embodiments thereof, the compound is according to formula (Iwxiv): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Iwxv), preferably In the embodiment of the present invention and / or its embodiments, The compound is according to formula (Iwxvi), preferably the (S)-enantiomer. In an embodiment of the invention and / or embodiments thereof, the compound is , according to formula (Iwxvii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iwxv iii) and preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiments thereof, the compound is according to formula (Iwxix) and preferably in the form of the (S)-enantiomer. In one embodiment thereof, the compound is according to formula (Iwxx), preferably is in the form of the (S)-enantiomer. wherein the compound is according to formula (Iwxxi), preferably (S)-enanthracene In an embodiment of the present invention and / or embodiments thereof, the compound The product is according to formula (Iwxxii), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iw xxiii), preferably in the form of the (S)-enantiomer. In certain embodiments and / or embodiments thereof, the compound is of formula (Iwxxiv) and preferably in the form of the (S)-enantiomer.

[0272] The present invention is 7 , R 13 , R 14 , A1, A2, A3, A4 and R 25 As shown above, Provided are compounds according to the invention and / or embodiments thereof as defined.

[0273] Optionally, in embodiments of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 -a Lucoxy C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, sia No, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 1 2′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10-aryl and 5- to 10-membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independent C 1-3 -alkyl, R 25 is hydrogen or C 1-3 - alkyl.

[0274] In one embodiment of the present invention and / or embodiments thereof, R 7 teeth, Methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, di Methylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydro (methoxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl) Amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine- From the group consisting of 1-yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Independently selected, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 25 is hydrogen or methyl, preferably hydrogen.

[0275] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ixi): (Ixii), (Ixiii), (Ixiv), (Ixv) or (Ixvi): [ka] TIFF2025134777000091.tif126155, or its stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs R 1 and R 19 is any of the embodiments described herein. It is defined as either

[0276] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Ixi) and preferably in the form of the (S)-enantiomer. and / or embodiments thereof, the compound is according to formula (Ixii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Ixiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Ixiv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I xv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Ixvi): and preferably in the form of the (S)-enantiomer.

[0277] Optionally, in embodiments of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 -a Lucoxy C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, sia No, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 1 2′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R 8 and R 9together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, R 25 is hydrogen or C 1-3 - alkyl.

[0278] In one embodiment of the present invention and / or embodiments thereof, R 7 teeth, Methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, di Methylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydro (methoxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl) Amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine- From the group consisting of 1-yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Independently selected, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 25 is hydrogen or methyl, preferably hydrogen.

[0279] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Ixvii ), (Ixviii), (Ixix), (Ixx), (Ixxi) or (Ixxii) [ka] TIFF2025134777000093.tif125156 or its stereoisomers, physiologically acceptable salts, esters, solvates and polymorphs R 1 and R 19 is any of the embodiments described herein. It is defined as either

[0280] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Ixvii ), preferably in the form of the (S)-enantiomer. In certain aspects and / or embodiments thereof, the compound is according to formula (Ixviii): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Ixix), preferably In the embodiment of the present invention and / or its embodiments, The compound is according to formula (Ixx), preferably the (S)-enantiomer In an embodiment of the invention and / or embodiments thereof, the compound is of the formula (Ixxi), preferably in the form of the (S)-enantiomer. In certain and / or embodiments thereof, the compound is according to formula (Ixxii) and preferably in the form of the (S)-enantiomer.

[0281] The present invention is 7 , R 19 and R 25 The compounds according to the present invention are as defined above. and / or embodiments thereof.

[0282] Optionally, in embodiments of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle, C 1-3 - Alkoxy, hydroxy, NR 8 R 9 , S.R. 10 , SOR 10 and SO2R 10 Consists of are independently selected from the group, Each C 1-6 -alkyl, C2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 - Alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -Alkoxy, halogen, chlorine Ano, Hydroxy, NR 8′ R 9′ , C(=O)OR 10′ and C(=O)NR 11′ R 12′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -aryl and 5- to 10-membered heteroaryl or R8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C 1-6 -Alkyl, C 6-10 -aryl or 5-10 membered heteroaryl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, hydroxy and NR 8″ R 9″ from may be substituted with one or more substituents independently selected from the group consisting of: R 10 is hydrogen or C 1-3 from alkyl, preferably from hydrogen, methyl or ethyl Independently selected, R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen or C 1-3 -Alkyl are independently selected from, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - alkyl, preferably hydrogen, methyl or ethyl; R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6-Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of: R 25 is hydrogen or C 1-3 - alkyl.

[0283] In one embodiment of the present invention and / or embodiments thereof, R 7 teeth, Methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropyl isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino , methylamino, ethylamino, (ethyl)(methyl)amino, isopropylamino, dimethicone ethylamino, (isopropyl)(methyl)amino, hydroxyethylamino, (hydroxy (Methoxyethyl)(methyl)amino, methoxyethylamino, (Methoxyethyl)(methyl)amino amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine-1 -yl 3-fluoroazetidinyl and 3,3-difluoroazetidinyl Selected to be a R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro independently selected from the group consisting of 3,5-dichlorophenyl and 3,5-dichlorophenyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0284] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iyi): (Iyii), (Iyiii) or (Iyiv): [ka] TIFF2025134777000095.tif234157 or its stereoisomers, physiologically acceptable salts, esters, solvates and polymorphs R 1 , R 13 , R 14 , A1, A2, A3 and A4 is defined as in any of the embodiments described herein.

[0285] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Iyi) and preferably in the form of the (S)-enantiomer. and / or in embodiments thereof, the compound is according to formula (Iyii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Iyiii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iyiv), preferably in the form of the (S)-enantiomer It is a posture.

[0286] The present invention is 13 , R 14 , A1, A2, A3, A4, R 19 and R 25 As shown above The present invention provides compounds according to the invention and / or embodiments thereof, as defined in

[0287] Optionally, in embodiments of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the non-aromatic ring comprises one or more C 1-3 -Alkyl or =O and / or one or more of the ring-forming carbon atoms may be substituted by -NH-, -O may be replaced by -, -S(O)-, -S(O)2- or -S-, A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independent C 1-3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independent C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independent C 1-3 -alkyl, A4 is N or CR 18 and R 18are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independent C 1-3 -alkyl, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of: R 25 is hydrogen or C 1-3 - alkyl.

[0288] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is substituted by -NH- or -O-. It may be replaced with A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro independently selected from the group consisting of 3,5-dichlorophenyl and 3,5-dichlorophenyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0289] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Izi): (Izii), (Iziii), (Iziv), (Izv) or (Izvi): [ka] TIFF2025134777000097.tif221161TIFF2025134777000098.tif147160, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 and R 7 may be any of the embodiments described herein. It is defined as follows:

[0290] In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (Izi) and preferably in the form of the (S)-enantiomer. and / or in embodiments thereof, the compound is according to formula (Izii), preferably Preferably in the form of the (S)-enantiomer. In the form, the compound is according to formula (Iziii), preferably (S)- In an embodiment of the present invention and / or in an embodiment thereof, The compound is according to formula (Iziv), preferably in the form of the (S)-enantiomer In an embodiment of the present invention and / or embodiments thereof, the compound is of formula (I zv), preferably in the form of the (S)-enantiomer. In one embodiment and / or embodiment thereof, the compound is according to formula (Izvi): and preferably in the form of the (S)-enantiomer.

[0291] Optionally, in embodiments of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the aromatic ring comprises one or more C 1-3 -substituted by alkyl and / or one or more of the ring-forming carbon atoms may be -NH-, -N=, =N-, may be replaced by -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R 15″and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen, C 1-3 Alkyl , C 1-3 Alkoxy or NR 15′ R 15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, R 19 teeth, C 6-10 - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl , Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro and hydroxy and optionally substituted with one or more substituents independently selected from the group consisting of: R 25 is hydrogen or C 1-3 - alkyl.

[0292] Optionally, in embodiments of the present invention and / or embodiments thereof, R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and one or more of the ring-forming carbon atoms is -NH-, -N=, =N- or may be replaced by -S-, A1 is N or CR 15 and R 15 are independently hydrogen or C 1-3 It is alkoxy , A2 is N or CR 16 and R 16 are independently hydrogen or C 1-3 It is alkoxy , A3 is N or CR 17 and R 17 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, A4 is N or CR 18 and R 18 are independently hydrogen or C 1-3 Alkoxy, preferred or hydrogen, 0, 1 or 2 of A1, A2, A3 and A4 are N; R 19 teeth, 3-chlorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, 3, 5-difluorophenyl, 2,3,5-trifluorophenyl, 3,4,5-trifluorophenyl chlorophenyl, 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-dichloro independently selected from the group consisting of 3,5-dichlorophenyl and 3,5-dichlorophenyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0293] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Izvii ), (Izviii), (Izix), (Izx), (Izxi) or (Izxii): [ka] TIFF2025134777000100.tif196156TIFF2025134777000101.tif70155, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs thereof R 1 and R 7 may be any of the embodiments described herein. It is defined as follows:

[0294] In one embodiment of the present invention and / or embodiments thereof, the compound has the formula (Izvii ), preferably in the form of the (S)-enantiomer. In certain aspects and / or embodiments thereof, the compound is according to formula (Izviii): and preferably in the form of the (S)-enantiomer. In this embodiment, the compound is according to formula (Izix), preferably In the embodiment of the present invention and / or its embodiments, The compound is according to formula (Izx), preferably the (S)-enantiomer In an embodiment of the invention and / or embodiments thereof, the compound is of the formula (Izxi), preferably in the form of the (S)-enantiomer. In certain and / or certain embodiments thereof, the compound is represented by formula (Izxii): and preferably in the form of the (S)-enantiomer.

[0295] The compounds according to the invention can be considered "active" agents, which in this context means that Dirofilaria, especially Dirofilaria immitis It is considered to be a substance that inhibits the growth of helminths such as helminths (e.g., helminths of the family Lamium spp.). The term "inhibition" refers to a reduction in the rate of growth of the worm population. The term refers to a situation in which the worm population grows but at a low rate, as well as a situation in which the population stops growing, and This includes situations where the number of worms in the population decreases or the population disappears.

[0296] Furthermore, the present invention provides Compounds of formula (A): [ka] with a compound of formula (B): [ka] [In the formula, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3- 10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 Aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -alkoxy, C 1-6-Alkyl mercapto, halogen, cyano, nitrite B, hydroxy, mercapto, NR 2 R 3 , COOH, C(=O)OR 4 , S.R. 4 , SO R 4 , SO2R 4 , SO2NR 5 R 6 and C(=O)NR 5 R 6 Independently selected from the group consisting of Selected, Each C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10 Aryl, 5-10 membered heteroaryl Lu, C 1-6 -alkoxy or C 1-6 -Alkyl mercapto C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -alkoxy, C 1-6 -Alkyl mercapto, halogen, cyano, nitrite B, hydroxy, mercapto, NR 2′ R 3′ , C(=O)OR 4′ , S.R. 4′ , SOR 4′ , SO2R 4′ , SO2NR 5′ R 6′ and C(=O)NR 5′ R 6′ A group consisting of may be substituted by one or more substituents independently selected from R 2 and R3 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3- 10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Lille, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -cycloalkyl Replaced C 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C6 -10 -aryl-substituted C 1-6 -substituted with alkyl and 5-10 membered heteroaryl C 1-6 -alkyl, or R 2 and R 3 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, and 0, 1, 2 or 3 further ring atoms are N , S and O; Each C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Lu, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -cycloalkyl substituted C 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6-1 C substituted with O-aryl 1-6 -substituted with alkyl or 5-10 membered heteroaryl TaC 1-6 -alkyl or R 2 and R 3 are formed together with the N atoms to which they are attached. The heterocycle is C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Lu, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR 2″ R 3″ , C(=O)OR 4″ , S.R. 4″ , SOR 4 , SO2R 4″ , SO2NR 5″ R 6″ and C(=O)NR 5″ R 6″ one or more substitutions independently selected from the group consisting of optionally substituted with a group; R 4 , R 5 and R 6 is hydrogen and C 1-6 -alkyl; R 2′ , R 3′ , R 4′ , R 5′ and R 6′ is hydrogen and C 1-6 -Independent of alkyl Selected by R 2″ , R 3″ , R 4″ , R 5″ and R 6″ is hydrogen and C 1-6 -Independent of alkyl Selected by R 7 teeth, Hydrogen, C 1-6 -Alkyl, C2-6 -Alkenyl, C 2-6 -alkynyl, C 3- 10 -cycloalkyl, 4-10 membered heterocycle, C 6-10 Aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -alkoxy, C 1-6 -Alkyl mercapto, halogen, cyano, nitrite B, hydroxy, mercapto, NR 8 R 9 , COOH, C(=O)OR 10 , S.R. 10 , SOR 10 , SO2R 10 , SO2NR 11 R 12 and C(=O)NR 11 R 12 Because are independently selected from the group Each C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 4-10 membered heterocycle, C 6-10 Aryl, 5-10 membered heteroaryl Lu, C 1-6 -alkoxy or C 1-6 -Alkyl mercapto C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-1 0-Cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Ruhle, C 1-6 -alkoxy, C 1-6 -Alkyl mercapto, halogen, cyano, nitrite B, hydroxy, mercapto, NR 8′ R 9′ , C(=O)OR 10′ , S.R. 10′ , S OR10′ , SO2R 10′ , SO2NR 11′ R 12′ and C(=O)NR 11′ R 1 2′ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3- 10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Lille, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -cycloalkyl Replaced C 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C6 -10 -aryl-substituted C 1-6 -substituted with alkyl, 5-10 membered heteroaryl C 1-6 -alkyl, or R 8 and R 9 together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, and 0, 1, 2 or 3 further ring atoms are N , S and O; Each C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Lu, C 1-6 -Alkoxy-C1-6 -Alkyl, C 3-10 -cycloalkyl substituted C 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6-1 C substituted with O-aryl 1-6 -substituted with alkyl or 5-10 membered heteroaryl TaC 1-6 -alkyl or R 8 and R 9 are formed together with the N atoms to which they are attached. The heterocycle is C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Lu, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR 8″ R 9″ , C(=O)OR 10″ , S.R. 10″ , SOR 10″ , SO2R 10″ , SO2NR 11″ R 12″ and C(=O)NR 11″ R 12″ Independently selected from the group consisting of may be substituted with one or more substituents selected from the group consisting of aryl, aryl, aryl- ... R 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R 12′ is hydrogen and C 1-6 -Alkyl are independently selected from R8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -Alkyl are independently selected from R 13 is hydrogen or C 1-3 is alkyl, R 14 is hydrogen, C 1-3 Alkyl, C 1-3 Alkoxy, NR 14′ R 14″ and R 14′ and R 14″ is independently C 1-3 -alkyl, or R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the ring containing 5 or 6 carbon atoms has one or more C 1-3 -alkyl or ═O, and / or the ring carbons One or more of -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S- may be replaced by or R 13 and R 14 together with the atoms to which they are attached, 5 or 6 carbon atoms and the ring containing 5 or 6 carbon atoms has one or more C1 -3 and / or one or more of the ring carbons may be substituted by -alkyl. may be replaced by -NH-, -N=, =N-, -O- or -S-; A1 is N or CR 15 and R 15 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR15′ R 15″ and R 15′ and R 15″ is independently C1 -3 -alkyl, A2 is N or CR 16 and R 16 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16′ R 16″ and R 16′ and R 16″ is independently C1 -3 -alkyl, A3 is N or CR 17 and R 17 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17′ R 17″ and R 17′ and R 17″ is independently C 1-3 -alkyl, A4 is N or CR 18 and R 18 are independently hydrogen, halogen C 1-3 Alkyl, C1 -3 Alkoxy or NR 18′ R 18″ and R 18′ and R 18″ is independently C 1- 3-alkyl, R 19 is C 6-10 -independently from the group consisting of aryl and 5-10 membered heteroaryl Selected, Each C 6-10 -aryl or 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 5 10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, C 1-6 -Alcoki C 1-6 -Alkyl mercapto, halogen, cyano, nitro, hydroxy, mercapto To, NR 20 R 21 , C(=O)OR 22 , S.R. 22 , SOR 22 , SO2R 22 , SO 2NR 23 R 24 and C(=O)NR 23 R 24 One or more independently selected from the group consisting of and optionally substituted with a substituent of R 20 and R 21 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5-10 membered heteroaryl, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 6-10 - C1-C6-alkyl substituted with aryl, C substituted with 5-10 membered heteroaryl 1-6 -alkyl, or R 20 and R 21 have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C 1-6 -Alkyl, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 5 10-membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl, C 1-6 -Alcoki Shi or C1-6 -alkylmercapto or R 20 and R 21 The N atoms to which they are bonded The heterocycle formed together with the alkyl group is C 1-6 -Alkyl, C 2-6 -Alkenyl, C 2-6 -alkynyl, C 3-10 -cycloalkyl, 5-10 membered heterocycle, C 6-10 -aryl, 5-10 membered heteroaryl Lu, C 1-6 -alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR 20′ R 21′ , C(=O)OR 22′ , S.R. 22′ , SOR 22′ , SO2R 22 ′ , SO2NR 23′ R 24′ , and C(=O)NR 23′ R 24′ Independent from the group consisting of and optionally substituted with one or more substituents selected from R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -Arki are independently selected from the R 25 is hydrogen and C 1-6 -alkyl, A method for preparing a compound according to formula (I) is provided, comprising the step of obtaining a compound according to formula (I): do.

[0297] In an embodiment of the present invention and / or embodiments thereof, R 1 , R 7 , R 13 , R 14 , A1, A2, A3, A4, R 19 and R 25 As far as is concerned, with regard to the compounds according to the invention The same applies as above.

[0298] Compounds of formula (A) and formula (B) are commercially available or synthetically available.

[0299] In one embodiment of the present invention and / or embodiments thereof, an amine of formula (A) and an amine of formula (B) The corresponding amide group is formed using the carboxylic acid in the presence of a coupling reagent in an organic solvent. It can be achieved. Coupling agents can generally be considered as substances that facilitate the formation of esters or amides. The coupling agent reacts with the carboxyl group to form a reactive intermediate, which is then reacted with the alcohol. further reacting with an alcohol or amine to form the final product, i.e., an ester or amide. .

[0300] Examples of coupling agents include carbodiimides, such as N,N'-dicyclohexylcarbodiimides, Diimide (DCC), diisopropylcarbodiimide (DIC), 1-ethyl-3-(3 -dimethylaminopropyl)carbodiimide (EDC), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide N-Cyclohexyl- N'-(2-morpholinoethyl)carbodiimide-methyl-p-toluenesulfonate ( CMC), phosphonium salts, such as benzotriazol-1-yl-oxytripyrrolidine phosphonium hexafluorophosphate (PyBOP), aminium salts, such as 3- [Bis(dimethylamino)methyliumyl]-3H-benzoto Triazole-1-oxide-hexafluorophosphate (HBTU) and carbonyldi These include, but are not limited to, imidazole (CDI).

[0301] In an embodiment of the present invention and / or embodiments thereof, the coupling agent is N,N'- Dicyclohexylcarbodiimide (DCC), diisopropylcarbodiimide (DIC) , 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), 1-ethyl Ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (EDCxHCl) and and carbonyldiimidazole (CDI). More preferably, the coupling The agent is 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride.

[0302] Organic solvents are known to those skilled in the art.

[0303] Suitable organic solvents for the process according to the invention are, for example, acetonitrile, dioxane, tetrahydrofuran ... Tetrahydrofuran (THF) and dimethylformamide (DMF), dimethyl sulfoxide The solvent may be dimethyl sulfoxide (DMSO), or preferably dimethylformamide (DMF).

[0304] In an embodiment of the present invention and / or embodiments thereof, the process comprises the steps of: Suitable alkaline compounds include pyridines, for example 4- (Dimethylamino)pyridine (DMAP), amidine, e.g., 1,8-diazabicyclo[4.2.1.2]pyridine, 2[5.4.0]indec-7-ene (DBU) and amines, such as triethylamine and diisopropylethylamine (DIPEA), preferably 4-(dimethylamino)pi Examples include, but are not limited to, lysine (DMAP).

[0305] In an embodiment of the present invention and / or embodiments thereof, the process is carried out at a temperature of 5°C to 120°C. The reaction can be carried out at a temperature of 20 to 100°C, preferably 20 to 100°C.

[0306] In another embodiment of the present invention and / or embodiments thereof, a carboxylic acid according to formula (B) with thionyl chloride or oxalyl chloride, preferably oxalyl chloride, The corresponding acid chloride can then be converted into a compound according to formula (A): It can be used in reactions with amines to give compounds of formula (I).

[0307] In another embodiment of the present invention and / or embodiments thereof, the other process comprises: It can be carried out in a solvent and / or in the presence of an auxiliary alkaline compound.

[0308] Suitable organic solvents are, for example, acetonitrile, toluene, dioxane, tetrahydrofuran, The solvent may be toluene, chloroform or dichloromethane.

[0309] As far as auxiliary alkaline compounds are concerned, the same applies as above and are preferred. are pyridine, DMAP, triethylamine and diisopropylethylamine.

[0310] Furthermore, the present invention provides a pharmaceutical composition comprising a compound according to the present invention and one or more physiologically acceptable excipients. Veterinary drug compositions are provided.

[0311] The veterinary compositions of the present invention and / or embodiments thereof may be administered in one or more physiologically acceptable excipients. The present invention includes a therapeutically effective amount of a compound of the present invention and / or an embodiment thereof formulated with an agent.

[0312] Physiologically acceptable excipients are well known in the art. naro, Remington: The Science and Practice of Pharmacy″ (20 th Edition, 2000). All such physiologically acceptable excipients are substantially pharmaceutically or veterinarily pure and It must be non-toxic in the amounts used and must be compatible with the active ingredient. In one preferred embodiment of the present invention and / or embodiments thereof, said one or more The physiologically acceptable excipients include carriers, binders, antioxidants, buffers, sugar components, surfactants, The additives are selected from lubricants, stabilizers, flow agents, disintegrants and preservatives, and mixtures thereof.

[0313] As used herein, the term "carrier" refers to any type of non-toxic, inert, solid carrier. means a carrying / encapsulating material of a solid, semi-solid or liquid filler or diluent. Some examples of materials that can function as acceptable carriers are lactose, glucose, sugars such as cornstarch and potato starch; Cellulose such as sodium dimethylcellulose, ethylcellulose and cellulose acetate and derivatives thereof; powdered tragacanth; malt; gelatin; talc; cocoa butter and suppositories Excipients such as waxes; peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oils such as corn and soybean oil; esters such as ethyl oleate and ethyl laurate; Heaven, but is not limited to these.

[0314] A binder is a substance that can make other substances adhere to each other. When the polymer is used, the temperature is preferably 25 to 100°C, more preferably 35 to 85°C, and particularly preferably 40 to 7 Melting point or glass transition temperature (T g ) is a component having the glass transition temperature , the temperature at which a polymer becomes brittle when cooled and softens when heated. When the polymer reaches the glass transition temperature (T g ) softens at higher temperatures and can be plastically deformed without fracture The glass transition temperature or melting point can be determined by methods known to those skilled in the art. It is measured as follows.

[0315] In one preferred embodiment of the present invention and / or embodiments thereof, the binder is a poly Ethylene glycol, polypropylene glycol, polyethylene glycol-polypropylene Polyethylene Glycol Copolymer, Microcrystalline Wax, Glycerol Monostearate, Hydrogenated Castor Oil Oil, polyethylene glycol glycerol hydroxystearate, polysaccharides, polyvinyl Pyrrolidone, polyvinyl alcohol, poly(meth)acrylate, polyvinylpyrrolidone - polyacetic acid copolymers and mixtures thereof.

[0316] Antioxidants are substances used to inhibit oxidation. Suitable antioxidants for incorporation into formulations include ascorbic acid, glutathione, and tocopherol. and its esters, tert-butylhydroquinone (TBHQ), butylhydroxy Anisole (2-tert-butyl-4-hydroxyanisole, 3-tert-butyl butyl hydroxyanisole (BHA, also known as 4-hydroxyanisole, or mixtures thereof) and xytoluene (also known as 2,6-ditert-butyl 4-methylphenol, BHT) Antioxidants may be present in agglomerates. In one preferred embodiment of the present invention and / or embodiments thereof, The antioxidant contained in the pharmaceutical formulation can range from 0.001 to 1.00% by weight. do.

[0317] Buffers are substances that maintain / regulate the pH value of a product. Non-limiting examples of buffers Examples include bicarbonate, dihydrogen phosphate, and hydrogen phosphate.

[0318] Sugar ingredients are used to sweeten the taste of the product. They are naturally occurring sugars (carbohydrates) and and sugar substitutes. In one preferred embodiment of the present invention and / or its embodiments In this case, the amount of buffering agent contained in the animal dosage form can be in the range of 1 to 10% by weight.

[0319] A surfactant can be considered as a substance that reduces the interfacial tension between two phases. Surfactants include alkyl sulfates (e.g., sodium lauryl sulfate), alkyl trimethyl ammonium salts, alcohol ethoxylates, etc. One preferred embodiment of the present invention In one embodiment, the surfactant contained in the animal drug form is 0.1 to 1 It can range from 0.0% by weight.

[0320] Lubricants are generally used to reduce friction such as static friction, sliding friction, and rolling friction. The lubricant is preferably stearic acid or a fatty acid, more preferably The preferred stearate is an alkaline earth metal stearate such as magnesium stearate. In one preferred embodiment and / or embodiments thereof, the moisturizing agent contained in the animal dosage form The lubricant can range from 0.1 to 10.0% by weight.

[0321] Stabilizers are physiologically acceptable excipients that help preserve the product. Examples include: , alginates, carrageen, gelatin, pectin and natural gums, among others. It is not intended to be limiting. In this case, the surfactant contained in the animal drug form is in the range of 0.01 to 3.0% by weight. can be done.

[0322] Flow agents, also called glidants, can be used to improve fluidity. Traditionally, talc was used as a glidant, but today it is almost entirely colloidal silica. In one preferred embodiment of the present invention and / or its embodiments, Therefore, the amount of the flow agent contained in the animal dosage form can be in the range of 1 to 3% by weight.

[0323] Disintegrants, also called tablet disintegrants, disintegrate the dosage form, Preferably, the disintegrant is a compound that enhances the ability of the tablet to disintegrate into smaller pieces. Typical examples include sodium carboxymethyl starch and sodium starch glycolate. cross-linked polyvinylpyrrolidone, sodium carboxymethyl glycolate, preferably One preferred embodiment of the present invention and / or In one embodiment thereof, the surfactant contained in the animal drug form is 1.0 to 7.0 wt.% The range can be:

[0324] Preservatives are microorganisms By proliferation Decomposition or undesirable chemical changes by Decomposition Added to prevent Non-limiting examples include lactate, benzoate, and hydroxybenzoates. In one preferred embodiment of the present invention and / or its embodiments, In animal drug formulations, the surfactant content should be in the range of 0.01 to 1.0% by weight. can.

[0325] The compounds according to the present invention can be administered in a variety of dosage forms. The compounds of the invention are formulated into products suitable for administration to animals via the intended route of administration. Such dosage forms are referred to herein as formulations or pharmaceutical compositions. This may be the case.

[0326] The pharmaceutical compositions of this invention and / or embodiments thereof may be administered to animals orally, rectally, vaginally, parenterally, or intravenously. Administration can be orally, topically, bucally or nasally.

[0327] In one preferred embodiment of the present invention and / or embodiments thereof, the composition is useful for oral administration. The dosage form can be a liquid or solid dosage form.

[0328] Liquid dosage forms of compounds are generally solutions, suspensions, or emulsions. A suspension is a mixture of two or more components that form a single phase in a liquid medium until homogeneous. The solid particles comprise insoluble solid particles dispersed in the suspension, and these solid particles account for approximately 0.5% to 30% of the suspension. Liquids may be aqueous, oily, or both. Emulsions are a type of immiscible liquid. It is a heterogeneous dispersion in a liquid and requires an emulsifier to maintain stability. The powder (or granules) is added to a diluent (e.g., water) as a liquid or suspension immediately prior to injection. The main advantage of this dosage form is that it overcomes the instability problems of solutions or suspensions. The key is to overcome this.

[0329] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, These include liquids, suspensions, syrups, drenches, preparations in feed or drinking water, and elixirs. The drench is administered into the mouth / mouth of the animal, particularly a dog, by means of a "drench gun" or syringe or other suitable device. It is a liquid oral formulation that is administered directly to the throat. The composition is added to the drinking water of the recipient animal or as a drench. When administered intravenously, it may be convenient to use a liquid or suspension formulation. For example, a concentrated suspension that is mixed with water, or a dry preparation that is mixed and suspended in water. In addition to the active compound, liquid dosage forms may contain, for example, water or other solvent, solubilizing agent, and emulsion. Acidifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol ethanol, dimethylformamide, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil) (castor oil, and sesame oil), glycerol, tetrahydrofurfuryl alcohol, poly Fatty acid esters of ethylene glycol and sorbitan and mixtures thereof In addition to the inert diluents, oral Compositions may also comprise adjuvants, such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. This can be done.

[0330] Solid dosage forms for oral administration include capsules, tablets, dragees, pills, powders and granules, chewable tablets, and These solid dosage forms include feeds, premixes, and medicated blocks. sodium phosphate or dicalcium phosphate, and / or a) starch, lactose, sucrose, glucose b) fillers or extenders such as carboxymethylcellulose, mannitol, and silicic acid; Cellulose, alginate, gelatin, polyvinylpyrrolidinone, sucrose and acacia c) humectants such as glycerol; d) agar, calcium carbonate, potato or crumbly materials such as tapioca starch, alginic acid, certain silicates and sodium carbonate disintegrants; e) dissolution retarders such as paraffin; f) absorption enhancers such as quaternary ammonium compounds. g) wetting agents such as acetyl alcohol and glycerol monostearate; h) adsorbents such as kaolin and bentonite clay; i) talc, calcium stearate, Magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and at least one inert pharmaceutically acceptable excipient, such as a lubricant, including mixtures thereof; In the case of capsules, tablets and pills, the dosage form may also be It may also contain a buffer.

[0331] The active compounds may also be in microencapsulated form with one or more excipients as noted above. Solid dosage forms of tablets, dragees, capsules, pills and granules may be enteric coated, as well as enteric coated. coatings, sustained release coatings and other coatings The coatings and shells may be prepared as well, such as other coatings known in the art. In such solid dosage forms, the active compound is preferably present in at least one sugar, such as sucrose, lactose, or starch. Such dosage forms may also be mixed with an inert diluent, as is normal practice. Other substances than inert diluents, such as magnesium stearate and microcrystalline cellulose, may be used. For capsules, tablets and pills, any tableting lubricants and other tableting aids may be included. The dosage forms may also contain buffering agents. They may optionally contain opacifying agents, In addition, they may be administered only or preferentially, optionally in a delayed manner, in certain parts of the intestinal tract. Examples of the implantable composition include a polymeric substance. and wax.

[0332] In addition, excipients such as lactose or milk sugar and high molecular weight polyethylene glycols may be used. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules. This can be done.

[0333] Solid oral formulations can be administered directly to animals (tablets, capsules) or mixed into the feed. , administered via a medicated feed block.

[0334] When the oral formulation is administered via the feed of a non-human animal, it may be administered, for example, as a discrete feed. Alternatively (or additionally), it can be given as a chewable food, e.g. It can be dispersed thoroughly in the treated animal's normal feed or used as a top dressing. or in the form of solid pellets, pastes or liquids to be added to finished feed. When the oral formulation is administered as a feed additive, it is advisable to mix the oral formulation with a small amount of liquid or solid carrier. It may be convenient to prepare a "premix" in which the components are dispersed in the "premix". is then dispersed in the animal's normal feed using, for example, a conventional mixer.

[0335] In one preferred embodiment of the present invention and / or embodiments thereof, rectal and vaginal administration The dosage form useful for can be considered a semi-solid dosage form.

[0336] Compositions for rectal or vaginal administration contain the compounds of the invention in a form that is solid at ambient temperature but is hydrophilic at body temperature. Cocoa butter is liquid and therefore dissolves in the rectum or vaginal cavity to release the active compounds. - mixed with a suitable non-irritating excipient or carrier such as polyethylene glycol or a suppository wax It can be prepared by

[0337] In one preferred embodiment of the present invention and / or embodiments thereof, the dosage form is a parenteral One route of administration is parenteral administration, particularly by injection (e.g. Parenteral formulations and delivery systems are liquid (e.g., solutions, suspensions, emulsions and dry powders for reconstitution), semi-solids and solids (e.g., Most implants used in veterinary medicine contain drugs in non-degradable polymers. It is a compressed tablet or dispersion matrix system in which the granules are uniformly dispersed within the matrix, or an extruded product. In one embodiment, the compounds of the invention are administered subcutaneously.

[0338] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions, can be prepared using suitable dispersing or wetting agents and suspending agents. Sterile injectable preparations can also be formulated using suspending agents according to known techniques. As a solution in 3-butanediol, in a non-toxic parenterally acceptable diluent or solvent It may be a sterile injectable solution, suspension or emulsion. Among the solvents are water, Ringer's solution, and isotonic sodium chloride solution. Bulk, fixed oils are conventionally employed as a solvent or suspending medium. In this regard, synthetic mono- or di-glycerides are also preferred. Any bland fixed oil may be used, including diglycerides of oleic acid. Such fatty acids are used in the preparation of injectables.

[0339] Injectable preparations may be prepared by, for example, filtration through a bacteria-retaining filter, or by adding sterilized water or is in the form of a sterile solid composition that can be dissolved or dispersed in other sterile injectable media. It can be sterilized by incorporating

[0340] Slowing the absorption of drugs from subcutaneous or intramuscular injections to prolong the drug's effect This is often desirable because liquid suspensions of crystalline or amorphous material with poor water solubility are used. The rate of absorption of a drug is determined by its dissolution rate, which The dissolution rate of a drug may further depend on the crystal size and crystalline form. Delayed absorption of a drug can be accomplished by dissolving or suspending the drug in an oil solution. Possible depot formulations include microencapsulation of drugs in biodegradable polymers such as polylactide-polyglycolide. The drug:polymer ratio and use are controlled by forming an encapsulation matrix. Depending on the nature of the particular polymer used, the rate of drug release can be controlled. Examples of biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations are also available in liposomes or microemulsions that are compatible with body tissues. It can also be prepared by entrapment of an object.

[0341] In one preferred embodiment of the invention and / or embodiments thereof, the compound of the invention Dosage forms useful for topical administration (also called transdermal administration) include ointments, pastes, creams, lotions, and the like. This includes ointments, gels, powders, solutions, sprays, inhalants or patches. in admixture with a pharmaceutically acceptable carrier and, if necessary, a preservative or buffer. Ear drops and the like are also contemplated as being within the scope of this invention.

[0342] Ointments, pastes, creams and gels may contain, in addition to the active compounds of the present invention, animal and plant based compounds. Fatty fats, oils, waxes, paraffins, starches, tragacanth, cellulose derivatives, polyesters ethylene glycol, silicone, bentonite, silicic acid, talc and zinc oxide or The composition may contain excipients such as mixtures of

[0343] The compound of the present invention may also be prepared by adding, in addition to the compound of the present invention, lactose, talc, silicic acid, aluminum hydroxide, etc. Excipients such as aluminum, calcium silicate and polyamide powder or mixtures of these materials It can be formulated for use as a topical powder or spray containing .

[0344] Sprays may further contain customary propellants, such as chlorofluorohydrocarbons. do.

[0345] Transdermal patches have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the compound in the proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. .

[0346] The rate can be determined by either providing a rate-controlling membrane or dispersing the compound in a polymer matrix or gel. This can be controlled by making the

[0347] In one preferred embodiment of the invention and / or embodiments thereof, the compound of the invention Dosage forms useful for buccal administration include orally disintegrating tablets (ODTs), films, sublingual drops, and lozenges. , effervescent oral tablets, toothpaste and mouthwash.

[0348] In one preferred embodiment of the invention and / or embodiments thereof, the compound of the invention Dosage forms useful for intranasal administration include liquid aerosols or inhaled dry powders. The nebulizer formulation can be nebulized to a particle size that can be delivered primarily to the terminal and respiratory bronchioles. .

[0349] Liquid aerosol and inhaled dry powder formulations preferably deliver the entire endobronchial tree up to the terminal bronchi. and ultimately delivered to the parenchymal tissue.

[0350] The aerosolized formulations of the present invention preferably have a median mass (m) of primarily 1 to 5 pm. Jets selected to allow the formation of aerosol particles with a mean diameter of 1000 mm Delivery may be by using an aerosol-forming device such as a nebulizer, vibrating porous plate, or ultrasonic nebulizer. This can be done.

[0351] Additionally, the formulation preferably has a balanced osmolarity, ionic strength and chloride content. The smallest aerosol that has a maximal concentration and is capable of delivering an effective dose of the compound of the present invention to the site of infection. In addition, the aerosolized formulation preferably has a volume that allows it to be solated. It reduces sensitivity and does not cause unwanted side effects.

[0352] Aerosolization devices suitable for administering the aerosol formulations of the present invention include, for example, A jet that can atomize the air into aerosol particles with a diameter range of 1 to 5 pm. These include nebulizers, vibrating perforated plates, ultrasonic nebulizers and high-energy dry powder inhalers. In this application, at least 70% of all generated aerosol particles, but Preferably, more than 90% of the dose is within the range of 1 to 5 pm. Jet nebulizer The vibrating porous device acts by using air pressure to break up the liquid solution into aerosol droplets. Plate nebulizers use an ultrasonic vacuum created by a rapidly vibrating porous plate. It works by using an acuum to push the solvent droplets through a porous plate. The aerosol works by shearing a liquid into small aerosol droplets using a piezoelectric crystal.

[0353] The concentration of the compound according to the invention in the applied dosage form will vary depending, for example, on the route of administration. Generally, the compound of the invention in a formulation according to the invention or an embodiment thereof The concentration in an embodiment thereof is 1 to 70% by weight based on the total weight of the formulation. In some embodiments, the concentration is 1 to 50% by weight, or 10 to 50% by weight. The concentration is 35 to 65% by weight, 40 to 60% by weight, 45 to 55% by weight, or about 50% by weight. % by volume.

[0354] A preferred concentration of a compound according to the present invention or an embodiment thereof dissolved in drinking water is 0.0 1 to 0.05% by weight, especially 0.01 to 0.025%, infeed 100 to 400pp m (g / metric ton), especially 100-200 ppm.

[0355] In a preferred embodiment of the present invention or embodiments thereof, the veterinary composition and / or or an embodiment thereof, comprising a therapeutically effective amount of a compound of the invention as the sole active agent and / or Including embodiments thereof.

[0356] In a preferred embodiment of the present invention or embodiments thereof, the veterinary composition and / or or embodiments thereof, comprising a therapeutically effective amount of a compound of the present invention in combination with one or more other known active agents. These one or more other known active agents include compounds and / or embodiments thereof of the present invention. The spectrum of the compound of the present invention is similar to that of the compound of the present invention. Alternatively, the combination of one or more of these compounds can synergistically enhance the treatment of infections encompassed by these compounds. The above other known active agents may require, in addition to the present compound, another agent with a different spectrum. If multiple organisms are suspected of being affected, they may have different spectra from the present compound. Treatment may involve administering a composition comprising a compound of the present invention and one or more additional known active agents; Alternatively, administration of a compound of the present invention may be followed by administration of one or more additional active agents, or It may involve administering the compound prior to administration of the compound of interest.

[0357] Further aspects regarding the formulation of drugs and various excipients are found in, for example, Gennaro, A. R., et al., eds., Remington: The Science and Practice of Pharmacy (Lippincott Wi lliams&Wilkins, 20 th Ed., 2000). Methods for preparing such compounds are known in the art and are described, for example, in Remington: The Science and Practice of Pharmacy, Mack Publishing ng Company, Easton, Pa., 19th Edition (1 995).

[0358] As indicated above, the compounds according to the present invention can be considered "active" agents, which are , Dirofilaria, especially Dirofilaria immitis It is considered to be a substance that inhibits the growth of helminths such as rofilaria immitis. The term "inhibits growth" refers to a reduction in the rate of increase in the number of worm populations. vinegar.

[0359] In a preferred embodiment, the compounds according to the invention are used to treat helminth infections, such as a) tapeworms: e.g. , Anaplocephala species; Dipylidium Diphyllobothrium species; Echinococcus species;Moniezia species; Taenia species; b) Trematodes: e.g., Dicrocoel ium) species;Fasciola species;Param Schistosoma species; c) nematodes, For example, Acanthocheilonema species; Ancylostoma species; Anecator species; Ascari Ascaridia species; Ascaris species; Br ugia species; Bunostomum species; Capillaria laria species; Chabertia species; Cooperia ria) species; Cyathostomum species; Silicocyclus (C ylicocyclus species; Cylicodontphorus rus species; Cylicostephanus species; Cratero Craterostomum species; Dictyocaulus lus species; Dipetalonema species; Dirofilaria rofilaria species; Dracunculus species; Entero Enterobius species; Filaroides species; Habronema species; Haemonchus species; Heterakis species; Hyostrongylus ) genus species; Metastrongylus genus species; Meurelius ullerius species; Necator species; Nematodirus todirus) species; Nippostrongylus species ;Oesophagostomum species;Onchocerca ocerca species; Onchocercidae species; Oster Ostertagia species; Oxyuris species; Parasca Parascaris species; Stephanurus species; Strongylus species; Syngamus species; Toxocara species; Strongyloides s) genus species; Teladorsagia genus species; Toxuscaris ascaris species; Trichinella species; Trichinella species ichuris species; Trichostrongylus species Species; Triodontophorus genus species; Uncinaria ( Uncinaria spp. and / or Wuchereria spp.; preferred Nematodes; especially Dirofilaria species; Haemonchus monchus species; Ascaridia species; Strongylus (S trongylus species; specifically, Dirofilaria immitis ia immitis) It can be used to treat infections.

[0360] As used herein, "treating" or "treatment" refers to The term "prophylactic, meta-prophylactic and therapeutic or curative treatment" includes prophylactic, meta-prophylactic and therapeutic or curative treatment. It is understood that preventative or meta-preventative treatment, i.e., deworming, generally involves preventing helminth infections. It is used to prevent and control parasitic infections in animals. It also poses a threat to human health because it can infect humans. , procedures performed at regular intervals such as 1-6 times per year, or 2-4 times per year, or 1-4 times per month, or This includes continuous treatment, for example via drinking water. Meta-prophylaxis is when a certain number of animals are diagnosed. In some cases, for example, treating all animals in the same area can prevent the parasite from spreading to other animals. Meta-prophylaxis and prophylaxis may also be seasonal. This can be done, for example, at a time when the vector is particularly active.

[0361] In therapeutic or curative treatments, the compounds are administered after clinical diagnosis. The cost of treatment is reduced and the likelihood of resistance selection is greatly reduced if only a portion of the animals are treated. This ensures the presence of susceptible parasite populations within the flock or flock, but the absence of The key point is that it requires regular monitoring to increase labor input.

[0362] The present invention relates to a compound according to the invention or a veterinary drug according to the invention for use as a pharmaceutical. In a preferred embodiment, a compound according to the present invention or a veterinary drug according to the present invention is provided. The composition may be used as a pharmaceutical for the treatment of helminth infections such as filariasis and particularly dirofilariasis. Suitable for all uses.

[0363] The compound according to the present invention or the veterinary drug composition according to the present invention is used to manufacture a medicament. In one embodiment, the compound according to the invention or the veterinary composition according to the invention is used to treat filariasis and and in particular for the manufacture of medicaments for the treatment of helminth infections such as heartworm disease.

[0364] Furthermore, the present invention relates to a compound according to the invention or a veterinary composition according to the invention for the manufacture of a medicament. Providing use of an object.

[0365] Furthermore, the present invention relates to a method for treating helminth infections such as filariasis and particularly dirofilariasis. There is provided the use of a compound of the invention or a veterinary composition according to the invention for the manufacture of a medicament. Preferably, the compounds of the invention or the veterinary pharmaceutical compositions according to the invention are used to treat filariasis and especially ileal filariasis. It is used in the manufacture of drugs for the treatment of helminth infections such as filariasis.

[0366] Furthermore, the present invention relates to the treatment of helminths, preferably a) cestodes: for example, Anaplocephala ( Anaplocephala species; Dipylidium species; Diphyllobothrium species; Echinococcus nococcus genus; Moniezia genus; Taenia ) genus and species; b) Trematodes: e.g., Dicrocoelium spp.; Fasci Fasciola species; Paramphistomum genus and species; Schistosoma genus and species; c) nematodes, e.g., Acanthocheiro Acanthocheilonema species; Ancylostoma oma species; Anecator species; Ascarid Ascaris species; Brugia species; Buno Bunostomum species; Capillaria species; Chi Chabertia species; Cooperia species; Cyathium Cyathostomum species; Cylicocyclus s) genus and species; Cylicodontophorus genus and species; Silico Stephanus (Cylicostephanus species); Craterostomum (Crate rostomum species;Dictyocaulus species;Zipeta Dipetalonema species; Dirofilaria Genus and species: Dracunculus; Enterobius bius species; Filaroides species; Habronema onema species; Haemonchus species; Heterakis akis genus species; Hyostrongylus genus species; Metastrogi Metastrongylus species; Meullerius species Species: Necator species; Nematodirus species ;Nippostrongylus species;Esophagostomum Oesophagostomum species; Oncocerca species; Onchocercidae species; Ostertagia agia species; Oxyuris species; Parasca ris genus species; Stephanurus genus species; Strongylus rongylus species; Syngamus species; Toxocara cara) species; Strongyloides species; Terradorsa Teladorsagia species; Toxascaris species ;Trichinella species;Trichuris species ;Trichostrongylus species;Triodontophos Triodontophorous species; Uncinaria species and / or Wuchereria species; more preferably nematodes; in particular Dirofilaria species; Haemonchus Ascaridia species;Strongylus s) genus species and Oesophagostomum dentatum (Oesophagostomum de ntatum, especially Dirofilaria immitis Disorders / diseases caused by one or more helminths selected from the group consisting of: The present invention provides a compound according to the invention or a composition according to the invention for use in the treatment of

[0367] In a preferred embodiment of the invention or an embodiment thereof, the compound according to the invention or The disclosed compositions are for use in the treatment of helminth infections such as filariasis and particularly dirofilariasis. In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention is The compound or composition of the present invention is preferably a compound or composition of the present invention, wherein the helminth is Dirofilaria species, such as Dirofilaria spp. More specifically, Dirofilaria repens or Dirofilaria Dirofilaria immitis is a helminth The present invention is for use in the treatment of disorders / diseases caused by

[0368] In a preferred embodiment of the invention or an embodiment thereof, the compound according to the invention or The disclosed compositions are for use in the treatment of haemonchosis. In one embodiment thereof, the compound according to the invention or the composition of the invention is Haemonchus species, especially Haemonchus prasei hus placei) and Haemonchus contortus (Haemonchus contortus) tortus) for use in the treatment of disorders / diseases caused by helminths It is something.

[0369] In a preferred embodiment of the invention or an embodiment thereof, the compound according to the invention or The disclosed composition is for use in the treatment of ascariasis. In one aspect or embodiment thereof, the compound according to the invention or the composition of the invention is It is caused by the helminth Ascaridia galli The invention is for use in the treatment of certain disorders / diseases.

[0370] In a preferred embodiment of the invention or an embodiment thereof, the compound according to the invention or The disclosed composition is for use in the treatment of esophagostomy. In a preferred embodiment or embodiments thereof, the compound according to the invention or the composition of the invention The worms are Oesophagostomum species, especially Oesophagostomum Oesophagostomum venulosum and Oesophagostomum dentalum ) for use in the treatment of disorders / diseases caused by helminths. do.

[0371] In a preferred embodiment of the invention or an embodiment thereof, the compound according to the invention or The disclosed compositions are for use in the treatment of Trichostrongylus infections. In one embodiment or an embodiment thereof, the compound according to the invention or the composition of the invention is However, Trichostrongylus species, especially Trichostrongylus Trichostrongylus axei and Tricostrum Trichostrongylus colubriformis formis) for use in the treatment of disorders / diseases caused by helminths. This is what we want to achieve.

[0372] In a preferred embodiment of the invention or an embodiment thereof, the compound according to the invention or The disclosed compositions are for use in the treatment of ostertagia. In a preferred embodiment or embodiments thereof, the compound according to the invention or the composition of the invention comprises The helminth is Ostertagia species, especially Ostertagia osterta Caused by a helminth, Ostertagia ostertagi For use in the treatment of disorders / diseases.

[0373] In a preferred embodiment of the invention or an embodiment thereof, the compound according to the invention or The disclosed compositions are for use in the treatment of Cooperia infections. In one embodiment or embodiments thereof, the compound according to the invention or the composition of the invention is The insects are Cooperia species, especially Cooperia oncophora for the treatment of disorders / diseases caused by helminths, such as Paramecium gallate (Paramecium gallate), It is for use in

[0374] In a preferred embodiment of the invention or an embodiment thereof, the compound according to the invention or The disclosed composition is for use in the treatment of nematodiriasis. In a preferred embodiment of the present invention or an embodiment thereof, the compound according to the present invention Alternatively, the composition of the present invention may be used when the helminth is a Nematodirus species, particularly a Nema Nematodirus helvetianus, Nema The helminth, Nematodirus spathiger, The present invention is for use in the treatment of disorders / diseases caused by

[0375] The compounds according to the invention and the corresponding uses according to the invention can be administered to humans and non-human animals, It is particularly envisioned that such compounds may be used to treat animals, including non-human mammals. Suitable non-human mammals include, for example, domestic mammals (e.g., pigs, domestic ruminants, e.g., cows, animals (e.g., mice, rats, gerbils, etc.), Companion mammals (e.g., dogs, cats, horses, etc.), as well as wild and zoo mammals (e.g., buffalo, deer, etc.). The compound is also effective against poultry (e.g., turkey, , chickens, ducks, etc.) and non-mammals such as fish (e.g., salmon, trout, carp, etc.) It is envisaged that the compound is suitable for treating

[0376] Dirofilaria, especially Dirofilaria immitis ( filariasis and special cases associated with Dirofilaria immitis and a method for treating canine heartworm infections, comprising administering to a dog a compound of formula (I) or (II) of the general structure disclosed herein. The uses of the compounds disclosed and covered may be referred to as "uses according to the invention."

[0377] The compounds of the invention as disclosed and defined above are useful in treating heartworm disease, especially in dogs, and in particular in dogs. The present inventors have shown that the compound is particularly suitable for treating helminth infections such as filariasis. It became. The compounds according to the invention or the veterinary composition according to the invention can be used to treat a) cestodes: e.g. Acanthopanax erythroderma Acanthocheilonema species; Anaplocephala ocephala species; Dipylidium species; Dipylidium Diphyllobothrium species; Echinococcus cus species; Moniezia species; Taenia species; b ) Trematodes: e.g. Dicrocoelium species; Fasciola sciola species; Paramphistomum species; Sciola Schistosoma species; c) nematodes, e.g., Ancylostoma lostoma species; Anecator species; Ascaria species Ascaris species; Brugia species Species; Bunostomum species; Capillaria Genus and species; Chabertia species; Cooperia species ;Cyathostomum species;Cylicoc Cylicodontphorus species; Cylicodontphorus species ;Cylicostephanus species;Craterostomum raterostomum species; Dictyocaulus species ;Dipetalonema species;Dirofilaria ria) species; Dracunculus species; Enterobius terobius species; Filaroides species; Habronema ( Habronema species; Haemonchus species; Heterakis eterakis species;Hyostrongylus species;Meta Metastrongylus species; Meulleri us) genus species; Necator genus species; Nematodiru s) genus and species; Nippostrongylus genus and species; Esophagus Oesophagostomum species; Oncocerca ) genus species; Onchocercidae genus species; Ostertagia (Os tertagia species; Oxyuris species; Parascalis species ascaris species; Stephanurus species; Strongyl ...

Claims

1. A compound of the following formula (I) or a stereoisomer, physiologically acceptable salt, ester or solvate thereof: Substances, polymorphs, prodrugs and mixtures. 【Chemical 1】 [In the formula, R １ teeth, Hydrogen, C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－ １０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ Aryl, 5- to 10-membered heteroaryl Ru, C １－６ -alkoxy, C １－６ -Alkyl mercapto, halogen, cyano, nitrite b, hydroxy, mercapto, NR ２ R ３ , COOH, C(=O)OR ４ , S.R. ４ , S.O. R ４ , S.O. ２ R ４ , S.O. ２ NR ５ R ６ and C(=O)NR ５ R ６ Independently selected from the group consisting of Selected, Each C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－１ ０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ Aryl, 5- to 10-membered heteroaryl Lu, C １－６ -alkoxy or C １－６ -Alkylmercapto is C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－１ ０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl Ru, C １－６ -alkoxy, C １－６ -Alkyl mercapto, halogen, cyano, nitrite b, hydroxy, mercapto, NR ２′ R ３′ , C(=O)OR ４′ , S.R. ４′ , SOR ４′ , S.O. ２ R ４′ , S.O. ２ NR ５′ R ６′ and C(=O)NR ５′ R ６′ A group consisting of may be substituted by one or more substituents independently selected from R ２ and R ３ teeth, Hydrogen, C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－ １０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl Lille, C １－６ -alkoxy-C １－６ -Alkyl, C ３－１０ -cycloalkyl Replaced C １－６ -C substituted with alkyl, 5- to 10-membered heterocycle １－６ -Alkyl, C ６ －１０ -aryl-substituted C １－６ -substituted with alkyl and 5-10 membered heteroaryl C was １－６ - alkyl, or R ２ and R ３ together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, and 0, 1, 2 or 3 further ring atoms are N , S and O; Each C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－１ ０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl Ru, C １－６ -alkoxy-C １－６ -Alkyl, C ３－１０ -substituted with cycloalkyl C was １－６ -C substituted with alkyl, 5- to 10-membered heterocycle １－６ -Alkyl, C ６－ １０ -aryl-substituted C １－６ -substituted with alkyl or 5-10 membered heteroaryl C １－６ - alkyl or R ２ and R ３ are formed together with the N atom to which they are attached The heterocycle is C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－１ ０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl Ru, C １－６ -Alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto 、NR ２″ R ３″ 、C(=O)OR ４″ 、SR ４″ 、SOR ４ 、SO ２ R ４″ 、SO ２ N R ５″ R ６″ and C(=O)NR ５″ R ６″ one or more substituents independently selected from the group consisting of may be substituted with a substituent; R ４ , R ５ and R ６ is hydrogen and C １－６ -alkyl; R ２′ , R ３′ , R ４′ , R ５′ and R ６′ is hydrogen and C １－６ - Independent of alkyl Selected by R ２″ , R ３″ , R ４″ , R ５″ and R ６″ is hydrogen and C １－６ - Independent of alkyl Selected by R ７ teeth, Hydrogen, C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－ １０ -cycloalkyl, 4- to 10-membered heterocycle, C ６－１０ Aryl, 5- to 10-membered heteroaryl Ru, C １－６ -alkoxy, C １－６ -Alkyl mercapto, halogen, cyano, nitrite b, hydroxy, mercapto, NR ８ R ９ , COOH, C(=O)OR １０ , S.R. １０ , SOR １０ , S.O. ２ R １０ , S.O. ２ NR １１ R １２ and C(=O)NR １１ R １２ Because are independently selected from the group Each C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－１ ０ -cycloalkyl, 4- to 10-membered heterocycle, C ６－１０ Aryl, 5- to 10-membered heteroaryl Lu, C １－６ -alkoxy or C １－６ -Alkylmercapto is C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－１ ０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl Ru, C １－６ -alkoxy, C １－６ -Alkyl mercapto, halogen, cyano, nitrite b, hydroxy, mercapto, NR ８′ R ９′ , C(=O)OR １０′ , S.R. １０′ , S OR １０′ , S.O. ２ R １０′ , S.O. ２ NR １１′ R １２′ and C(=O)NR １１′ R １ ２′ and optionally substituted with one or more substituents independently selected from the group consisting of: R ８ and R ９ teeth, Hydrogen, C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－ １０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl Lille, C １－６ -alkoxy-C １－６ -Alkyl, C ３－１０ -cycloalkyl Replaced C １－６ -C substituted with alkyl, 5- to 10-membered heterocycle １－６ -Alkyl, C ６ －１０ -aryl-substituted C １－６ -substituted with alkyl, 5- to 10-membered heteroaryl C １－６ - alkyl, or R ８ and R ９ together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, and 0, 1, 2 or 3 further ring atoms are N , S and O; Each C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－１ ０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl Ru, C １－６ -alkoxy-C １－６ -Alkyl, C ３－１０ -substituted with cycloalkyl C was １－６ -C substituted with alkyl, 5- to 10-membered heterocycle １－６ -Alkyl, C ６－ １０ -aryl-substituted C １－６ -substituted with alkyl or 5-10 membered heteroaryl C １－６ - alkyl or R ８ and R ９ are formed together with the N atom to which they are attached The heterocycle is C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－１ ０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl Ru, C １－６ -Alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto 、NR ８″ R ９″ 、C(=O)OR １０″ 、SR １０″ 、SOR １０″ ,SO ２ R １０″ , S.O. ２ NR １１″ R １２″ and C(=O)NR １１″ R １２″ Independently selected from the group consisting of may be substituted with one or more substituents selected from the group consisting of aryl, ... R １０ , R １１ and R １２ is hydrogen and C １－６ -alkyl; R ８′ , R ９′ , R １０′ , R １１′ and R １２′ is hydrogen and C １－６ -Alkyl? are independently selected from R ８″ , R ９″ , R １０″ , R １１″ and R １２″ is hydrogen and C １－６ -Alkyl? are independently selected from R １３ is hydrogen or C １－３ is alkyl, R １４ is hydrogen, C １－３ Alkyl, C １－３ Alkoxy, NR １４′ R １４″ and R １４′ and R １４″ is independently C １－３ - alkyl, or R １３ and R １４ together with the atoms to which they are attached, 5 or 6 carbon atoms and the ring containing 5 or 6 carbon atoms is formed with one or more C １－３ -alkyl or ═O, and / or the ring carbons One or more of -NH-, -N=, =N-, -O-, -S(O)-, -S(O) ２ -or-S- may be replaced by or R １３ and R １４ together with the atoms to which they are attached, 5 or 6 carbon atoms and the ring containing 5 or 6 carbon atoms is formed with one or more C １ －３ -alkyl, and / or one or more of the ring carbons may be - may be replaced by NH-, -N=, =N-, -O- or -S-, A1 is N or CR １５ and R １５ are independently hydrogen, halogen, C １－３ Alkyl, C １－３ Alkoxy or NR １５′ R １５″ and R １５′ and R １５″ is independently C １－ ３ - alkyl, A2 is N or CR １６ and R １６ are independently hydrogen, halogen, C １－３ Alkyl, C １－３ Alkoxy or NR １６′ R １６″ and R １６′ and R １６″ is independently C １ －３ - alkyl, A3 is N or CR １７ and R １７ are independently hydrogen, halogen, C １－３ Alkyl, C １－３ Alkoxy or NR １７′ R １７″ and R １７′ and R １７″ is independently C １－ ３ - alkyl, A4 is N or CR １８ and R １８ are independently hydrogen, halogen C １－３ Alkyl, C １ －３ Alkoxy or NR １８′ R １８″ and R １８′ and R １８″ is independently C １－ ３ - alkyl, R １９ is C ６－１０ - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl Selected, Each C ６－１０ aryl or 5- to 10-membered heteroaryl, C １－６ -Alkyl, C ２－６ -alkenyl, C ３－１０ -cycloalkyl, 5 to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl, C １－６ -Arco Kishi, C １－６ -Alkyl mercapto, halogen, cyano, nitro, hydroxy, mercapto プト、NR ２０ R ２１ 、C(=O)OR ２２ 、SR ２２ 、SOR ２２ 、SO ２ R ２２ 、S O ２ NR ２３ R ２４ and C(=O)NR ２３ R ２４ One or more independently selected from the group consisting of may be substituted with the above substituents, R ２０ and R ２１ teeth, Hydrogen, C １－６ -Alkyl, C ３－１０ -cycloalkyl, C ６－１０ -aryl, 5-10 membered heteroaryl, C １－６ -alkoxy-C １－６ -Alkyl, C ６－１０ - Aryl-substituted C １ -C ６ -C substituted with alkyl, 5-10 membered heteroaryl １－６ - alkyl, or R ２０ and R ２１ have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C １－６ -Alkyl, C ２－６ -alkenyl, C ３－１０ -cycloalkyl, 5 to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl, C １－６ -Arco Kishi or C １－６ - alkylmercapto or R ２０ and R ２１ are the N to which they are bonded The heterocycle formed together with the atoms is C １－６ -Alkyl, C ２－６ -alkenyl, C ２－６ -alkynyl, C ３－１ ０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl Ru, C １－６ -Alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto 、NR ２０′ R ２１′ 、C(=O)OR ２２′ 、SR ２２′ 、SOR ２２′ 、SO ２ R ２ ２′ , S.O. ２ NR ２３′ R ２４′ and C(=O)NR ２３′ R ２４′ Independent from the group consisting of and optionally substituted with one or more substituents selected from R ２２ , R ２３ and R ２４ is hydrogen and C １－６ -alkyl; R ２０′ , R ２１′ , R ２２′ , R ２３′ and R ２４′ is hydrogen and C １－６ -Arki are independently selected from the R ２５ is hydrogen and C １－６ -alkyl.

2. R １ but, Hydrogen, C １－６ -Alkyl, C １－６ -Alkoxy, halogen, cyano, nitro, hydroxy Droxi, NR ２ R ３ , C(=O)OR ４ and C(=O)NR ５ R ６ Independent from the group consisting of Selected by Each C １－６ -Alkyl or C １－６ -alkoxy is C １－６ -Alkyl, C １－６ -Alkoxy, halogen, cyano, nitro, hydroxy Roxy and NR ２′ R ３′ substituted with one or more substituents independently selected from the group consisting of It may be R ２ and R ３ but, Hydrogen, C １－６ -Alkyl, C ３－１０ -cycloalkyl, C ６－１０ -aryl and and 5- to 10-membered heteroaryl; or R ２ and R ３ together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Each C １－６ -Alkyl, C ３－１０ -cycloalkyl, C ６－１０－ Aryl or 5- to 10-membered heteroaryl or R ２ and R ３ are formed along with the N atom to which they are attached The heterocycle is C １－６ -Alkyl, C ３－１０ -cycloalkyl and C １－６ -Alkoxy? and optionally substituted with one or more substituents independently selected from the group consisting of: R ４ , R ５ and R ６ is hydrogen and C １－６ -alkyl; R ２′ and R ３′ is hydrogen and C １－６ -alkyl The compound described.

3. R １ but, Hydrogen, C １－６ -Alkyl, C １－６ - Independent from the group consisting of alkoxy and halogen Selected by Each C １－６ -Alkyl or C １－６ -alkoxy is C １－６ -Alkyl, C １－６ -alkoxy, halogen, cyano, hydroxy and and NR ２′ R ３′ may be substituted with one or more substituents independently selected from the group consisting of Ku, R ２′ and R ３ ' is hydrogen and C １－３ -alkyl is a compound according to 2.

4. R １ but, Hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and The compound of any one of claims 1 to 3, independently selected from the group consisting of chlorides. 。

5. R ７ but, Hydrogen, C １－６ -Alkyl, C ２ - ６ -alkenyl, C ３－１０ -cycloalkyl, 4- to 10-membered heterocycle, C １－６ -alkoxy, halogen, cyano, hydroxy, NR ８ R ９ , C(=O)OR １０ , SR １０ , SOR １０ , SO ２ R １０ and C(=O)NR １１ R １２ are independently selected from the group consisting of: Each C １－６ -Alkyl, C ２ - ６ -alkenyl, C ３－１０ -cycloalkyl, 4 to 10-membered heterocycle or C １－６ -alkoxy is C １－６ -Alkyl, C ３－１０ -cycloalkyl, 5- to 10-membered heterocycle, C １－ ６ -alkoxy, halogen, cyano, hydroxy, NR ８′ R ９′ , C(=O)OR １０ ′ and C(═O)NR １１′ R １２′ one or more substituents independently selected from the group consisting of may be substituted with R ８ and R ９ but, Hydrogen, C １－６ -Alkyl, C ３－１０ -cycloalkyl, C ６－１０ -aryl, independently selected from the group consisting of 5- to 10-membered heterocycle and 5- to 10-membered heteroaryl; or R ８ and R ９ together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Each C １－６ -Alkyl, C ３－１０ -cycloalkyl, C ６－１０－ Aryl, 5- 10-membered heterocycle, and 5- to 10-membered heteroaryl or R ８ and R ９ But they are combined The heterocycle formed together with the N atom is C １－６ -Alkyl, C １－６ -alkoxy, halogen, cyano, hydroxy, N R ８″ R ９″ , C(═O)—OR １０″ and C(=O)NR １１″ R １２″ A group consisting of may be substituted with one or more substituents independently selected from: R １０ , R １１ and R １２ is hydrogen and C １－６ -alkyl; R ８′ , R ９′ , R １０′ , R １１′ and R １２′ is hydrogen and C １－６ -Alkyl? are independently selected from R ８″ , R ９″ , R １０″ , R １１″ and R １２″ is hydrogen and C １－６ -Alkyl? The compound according to any one of claims 1 to 4, independently selected from:

6. R ７ but, Hydrogen, C １－６ -Alkyl, C ２ - ６ -alkenyl, 4- to 10-membered heterocycle, C １－６ - Alkoxy, hydroxy, NR ８ R ９ , C(=O)OR １０ , S.R. １０ , SOR １０ , S O ２ R １０ and C(=O)NR １１ R １２ are independently selected from the group consisting of: Each C １－６ -Alkyl, C ２ - ６ -alkenyl, 4- to 10-membered heterocycle or C １－６ - Alkoxy is C １－６ - alkyl, 5- to 10-membered heterocycle, C １－６ -Alkoxy, halogen, chloro Ano, Hydroxy, NR ８′ R ９′ , C(=O)OR １０′ and C(=O)NR １１′ R １２′ and optionally substituted with one or more substituents independently selected from the group consisting of: R ８ and R ９ but, Hydrogen, C １－６ -Alkyl, C ６－１０ -aryl and 5- to 10-membered heteroaryl or R ８ and R ９ together with the N atom to which they are attached, form a saturated ring of 3 to 12 atoms. forming a saturated or unsaturated heterocyclic ring, one ring atom of which is N, and 0, 1, 2 or three additional ring atoms are selected from N, S, and O; Said C １－６ -Alkyl, C ６－１０ -aryl and 5- to 10-membered heteroaryl or is R ８ and R ９ together with the N atom to which they are attached form a heterocycle C １－６ -Alkyl, C １－６ -alkoxy, hydroxy and NR ８″ R ９″ from may be substituted with one or more substituents independently selected from the group consisting of: R １０ , R １１ and R １２ is hydrogen or C １－６ -alkyl; R ８′ , R ９′ , R １０′ , R １１′ and R １２′ is hydrogen or C １－６ -Alkyl? are independently selected from R ８″ and R ９″ is hydrogen or C １－６ -alkyl, 5. The compound according to any one of claims 1 to 4.

7. R ７ but, Methyl, ethyl, propyl, isopropyl, isopropenyl, methoxy, ethoxy, Isopropoxy, hydroxy, methylsulfoxyl, methylsulfonylmethylthio, amino methylamino, ethylamino, (ethyl) (methyl) amino, isopropylamino, Dimethylamino, (isopropyl) (methyl) amino, hydroxyethylamino, (hydro (methoxyethyl)(methyl)amino, methoxyethylamino, (methoxyethyl)(methyl ) Amino, morpholin-4-yl, pyrrolidin-1-yl, 3-hydroxy-pyrrolidine from the group consisting of 3,3-difluoroazetidinyl and 3,3-difluoroazetidinyl The compound according to any one of claims 1 to 6, independently selected from:

8. R １３ and R １４ together with the atoms to which they are attached, 5 or 6 carbon atoms and the ring containing 5 or 6 carbon atoms is formed with one or more C １－３ -alkyl or ═O, and / or the ring carbons One or more of -NH-, -N=, =N-, -O-, -S(O)-, -S(O) ２ -or-S- may be replaced by A1 is N or CR １５ and R １５ are independently hydrogen, halogen, C １－３ Alkyl, C １－３ Alkoxy or NR １５′ R １５″ and R １５′ and R １５″ is independently C １ －３ - alkyl, A2 is N or CR １６ and R １６ are independently hydrogen, halogen, C １－３ Alkyl, C １－３ Alkoxy or NR １６′ R １６″ and R １６′ and R １６″ is independently C １ －３ - alkyl, A3 is N or CR １７ and R １７ are independently hydrogen, halogen, C １－３ Alkyl, C １－３ Alkoxy or NR １５′ R １５″ and R １５′ and R １５″ is independently C １ －３ - alkyl, A4 is N or CR １８ and R １８ are independently hydrogen, halogen C １－３ Alkyl, C １ －３ Alkoxy or NR １５′ R １５″ and R １５′ and R １５″ is independently C １－ ３ The compound according to any one of claims 1 to 7, wherein: - alkyl.

9. R １３ and R １４ together with the atoms to which they are attached, 5 or 6 carbon atoms and the ring containing 5 or 6 carbon atoms is formed with one or more C １ －３ -alkyl, and / or one or more of the ring carbons may be - may be replaced by NH-, -N=, =N-, -O- or -S-, A1 is N or CR １５ and R １５ are independently hydrogen, halogen, C １－３ Alkyl, C １－３ Alkoxy or NR １５′ R １５″ and R １５′ and R １５″ is independently C １ －３ - alkyl, A2 is N or CR １６ and R １６ are independently hydrogen, halogen, C １－３ Alkyl, C １－３ Alkoxy or NR １６′ R １６″ and R １６′ and R １６″ is independently C １ －３ - alkyl, A3 is N or CR １７ and R １７ are independently hydrogen, halogen, C １－３ Alkyl, C １－３ Alkoxy or NR １５′ R １５″ and R １５′ and R １５″ is independently C １ －３ - alkyl, A4 is N or CR １８ and R １８ are independently hydrogen, halogen, C １－３ Alkyl, C １－３ Alkoxy or NR １５′ R １５″ and R １５′ and R １５″ is independently C １ －３ The compound according to any one of claims 1 to 7, wherein: - alkyl.

10. 1. Claim 1, wherein 0, 1 or 2 of residues A1, A2, A3 and A4 are N.

10. The compound according to any one of claims 1 to 9.

11. A1 is CR １５ and A2 is CR １６ and A3 is CR １７ and A4 is CR １ ８ The compound according to any one of claims 1 to 10,

12. R １９ but, C ６－１０ - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl 、 Each C ６－１０ aryl or 5- to 10-membered heteroaryl, C １－６ -Alkyl, C ３－１０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－ １０ -aryl, 5- to 10-membered heteroaryl, C １－６ -Alkoxy, halogen, cyano , nitro, hydroxy, NR ２０ R ２１ , C(=O)OR ２２ and C(=O)NR ２３ R ２４ and optionally substituted with one or more substituents independently selected from the group consisting of: R ２０ and R ２１ but, Hydrogen, C １－６ -Alkyl, C ３－１０ -cycloalkyl and C ６－１０ -aryl or R ２０ and R ２１ have 3 to 12 ring atoms together with the N atom to which they are attached and forming a saturated or unsaturated heterocyclic ring having 0, 1, 2 or 3 further ring atoms. is selected from N, S and O; Each C １－６ -Alkyl, C ３－１０ -cycloalkyl or C ６－１０ -aryl or R ２０ and R ２１ together with the N atom to which they are attached form a heterocycle C １－６ -Alkyl, C ３－１０ -cycloalkyl, 5- to 10-membered heterocycle, C ６－１ ０ -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 ２ ４′ and optionally substituted with one or more substituents independently selected from the group consisting of: R ２２ , R ２３ and R ２４ is hydrogen and C １－６ -alkyl; R ２０′ , R ２１′ , R ２２′ , R ２３′ and R ２４′ is hydrogen and C １－６ -Arki 12. The compound according to any one of claims 1 to 11, independently selected from:

13. R １９ but, C ６－１０ - independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl 、 Each C ６－１０ aryl or 5- to 10-membered heteroaryl, C １－６ -Alkyl, C １－６ -Alkoxy, halogen, cyano, nitro and hydroxyl and optionally substituted with one or more substituents independently selected from the group consisting of hydroxyl, Item 13. The compound according to any one of items 1 to 12.

14. R １９ is C ６－１０ -aryl, Said C ６－１０ -aryl is C １－６ independently selected from the group consisting of alkyl, halogen, cyano and nitro The compound according to any one of claims 1 to 13, which may be substituted with one or more substituents. thing.

15. R １９ is C ６－１０ -aryl, Said C ６－１０ -aryl is one, two or more independently selected from the group consisting of fluoride, chloride and bromide; 15. The compound according to claim 1, wherein the phenyl is substituted with one or three substituents. Compound.

16. The compound according to any one of claims 1 to 15, which is present in the form of the (S)-enantiomer. Compound.

17. A method for preparing a compound according to formula (I), comprising the steps of: Compound of formula (A): 【Chemistry 2】 with a compound of formula (B): 【Chemistry 3】 [R １ , R ７ , R １３ , R １４ , A1, A2, A3, A4, R １９ and R ２５ Claim 1 to 16] to form a compound according to formula (I). A method that includes the step of obtaining something.

18. a compound according to formula (I) as defined in any one of claims 1 to 16, and - one or more physiologically acceptable excipients 10. A veterinary drug composition comprising:

19. The one or more physiologically acceptable excipients may be a carrier, a filler, a flavoring agent, a binder, an antioxidant, agents, buffers, sugar components, lubricants, surfactants, stabilizers, flow agents, disintegrants and preservatives, and 19. The veterinary composition of claim 18, selected from a mixture thereof.

20. A compound according to formula (I) according to any one of claims 1 to 16 for use as a medicament.

20. The veterinary drug composition according to claim 18 or 19.

21. Claims 1 to 1 for use in the treatment of disorders / diseases caused by helminths 6 or the compound according to formula (I) of claim 18 or 19. Pharmaceutical composition.

22. The method according to claims 1 to 16 for use according to claim 21, wherein the disease is canine heartworm disease. A compound according to formula (I) as defined in any one of claims 18 and 19 or a veterinary drug as defined in claim 19. composition.

23. The helminth is Dirofilaria immitis.

23. The method according to claim 1, wherein the compound is a compound selected from the group consisting of hydroxybenzoates, ... or a veterinary composition according to claim 18 or 19.

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