Anthelmintic Compounds Containing an Azaindole Structure

Abstract

The present invention relates to novel anthelmintic compounds that can be used, for example, in the treatment of helminthic diseases of the type caused by Dirofilaria, particularly Dirofilaria immitis.

Description

[Technical Field]

[0001] The present invention relates to novel anthelmintic compounds that can be used in the treatment of diseases caused by helminths such as, for example, heartworms, especially Dirofilaria immitis. [Background technology]

[0002] Several important animal diseases are caused by helminths, which belong to the following groups: a) cestodes, such as Anaplocephala spp.; Dipylidium spp.; Diphyllobothrium spp.; Echinococcus spp.; Moniezia spp.; Taenia spp.; b) trematodes, such as Dicrocoelium spp.; Fasciola spp.; Paramphistomum spp.; Schistosoma spp.; c) nematodes, such as AcanthocheilonemaGenus and species; Ancylostoma species; Anecator species; Ascaridia species; Ascaris species; Brugia species; Bunostomum species; Capillaria species; Chabertia species; Cooperia species; Cyathostomum species; Cylicocyclus species; Cylicodont Ophorus species; Cylicostephanus species; Craterostomum species; Dictyocaulus species; Dipetalonema species; Dirofilaria species; Dracunculus species; Enterobius species; Filaroides species; Habronema species; Haemonchus species; Hete Heterakis species; Hyostrongylus species; Metastrongylus species; Meullerius species; Necator species; Nematodirus species; Nippostrongylus species; Oesophagostomum species; Onchocerca species; Onchocercidae species; Ostertagia species stertagia spp.; Oxyuris spp.; Parascaris spp.; Stephanurus spp.; Strongylus spp.; Syngamus spp.; Toxocara spp.; Strongyloides spp.; Teladorsagia spp.; Toxascaris spp.; Trichinella spp.; Trichuris spp.;They can be classified into the genus Trichostrongylus, Triodontophorous, Uncinaria and / or Wuchereria.

[0003] The above-mentioned helminths cause helminthiasis, also known as parasitic infection. These helminths often reside within the host's digestive tract but can also invade other organs, causing physiological disorders there. For example, Ascaridia species have been reported to infect the small intestine, resulting in partial or complete obstruction of the digestive tract in affected animals, particularly feathered animals such as birds. Furthermore, another helminth, Haemonchus species, is known to infect animals such as sheep and goats. Such infestation often results in the helminth attaching to the abdominal mucosa to feed on the host's blood. This can lead to anemia and shortness of breath in affected animals. Furthermore, Oesophagostomum species is known to form nodules in the intestines of infected hosts, potentially causing dysentery.

[0004] Heartworm disease, also known as cardiovascular dirofilariasis, is a severe and often fatal disease that can affect internal organs such as the lungs and heart of pets and certain mammals. The disease is caused by a parasitic nematode (Dirofilaria immitis), which can measure up to 30 centimeters in length and approximately 1 millimeter in diameter as an adult. These nematodes live in the heart, lungs, and associated blood vessels, causing severe lung disease, heart failure, and damage to internal organs such as the liver and kidneys. Heartworm infection therefore leads to host complications and typically leads to death.

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

[0006] Heartworm must pass through different stages before becoming an adult worm that inhabits a host animal. Mosquitoes play a crucial role in the heartworm life cycle because they are required as an intermediate host. Adult female heartworms living in an infected host develop into larvae called microfilariae, which can circulate in the bloodstream for as long as two years and are ingested by blood-sucking mosquitoes. When a mosquito bites such an infected host and ingests blood, it ingests the microfilariae, which begin development within the mosquito's body, resulting in the first and second larval stages (L1 and L2) of heartworm development. The larvae mature into the third larval stage (L3), which is an infective larva. When the mosquito finds and bites a host, these infective larvae are deposited on the host's skin surface and enter the new host through the mosquito bite, resident beneath the skin at the site of the bite wound. After a brief further growth period of approximately two weeks, the larvae mature to the fourth larval stage (L4) and migrate to the muscles of the chest and abdomen. 45–60 days after infection, the larvae develop into immature adult worms (fifth larval stage; L5). 75–120 days after infection (mosquito bite), these immature heartworms enter the bloodstream and are transported to the heart and pulmonary system, where they undergo significant growth over the next approximately three months. By seven months after infection (mosquito bite), the adult worms have mated, and females begin producing the microfilariae described above. Mature heartworms can live up to approximately seven years in dogs and three years in cats. The longevity of these worms can lead to increased heartworm populations in infected pets with each mosquito season. 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, and the development of such resistance to known anthelmintic drugs is believed to pose a major problem in the successful treatment of these diseases. WO2017 / 178416 discloses compounds that are believed to be anthelmintic agents, namely pyrazolopyrimidine derivatives of the following structure: [ka] In the formula, the residue R 1 , R 2 , R 3 , R 4 , Q, X and Y are defined accordingly.

[0008] This molecule is thought to be a modulator of the nematode calcium-activated potassium channel Slo-1, which can be considered the helminth ortholog of the human KCa1.1 channel (potassium-calcium-activated channel subfamily Mα1) encoded by the KCNMA1 gene (KCa1.1 and KCNMA1 are often used interchangeably). Slo-1 exhibits calcium-activated potassium channel activity and voltage-gated potassium channel activity. Slo-1 channels play important roles in the neuromuscular system and secretory cells, among others. Therefore, Slo-1 modulators have been reported to be involved in several processes, including behavioral responses to ethanol, locomotion, and pharyngeal pumping. More specifically, it inhibits neuromuscular transmission, causing flaccid paralysis and affecting feeding and egg production. Furthermore, it retards the development of the corresponding larvae and adults of helminths.

[0009] Even so, there remains an urgent need for new active pharmaceutical ingredients capable of combating helminth infections, especially in view of the development of resistance to known anthelmintic compounds.

[0010] 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.

[0011] It is an object to provide novel anthelmintic compounds which can be used to combat infections in mammals, particularly pets such as cats and dogs, especially dogs. In particular, parasitic helminths such as Ostertagia ostertagi, Cooperia oncophora, Cooperia punctata, Trichostrongylus axei, Haemonchus placei, Haemonchus contortus, Nematodirus helvetianus, Nematodirus spathiger, Trichostrongylus colubriformis, Trichostrongylus circumcincta, Oesophagostomum venulosum, Chabertia ovina, Dictyocaulus viviparous, Dictyocaulus filaria, Dirofilaria immitis, Dirofilaria repens;b) Trematodes: Fasciola hepatica, Fascioloides magna, Dicrocoelium dentriticum, Paramphistomum cervi, c) Cestodes: Monezia expansai, especially Ascaridia galli, Haemonchus contortus, Oesophagostomum dentatum, and Acanthocheilonema viteae, and infections in mammals by Dirofilaria immitis, especially Dirofilaria The present invention aims to provide new anthelmintic compounds that can be used to combat infections with Dirofilaria immitis (dog heartworm);

[0012] Another object is to provide novel anthelmintic compounds that can be used to combat infections in mammals, which compounds are compatible with standard antiparasitic treatments in pets, particularly cats and dogs, especially dogs. In particular, it is an object to provide novel anthelmintic compounds that can be used to combat infections in pets such as cats and dogs, and that can be administered orally or topically.

[0013] More specifically, the objective is to provide novel anthelmintic compounds that can be used to combat infections in mammals by parasitic helminths, in particular infections by Dirofilaria immitis (dog heartworm), but which do not adversely affect the host with unwanted side effects. It is further an object that the novel anthelmintic compounds can be used in different treatment regimens, in particular monthly or longer treatment regimens. [Means for solving the problem]

[0014] Surprisingly, it has been found that at least one of these objects can be met by providing a compound according to formula (I) or a stereoisomer, physiologically acceptable salt, ester, solvate, polymorph, prodrug and mixture thereof. [ka]

[0015] 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, C 1-6 -alkoxy, C 1-6 -Alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR 2 R 3 , COOH, C(=O)OR 4 , S.R. 4 , SOR 4 , SO2R 4 , SO2NR 5 R 6 and C(=O)NR 5 R 6 are independently selected from the group consisting of: 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, C 1-6 -alkoxy or C 1-6 -Alkyl mercapto 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, C 1-6 -alkoxy, C 1-6 -Alkylmercapto, halogen, cyano, nitro, 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′ and optionally substituted with one or more substituents independently selected from the group consisting of:

[0016] 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, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -C substituted with cycloalkyl 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6-10 -aryl-substituted C 1-6 -C substituted with alkyl and 5-10 membered heteroaryl 1-6 -alkyl, or R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms selected from 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, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -C substituted with cycloalkyl 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6-10 -aryl-substituted C 1-6 -C substituted with alkyl or 5-10 membered heteroaryl 1-6 -alkyl or R 2 and R 3 together with the N atom to which they are attached form a heterocycle 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, 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″ and optionally substituted with one or more substituents independently selected from the group consisting of:

[0017] R 4 , R 5 and R 6 is hydrogen and C 1-6 -alkyl;

[0018] R 2′ , R 3′ , R 4′ , R 5′ and R 6′ is hydrogen and C 1-6 -alkyl; R 2″ , R 3″ , R4″ , R 5″ and R 6″ is hydrogen and C 1-6 -alkyl;

[0019] 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, C 1-6 -alkoxy, C 1-6 -Alkylmercapto, halogen, cyano, nitro, 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 are independently selected from the group consisting of: Each 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, C 1-6 -alkoxy or C 1-6 -Alkyl mercapto 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, C 1-6 -alkoxy, C 1-6 -Alkylmercapto, halogen, cyano, nitro, 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′ and optionally substituted with one or more substituents independently selected from the group consisting of:

[0020] 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, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -C substituted with cycloalkyl 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6-10 -aryl-substituted C 1-6 -C substituted with alkyl, 5-10 membered heteroaryl 1-6 -alkyl, or R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms selected from 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, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -C substituted with cycloalkyl 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6-10 -aryl-substituted C1-6 -C substituted with alkyl or 5-10 membered heteroaryl 1-6 -alkyl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle 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, 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″ and optionally substituted with one or more substituents independently selected from the group consisting of:

[0021] 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl;

[0022] R 13 is hydrogen or C 1-3 is alkyl, R 14 is hydrogen, C 1-3Alkyl, 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 atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, and the ring containing 5 or 6 carbon atoms contains one or more C 1-3 -alkyl or =O, and / or one or more of the ring carbons may be replaced by -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S-; or R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, and the ring containing 5 or 6 carbon atoms contains one or more C 1-3 -alkyl, and / or one or more of the ring carbons may be replaced by -NH-, -N=, =N-, -O-, or -S-;

[0023] 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 17′ R17″ and R 17′ and R 17″ is independently C 1-3 -alkyl, R 18 are independently hydrogen, 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; 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 -alkoxy, C 1-6 -Alkylmercapto, halogen, cyano, nitro, 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 and optionally substituted with one or more substituents independently selected from the group consisting of:

[0024] 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 additional ring atoms 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 -alkoxy or C 1-6 -alkylmercapto or R 20 and R 21 together with the N atom to which they are attached form a heterocycle 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, 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′ and optionally substituted with one or more substituents independently selected from the group consisting of:

[0025] R 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl; R 20′ , R 21′ , R22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl; R 25 is hydrogen and C 1-6 -alkyl.

[0026] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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 R2 and R 3 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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.

[0027] In one embodiment 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; Each C 1-6 -alkyl or 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.

[0028] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, are independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride.

[0029] 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, C 3-10 -cycloalkyl, 4- to 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further ring atoms are selected from N, S and O; Each C 1-6 -Alkyl, C 3-10-cycloalkyl, C 6-10- Aryl, 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 heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8″ R 9″ , C(=O)-OR 10″ and C(=O)NR 11″ R 12″ and optionally substituted with one or more substituents independently selected from the group consisting of: 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl.

[0030] 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 , 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, 4- to 10-membered heterocycle or C 1-6 -alkoxy is C 1-6 -Alkyl, 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 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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 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″ and optionally 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. R 8″ and R 9″ is hydrogen or C 1-6 -alkyl.

[0031] In one embodiment of the present invention and / or embodiments thereof, R 7 teeth, Independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonylmethylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl.

[0032] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, and the ring containing 5 or 6 carbon atoms contains one or more C 1-3 -alkyl or ═O, and / or one or more of the ring carbons may be replaced by -NH-, -N═, ═N-, -O-, -S(O)-, -S(O)2- or -S-; 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, R 16 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16′ R 16″ and R16′ and R 16″ is independently C 1-3 -alkyl, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0033] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, and the ring containing 5 or 6 carbon atoms contains one or more C 1-3 -alkyl, and / or one or more of the ring carbons may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0034] 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 additional ring atoms 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 6-10 -aryl, 5-10 membered heteroaryl, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 20′ R21′ , 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 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 -alkyl.

[0035] 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 heterocycle, 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 21together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 additional ring atoms 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 6-10 -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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl.

[0036] 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 additional ring atoms 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 6-10 -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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C1-6 -alkyl.

[0037] 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 1-6 -Optionally substituted with one or more substituents independently selected from the group consisting of alkoxy, halogen, cyano, nitro and hydroxy.

[0038] In one embodiment of the present invention and / or embodiments thereof, R 19 is C 6-10 -aryl, Said C 6-10 -aryl is C 1-6 -optionally substituted with one or more substituents independently selected from the group consisting of alkyl, halogen, cyano and nitro.

[0039] In one embodiment of the present invention and / or embodiments thereof, R 19 is C 6-10 -aryl, Said C 6-10 -aryl is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide.

[0040] In one embodiment of the present invention and / or embodiments thereof, R 25 is hydrogen.

[0041] In one embodiment of the present invention and / or embodiments thereof, said compound according to formula (I) is present in the form of the (S)-enantiomer.

[0042] 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] [Hal is a halogen, R 1 , R 7 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 and R 25 is defined as in any one of claims 1 to 13.] to obtain a compound according to formula (I).

[0043] Furthermore, the present invention provides a compound according to formula (I), and -One or more physiologically acceptable excipients The present invention provides a veterinary drug composition comprising:

[0044] In one embodiment of the invention and / or embodiments thereof, the one or more physiologically acceptable excipients are selected from carriers, fillers, flavoring agents, binders, antioxidants, buffers, sugar components, lubricants, surfactants, stabilizers, flow agents, disintegrants and preservatives, and mixtures thereof.

[0045] The present invention further provides a compound according to formula (I) or a veterinary composition according to the present invention for use as a medicament.

[0046] Furthermore, the present invention provides a compound according to formula (I) or a veterinary composition according to the present invention for use in the treatment of a disorder / disease caused by helminths.

[0047] In one embodiment of the invention and / or embodiments thereof, the disease is filariasis, in particular dirofilariasis.

[0048] In one embodiment of the invention and / or embodiments thereof, the helminth is Dirofilaria immitis. DETAILED DESCRIPTION OF THE INVENTION

[0049] The compounds according to formula (I) or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof may be used to treat or inhibit the growth of Ostertagia ostertagi, Cooperia oncophora, Cooperia punctata, Trichostrongylus axei, Haemonchus placei, Haemonchus contortus, Nematodirus helvetianus, Nematodirus spathiger, Trichostrongylus colubriformis, Trichostrongylus silcineta, Trichostrongylus circumcincta, Oesophagostomum venulosum, Chabertia ovina, Dictyocaulus viviparous, Dictyocaulus filaria, Dirofilaria immitis, Dirofilaria repens;b) Trematodes: Fasciola hepatica, Fascioloides magna, Dicrocoelium dentriticum, Paramphistomum cervi; c) Cestoda: Monezia expansa, in particular helminths such as Ascaridia galli, Haemonchus contortus, and Oesophagostomum dentatum, and Dirofilaria immitis. In particular, the compounds according to the invention and / or any embodiment thereof are useful in the treatment of disorders / diseases caused by helminth infections, such as filariasis and, in particular, heartworm disease. Optionally, the compounds according to the invention and / or any embodiment thereof are useful in the treatment of disorders / diseases caused by helminths, such as nematodes, in particular Dirofilaria immitis, wherein said disorder / disease caused by Dirofilaria immitis is heartworm disease; Advantageously, the compounds according to the present invention and / or any embodiment thereof are effective against helminths such as Dirofilaria immitis, but are not effective against bacteria particularly relevant to mammalian health, particularly canine health, such as Acinetobacter baumannii or Staphylococcus spp. or Streptococcus spp.

[0050] The present inventors have found that the compounds of the present invention meet such a need and are therefore highly useful in the treatment (and prevention) of diseases caused by helminths, such as heartworm disease.

[0051] The following abbreviations and definitions are used throughout this application:

[0052] In general, when a particular element is referred to, the reference is intended to encompass all isotopes of that element. For example, if a group is defined to include hydrogen or a residue includes H, it also encompasses deuterium and tritium.

[0053] "C 1-6 The term "-alkyl" refers to an alkyl group having 1 to 6 carbon atoms, not including heteroatoms. Thus, the term includes straight chain alkyl groups such as methyl, ethyl, propyl, butyl, pentyl, and hexyl. The term also includes branched isomers of straight chain alkyl groups, such as, by way of example, but not limited to, -CH(CH3)2, -CH(CH3)(CH2CH3), -CH(CH2CH3), -C(CH3)3, -CH2CH(CH3)2, -CH2CH(CH2CH3), -CH2C(CH3)3, -CH(CH3)CH(CH3)(CH2CH3), -CH2CH2CH(CH3)2, -CH2CH2CH(CH3)(CH2CH3), -CH2CH2CH(CH3)3, and others. Thus, the term "C 1-6 The term "-alkyl" includes primary alkyl groups having 1 to 6 carbon atoms, secondary alkyl groups having 3 to 6 carbon atoms, and tertiary alkyl groups having 4 to 6 carbon atoms.

[0054] In response, "C 1-3 The term "C-alkyl" refers to an alkyl group having 1 to 3 carbon atoms, not including heteroatoms. Thus, the term includes straight chain alkyl groups such as methyl, ethyl, and propyl. The term also includes branched isomers of straight chain alkyl groups, i.e., CH(CH3)2. Thus, "C 1-3 The term "-alkyl" includes primary alkyl groups having 1 to 3 carbon atoms and secondary alkyl groups having 3 carbon atoms.

[0055] "C 2-6 The term "C-alkenyl" refers to any of the above defined "C-alkenyl" and "C-alkenyl" groups except that at least one double bond exists between two carbon atoms. 2-6 -alkyl" refers to straight-chain and branched alkenyl groups such as those described for "-alkyl." Examples include, but are not limited to, -CH=CH2, -C(CH3)=CH2, -CH=CH(CH3), -CH=C(CH3)2, -CH=CH(CH3), -C(CH3)=CH(CH3), -C(CH2CH3)H=CH2, -CH2=CH(CH2CH3), -CH2CH2-CH=CH2, CH2CH2-C(CH3)=CH2, CH2CH2-CH=C(CH3)H, -CH=CH-(CH2)2CH3, -CH=C(CH3)-CH2CH3, -(CH2)3-CH=CH2, -(CH2)4-CH=CH2, -(CH2)2-CH=C(CH3)2, butadienyl, pentadienyl, and hexadienyl, among others.

[0056] "C 2-6 The term "alkynyl" refers to the above-defined "C-alkynyl" group, except that at least one triple bond exists between two carbon atoms. 2-6 -C≡CCH, -C≡C-CHCH, -CH-C≡CH, -CH(CH)-C≡CH, -C(CH)-C≡CH, -CH-C≡CCH, -CH(CH)-C≡CH, -CH-C≡CCH, -CH(CH)-C≡CCH, -C(CH)-C≡CCH, -C(CH)-C≡CCH, among others. 3、 Examples include, but are not limited to, -CH2-C≡C-CH2CH3, -CH(CH3)-C≡C-CH2CH3, -C(CH3)2-C≡C-CH2CH3, -(CH2)2-C≡C-CH2CH3, and -(CH2)3-C≡C-CH3.

[0057] "C 3-10The term "cycloalkyl" refers to a non-aromatic monocyclic alkyl group having 3 to 10 carbon atoms or a non-aromatic polycyclic alkyl group having 3 to 10 carbon atoms, said group consisting solely of carbon and hydrogen atoms. Cycloalkyl can include fused or bridged ring systems having 3 to 10 carbon atoms. Non-aromatic monocyclic alkyl groups having 3 to 10 carbon atoms include, but are not limited to, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and cyclooctyl. Non-aromatic polycyclic alkyl groups having 3 to 10 carbon atoms include, but are not limited to, adamantine, norbornane, decalinyl, and 7,7-dimethyl-bicyclo[2.2.1]heptanyl.

[0058] The term "5- to 10-membered heterocycle" refers to a cyclic group having 5 to 10 members (atoms) forming a backbone, the backbone of the cyclic compound containing at least one carbon atom and at least one heteroatom. Examples of heteroatoms include, but are not limited to, N, O, and S. Unless otherwise specifically stated in the specification, the "5- to 10-membered heterocycle" can be a monocyclic, bicyclic, or polycyclic group that can include fused or bridged systems, and a portion of the fused ring system can be aromatic; the nitrogen, carbon, or sulfur atom in the "5- to 10-membered heterocycle" can be oxidized; the nitrogen atom can be quaternized; and the group of the heterocyclic residue can be partially saturated.

[0059] Examples of heterocycles include, but are not limited to, pyrrolinyl, 3H-pyrazolyl, 4H-pyrazolyldihydropyridyl, pyrrolidinyl, imidazolidinyl, piperidinyl, piperazinyl, homopiperazinyl, indolinyl, quinuclidinyl, morpholinyl, thiomorpholinylthiazolodinyl, dihydrodithionyl, dihydrodithionyl, tetrahydrothiophene, tetrahydrothiopyran, benzothiazinyl, e.g., 2H-1,4-benzothiazinyl, dihydrobenzothiazinyl, e.g., 2H-3,4-dihydrobenzothiazinyl, benzodioxolyl, e.g., 1,3-benzodioxoyl, dihydrooxathiinyl, 1,4-oxathianyl, and the like. Further examples of heterocyclic groups include those described above in which one or more S atoms in the ring are double-bonded to one or two oxygen atoms (sulfoxides and sulfones), such as, but not limited to, tetrahydrothiophene, tetrahydrothiophene oxide, and tetrahydrothiophene-1,1-dioxide, and thiomorpholine, thiomorpholine oxide, and thiomorpholine-1,1-dioxide.

[0060] "C 6-10 The term "aryl" refers to a group that has an aromatic skeletal structure in which the ring atoms of the aromatic skeletal structure are carbon atoms. 6-10 "Aryl" does not contain heteroatoms such as N, S, O in the aromatic backbone structure.

[0061] Examples of aryl groups include, but are not limited to, phenyl, biphenyl, and naphthyl.

[0062] The term "5- to 10-membered heteroaryl" refers to an aromatic group in which 5 to 10 members (atoms) form a backbone, and the backbone of the cyclic compound contains at least one carbon atom and at least one heteroatom. Examples of heteroatoms include, but are not limited to, N, O, and S. Unless otherwise specifically stated in this specification, a "5- to 10-membered heterocycle" can be a monocyclic, bicyclic, or polycyclic group, and it can include fused ring systems.

[0063] Examples of 5- to 10-membered heteroaryl groups include pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrimidyl, pyrazinyl, pyridazinyl, triazolyl such as 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl and 4H-1,2,4-triazlyl, tetrazolyl such as 1H-tetrazolyl, 2H-tetrazolyl and 5H-tetrazoyl, indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl, indazolyl, naphthyridinyl, benzotriazolyl, oxazolyl, isoxazolyl, oxadiazolyl such as 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, Examples of thiadiazolyl include, but are not limited to, thiadiazolyl, benzoxazolyl, benzoxadiazolyl, benzoxazinyl, such as 2H-1,4-benzoxazinylthiazolyl, isothiazolyl, thiadiazolyl, such as 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, thienyl, benzothiazolyl, benzothiadiazolyl, benzothiazinyl, benzofuranyl, quinolinyl, isoquinoline, cinnolinyl, quinaxolinyl, quinoxalinyl, triazinyl, tetrazinyl, purinyl, pteridinyl, furyl, benzodioxolyl, such as 1,3-benzodioxoyl, benzothienyl, benzodithiinyl, and benzoxathiinyl.

[0064] "C 1-6 The term "-alkoxy" refers to a radical based on an alkyl group having 1 to 6 carbon atoms attached to an oxygen. An alkyl group having 1 to 6 carbon atoms is defined above as "C 1-6 -alkyl" refers to straight and branched chains such as those described for "-alkyl".

[0065] Correspondingly, "C 1-3 The term "alkoxy" refers to a radical based on an alkyl group having 1 to 3 carbon atoms attached to an oxygen. An alkyl group having 1 to 3 carbon atoms is defined above as "C1-3 -alkyl" refers to straight and branched chains such as those described for "-alkyl".

[0066] "C 1-6 The term "-alkylmercapto" refers to a group based on an alkyl group having 1 to 6 carbon atoms attached to a sulfur. An alkyl group having 1 to 6 carbon atoms is defined above as "C 1-6 -alkyl" refers to straight and branched chains such as those described for "-alkyl".

[0067] "Optionally substituted" refers to the optional replacement of one or more hydrogens of a group with one or more of the defined substituents.

[0068] Further, amine, hydroxyl, and mercapto groups can be protected. The term "protected" with respect to these groups refers to forms of these functional groups that have a protecting group to prevent the group from reacting undesirably. Such protecting groups can be found, for example, in Protective Groups in Organic Synthesis; Wuts, PGM, John Wiley & Sons, New York, NY, (53 th Protecting groups can be added or removed using procedures described therein.

[0069] Examples of protected hydroxyl groups include, but are not limited to, silyl ethers such as those obtained by reaction with reagents such as, but not limited to, t-butyldimethyl-chlorosilane, trimethylchlorosilane, triisopropylchlorosilane, triethylchlorosilane; substituted methyl and ethyl ethers such as, but not limited to, methoxymethyl ether, methylthiomethyl ether, benzyloxymethyl ether, t-butoxymethyl ether, 2-methoxyethoxymethyl ether, tetrahydropyranyl ethers, 1-ethoxyethyl ether, allyl ether, benzyl ether; esters such as, but not limited to, benzoylformate, formate, acetate, trichloroacetate, and trifluoroacetate.

[0070] Examples of protected amine groups include, but are not limited to, amides such as formamide, acetamide, trifluoroacetamide, and benzamide; imides such as phthalimide and dithiosuccinimide; carbamates such as tert-butyloxycarbonyl (Boc), and others.

[0071] Examples of protected mercapto groups include, but are not limited to, thioethers such as S-benzylthioether, and S-4-picolylthioether; substituted S-methyl derivatives such as hemithio, dithio, and aminothioacetals; and others.

[0072] Stereoisomers include compounds that consist of the same atoms joined in the same order, but where the atoms are in different positions in space. Stereoisomers include diastereomers and enantiomers.

[0073] A "physiologically acceptable salt" refers to a salt with an inorganic base, an organic base, an inorganic acid, an organic acid, or a basic or acidic amino acid.

[0074] Examples of suitable inorganic acids for forming (physiologically acceptable) salts include, but are not limited to, hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuric, and phosphoric acid. 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, glucuronic acid, maleic acid, fumaric acid, pyruvic acid, aspartic acid, glutamic acid, benzoic acid, anthranilic acid, mesylic acid, stearic acid, salicylic acid, p-hydroxybenzoic acid, phenylacetic acid, mandelic acid, embonic acid, ethanesulfonic acid, benzenesulfonic acid, toluenesulfonic 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, cyclopentanepropionic acid, dodecylsulfuric acid, glycoheptanoic acid, glycerophosphate, heptanoic acid, hexanoic acid, nicotinic acid, 2-naphthalenesulfonic acid, oxalic acid, palmoic acid, pectinic acid, 3-phenylpropionic acid, picric acid, pivalic acid, thiocyanic acid, tosylic acid, undecanoic acid, and acidic amino acids such as aspartic acid and glutamic acid.

[0075] Examples of base addition salts may include, for example, metallic salts and organic salts.

[0076] Metallic salts include, but are not limited to, alkali metal (group Ia) salts, alkaline earth metal (group IIa) salts, and other physiologically acceptable metal salts. Examples of such salts can be made from aluminum, calcium, lithium, magnesium, potassium, sodium, and zinc. For example, free acid compounds can be mixed with sodium hydroxide to form such base addition salts.

[0077] Organic salts can be prepared from amines such as trimethylamine, diethylamine, N,N'-dibenzylethylenediamine, chloroprocaine, ethanolamine, diethanolamine, ethylenediamine, N-methylglucamine, procaine, and basic amino acids such as arginine, lysine, and ornithine.

[0078] As used herein, the term "pharmaceutically acceptable ester" refers to an ester that hydrolyzes in vivo, including those that readily decompose in the human body to leave the parent compound or a salt thereof. Suitable ester groups include, for example, those derived from pharmaceutically acceptable aliphatic carboxylic acids, particularly alkanoic, alkenoic, cycloalkanoic, and alkanedicarboxylic acids, each alkyl or alkenyl moiety preferably having six or fewer carbon atoms. Representative examples of specific esters include, but are not limited to, formates, acetates, propionates, butyrates, acrylates, and ethylsuccinates.

[0079] A solvate of a compound can be considered a compound in which an organic solvent or water is attached to the compound. Organic solvents refer to those known to those skilled in the art. When water is attached to the compound, the corresponding compound is known as a hydrate.

[0080] As used herein, and as generally understood by those skilled in the art, the term "polymorph" refers to different crystalline forms of the same molecular entity. Thus, due to their different chemical composition, the solvates and hydrates described above are not included in the definition of polymorphs, but rather are referred to as "pseudopolymorphs."

[0081] The term "prodrug" refers to compounds that are rapidly transformed in vivo to yield the parent compound of formula (I) above, for example, by hydrolysis in blood. A detailed discussion can be found in T. Higuchi and V. Stella, Pro-drugs as Novel Delivery 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.

[0082] As used herein, the term "pharmaceutically acceptable prodrugs" refers to prodrugs of compounds of the present invention, and where possible, zwitterionic forms of compounds of the present invention, that are, within the scope of sound medical judgment, suitable for use in contact with the tissues of human beings and lower animals without undue toxicity, irritation, allergic response, and the like, commensurate with a reasonable benefit / risk ratio, and that are effective for their intended use.

[0083] The present invention is 1

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0084] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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.

[0085] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C1-6 -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, hydroxy and NR 2 ′R 3 ', and R 5 and R 6 is hydrogen and C 1-3 -alkyl; R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl.

[0086] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 -alkyl, more preferably hydrogen and methyl.

[0087] In one embodiment of the present invention and / or embodiments thereof, R1 teeth, are independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride and chloride.

[0088] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iai), (Iaii) or (Iaiii): [ka] TIFF0007644121000006.tif94158 or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 7 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 and R 25 is defined as in any of the embodiments described herein.

[0089] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iai), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iaii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iaiii), preferably in the form of the (S)-enantiomer.

[0090] The present invention is 7

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0091] In an 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, C 3-10 -cycloalkyl, 4- to 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further ring atoms are selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl.

[0092] 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 -alkoxy, 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, 4- to 10-membered heterocycle or C 1-6 -alkoxy is C 1-6 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR8′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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″ and optionally 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, preferably hydrogen or C 1-3 -alkyl; R 8″ and R 9″ is hydrogen or C 1-6 -alkyl, preferably hydrogen or C1-3 -alkyl.

[0093] In an embodiment of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 -alkyl, preferably independently selected from hydrogen, methyl or ethyl.

[0094] In an embodiment of the present invention and / or embodiments thereof, R 7 teeth, Independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl and 3,3-difluoroazetidinyl, preferably dimethylamino and morpholin-4-yl.

[0095] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ibi), (Ibii), (Ibiii), (Ibiv), (Ibv), (Ibvi), (Ibvii), (Ibvii), (Ibix), (Ibx) or (Ibxi): [ka] TIFF0007644121000008.tif240145TIFF0007644121000009.tif236146, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18, R 19 and R 25 is defined as in any of the embodiments described herein.

[0096] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ibi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ibii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ibiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Ibv), preferably in the form of the (S)-enantiomer.

[0097] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ibvi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ibvii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ibviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ibix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ibx), preferably in the form of the (S)-enantiomer.

[0098] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ibxi), preferably in the form of the (S)-enantiomer.

[0099] The present invention is 13 and R 14 and R 15 , R 16 , R 17 and R 18

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0100] 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. 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. 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.

[0101] In another embodiment of the present invention and / or in embodiments thereof, 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0102] 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, 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, 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, R 17 is hydrogen or C 1-3 -alkyl, R 18 is hydrogen or C 1-3 - alkyl.

[0103] In another embodiment of the present invention and / or in embodiments thereof, R 13 is hydrogen, methyl or ethyl, preferably hydrogen or methyl, R 14is hydrogen or methyl, preferably hydrogen, R 15 is hydrogen or C 1-3 alkyl, preferably hydrogen or methyl; R 16 is hydrogen or C 1-3 alkyl, preferably hydrogen or methyl; R 17 and R 18 is hydrogen.

[0104] 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, R 15 , R 16 , R 17 and R 18 is hydrogen.

[0105] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ic): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 , R 7 , R 19 and R 25 is defined as in any of the embodiments described herein.

[0106] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ic), preferably in the form of the (S)-enantiomer.

[0107] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, and said ring containing 5 or 6 carbon atoms contains one or more C 1-3 -alkyl or =O, and / or one or more of the ring carbons may be replaced by -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S-; or R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, and said ring containing 5 or 6 carbon atoms contains one or more C 1-3 -alkyl, and / or one or more of the ring carbons may be replaced by -NH-, -N=, =N-, -O-, or -S-.

[0108] The non-aromatic ring containing 5 or 6 carbon atoms is one or more C 1-3 -alkyl or ═O, and / or one or more of the ring carbons may be replaced by —NH—, —N═, ═N—, —O—, —S(O)—, —S(O)2— or —S—; or the aromatic ring containing 5 or 6 carbon atoms may be replaced by one or more C 1-3 Examples of the non-aromatic or aromatic rings containing 5 or 6 carbon atoms, which may be optionally substituted by -alkyl and / or one or more of the ring carbons may be replaced by -NH-, -N=, =N-, -O-, or -S-, include, but are not limited to, residues represented by the following structures: [ka] During the ceremony, ······ indicates a bond to an amide group; -·- indicates that the ring system is fused to an aromatic ring.

[0109] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3 -alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is.

[0110] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0111] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 It is an alkoxy.

[0112] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Idi), (Idii), (Idiii) or (Idiv): [ka] TIFF0007644121000013.tif140160, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 , R 7 , R 19 and R 25 is defined as in any of the embodiments described herein.

[0113] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Idi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Idii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Idiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Idiv), preferably in the form of the (S)-enantiomer.

[0114] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C 1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3Alkyl or C 1-3 It is an alkoxy.

[0115] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0116] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 It is an alkoxy.

[0117] In an embodiment of the invention and / or embodiments thereof, the compound has formula (Idv), (Idvi) or (Idvii): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 , R 7 , R 19 and R 25 is defined as in any of the embodiments described herein.

[0118] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Idv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Idvi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Idvii), preferably in the form of the (S)-enantiomer.

[0119] The present invention is 19

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0120] 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 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl.

[0121] 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, hydroxy, C(=O)OR 22 , SO2R 22 , SO2NR 23 R 24 and C(=O)NR 23 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.

[0122] In an embodiment of the present invention and / or embodiments thereof, R 19 is 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, 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 22 , R 23 and R 24 is hydrogen and C 1-6 -alkyl, preferably hydrogen and C 1-3 -alkyl.

[0123] In an embodiment of the present invention and / or embodiments thereof, R19 is 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 -Optionally substituted with one or more substituents independently selected from the group consisting of alkoxy, halogen, cyano, nitro and hydroxy.

[0124] In an embodiment of the present invention and / or embodiments thereof, R 19 is a 5- to 10-membered heteroaryl; The 5- to 10-membered heteroaryl is C 1-6 -Alkyl, C 1-6 -Optionally substituted with one or more substituents independently selected from the group consisting of alkoxy, halogen, cyano, nitro and hydroxy.

[0125] In an embodiment of the present invention and / or embodiments thereof, R 19 is a 5- to 10-membered heteroaryl; The 5- to 10-membered heteroaryl is C 1-6 - optionally substituted with one or more substituents independently selected from the group consisting of alkyl and halogen, preferably halogen.

[0126] Examples of 5-10 membered heteroaryl groups include pyrrolyl, imidazolyl, pyrazolyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrimidin-2-yl, pyrimidin-3-yl, pyrimidin-4-yl, pyrazinyl, pyridazinyl, triazolyl, such as 1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, 1H-1,2,4-triazolyl and 4H-1,2,4-triazuryl (t riazlyl), tetrazolyl such as 1H-tetrazolyl, 2H-tetrazolyl and 5H-tetrazoyl, indolyl, isoindolyl, indolinyl, indolizinyl, benzimidazolyl, quinolin-4-yl, quinolin-8-yl, isoquinolyl, indazolyl, naphthyridinyl, benzotriazolyl, oxazolyl, isoxazolyl, oxadiazolyl such as 1,2,4-oxadiazolyl Thiazolyl, 1,3,4-oxadiazolyl, 1,2,5-oxadiazolyl, benzoxazolyl, benzoxadiazolyl, benzoxazinyl such as 2H-1,4-benzoxazinylthiazolyl, isothiazolyl, thiadiazolyl such as 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, thien-2-yl, thien-3-ylbenzothiazolyl, benzothiadiazolyl, benzothiazinyl, benzofuranyl, quinolinyl, isoquinoline, cinnolinyl, quinaxolinyl, quinoxalinyl, triazinyl, tetrazinyl, purinyl, pteridinyl, furyl, benzodioxolyl such as 1,3-benzodioxoyl, benzothienyl, benzodithiinyl and benzoxathiinyl. Preferred are 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.

[0127] In an embodiment of the present invention and / or embodiments thereof, R 19 is a 5- to 10-membered heteroaryl; The 5- to 10-membered heteroaryl is C1-6 - substituted with one or more substituents independently selected from the group consisting of alkyl and halogen, preferably halogen.

[0128] In an embodiment of the present invention and / or embodiments thereof, R 19 is C 6-10 -aryl, Said C 6-10 The aryl is C 1-6 -optionally substituted with one or more substituents independently selected from the group consisting of alkyl, halogen, cyano and nitro.

[0129] In an embodiment of the present invention and / or embodiments thereof, R 19 is C 6-10 -aryl, C 6-10 The aryl is It is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide.

[0130] Examples of phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide include 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-bromophenyl, 3-bromophenyl, 4-bromophenyl, 2,3-difluorophenyl, 2,4-difluorophenyl, 2,5-difluorophenyl, 3,4-difluorophenyl, 3,5-difluorophenyl, 2,6-difluorophenyl, 2,3-dichlorophenyl, nyl, 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-tribromopheny chloro, 3,4,5-tribromophenyl, 2-chloro-3-fluorophenyl, 2-chloro-4-fluorophenyl, 2-chloro-5-fluorophenyl, 3-chloro-2-fluorophenyl, 3-chloro-4-fluorophenyl, 3-chloro-5-fluorophenyl, 4-chloro-2-fluorophenyl, 4-chloro-3-fluorophenyl, 4-chloro-5-fluorophenyl, 5-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-4-fluorophenyl, 3-bromo-2-fluorophenyl, 4-bromo-2-chlorophenyl bromophenyl, 4-bromo-3-chlorophenyl, 3,4-dichloro-2-fluorophenyl, 3,5-dichloro-2-fluorophenyl, 3,5-dichloro-4-fluorophenyl, 4,5-dichloro-3-fluorophenyl, 3,4-dibromo-2-fluorophenyl, 3,5-dibromo-2-fluorophenyl, 4,5-dibromo-3-fluorophenyl, 2-chloro-3,4-difluorophenyl, 2-chloro-3,5-difluorophenyl, 3-chloro-4,5-difluorophenyl, 3,4-dibromo-2-chlorophenyl, 3,Examples include, but are not limited to, 5-dibromo-2-chlorophenyl, 4,5-dibromo-3-chlorophenyl, 2-bromo-3,4-difluorophenyl, 2-bromo-3,5-difluorophenyl, 3-bromo-4,5-difluorophenyl, 2-bromo-3,4-dichlorophenyl, 2-bromo-3,5-dichlorophenyl, 3-bromo-4,5-dichlorophenyl, 4-bromo-3-chloro-2-fluorophenyl, 4-bromo-2-chloro-3-fluorophenyl, 2-bromo-3-chloro-4-fluorophenyl, 5-bromo-3-chloro-2-fluorophenyl, 5-bromo-2-chloro-3-fluorophenyl, 2-bromo-3-chloro-5-fluorophenyl, 5-bromo-4-chloro-3-fluorophenyl, 5-bromo-3-chloro-4-fluorophenyl, and 3-bromo-4-chloro-5-fluorophenyl.

[0131] Preferred are 3-fluorophenyl, 3-chlorophenyl, 2,3-difluorophenyl, 3,5-difluorophenyl, 2,3-dichlorophenyl, 2,6-difluorophenyl, 3,5-dichlorophenyl, 2-chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-3-fluorophenyl, 5-chloro-2-fluorophenyl, 3,4,5-trifluorophenyl, 2,3,5-trifluorophenyl, 3,5-dichloro-4-fluorophenyl and 3,4,5-trifluorophenyl. Chlorophenyl, more preferably 2,3-difluorophenyl, 2,6-difluorophenyl, 3,5-difluorophenyl, 2,3,5-trifluorophenyl, 2-chloro-3-fluorophenyl, 3-chloro-2-fluorophenyl, 5-chloro-2-fluorophenyl, 2,3-dichlorophenyl, 3,5-dichlorophenyl, in particular 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl and 3,5-dichlorophenyl.

[0132] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iei), (Ieii), (Ieiii), (Ieiv), (Iev), (Ievi), (Ievii), (Ieviii), (Ieix) or (Iex): [ka] TIFF0007644121000016.tif206146TIFF0007644121000017.tif246146TIFF0007644121000018.tif67144, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 , R 7 , R 13 , R 14 , R 15 , R 16 , R 17 R 18 and R 25 is defined as in any of the embodiments described herein.

[0133] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iei), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ieii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ieiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ieiv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iev), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ievi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ievii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ieviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ieix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iex), preferably in the form of the (S)-enantiomer.

[0134] The present invention is 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0135] In an embodiment of the present invention and / or embodiments thereof, R 25 is hydrogen or methyl.

[0136] In an embodiment of the present invention and / or embodiments thereof, R 25 is hydrogen.

[0137] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (If): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 , R 7 , R 13 , R 14 , R 15 , R 16 , R 17 R 18 and R 19 is defined as in any of the embodiments described herein.

[0138] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (If), preferably in the form of the (S)-enantiomer. The present invention is 1 and R 7 provides compounds according to the invention and / or embodiments thereof, as defined above.

[0139] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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, C 2-6 -Alkenyl, C 3-10 -cycloalkyl, 4-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8 R9 , 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, 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, 5-10 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further ring atoms are selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl.

[0140] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 7 teeth, Hydrogen, C 1-6-Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″is hydrogen or C 1-3 -alkyl, preferably independently selected from hydrogen, methyl or ethyl.

[0141] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 7 teeth, Independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl.

[0142] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Igi), (Igii), (Igiii), or (Igiv): [ka] TIFF0007644121000021.tif101158, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 and R 25 is defined as in any of the embodiments described herein.

[0143] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Igi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Igii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Igiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Igiv), preferably in the form of the (S)-enantiomer.

[0144] The present invention is 1 and R 13 , R 14 , R 15 , R 16 , R 17 and R 18

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0145] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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 atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3 -alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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 independently C 1-3 -alkyl, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0146] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 13 and R 14together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0147] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 It is an alkoxy.

[0148] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Ihi), (Ihii) (Ihiii), (Ihiv), (Ihv) or (Ihvi): [ka] TIFF0007644121000023.tif48145 or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 7 , R 19 and R 25 is defined as in any of the embodiments described herein.

[0149] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ihi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ihii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ihiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Ihv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ihvi), preferably in the form of the (S)-enantiomer.

[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 -Alkoxy, halogen, cyano, nitro, hydroxy, NR 2 R 3 , C(=O)OR 4 and C(=O)NR5 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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 C1-3 -alkyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C 1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0151] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0152] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 It is an alkoxy.

[0153] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ihvii), (Ihviii) (Ihix) or (Ihx): [ka] TIFF0007644121000025.tif160159, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 7 , R 19 and R 25 is defined as in any of the embodiments described herein.

[0154] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ihvii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ihviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ihix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ihx), preferably in the form of the (S)-enantiomer.

[0155] The present invention is 1 and R 19

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0156] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; R4 , 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 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 additional ring atoms 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 21together 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl.

[0157] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 19 is C6-10 -aryl, C 6-10 The aryl is It is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide.

[0158] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 19 teeth, Independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[0159] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iii), (Iiii), (Iiii), (Iiiv), (Iiv) or (Iivi): [ka] TIFF0007644121000027.tif178159, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 7 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 25 is defined as in any of the embodiments described herein.

[0160] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Iiv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iivi), preferably in the form of the (S)-enantiomer.

[0161] The present invention is 1 and R 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0162] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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 25 is hydrogen or methyl, preferably hydrogen. 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; C1-6 -alkyl and C 1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxy and NR 2 ′R 3 ', and R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0163] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 25 is hydrogen or methyl, preferably hydrogen.

[0164] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iji) or (Ijii): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 7 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 19 is defined as in any of the embodiments described herein.

[0165] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iji), preferably in the form of the (S)-enantiomer.In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ijii), preferably in the form of the (S)-enantiomer.

[0166] The present invention is 7 and R 13 , R 14 , R 15 , R 16 , R 17 and R 18

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0167] In an embodiment of the present invention and / or in an embodiment 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, 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, 5-10 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O, Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C1-6 -alkyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3 -alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0168] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6-alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0169] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 It is an alkoxy.

[0170] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iki), (Ikii), (Ikiii), (Ikiv), (Ikv) or (Ikvi): [ka] TIFF0007644121000030.tif106158, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 , R 19 and R 25 is defined as in any of the embodiments described herein.

[0171] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iki), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ikii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ikiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Ikv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ikvi), preferably in the form of the (S)-enantiomer.

[0172] In an embodiment of the present invention and / or in an embodiment 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, 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, 5-10 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C 1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, R16 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 -alkoxy. 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 are independently selected from the group consisting of: 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, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0173] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 It is an alkoxy.

[0174] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ikvii), (Ikviii), (Ikix) or (Ikx): [ka] TIFF0007644121000032.tif167158, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 , R 19 and R 25 is defined as in any of the embodiments described herein.

[0175] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ikvii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ikviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ikix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ikx), preferably in the form of the (S)-enantiomer.

[0176] The present invention is 7 and R 19

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0177] In an embodiment of the present invention and / or in an embodiment 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, 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, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR8′ 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 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; R8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -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, 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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, C6-10 -aryl, 5-10 membered heteroaryl, halogen, cyano, 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 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 -alkyl.

[0178] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 19 is C 6-10 -aryl, C 6-10 The aryl is It is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide. In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 19 teeth, Independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[0179] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ili), (Ilii), (Iliii), (Iliv), (Ilv) or (Ilvi): [ka] TIFF0007644121000034.tif205145, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 25 is defined as in any of the embodiments described herein.

[0180] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ili), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ilii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iliii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Ilv). In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ilvi), preferably in the form of the (S)-enantiomer.

[0181] The present invention is 7 and R 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0182] In an embodiment of the present invention and / or in an embodiment 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, 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, 5-10 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R9′ , 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; R 25 is hydrogen or methyl, preferably hydrogen.

[0183] 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 are independently selected from the group consisting of: 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, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 25 is hydrogen or methyl, preferably hydrogen. In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0184] In an embodiment of the invention and / or embodiments thereof, the compound has formula (Imi) or (Imii): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 19 is defined as in any of the embodiments described herein.

[0185] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Imi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Imii), preferably in the form of the (S)-enantiomer.

[0186] The present invention is 13 , R 14 , R 15 , R 16 , R 17 and R 18 and R 19

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0187] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3 -alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, 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 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl.

[0188] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 19 is C 6-10 -aryl, C 6-10 The aryl is It is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide.

[0189] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 19 teeth, Independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[0190] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ini), (Inii), (Iniii), (Iniv), (Inv), (Invi), (Invii), (Inviii) or (Inix): [ka] TIFF0007644121000037.tif241145TIFF0007644121000038.tif114144, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 , R 7 and R 25 is defined as in any of the embodiments described herein. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ini), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Inii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iniii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Inv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Invi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Invii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Inviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Inix), preferably in the form of the (S)-enantiomer.

[0191] In one embodiment of the present invention and / or embodiments thereof, R 13 and R14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C 1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, 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 20 R 21 , C(=O)OR 22 and C(=O)NR 23 R 24and 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl.

[0192] In one embodiment of the present invention and / or embodiments thereof, R13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 19 is C 6-10 -aryl, C 6-10 The aryl is It is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide.

[0193] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18are independently hydrogen or C 1-3 is an alkoxy, R 19 teeth, Independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[0194] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Inx), (Inxi), (Inxii), (Inxiii), (Inxiv) or (Inxv): [ka] TIFF0007644121000040.tif186144, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 , R 7 and R 25 is defined as in any of the embodiments described herein.

[0195] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Inx), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Inxi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Inxii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Inxiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Inxiv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Inxv), preferably in the form of the (S)-enantiomer. The present invention is 13 , R 14 , R 15 , R 16 , R 17 and R 18 and R 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0196] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3 -alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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, R 16 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 16′ R 16″ R 16′ and R 16″ is independently C 1-3 -alkyl, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen. In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0197] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0198] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ioi), (Ioii) or (Ioiii): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 , R 7 and R 19 is defined as in any of the embodiments described herein.

[0199] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ioi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ioii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ioiii), preferably in the form of the (S)-enantiomer.

[0200] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C 1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 and R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0201] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0202] In one embodiment of the present invention and / or embodiments thereof, R 13 and R14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0203] In an embodiment of the invention and / or embodiments thereof, the compound has formula (Ioiv) or (Iov): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 , R 7 and R 19 is defined as in any of the embodiments described herein. In an embodiment of the present invention and / or embodiments 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 according to formula (Iov), preferably in the form of the (S)-enantiomer. The present invention is 19 and R 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0204] In one embodiment of the present invention and / or embodiments thereof, R19 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 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 additional ring atoms 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′ R24′ 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 -alkyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0205] In an embodiment of the present invention and / or in an embodiment thereof, R 19 is C 6-10 -aryl, C 6-10 aryl is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide; R 25 is hydrogen or methyl, preferably hydrogen.

[0206] In an embodiment of the present invention and / or in an embodiment thereof, R 19 teeth, independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0207] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ipi), (Ipii) or (Ipiii): [ka] TIFF0007644121000044.tif57159, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 , R 7 and R 13 , R 14 , R 15 , R 16 , R 17 and R 18 is defined as in any of the embodiments described herein.

[0208] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ipi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ipii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ipiii), preferably in the form of the (S)-enantiomer. The present invention is 1 , R 7 and R 13 , R 14 , R 15 .R 16 , R 17 and R 18

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0209] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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, 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, 5-10 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 10-membered heteroaryl or R 8 and R9 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8″ R 9″ , C(=O)OR 10″ and C(=O)NR 11″ R 12″ and optionally substituted with one or more substituents independently selected from the group consisting of: 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3 -alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0210] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0211] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 It is an alkoxy.

[0212] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iqi), (Iqii), (Iqiii), (Iqiv), (Iqv) or (Iqvi): [ka] TIFF0007644121000046.tif214158, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 19 and R 25 is defined as in any of the embodiments described herein.

[0213] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iqi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iqii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iqiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Iqv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iqvi), preferably in the form of the (S)-enantiomer.

[0214] In an embodiment of the present invention and / or in an embodiment thereof, R 1teeth, Hydrogen, C 1-6 -Alkyl, C 1-6 -Alkoxy, halogen, cyano, nitro, hydroxy, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R 6 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; R 4 , R 5 and R 6 is hydrogen and C1-6 -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, 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, 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, 5-10 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 5- to 10-membered heterocycle, and 5- to 10-membered heteroaryl; or R 8 and R9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C 1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; R15 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 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0215] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 7 teeth, Hydrogen, C 1-6-Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 It is an alkoxy.

[0216] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 13 and R14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 It is an alkoxy.

[0217] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iqvii), (Iqviii), (Iqix) or (Iqx): [ka] TIFF0007644121000048.tif59158, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 19 and R 25 is defined as in any of the embodiments described herein.

[0218] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iqvii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iqviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iqix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iqx), preferably in the form of the (S)-enantiomer. The present invention is1 , R 7 and R 19

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0219] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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, 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, 5-10 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 optionally substituted with one or more substituents independently selected from the group consisting of: R 8 and R9 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further ring atoms are selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -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, 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 additional ring atoms 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl.

[0220] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3-Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 19 is C 6-10 -aryl, C 6-10 The aryl is It is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide.

[0221] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 19 teeth, Independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[0222] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iri), (Irii), (Iriii), (Iriv), (Irv) or (Irvi): [ka] TIFF0007644121000050.tif189145TIFF0007644121000051.tif146143, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 13 , R 14 , R 15 , R 16 , R 17 and R 18 and R25 is defined as in any of the embodiments described herein.

[0223] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iri), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Irii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iriii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Irv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Irvi), preferably in the form of the (S)-enantiomer.

[0224] The present invention is 1 , R 7 and R 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0225] 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, NR 2 R 3 , C(=O)OR 4 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, C1-6 -alkoxy, halogen, cyano, nitro, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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, 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- to 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0226] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C1-3 - alkyl, more preferably hydrogen and methyl; R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0227] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0228] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Isi) or (Isii): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 13 , R 14 , R 15 , R 16 , R 17and R 18 and R 19 is defined as in any of the embodiments described herein.

[0229] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Isi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Isii), preferably in the form of the (S)-enantiomer. The present invention is 1 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 19

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0230] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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 atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3 -alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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 C 1-3 -alkyl, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, 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 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 21together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl. 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 19 is C 6-10 -aryl, C 6-10 The aryl is It is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide.

[0231] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 13 and R 14together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 19 teeth, Independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[0232] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iti), (Itii) (Itiii), (Itiv), (Itv), (Itvi), (Itvii), (Itviii) or (Itix): [ka] TIFF0007644121000054.tif228144TIFF0007644121000055.tif121144, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 7 and R 25 is defined as in any of the embodiments described herein.

[0233] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iti), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Itii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Itiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Itv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Itvi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Itvii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Itviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Itix), preferably in the form of the (S)-enantiomer.

[0234] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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 atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, 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 24 and optionally substituted with one or more substituents independently selected from the group consisting of: R20 and R 21 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 6-10 -aryl, or R 20 and R 21 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl.

[0235] Optionally, in embodiments of the present invention and / or embodiments thereof, R 1 teeth, Hydrogen, C 1-6 -Alkyl, C1-6 - independently selected from the group consisting of alkoxy and halogen; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 19 is C 6-10 -aryl, C 6-10 The aryl is It is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide.

[0236] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 19 teeth, Independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[0237] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Itx), (Itxi) (Itxii), (Itxiii), (Itxiv) or (Itxv): [ka] TIFF0007644121000057.tif249145 or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 7 and R 25 is defined as in any of the embodiments described herein.

[0238] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Itx), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Itxi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Itxii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Itxiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Ixitv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Itxv), preferably in the form of the (S)-enantiomer. The present invention is 1 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0239] 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, NR 2 R 3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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 atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3-alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0240] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0241] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0242] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iui), (Iuii) or (Iuiii): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 7 and R 19 is defined as in any of the embodiments described herein.

[0243] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iui), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iuii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iuiii), preferably in the form of the (S)-enantiomer.

[0244] 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, NR 2 R 3 , C(=O)OR 4 and C(=O)NR 5 R 6 are independently selected from the group consisting of: Each C 1-6 -alkyl or C1-6 -alkoxy is C 1-6 -Alkyl, C 1-6 -alkoxy, halogen, cyano, nitro, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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 14together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C 1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0245] 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0246] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15 are independently hydrogen or C 1-3is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0247] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iuiv) or (Iuv): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 7 and R 19 is defined as in any of the embodiments described herein.

[0248] In an embodiment of the present invention and / or embodiments 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 according to formula (Iuv), preferably in the form of the (S)-enantiomer.

[0249] The present invention is 1 , R 19 and R 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0250] 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, NR 2 R3 , C(=O)OR 4 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, 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 teeth, Hydrogen, C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10- independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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 together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 3-10 -cycloalkyl and C 1-6 -alkoxy; 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, 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl; R 25 is hydrogen or methyl, preferably hydrogen. 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; 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 R 2 ′ and R 3 ′ is hydrogen and C 1-3 - alkyl, more preferably hydrogen and methyl; R 19 is C 6-10 -aryl, C 6-10 The aryl is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide; R 25 is hydrogen or methyl, preferably hydrogen.

[0251] In one embodiment of the present invention and / or embodiments thereof, R 1 teeth, independently selected from the group consisting of hydrogen, methyl, trifluoromethyl, ethyl, methoxy, ethoxy, fluoride, and chloride; R 19 teeth, independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0252] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ivi), (Ivii) or (Iviii): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 7 , R 13 , R 14 , R 15 , R 16 , R 17 and R 18 is defined as in any of the embodiments described herein.

[0253] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ivi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ivii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iviii), preferably in the form of the (S)-enantiomer.

[0254] The present invention is 7 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 19

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0255] In an embodiment of the present invention and / or in an embodiment 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, 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, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR8′ 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 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; R8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3 -alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, 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, C1-6 -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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 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; R 20′ , R 21′, R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl.

[0256] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 19 is C 6-10 -aryl, C 6-10 The aryl is It is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide.

[0257] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 19 teeth, Independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[0258] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iwi), (Iwii), (Iwiii), (Iwiv), (Iwv), (Iwvi), (Iwvii), (Iwviii), (Iwix), (Iwx), (Iwxi) or (Iwxii): [ka] TIFF0007644121000062.tif180145TIFF0007644121000063.tif226145TIFF0007644121000064.tif222144, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 and R 25 is defined as in any of the embodiments described herein.

[0259] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Iwv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwvi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwvii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwx), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwxi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwxii), preferably in the form of the (S)-enantiomer.

[0260] In an embodiment of the present invention and / or in an embodiment 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, 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, 5-10 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 10-membered heteroaryl or R 8 and R 9together with the N atom to which they are attached form a heterocycle C 1-6 -Alkyl, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8″ R 9″ , C(=O)OR 10″ and C(=O)NR 11″ R 12″ and optionally substituted with one or more substituents independently selected from the group consisting of: 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C 1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, R 16 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR16′ R 16″ and R 16′ and R 16″ is independently C 1-3 -alkyl, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, 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 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms selected from N, S and O; Each C 1-6 -Alkyl, C 3-10 -cycloalkyl or C 6-10 -aryl or R 20and 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl.

[0261] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ and optionally substituted with one or more substituents independently selected from the group consisting of: R8 and R 9 teeth, Hydrogen, C 1-6 -Alkyl, C 6-10 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 19 is C 6-10 -aryl, C 6-10 The aryl is It is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide.

[0262] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R18 are independently hydrogen or C 1-3 is an alkoxy, R 19 teeth, Independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl.

[0263] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Iwxiii), (Iwxiv), (Iwxv), (Iwxvi), (Iwxvii), (Iwxviii) (Iwxix) or (Iwxx): [ka] TIFF0007644121000066.tif204145TIFF0007644121000067.tif217145, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 and R 25 is defined as in any of the embodiments described herein.

[0264] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwxiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwxiv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwxv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwxvi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment 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 an embodiment thereof, the compound is according to formula (Iwxviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iwxix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Iwxx), preferably in the form of the (S)-enantiomer. The present invention is 7 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 and R 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0265] In an embodiment of the present invention and / or in an embodiment 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, 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, 5-10 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, hydroxy, NR8″ 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 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3 -alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0266] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0267] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0268] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ixi), (Ixii), (Ixiii), (Ixiv), (Ixv) or (Ixvi): [ka] TIFF0007644121000069.tif221160, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 and R 19 is defined as in any of the embodiments described herein.

[0269] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ixi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ixii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ixiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments 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 according to formula (Ixv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ixvi), preferably in the form of the (S)-enantiomer.

[0270] In an embodiment of the present invention and / or in an embodiment 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, 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, 5-10 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 10 , R 11 and R 12 is hydrogen and C 1-6 -alkyl; R 8′ , R 9′ , R 10′ , R 11′ and R12′ 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; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C 1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0271] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0272] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 13 and R 14together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 25 is hydrogen or methyl, preferably hydrogen.

[0273] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Ixvii), (Ixviii), (Ixix) or (Ixx): [ka] TIFF0007644121000071.tif116158, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 and R 19 is defined as in any of the embodiments described herein.

[0274] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ixvii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ixviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ixix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Ixx), preferably in the form of the (S)-enantiomer. The present invention is 7 , R 19 and R 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0275] In an embodiment of the present invention and / or in an embodiment 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, 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, 5-10 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 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 3-10 -cycloalkyl, C 6-10 - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, one ring atom being N and 0, 1, 2 or 3 further ring atoms being selected from N, S and O; Said C 1-6 -Alkyl, C 3-10 -cycloalkyl, C 6-10 -aryl, 5- to 10-membered heterocycle or 5- to 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, halogen, cyano, 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 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; R 8″ , R9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -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, 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0276] In an embodiment of the present invention and / or embodiments thereof, R 7 teeth, Hydrogen, C 1-6 -Alkyl, C 2-6 -alkenyl, 4-10 membered heterocycle, C 1-3 -alkoxy, hydroxy, NR 8 R 9 are independently selected from the group consisting of: Each C 1-6 -Alkyl, C 2-6 -alkenyl, 4- to 10-membered heterocycle or C 1-3 -alkoxy is C 1-3 -Alkyl, 5-10 membered heterocycle, C 1-6 -alkoxy, halogen, cyano, hydroxy, NR 8′ R 9′ 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 -independently selected from the group consisting of aryl and 5- to 10-membered heteroaryl; R 8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: R 8′ and R 9′ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 8″ and R 9″ is hydrogen or C 1-3 - independently selected from alkyl, preferably hydrogen, methyl or ethyl; R 19 is C 6-10 -aryl, C 6-10 The aryl is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide; R 25 is hydrogen or methyl, preferably hydrogen.

[0277] In an embodiment of the present invention and / or in an embodiment thereof, R 7 teeth, independently selected from the group consisting of methyl, ethyl, isopropyl, isopropenyl, methoxy, ethoxy, isopropoxy, hydroxy, methylmercapto, ethylmercapto, methylsulfoxyl, methylsulfonyl, methylthio, amino, methylamino, ethylamino, isopropylamino, dimethylamino, isopropylmethylamino, hydroxyethylamino, methoxyethylamino, morpholin-4-yl, 4-methylpiperazin-1-yl, 3-hydroxy-pyrrolidin-1-yl, 3-fluoroazetidinyl, and 3,3-difluoroazetidinyl; R 19 teeth, independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0278] In an embodiment of the present invention and / or embodiments thereof, the compound has the formula (Iyi), (Iyii), (Iyiii), (Iyiv), (Iyv) or (Iyvi): [ka] TIFF0007644121000073.tif225145, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 , R 13 , R 14 , R 15 , R 16 , R 17 and R 18 is defined as in any of the embodiments described herein.

[0279] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iyi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iyii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iyiii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iyiv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iyv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iyvi), preferably in the form of the (S)-enantiomer.

[0280] The present invention is 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 and R 25

[0023] In accordance with the present invention, there is provided a compound and / or an embodiment thereof, wherein:

[0281] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said non-aromatic ring containing one or more C 1-3 -alkyl or ═O, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -O-, -S(O)-, -S(O)2- or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, 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 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 21together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0282] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms are optionally replaced by -NH-, -O-, or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 19 is C 6-10 -aryl, C 6-10 The aryl is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide; R 25 is hydrogen or methyl, preferably hydrogen. In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH- or -O-; R 15 are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 19 teeth, independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0283] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Izi), (Izii), (Iziii), (Iziv), (Izv) or (Izvi): [ka] TIFF0007644121000075.tif246144TIFF0007644121000076.tif55143, or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, R 1 and R 7 is defined as in any of the embodiments described herein.

[0284] In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Izi), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Izii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Iziii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or 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 an embodiment thereof, the compound is according to formula (Izv), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or an embodiment thereof, the compound is according to formula (Izvi), preferably in the form of the (S)-enantiomer.

[0285] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said aromatic ring containing one or more C 1-3 -alkyl, and / or one or more of the ring-forming carbon atoms may be replaced by -NH-, -N=, =N-, -O-, or -S-; 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, 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, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, 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, NR20 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0286] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N-, -O- or -S-; R 15 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 16 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 17 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 18 are independently hydrogen, C 1-3 Alkyl or C 1-3 is an alkoxy, R 19 is C 6-10 -aryl, C 6-10 The aryl is phenyl substituted with one, two, or three substituents independently selected from the group consisting of fluoride, chloride, and bromide; R 25 is hydrogen or methyl, preferably hydrogen.

[0287] In one embodiment of the present invention and / or embodiments thereof, R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, one or more of which ring carbon atoms may be replaced by -NH-, -N=, =N- or -S-; R 15are independently hydrogen or C 1-3 is an alkoxy, R 16 are independently hydrogen or C 1-3 is an alkoxy, R 17 are independently hydrogen or C 1-3 is an alkoxy, R 18 are independently hydrogen or C 1-3 is an alkoxy, R 19 teeth, independently selected from the group consisting of 2,3-difluorophenyl, 2,6-difluorophenyl, 2,3,5-trifluorophenyl, 3-chloro-2-fluorophenyl, 2,3-dichlorophenyl, and 3,5-dichlorophenyl; R 25 is hydrogen or methyl, preferably hydrogen.

[0288] In an embodiment of the present invention and / or embodiments thereof, the compound has formula (Izvii), (Izviii), (Izix) or (Izx): [ka] or stereoisomers, physiologically acceptable salts, esters, solvates, polymorphs, prodrugs and mixtures thereof, wherein R 1 and R 7 is defined as in any of the embodiments described herein.

[0289] In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Izvii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Izviii), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Izix), preferably in the form of the (S)-enantiomer. In an embodiment of the present invention and / or embodiments thereof, the compound is according to formula (Izx), preferably in the form of the (S)-enantiomer.

[0290] The compounds according to the present invention can be considered "active" agents, which in this context are considered to be substances that inhibit the growth of helminths, such as Dirofilaria, particularly Dirofilaria immitis. The term "growth inhibition" refers to a reduction in the rate of growth of the helminth population. Thus, the term encompasses situations in which the helminth population increases but at a slow rate, as well as situations in which the population stops growing, and situations in which the number of helminths in the population decreases or the population disappears.

[0291] Furthermore, the present invention provides Compounds of formula (A): [ka] with a compound of formula (B): [ka] [In the formula, Hal is a halogen, 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, C 1-6 -alkoxy, C1-6 -Alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR 2 R 3 , COOH, C(=O)OR 4 , S.R. 4 , SOR 4 , SO2R 4 , SO2NR 5 R 6 and C(=O)NR 5 R 6 are independently selected from the group consisting of: 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, C 1-6 -alkoxy or C 1-6 -Alkyl mercapto 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, C 1-6 -alkoxy, C 1-6 -Alkylmercapto, halogen, cyano, nitro, 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′ and optionally substituted with one or more substituents independently selected from the group consisting of: 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, C6-10 -aryl, 5-10 membered heteroaryl, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -C substituted with cycloalkyl 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6-10 -aryl-substituted C 1-6 -C substituted with alkyl and 5-10 membered heteroaryl 1-6 -alkyl, or R 2 and R 3 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms selected from 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, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -C substituted with cycloalkyl 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6-10 -aryl-substituted C 1-6 -C substituted with alkyl or 5-10 membered heteroaryl 1-6 -alkyl or R 2 and R 3 together with the N atom to which they are attached form a heterocycle 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, C 1-6 -Alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR 2″ R3″ , C(=O)OR 4″ , S.R. 4″ , SOR 4 , SO2R 4″ , SO2NR 5″ R 6″ and C(=O)NR 5″ R 6″ 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′ , R 3′ , 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 -alkyl; 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, C 1-6 -alkoxy, C 1-6 -Alkylmercapto, halogen, cyano, nitro, 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 are independently selected from the group consisting of: Each 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, C 1-6 -alkoxy or C 1-6 -Alkyl mercapto 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, C 1-6 -alkoxy, C 1-6 -Alkylmercapto, halogen, cyano, nitro, 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′ 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, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -C substituted with cycloalkyl 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6-10 -aryl-substituted C 1-6 -C substituted with alkyl, 5-10 membered heteroaryl 1-6 -alkyl, or R8 and R 9 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms selected from 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, C 1-6 -Alkoxy-C 1-6 -Alkyl, C 3-10 -C substituted with cycloalkyl 1-6 -C substituted with alkyl, 5-10 membered heterocycle 1-6 -Alkyl, C 6-10 -aryl-substituted C 1-6 -C substituted with alkyl or 5-10 membered heteroaryl 1-6 -alkyl or R 8 and R 9 together with the N atom to which they are attached form a heterocycle 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, 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″ and optionally substituted with one or more substituents independently selected from the group consisting of: 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; R 8″ , R 9″ , R 10″ , R 11″ and R 12″ is hydrogen and C 1-6 -alkyl; 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 atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, and the ring containing 5 or 6 carbon atoms contains one or more C 1-3 -alkyl or =O, and / or one or more of the ring carbons may be replaced by -NH-, -N=, =N-, -O-, -S(O)-, -S(O)2- or -S-; or R 13 and R 14 together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, and the ring containing 5 or 6 carbon atoms contains one or more C 1-3 -alkyl, and / or one or more of the ring carbons may be replaced by -NH-, -N=, =N-, -O-, or -S-; R 15 are independently hydrogen, halogen, C 1-3 Alkyl, C 1-3 Alkoxy or NR 15′ R15″ and R 15′ and R 15″ is independently C 1-3 -alkyl, 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, R 17 are independently hydrogen, 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, R 18 are independently hydrogen, 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; 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 -alkoxy, C 1-6 -Alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR 20 R 21 , C(=O)OR 22 , S.R. 22 , SOR 22 , SO2R 22 , SO2NR23 R 24 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, 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 additional ring atoms 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 -alkoxy or C 1-6 -alkylmercapto or R 20 and R 21 together with the N atom to which they are attached form a heterocycle 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, C 1-6 -Alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR 20′ R 21′ , C(=O)OR 22′ , S.R. 22′ , SOR 22′ , SO2R22′ , SO2NR 23′ R 24′ , and C(=O)NR 23′ 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; R 20′ , R 21′ , R 22′ , R 23′ and R 24′ is hydrogen and C 1-6 -alkyl; R 25 is hydrogen and C 1-6 -alkyl] to obtain a compound according to formula (I).

[0292] In an embodiment of the present invention and / or embodiments thereof, R 1 , R 7 , R 13 , R 14 , R 15 , R 16 , R 17 , R 18 , R 19 and R 25 As far as is concerned, the same applies as stated above in relation to the compounds according to the invention.

[0293] In this embodiment of the present invention and / or embodiments thereof, Hal is a halogen selected from the group consisting of chloride, bromide or iodide, preferably bromide or iodide, especially iodide.

[0294] Compounds of formula (A) and formula (B) are commercially available or synthetically available.

[0295] In an embodiment of the present invention and / or embodiments thereof, a compound of formula (A), which can be referred to as a compound comprising an azaindole structure in which the 7-position of the azaindole is not substituted with a compound according to formula (B), is subjected to a coupling reaction in an organic solvent in the presence of a coupling agent to convert the corresponding 7-position of the azaindole to a residue R 1 The formation of compounds containing azaindole structures substituted with

[0296] Examples of coupling agents include, but are not limited to, copper(I) salts such as CuCl, CuO, Cu(I), or copper(II) salts such as CuO, Cu(OAc) and preferably Cu(I). In this embodiment of the present invention and / or embodiments thereof, the process may be carried out in the presence of oxygen.

[0297] Organic solvents are known to those skilled in the art.

[0298] Suitable organic solvents for the process according to the invention can be, for example, acetonitrile, dioxane, tetrahydrofuran (THF), dimethylsulfoxide (DMSO) dimethylformamide (DMF), dimethylacetamide (DMA), N-methyl-2-pyrrolidone (NMP), preferably dimethylacetamide (DMA) or N-methyl-2-pyrrolidone (NMP), in particular (DMA).

[0299] In this embodiment of the present invention and / or embodiments thereof, the process may be carried out in the presence of an auxiliary alkaline compound.

[0300] Suitable alkaline compounds may include organic compounds, including, but not limited to, pyridines such as 4-(dimethylamino)pyridine (DMAP), amidines such as 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), and amines such as triethylamine and diisopropylethylamine, diamino compounds such as 1,2-dimethylethylenediamine, N,N'-dimethylcyclohexane-1,2-diamine, preferably 1,2-dimethylethylenediamine, N,N'-dimethylcyclohexane-1,2-diamine.

[0301] Suitable alkaline compounds may include inorganic compounds, such as, but not limited to, carbonates, such as sodium carbonate, potassium carbonate, or cesium carbonate, or hydroxides, such as sodium hydroxide, preferably carbonates, especially potassium carbonate.

[0302] In an embodiment of the present invention and / or embodiments thereof, the process can be carried out at an elevated temperature. By elevated temperature is meant a temperature from 23°C (room temperature) to the boiling point of the organic solvent. This means that when dimethylacetamide, which has a boiling temperature or boiling point of 165°C, is used as the organic solvent, the process can preferably be carried out at 23°C to 165°C. All temperatures indicated herein and relating to boiling temperatures or boiling points relate to temperatures measured at normal pressure of 101 kPa.

[0303] In an embodiment of the present invention and / or embodiments thereof, the method can be carried out in a closed vessel. When the process is carried out in a closed vessel, the reaction mixture can be heated to a temperature above the boiling point of the solvent, preferably at most 25°C above the boiling point of the solvent.

[0304] In this embodiment of the present invention and / or embodiments thereof, the process may preferably be carried out under mechanical motion, such as stirring and / or microwave treatment.

[0305] The present invention further provides a veterinary composition comprising a compound according to the invention and one or more physiologically acceptable excipients.

[0306] The veterinary compositions of the present invention and / or embodiments thereof comprise a therapeutically effective amount of a compound of the present invention and / or embodiments thereof formulated together with one or more physiologically acceptable excipients.

[0307] Physiologically acceptable excipients are well known in the art. See, for example, "Gennaro, Remington: The Science and Practice of Pharmacy" (2006). th Edition, 2000. All such physiologically acceptable excipients must be substantially pharmaceutically or veterinarily pure and non-toxic in the amounts employed, and must be compatible with the active ingredient.

[0308] In one preferred embodiment of the present invention and / or embodiments thereof, the one or more physiologically acceptable excipients are selected from carriers, binders, antioxidants, buffers, sugar components, surfactants, lubricants, stabilizers, flow agents, disintegrants and preservatives, and mixtures thereof.

[0309] As used herein, the term "carrier" refers to any type of non-toxic, inert, solid, semi-solid or liquid filler or diluent carrying / encapsulating material.Some examples of materials that can function as physiologically acceptable carriers include, but are not limited to, sugars such as lactose, glucose and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethylcellulose, ethylcellulose and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository wax; oils such as peanut oil, cottonseed oil, safflower oil, sesame oil, olive oil, corn oil and soybean oil; esters such as ethyl oleate and ethyl laurate; agar.

[0310] A binder is a substance that can bond other substances together. When the binder is a polymer, it preferably has a melting point or glass transition temperature (T) in the range of 25 to 100°C, preferably 35 to 85°C, and particularly 40 to 70°C. g ) is a component that has a glass transition temperature (T). The glass transition temperature is the temperature at which a polymer becomes brittle when cooled and softens when heated. g ) and become plastically deformable without fracture. The glass transition temperature or melting point is measured by methods known to those skilled in the art.

[0311] In one preferred embodiment of the present invention and / or embodiments thereof, the binder is selected from polyethylene glycol, polypropylene glycol, polyethylene glycol-polypropylene glycol copolymer, microcrystalline wax, glycerol monostearate, hydrogenated castor oil, polyethylene glycol glycerol hydroxystearate, polysaccharides, polyvinylpyrrolidone, polyvinyl alcohol, poly(meth)acrylates, polyvinylpyrrolidone-polyacetic acid copolymer and mixtures thereof.

[0312] Antioxidants are substances used to inhibit oxidation. Antioxidants suitable for incorporation into the soft chewable animal dosage form of the present invention include, but are not limited to, ascorbic acid, glutathione, tocopherol and its esters, tert-butylhydroquinone (TBHQ), butylhydroxyanisole (BHA, also known as 2-tert-butyl-4-hydroxyanisole, 3-tert-butyl-4-hydroxyanisole, or mixtures thereof), and butylhydroxytoluene (BHT, also known as 2,6-ditert-butyl-4-methylphenol). The antioxidant is preferably present in agglomerates. In one preferred embodiment of the present invention and / or its embodiments, the antioxidant contained in the animal dosage form may be in the range of 0.001 to 1.00% by weight.

[0313] Buffers are substances that maintain / regulate the pH value of a product. Non-limiting examples of buffers include bicarbonate, dihydrogen phosphate, and hydrogen phosphate.

[0314] Sugar components are used to sweeten the taste of the product. They include natural sugars (carbohydrates) as well as sugar substitutes. In one preferred embodiment of the present invention and / or embodiments thereof, the buffering agent included in the animal dosage form can range from 1 to 10% by weight.

[0315] A surfactant can be considered a substance that reduces the interfacial tension between two phases. Common surfactants include alkyl sulfates (e.g., sodium lauryl sulfate), alkyl trimethyl ammonium salts, alcohol ethoxylates, etc. In one preferred embodiment of the present invention and / or its embodiments, the surfactant contained in the veterinary pharmaceutical formulation can be in the range of 0.1 to 10.0% by weight.

[0316] A lubricant can generally be considered as a substance suitable for reducing friction, such as static friction, sliding friction, and rolling friction. The lubricant is preferably stearic acid or a fatty acid, more preferably an alkaline earth metal stearate, such as magnesium stearate. In one preferred embodiment of the present invention and / or embodiments thereof, the lubricant contained in the veterinary dosage form can be in the range of 0.1 to 10.0% by weight.

[0317] Stabilizers are physiologically acceptable excipients that help preserve the product. Examples include, but are not limited to, alginates, carrageen, gelatin, pectin, and natural gums. In one preferred embodiment of the present invention and / or its embodiments, the surfactant contained in the animal dosage form can range from 0.01 to 3.0% by weight.

[0318] Flow agents, also known as glidants, can be used to improve flowability. Traditionally, talc was used as a flow agent, but today it has been almost completely replaced by colloidal silica. In one preferred embodiment of the present invention and / or embodiments thereof, the flow agent contained in the veterinary dosage form can range from 1 to 3% by weight.

[0319] Disintegrants, also known as tablet disintegrants, are compounds that increase the ability of a dosage form, preferably a tablet, to break down into smaller pieces when contacted with a liquid, preferably water. Non-limiting examples of disintegrants include sodium carboxymethyl starch, sodium starch glycolate, cross-linked polyvinylpyrrolidone, sodium carboxymethyl glycolate, preferably sodium starch glycolate, etc. In one preferred embodiment of the present invention and / or embodiments thereof, the surfactant contained in the veterinary dosage form can be in the range of 1.0 to 7.0% by weight.

[0320] Preservatives are substances that can be added to prevent degradation due to microbial growth or undesirable chemical changes. Non-limiting examples include lactic acid, benzoates, and hydroxybenzoates. In one preferred embodiment of the present invention and / or its embodiments, the surfactant contained in the animal drug form can be in the range of 0.01 to 1.0% by weight.

[0321] The compounds according to the present invention can be administered in various dosage forms. The term "dosage form" means that the compounds according to the present invention are formulated into a product suitable for administration to animals via the intended administration route. Such dosage forms may be referred to herein as formulations or pharmaceutical compositions.

[0322] Pharmaceutical compositions of this invention and / or embodiments thereof may be administered to an animal orally, rectally, vaginally, parenterally, topically, bucally, or nasally.

[0323] In one preferred embodiment of the present invention and / or embodiments thereof, the dosage form useful for oral administration can be a liquid or solid dosage form.

[0324] Liquid dosage forms of compounds are generally solutions, suspensions, or emulsions. A solution is a mixture of two or more components that forms a single phase homogenized at the molecular level. A suspension consists of insoluble solid particles dispersed in a liquid medium, with the solid particles comprising about 0.5% to about 30% of the suspension. The liquid may be aqueous, oily, or both. An emulsion is a heterogeneous dispersion of one immiscible liquid in another and requires an emulsifier for stability. A dry powder (or granules) for reconstitution is mixed with a diluent (e.g., water) immediately before injection to form a solution or suspension, and then reconstituted. The main advantage of this dosage form is that it overcomes the instability problem of solutions or suspensions.

[0325] Liquid dosage forms for oral administration include pharmaceutically acceptable emulsions, microemulsions, solutions, suspensions, syrups, drenches, feed or drinking water formulations, and elixirs. Drenches are liquid oral formulations that are administered directly to the mouth / throat of an animal, particularly a dog, by a "drench gun" or syringe or other suitable device. When administering the composition in the recipient animal's drinking water or as a drench, it may be convenient to use a solution or suspension formulation. The formulation may be, for example, a concentrated suspension that is mixed with water, or a dry formulation that is mixed and suspended in water. In addition to the active compound, liquid dosage forms can contain inert diluents commonly used in the art, such as water or other solvents, solubilizing agents and emulsifiers, e.g., ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (especially cottonseed oil, peanut oil, corn oil, germ oil, olive oil, and sesame oil), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycol, and fatty acid esters of sorbitan, and mixtures thereof. In addition to inert diluents, oral compositions can also contain adjuvants, such as wetting agents, emulsifying and suspending agents, sweetening agents, flavoring agents, and perfuming agents.

[0326] Solid dosage forms for oral administration include capsules, tablets, dragees, pills, powders and granules, chewable feeds, premixes and lozenges. In such solid dosage forms, the active compound is admixed with at least one inert, pharmaceutically acceptable excipient or carrier such as sodium citrate or dicalcium phosphate, and / or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid; b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia; c) humectants such as glycerol; d) disintegrating agents such as agar-agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate; e) solution retarders such as paraffin; f) absorption accelerators such as quaternary ammonium compounds; g) wetting agents such as, for example, acetyl alcohol and glycerol monostearate; h) adsorbents such as kaolin and bentonite clay; or i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets and pills, the dosage forms may also comprise buffering agents.

[0327] The active compound may also be microencapsulated with one or more of the excipients described above. Solid dosage forms such as tablets, dragees, capsules, pills, and granules can be prepared with coatings and shells, such as enteric coatings and other coatings known in the pharmaceutical formulation art, such as enteric coatings, sustained-release coatings, and other coatings. In such solid dosage forms, the active compound may be mixed with at least one inert diluent, such as sucrose, lactose, or starch. Such dosage forms may also contain, as is common practice, additional substances other than inert diluents, such as tableting lubricants and other tableting aids, such as magnesium stearate and microcrystalline cellulose. In the case of capsules, tablets, and pills, the dosage forms may also contain buffering agents. They may optionally contain opacifying agents and be formulated to release the active ingredient only, or preferentially, in a certain part of the intestinal tract, optionally in a delayed manner. Examples of embedding compositions include polymeric substances and waxes.

[0328] Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like.

[0329] Solid oral formulations are administered directly to the animals (tablets, capsules), mixed with the feed, or via a medicated feed block.

[0330] When the oral formulation is administered via the feed of a non-human animal, it can be given, for example, as a discrete feed or as a chewable feed. Alternatively (or additionally), it can be used in the form of a solid pellet, paste, or liquid that is thoroughly dispersed in the recipient animal's regular feed, used as a top dressing, or added to the finished feed. When the oral formulation is administered as a feed additive, it can be convenient to prepare a "premix" in which the oral formulation is dispersed in a small amount of a liquid or solid carrier. This "premix" is then dispersed in the animal's regular feed, for example, using a conventional mixer.

[0331] In one preferred embodiment of the present invention and / or embodiments thereof, dosage forms useful for rectal and vaginal administration can be considered semi-solid dosage forms.

[0332] Compositions for rectal or vaginal administration can be prepared by mixing the compounds of the present invention with a suitable non-irritating excipient or carrier, such as cocoa butter, polyethylene glycol or a suppository wax, which is solid at ambient temperature but liquid at body temperature and therefore melts in the rectum or vaginal cavity to release the active compound.

[0333] In one preferred embodiment of the present invention and / or embodiments thereof, the dosage form is useful for parenteral administration. One route of administration is parenteral administration, particularly injection (e.g., subcutaneous, intravenous, intramuscular, etc.). Parenteral formulations and delivery systems include liquids (e.g., solutions, suspensions, emulsions, and dry powders for reconstitution), semi-solids, and solids (e.g., implants). Most implants used in veterinary medicine are compressed tablets or dispersion matrix systems in which the drug is homogeneously dispersed in a non-degradable polymer, or extrusions. In one embodiment, the compounds of the present invention are administered subcutaneously.

[0334] Injectable preparations, for example, sterile injectable aqueous or oleaginous suspensions, can be formulated according to known techniques using suitable dispersing or wetting agents and suspending agents. Sterile injectable preparations can also be sterile injectable solutions, suspensions, or emulsions in non-toxic parenterally acceptable diluents or solvents, for example, as solutions in 1,3-butanediol. Among the acceptable vehicles and solvents that can be employed are water, Ringer's solution, and isotonic sodium chloride solution. Additionally, sterile, fixed oils are conventionally employed as solvents or suspending media. In this regard, any bland fixed oil can be used, including synthetic mono- or diglycerides. Additionally, fatty acids, such as oleic acid, are used in the preparation of injectable preparations.

[0335] Injectable formulations can be sterilized, for example, by filtration through a bacterial-retaining filter, or by incorporating sterilizing agents in the form of sterile solid compositions which can be dissolved or dispersed in sterile water or other sterile injectable medium before use.

[0336] To prolong the effect of a drug, it is often desirable to slow the absorption of the drug from subcutaneous or intramuscular injection. This can be accomplished by using a suspension of crystalline or amorphous material with poor water solubility. The rate of absorption of the drug then depends on its rate of dissolution, which in turn may depend on crystalline size and crystalline form. Alternatively, delayed absorption of parenterally administered drugs can be accomplished by dissolving or suspending the drug in an oil solution. Injectable depot formulations are made by forming microencapsulated matrices of the drug in biodegradable polymers such as polylactide-polyglycolide. The rate of drug release can be controlled depending on the drug:polymer ratio and the nature of the particular polymer used. Examples of other biodegradable polymers include poly(orthoesters) and poly(anhydrides). Depot injectable formulations can also be prepared by entrapping the drug in liposomes or microemulsions that are compatible with body tissues.

[0337] In one preferred embodiment of the present invention and / or embodiments thereof, dosage forms useful for topical administration (also called transdermal administration) of a compound of the present invention include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, or patches. The active ingredient is admixed under sterile conditions with a pharmaceutically acceptable carrier and any preservatives or buffers that may be required. Ophthalmic formulations, ear drops, and the like are also contemplated as being within the scope of the present invention.

[0338] The ointments, pastes, creams and gels may contain, in addition to the active compounds of this invention, excipients such as animal and vegetable fats, oils, waxes, paraffin, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonite, silicic acid, talc and zinc oxide, or mixtures thereof.

[0339] The compounds of the present invention can also be formulated for use as topical powders and sprays which can contain, in addition to a compound of this invention, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder, or mixtures of these substances.

[0340] Sprays can additionally contain customary propellants, such as chlorofluorohydrocarbons.

[0341] Transdermal patches have the added advantage of providing controlled delivery of compounds into the body. Such dosage forms can be made by dissolving or dispensing the compound in a suitable medium. Absorption enhancers can also be used to increase the flux of the compound across the skin.

[0342] The rate can be controlled by either providing a rate controlling membrane or by dispersing the compound in a polymer matrix or gel.

[0343] In one preferred embodiment and / or embodiments thereof, dosage forms useful for buccal administration of the compounds of the invention include orally disintegrating tablets (ODTs), films, sublingual drops, lozenges, effervescent buccal tablets, toothpastes and mouthwashes.

[0344] In one preferred embodiment of the present invention and / or embodiments thereof, dosage forms useful for intranasal administration of the compounds of the present invention include liquid aerosols or inhaled dry powders. Liquid aerosol formulations can be nebulized to particle sizes that can be delivered primarily to the terminal and respiratory bronchioles.

[0345] Liquid aerosol and inhaled dry powder formulations are preferably delivered throughout the endobronchial tree to the terminal bronchi and ultimately to the parenchymal tissue.

[0346] The aerosolized formulations of the present invention can be delivered using an aerosol-forming device such as a jet, vibrating perforated plate, or ultrasonic nebulizer, preferably selected to allow the formation of aerosol particles having a mass median mean diameter of primarily 1 to 5 pm.

[0347] Furthermore, the formulation preferably has a balanced osmolarity, ionic strength, and chloride concentration, as well as the smallest aerosolizable volume capable of delivering an effective dose of a compound of the invention to the site of infection. Additionally, the aerosolized formulation preferably does not impair airway functionality and cause undesirable side effects.

[0348] Aerosolization devices suitable for administering the aerosol formulations of the present invention include, for example, jet, vibrating porous plate, ultrasonic nebulizers, and high-energy dry powder inhalers, which can nebulize the formulations of the present invention to aerosol particles primarily in the 1-5 pm diameter range. By primarily, in this application, we mean that at least 70%, but preferably greater than 90%, of all aerosol particles generated are in the 1-5 pm range. Jet nebulizers operate by using air pressure to break up liquid solutions into aerosol droplets. Vibrating porous plate nebulizers operate by using a sonic vacuum created by a rapidly vibrating porous plate to force solvent droplets through the porous plate. Ultrasonic nebulizers operate by using a piezoelectric crystal to shear a liquid into small aerosol droplets.

[0349] The concentration of the compound of the...

Claims

1. A compound of the following formula (I) or a stereoisomer, a physiologically acceptable salt, or a solvate thereof, or a mixture of any or all of these: 【Chemistry 1】 [In the formula, R １ teeth, independently selected from the group consisting of hydrogen, methyl, and trifluoromethyl; R ７ teeth, C １－６ -Alkyl, C ２－６ -Alkenyl, C １－６ -alkoxy, hydroxy and NR ８ R ９ are independently selected from the group consisting of Each C １－６ -Alkyl, C ２－６ -alkenyl, or C １－６ -Alkoxy 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- to 10-membered heteroaryl, C １－６ -Alkoxy, C １－６ -Alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR ８′ R ９′ , C(=O)OR １０′ , S.R. １０′ , S.O.R. １０′ , S.O. ２ R １０′ , S.O. ２ N.R. １１′ R １２′ 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 ２－６ -Alkenyl, C ２－６ -Alkynyl, C ３－１０ -cycloalkyl, 5-10 membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl, C １－６ -Alkoxy-C １－６ -Alkyl, C ３－１０ -Cycloalkyl-substituted C １－６ -C substituted with alkyl, 5-10 membered heterocycle １－６ -Alkyl, C ６－１０ -aryl substituted C １－６ -C substituted with alkyl, 5-10 membered heteroaryl １－６ - alkyl, or R ８ and R ９ together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms selected from 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- to 10-membered heteroaryl, 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 ６－１０ -aryl substituted C １－６ -C substituted with alkyl or 5-10 membered heteroaryl １－６ -Alkyl or R ８ and R ９ said heterocycle formed together with the N atom to which they are attached 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- to 10-membered heteroaryl, C １－６ -alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR ８″ R ９″ , C(=O)OR １０″ , S.R. １０″ , S.O.R. １０″ , S.O. ２ R １０″ , S.O. ２ N.R. １１″ R １２″ and C(=O)NR １１″ R １２″ may be substituted with one or more substituents independently selected from the group consisting of: R ８′ , R ９′ , 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; 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 atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said ring containing 5 or 6 carbon atoms containing one or more C １－３ and / or one or more of the ring carbons may be substituted by -NH-, -N=, -N-, -O-, -S(O)-, -S(O) ２ may be replaced by - or -S-, or R １３ and R １４ together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, said ring containing 5 or 6 carbon atoms containing one or more C １－３ -alkyl and / or one or more of the ring carbons may be replaced by -NH-, -N=, =N-, -O- or -S-; 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, 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, R １７ are independently hydrogen, 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, R １８ are independently hydrogen, 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 -aryl, C ６－１０ -aryl is C １－６ -Alkyl, C ２－６ -Alkenyl, C ３－１０ -cycloalkyl, 5-10 membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl, C １－６ -Alkoxy, C １－６ -Alkylmercapto, halogen, cyano, nitro, hydroxy, mercapto, NR ２０ R ２１ , C(=O)OR ２２ , S.R. ２２ , S.O.R. ２２ , S.O. ２ R ２２ , S.O. ２ N.R. ２３ R ２４ 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, C ６－１０ -aryl, 5- to 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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- to 10-membered heteroaryl, C １－６ -Alkoxy or C １－６ -Alkylmercapto or R ２０ and R ２１ said heterocycle formed together with the N atom to which they are attached 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- to 10-membered heteroaryl, C １－６ -alkoxy, carbonyl, halogen, cyano, hydroxy, mercapto, NR ２０′ R ２１′ , C(=O)OR ２２′ , S.R. ２２′ , S.O.R. ２２′ , S.O. ２ R ２２′ , S.O. ２ N.R. ２３′ R ２４′ and C(=O)NR ２３′ 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; R ２０′ , R ２１′ , R ２２′ , R ２３′ and R ２４′ is hydrogen and C １－６ -alkyl; R ２５ is hydrogen and C １－６ -alkyl.

2. R ７ but, C １－６ -Alkyl, C ２ - ６ -Alkenyl, C １－６ -alkoxy, hydroxy and NR ８ R ９ are independently selected from the group consisting of Each C １－６ -Alkyl, C ２ - ６ -Alkenyl 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 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 ３－１０ -Cycloalkyl, C ６－１０ - independently selected from the group consisting of aryl, 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further ring atoms are selected from N, S and O; Each C １－６ -Alkyl, C ３－１０ -Cycloalkyl, C ６－１０－ Aryl, 5- to 10-membered heterocycle, and 5- to 10-membered heteroaryl or R ８ and R ９ said heterocycle formed together with the N atom to which they are attached is C １－６ -Alkyl, C １－６ -alkoxy, halogen, cyano, hydroxy, NR ８″ R ９″ , C(=O)-OR １０″ and C(=O)NR １１″ R １２″ may be substituted with one or more substituents independently selected from the group consisting of: R ８′ , R ９′ , 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 2. The compound of claim 1, wherein each of the radicals is independently selected from: - alkyl.

3. R ７ but, C １－６ -Alkyl, C ２ - ６ -Alkenyl, C １－６ -alkoxy, hydroxy and NR ８ R ９ are independently selected from the group consisting of Each C １－６ -Alkyl, C ２ - ６ -Alkenyl or C １－６ -Alkoxy is C １－６ -alkyl, 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′ 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 - independently selected from the group consisting of 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 or unsaturated heterocyclic ring having 3 to 12 ring atoms, in which one ring atom is N and 0, 1, 2 or 3 further 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 R ８ and R ９ said heterocycle formed together with the N atom to which they are attached is C １－６ -Alkyl, C １－６ -alkoxy, hydroxy and NR ８″ R ９″ may be substituted with one or more substituents independently selected from the group consisting of: R ８′ , R ９′ , R １０′ , R １１′ and R １２′ is hydrogen or C １－６ -alkyl; R ８″ and R ９″ is hydrogen or C １－６ 3. The compound according to claim 1 or 2, wherein:

4. R ７ The compound of any one of claims 1 to 3, wherein is independently selected from the group consisting of methyl, ethyl, isopropyl, ethenyl, 2-propenyl, methoxy, ethoxy, hydroxy, dimethylamino, and morpholin-4-yl.

5. R １３ and R １４ together with the atom to which they are attached form a non-aromatic ring containing 5 or 6 carbon atoms, said ring containing 5 or 6 carbon atoms containing one or more C １－３ and / or one or more of the ring carbons may be substituted by -NH-, -N=, -N-, -O-, -S(O)-, -S(O) ２ may be replaced by - or -S-, 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″ Independently C １－３ - alkyl, 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″ Independently C １－３ - alkyl, R １７ are independently hydrogen, C １－３ Alkyl, or C １－３ is an alkoxy; R １８ are independently hydrogen, C １－３ Alkyl, or C １－３ The compound according to any one of claims 1 to 4, which is alkoxy.

6. R １３ and R １４ together with the atom to which they are attached form an aromatic ring containing 5 or 6 carbon atoms, and the ring containing 5 or 6 carbon atoms contains one or more C １－３ -alkyl and / or one or more of the ring carbons may be replaced by -NH-, -N=, =N-, -O- or -S-; 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″ Independently C １－３ - alkyl, 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″ Independently C １－３ - alkyl, R １７ are independently hydrogen, C １－３ Alkyl, or C １－３ is an alkoxy; R １８ are independently hydrogen, C １－３ Alkyl, or C １－３ The compound according to any one of claims 1 to 5, which is alkoxy.

7. R １９ but, C ６－１０ -aryl, C ６－１０ -aryl is C １－６ -Alkyl, C ３－１０ -cycloalkyl, 5-10 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 together with the N atom to which they are attached form a saturated or unsaturated heterocyclic ring having 3 to 12 ring atoms, with 0, 1, 2 or 3 further ring atoms 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 said heterocycle formed together with the N atom to which they are attached is C １－６ -Alkyl, C ３－１０ -cycloalkyl, 5-10 membered heterocycle, C ６－１０ -aryl, 5- to 10-membered heteroaryl, C １－６ -alkoxy, halogen, cyano, hydroxy, NR ２０′ R ２１′ , C(=O)OR ２２′ and C(=O)NR ２３′ R ２４′ 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 7. The compound according to claim 1, wherein:

8. R １９ but, C ６－１０ -aryl, C ６－１０ Aryl is C １－６ -Alkyl, C １－６ The compound according to any one of claims 1 to 7, which is optionally substituted with one or more substituents independently selected from the group consisting of alkoxy, halogen, cyano, nitro and hydroxy.

9. R １９ C ６－１０ -aryl, Said C ６－１０ Aryl is C １－６ The compound according to any one of claims 1 to 8, which is optionally substituted with one or more substituents independently selected from the group consisting of alkyl, halogen, cyano and nitro.

10. R １９ C ６－１０ -aryl, Said C ６－１０ The compound according to any one of claims 1 to 9, wherein aryl is phenyl substituted with one, two or three substituents independently selected from the group consisting of fluoride, chloride and bromide.

11. R ２５ The compound according to any one of claims 1 to 10, wherein is hydrogen.

12. The compound according to any one of claims 1 to 11, which exists in the form of the (S)-enantiomer.

13. A process for the preparation of a compound according to formula (I) comprising the steps of: Compound of formula (A): 【Chemistry 2】 with a compound of formula (B): 【Chemistry 3】 [Hal is a halogen, R １ , R ７ , R １３ , R １４ , R １５ , R １６ , R １７ , R １８ , R １９ and R ２５ is defined as in any one of claims 1 to 10, to obtain a compound according to formula (I).

14. a compound according to formula (I) as defined in any one of claims 1 to 12, and - A veterinary pharmaceutical composition comprising one or more physiologically acceptable excipients.

15. The veterinary pharmaceutical composition of claim 14, wherein the one or more physiologically acceptable excipients are selected from carriers, fillers, flavoring agents, binders, antioxidants, buffers, sugar components, lubricants, surfactants, stabilizers, flow agents, disintegrants and preservatives, and mixtures thereof.

16. A compound according to formula (I) as defined in any one of claims 1 to 12 or a veterinary composition as defined in claim 14 or 15 for use as a medicament.

17. A compound according to formula (I) as defined in any one of claims 1 to 12 or a veterinary composition as defined in claim 14 or 15 for use in the treatment of disorders / diseases caused by helminths.

18. A compound according to formula (I) as defined in any one of claims 1 to 12 or a veterinary composition as defined in claim 14 or 15 for the use as defined in claim 17, wherein said disease is canine heartworm disease.

19. A compound according to formula (I) as defined in any one of claims 1 to 12 or a veterinary composition as defined in claim 14 or 15 for the use as defined in claim 17 or 18, wherein the helminth is Dirofilaria immitis.

Images